ANATOMY

01.01- Gonad Development

1.How is the gonad development in embryo?

In week 4, primordial germ cells from wall of yolk sac migrate  indifferent gonad in the posterior of
abdominal wall.

Male: Y chromosome (Sry gene)  encodes TDF (testis determining factor)  formation of testis (
consisting 2 type of cells, Leydig cells secrete testosterone and DHT which induce the formation of male
genitalia from Wolffian Duct , sertoli cells secrete Mullerian Inhibiting Factor)

Female: doesn’t have Y chromosome not producing MIF WNT 4 gene in chromosome 1 
formation of female genitalia from Mullerian Duct.

2.How is the spermatogenesis in male?

Primordial germ cells arrive in indifferent gonad ( week 4) and remain dormant until puberty 
differentiate into type A spermatogonia when reaches puberty some differentiates into type B
spermatogonia (46, 2 n)  MEIOSIS 1 starts from DNA replication and form primary spermatocyte (46,
4 n) then goes through synapsis>crossover>cell division 2 secondary spermatocyte (23,2 n) 
MEIOSIS II causes the centromere splitting  4 spermatids (23, n) + spermiogenesis= spermatozoa

There’s blood testis barrier which is formed between type B spermatogonia and primary spermatocyte
to protect the spermatogonia from antibody attack.

3.How is the oogenesis in male?

Primordial germ cells arrive in indifferent gonad ( week 4) and differentiate into oogonia (46, 2n) 
MEIOSIS I starts from DNA replication and form completely primary oocyte (46, 4 n) arrested in
prophase in month 5 of fetal life > during each monthly cycle when the girl reaches puberty, one
primary oocyte becomes unarrested and forms a polar body and a secondary oocyte (23, 2n) 
MEIOSIS II and for the second time, secondary oocyte arrested in metaphase (developing in Graafian
follicle) and ovulated  FERTILIZATION in fallopian tube causes secondary oocyte completes meiosis II
 1 ovum + 3 polar bodies (lysis). Uneven cleavage of cytoplasm causes the greater reserve of energy
for the fetal development.

The meiosis 1 prophase stage coud last for 50 years in woman due to only one primary oocyte
undergoes meiosis 2 every monthly cycle.

01.02- First 8 Weeks of Development

1.How does the implantation occur after the fertilization?
Spermatozoa + secondary oocyte arrested in metaphase meiosis 2 fused in ampulla of fallopian tube=
zygote  2-cell blastula (D-2)  4- cell blastulal (D-3)  morula 32 cell (D-4)  blastocyst (D-5)
formed from morula which extracellular got tensely packed and created fluid cavity (blastocyst cavity).
This cavity divides blastocyst into 2 cells mass : inner cell mass= embryoblast (embryo) + outer cell
mass =trophoblast (placenta)  implantation must occur in D-6 of blastocyst in which embryonic pole
implants first, thus it can happen everywhere. The result of mitotic division in this phase results the cell
with the same size as the original cells.

2.What does spermatozoa undergo prior to fertilization?

It undergoes capacitation (removal of several proteins from the plasma membrane of the acrosome)
and acrosome reaction (release of hydrolytic enzyme to enter zona pellucida  cortical reaction to
inhibit penetration of other sperms, thus preventing polyspermy)

3.Why could HCG be detected in pregnancy woman?

At the end of first week, trophoblast differentiates into cytotrophoblast which is mitotically active and
syncytiotrophoblast which is formed from the fused of cytotrophoblast and villous-like to attach in
functional layer of endometrium in the posterior wall of uterus during the progestational phase of the
menstrual cycle. This syncytiotrophoblast secrete hCG to preserve corpus luteum producing
progesterone in order to maintain the pregnancy. Thus, it can be detected in the first week of
pregnancy.

Low hCG indicates spontaneous abortion or ectopic pregnancy.

High hCG indicates multiple pregnancy, hydatidiform mole, gestational trophoblastic disease.

4. How does the ectopic pregnancy occur?

It occurs when the blastocyst doesn’t reach the uterus, whereas the implantation should occur in D-6. In
addition, the secondary oocyte is released from ovary into the peritoneal cavity and then sucked into
the fallopian tube by the villous. The impairment of the sucking process can cause peritoneal cavity
fertilization which is known as the abdominal ectopic pregnancy, most commonly occurs in
rectouterine pouch.

On the other hand, the impairment of zygote migration into the uterus caused by endometrioris,
scarring of fallopian tube due to PID, pelvic surgery, and the usage of DES will result the tubal ectopic
pregnancy.

5.How does utero-placental circulation establish?

In the week 2, the syncytiotrophoblast erodes and invades the endometrium forming the villous like
fetal artery >< uterine artery fills the lacunae space  enable the circulation of small molecules
between fetal and maternal.

6. What are the results of week 2?

Inner cell mass= embryoblast becomes the bilaminar embryo and divided into:

Epiblast differentiate into functional organ of embryo, i.e. amniotic cavity + extraembyronal
mesoderm (somatic lines the cytotrophoblast, forms connecting stalk suspends with in chorionic
cavity, covers amniotic cavity, visceral  covering the yolk sac). The wall of chorionic cavity is chorion
consisting extraembryonal somatic mesoderm+ cytotrophoblast + syncytiotrophoblast).

Hypoblast  primary yolk sac where hematopoeisis occurs in the surrounding mesoderm (up to 6
weeks)  disappearing as primitive organ.

The fusion of epiblast and hypoblast form prechordal plate which becomes the future mouth. Thus,
prechordal plate determines the head polarity of the fetus.

7.Where does hematopoiesis occur in fetal life?

Young Liver Synthesizes The Blood  yolk sac (up to 6 weeks), liver, spleen, thymus (6 weeks to third
semester), bone marrow.

8. How is the process of gastrulation?

In the week 3, there’s a formation of primitive streak in the midline and elongate from cranio-caudal.
Then, the epiblast cells from the right and left side move to the midline and go down through to the
primitive streak.
- The cells invading the hypoblast and pushing it away become the endoderm.
-The cells which fill the gap between the epiblast and hypoblast is known as mesoderm.
-The epiblast cells which don’t migrate become the ectoderm (from medial-lateral: neuroectoderm,
neural crest, and surface ectoderm).
-The cells which migrate down through the primitive streak and stay in the midline would become the
notochord. This notochord sends the signals (Sonic Hedgehog factor) for cells differentiation and gives
rise to the nucleus pulposus in the adult life.
Thus, the gastrulation establishes the 3 layers embryo: ectoderm, mesoderm, and endoderm.

9.How is the process of body fold?

In the week 4, the flat embryo starts to fold from the lateral edges into the midline and forms 3 tubes.
The inner tube is known as gut tube covered by endoderm. The second tube is covered by mesoderm
and will rise into the muscle, bone, and connective tissue. The outer part is covered by ectoderm and
will rise into various derivatives, such as epidermis. The failure of the body fold will cause the
gastroschisis in which the bowel loop grows out from the abdominal wall defect.

01.03-Histology: Epithelia
1.What are the subtypes of epithelium cells?
-simple columnar (small intestine)/ cuboidal (renal tubule)/ squamous (endothelium)
-stratified cuboidal (salivary duct) / squamous (with keratine: skin, without keratine: esophagus)
-pseudostratified columnar with cilia (respiratory tract)

2.Why does cystic fibrosis have thick mucous?

The defect of Cl transporter in the epithelium lining the respiraroty and GI tract causes the NaCl couldn’t
pass the epithelium from the luminal into the cells.

3.What are the pathways of the cells?

-Transcellular pathway: larger molecules or ion pass throught he cells
-Paracellular pathway: movement between cells and involved the cell junctions.

4.What are the types of cytoskeletal elements?

-Microfilament: actin microfilament that polymerize and depolymerize continuously required ATP,
found in microvili.
-Intermediate filament: usually stable once formed thus functions as anchoring junctions in the
desmosome and hemidesmosome. There are 4 types: type 1 (keratin), type 2 (desmin: GI tract, cardiac
& skeletal muscle, vimentin: fibroblast, endothelial cells, glial fibrillary acidic protein: astrocyte), type 3
(neurofilaments in neuron), type 4 (lamins).
-Microtubules: undergoes polymerize and depolymerize continuously  required ATP. It provides the
tracks for intracellular transport by using ATPase motor moleculues (kinesin for anterograde transport &
dynein for retrograde transport). Microtubules are the components of true cilia in the respiratory tract
and flagella in the sperm. The defect of dynein can result as kartagener syndrome.

5. What are types of cellular junction?

It can be divided into 3:
-Barrier junction: tight junction (zonula occluden) and zonula adheren. Both consist of microfilament
and protect the integrity of the cells. The tight junction also creates the cell polarity.
-Anchoring junction: desmosome (cell to cell) and hemidesmosome (cell to basal lamina/ extracellular
matrix). Both are stable, thus made from thick intermediate filaments, seen darker in the electrone
microscopy. Auntoantibodies to desmosome  pemphigus vulgaris, hemidesmosome  bullous
pemphigoid.
-Gap junction: connecting the cell to cell directly through connexon, found in the cardiac muscles. It
permits the transport of calcium and cAMP.
Every junction has the specific adhesion molecules to allow cells to adhere to one another or to
components of extracellular matrix, such as cadherin (calcium dependent) and integrin (calcium
independent) which attaches the basal surface of the cells to the basement membrane.

01.04-Back and Autonomic Nervous System

1.Why are lumbar puncture and epidural anesthesia performed in L4-L5?
Vertebral column consists of 33 vertebrae (7 cervical, 12 thorax, 5 lumbar, 5 fused sacrum, 3-4
coccyx) and 31 pairs spinal nerve (8 cervical, 12 thorax, 5 lumbar, 5 sacrum, coccyx 1) . The
cervical spinal nerves exit superiorly to their corresponding vertebra, while the thoracal nerves exit
inferiorly to their corresponding vertebra.

The spinal cord terminates at the level L2-L3 in the adult (L3 in the young children)and the meninges
terminates at the level S2-S3. Thus, we apply the lumbar puncture in between L4-L5. L4 is easily
identified by drawing the line from iliac crests from each side to the midline in the back. During the
lumbar puncture, needle passes: skin superficial fascia  deep fascia  supraspinous ligament 
interspinous ligament interlaminar space  epidural space (the epidural anesthesia is applied here)
 dura  arachnoid  subarachnoid space.

2.Why does the herniated nucleus pulposus affect the spinal nerve one number below the the involved
disk?

Herniation usually occurs in the C5/C6, C6/C7, or L4/L5. Note that the nucleus pulposus can herniate
through the annulus fibrous in the posteriolateral direction due to the strength and position of posterior
longitudinal ligament.

The spinal nerve exits from the spinal cord into the intervertebral foramen and above the intervertebral
disk. Each the intervertebral disk is numbered by the vertebral body above the disk. Thus the protrusion
of L4 nucleus pulposus will not compress the L4 spinal nerve because it has passed above the
intervertebral disk, except L5 .

3.Why is the ventral rami thicker than dorsal rami?

-Dorsal rami only innervates the skin of back and neck, deep muscle of back. Other than that is
innervated by ventral rami. Rami is formed from the mixed of ventral root (motor neuron) and dorsal
root (sensory neuron).

4.What are differences between somatic and autonomic nervous system (ANS)?
Both could work either voluntarily or involuntarily.
The differences are somatic nerves innervate skeletal muscle only, while the ANS innervates the
cardiac, smooth muscle, and gland. The somatic nervous system has one neuron pathway (extend from
CNS into the skeletal muscle), while in the PNS has the two neuron pathway (extend from CNS  motor
ganglion = preganglionic nerve fiber, motor ganglion target organ = post ganglionic nerve fiber),
except for adrenal medulla which has only one neuron pathway because it is derived from neural crest
and acts like neuron.

Location of cell body for somatic nerves is in the CNS which is in the brain or spinal cord (derived from
neuroectoderm ) and called nucleus, while the cell body for ANS is in the CNS (derived from
neuroectoderm) and PND (derived from neural crest) and called ganglion.

5.What are the main differences of sympathetic and parasympathetic nervous system?
The location of the preganglionic cell body: sympathetic in the spinal cord from T1-L2 (thoracolumbar
system), parasympathetic in the brain (nucleus N. III, VII, IX, X) and spinal cord from S2-S4 (craniosacral
system).
The distance from the CNS and postganglionic cell body: sympathetic is closer than parasympathetic .
On the other hand, distance of postganglionic cell body to endogen (terminal ganglia): sympathetic is
further than parasympathetic.

6. How is the innervations of sympathetic nervous system?

The first cell bodies of sympathetic nervous system is located in the spinal cords from T1-L2. The upper
part of T1 and below of L2 are innervated by the the closest preganglionic to them. For example, C3 is
innervated by T1. The divisions are (preganglionic  postganglionic  target organ):

1. Spinal cord level T1-L2 (somatic)  sympathetic chain ganglia (paravertebral ganglia contains 31
ganglia)  head (T1-T2), thoracic viscera (T1-T5), smooth+cardiac muscle+ glands of body wall
and limbs (T1-L2).
2. Thoracic splanchnic nerves T5-T12 (visceral)  prevertebral ganglia (celiac, aorticorenal,
superior mesenteric ganglia)  smooth muscle+ glands of the foregut and midgut.
3. Lumbar splanchnic nerves L1-L2  prevertebral gangia (inferior mesenteric + pelvic ganglia) 
smooth muscle+ glands of the hindgut and pelvic.
*splanchnic means the postganglionic nerves are located in the blood vessels corresponding to
the its name.
7. How is the innervations of the parasympathetic?
The N. X and S2-S4 acts similarly because they have postganglionic nerve fiber in the wall of organ.
01.05-Thorax
1.How is the pathophysiology of the peau d’orange?
-The tumor invades the cooper ligament and pulls in the ligament attached to the skin. While
the edema due to tumor protrudes to the skin and form peau d’orange.

2.Why is the breast tumor in the medial most likely to metastase to the contralateral part?
-Lymph drainage of the breast: lateral portion to the axillary node, whereas the medial portion
to the parasternal (internal thoracic nodes). This parasternal nodes has the direct connection to
the nodes in the contralateral side.

3.What causes the tracheoesophageal fistula?

-The failure of tracheosophageal septum fusion. In the 85% cases included the atresia
esophagus. The connection between the esophagus and the trachea manifests as the gastric
reflux, cyanosis after feeding, and abdominal distention after crying.

4.Where could we perform the pleural puncture?

In the intercostals 6-8 (midclavicular line), 8-10 (midaxillary line), and 10-12 (paravertebral line).

5.Where is the location of each fissure and lobe of the lung?

The horizontal fissure is in the 4th rib, and oblique fissure is in the 5th intercostals space.
The clinical correlate is the stabbing wound would result with injury of this organ if:
-Above the 4th rib would damage the right superior lobe, below the 4th would damage right
medial lobe.
-Below the 5th intercostals would damage both inferior lobe of the lung, above the left 5 th
intercostals would damage left superior lobe.

6.How is the drainage of lymphatic?

Right lung right lymphatic duct internal jugular vein
Left lung  thoracic duct  left subclavian vein. Thoracic duct carries all lymphatic drainage
from body below diaphragm, left side of the trunk and head thus the metastatic below
diaphragm passes this duct. The metastatic from the left lung into the right lung could occur
because the lower lobe of the lung also drains into the bronchomediastinal lymphatic trunk 
right lymphatic duct.

7.What are differences between trachea, bronchus, bronchioles, and alveolus?

From upper to lower= from more rigid to more elastic

Trachea Bronchi Bronchioles Alveolus

Pseudostratified Pseudostratified Simple cuboidal/ Simple squamous
ciliated columnar ciliated columnar  columnar, no
(Goblet cells), simple columnar, seromucous glands
cartilage + cartilage +
APUD + DNES + APUD + DNES + Clara cells: stem cell, Type I pneumocyte:
Kulchitsky cells Kulchitsky cells detoxify airborne post mitotic (given
(producing serotonin) (producing serotonin) pollution, secrete rise from type II), gas
serous like surfactant, exchange
relate to Cl Type II pneumocyte:
transporter (in CF) stem cell, produce
surfactant
Alveolar
macrophages= dust
cells

8. What is the projection of the heart?

Right side: 3-6, Left: 2-5. Landmark: anterior part of the heart: coronary sulcus= atrioventricular
sulcus encircles the heart from anterior to the upper posterior, dividing the right atrium and
right ventricle, other is interventricular sulcus divides the right and left ventricle. The right
border is the right atrium, anterior wall is right ventricle, posterior wall is the left atrium, and
left border and inferior border are left ventricle.
9. Where is the best location to hear the murmur?

10.How is the development of the heart?

The atria is formed from the fusion of the sinus venosus and primitive atrium, while the
ventricle is formed from the fusion of the primitive ventricle and bulbus cordis. As the atria and
ventricle get larger, they will fold downward and will make the atria being upper the ventricle.
The sinus venosus and bulbus cordis contain the smooth muscle, thus give rise to the smooth
part of atria and ventricle respectively.

11.How is the development of the atrium septum?

After heart has been formed, the neural crest migrates to the heart and forms the septum
primum. The septum primum is growing down to the endocardial cushion (while the endocarial
cushion is growing up) and creates the foramen primum as it hasn’t reached the cushion.
However, the septum primum will keep growing down and reaching the endocardial cushion. If
it happens, there is no opening that allows the blood flow from the R  L atrium. Therefore,
before it happens, the foramen secundum is formed from the apoptosis of upper part of
septum primum.

After that, the septum secundum is formed in the right side of the septum primum. This septum
secundum is thicker and more rigid than the septum primum. Since the growing of septum
secundum closes the opening of foramen secundum, the blood will flow from the bending of
septum primum due to the higher pressure in the right atrium. This “hole” is called foramen
ovale. In the postnatal life, the foramen ovale will remained open in the same cases and doesn’t
cause any pathology as long as the left atrium has the higher gradient than the right atrium.

12. How does ASD occur?

ASD is acyanotic condition which can be classified into primum type ASD and secundum type
ASD. Primum type ASD is caused by defect of neural crests migration in the endocardial cushion
resulting with the failure of septum primum and endocardial cushion fusion. The location of this
defect is near atrioventricular septum. On the other hand, secundum type ASD is the most
common ASD which is caused by excessive resorption of septum primum or the
underdevelopment of septum secundum.The location of this defect is in the upper border the
fossa ovalis. ASD patient is at risk of developing embolus.

13.How is the formation of the ventricular septum?

The development starts from week 4-8, embryonal ventricular septum (muscular IV septum)
grows in the floor of ventricle and fuses with the aorticopulmonary septum (membranous IV
septum). Aoticopulmonary septum is derived from the migration of the neural crest that
invaginates in the heart wall and separates the truncus arteriosus into the aorta and pulmonary
trunk.

14.What is the cause of Tetralogy of Fallot?

It is the most common cause of congenital heart defect and one of cyanotic condition (RL). It
occurs due to the failure of aorticopulmonary septum to align properly. It makes the aorta is
bigger than the pulmonary trunk and there’s defect in the ventricular septum. As the result,
right ventricle becomes hypertrophy.

15. What are differences between the persistent truncus arteriosus and transposition of the
great arteries?
Truncus arteriosus occurs when there is only partial development of aorticopulmonary septum
so only one large vessel leaves the heart from the both ventricles. It is always accompanied by
ventricular septal defect. While the transposition of the great arteries occur when the truncus
arteriosus fails to develop spiral version. Therefore, the deoxygenated blood from right
ventricle will leave the heart through the aorta and oxygenated blood from left ventricle will
leave the heart through the pulmonary trunk. This closed circuit is often accompanied by other
defects such as PDA, ASD, or VSD. The TGA is commonly found in the diabetic mother.
Persistent truncus arteriosus and TGA could lead to cyanotic condition because R L shunt
after birth.
16.Explain about the blood supply of the heart!
Right coronary artery sits in the coronary sulcus and supplies the right atrium and the right
ventricle. The branches are included sinoatrial nodal artery, AV nodal artery, and posterior
interventricular artery that goes posteriorly to the heart and supplies part of right and left
ventricle and posterior third of interventricular septum.

Left coronary artery is shorter that the right coronary artery. The first branch is the circumflex
artery that sits in the coronary sulcus (supplies the left border of the heart and posterior-
inferior of left ventricular wall) and goes posteriorly to form anastomosis in the posterior
interventricular septum, The second branch is anterior interventricular artery= left anterior
descending that supplies anterior wall of left ventricle, anterior two thirds of the
interventricular septum, bundle of His, and apex. This is the common site of occlusion (50%)
followed by right coronary arteri (30%) and circumflex artery (20%).

Right dominant heart if posterior interventricular artery arises from right coronary.

17. How is the conducting system of the heart?

The cardiac conduction system is a specialized group of myocardium that doesn’t have
innervations and could communicate one to another. The communication facilitated by the gap
junction allows the heart to contract at the same rate but not simultaneously.

SA (in the crista terminalis, supplied by RCA)  AV nodal (in the interatrial septum near the
opening of coronary sinus, supplied by RCA) that slows the rate from AV node to enable the
ventricular filling and determines the PR interval in the ECG (+- 0,15 s)  bundle of His
(supplied by LAD) that conducts the impulse to the right and left ventricle  purkinje fibers
run along in the endorcardial surface and rich of glycogen.

However, heart is innervated by the sympathetic (T1-T5 spinal cord) that increases the heart
rate and senses the ischemia (angina) then delivers this signal to the dorsal spinal cord 
ascending pathway  to the postcentral gyrus in the cortex  interpretation as the
dermatome pain around chest and the upper limb = referred pain.
While the parasympathetic nerve decreases the heart rate and monitors the cardiac reflexes
(PCO2, O2, and wall tension) then delivers this signal via vagal nerve to the brainstem
(unconscious response).

18. How do we differ the cardiac muscles from the skeletal muscles?
The cardiac muscles are striated muscles like the skeletal muscles, but they have centrally
located nuclei, branching pattern, and intercalated disk with the gap junction.

19.How is the division of mediastinum?

Superior mediastinum (above T4)  there are 5 organs from posterior to anterior, esophagus >
trachea > artery (part of ascending aorta, aortic arch, part of descending aorta) > vein (superior
vena cana  R and L brachiocephalic vein) > thymus.

Posterior mediastinum (below T4 and behind the pericardium)  esophagus is located

posteriorly of left atrium, therefore left atrium enlargement could cause dysphagia. Descending
aorta is located in the left and posterior to the esophagus.

20. What will we see in the CT scan images?

Figure out that the T2 is above T4. So, we’ll see as the rules: esophagus trachea 3 branches
of arteries (left subclavian artery, common carotid artery, brachiocephalic trunk)  vein (right
brachiocephalic vein) thymus.
Figure out in the T3, we start to see the aortic arch. The esophagus and trachea are in the same
position. Below the brachiocephalic vein, we start to see the superior vena cava.

Figure out in the T4, trachea starts to bifurcate so it looks larger. We can see the descending
aorta, ascending aorta, and superior vena cava.
Figure out in the T5, we couldn’t see the trachea anymore as it has bifurcated into the
bronchus. We could see the descending aorta, pulmonary trunk, ascending aorta, superior vena
cava.

In this image we could figure the part of the hearts based on its region. In the posterior, we
could see the descending aorta which is closed to the left atrium. Anterior view is dominated by
the right ventricle followed by the right ventricle in the right side and left ventricle in the left
side.
21.How is the fetal circulation and shunts?

Umbilical vein (ligamentum teres of the liver) contains oxygenated blood from placenta 
ductus venosus (ligamentum venosum)  mixed with blood from inferior vena cava that carries
deoxygenated blood from the lower limbs  enter right atrium pass through the foramen
ovale (fossa ovalis) into the left atrium  left ventricle  ascending aorta

Superior vena cava that carries deoxygenated blood from the head and upper limb enter the
right atrium  right ventricle  pulmonary trunk  pass through the ductus arteriosum
(ligamentum arteriosum) mixed blood flows into descending aorta  umbilical arteries
(median umbilical ligament). Prenatally, the pressure in the pulmonary is greater than the aorta
that allows the oxygenated blood flowing into the 3 major arteries (brachiocephalic artery, left
common carotid artery, left subclavian artery)  brain.

22.Why does the premature infant have the greater risk to develop patent ductus arteriosus?

Premature infant still has the high level of prostaglandin which will decrease in the 9th month of
the gestation. The low level of prostanglandin and high level of O2 and bradykinin will stimulate
the closure of ductus arteries by the contraction of smooth muscle in it. Therefore, in the
premie infant, the antagonist of prostaglandin such as indomethacin is administered. Besides
that, PDA is commonly found in the baby from the mother with rubella infection.
23. Why does the manifestation of postductal coarctatio aorta (adult type) occur later than the
preductal coarctatio aorta (infantile type)?

In the postductal coarctatio aorta (the most common type), the narrowing of the aorta is found
distal to the ductus arteriosus. It leads to the decrease flow of the oxygenated blood into the
lower limb. Thus, the intercostal arteries provide the collateral circulation between the thoracic
aorta and thoracic artery that results in rib notching. The manifestation in the adult is the blood
pressure in the upper limb> lower limb. In contrast, the preductal coarctatio is commonly
found in the patient with Turner Syndrome and the symptoms are developed earlier.

01.06-Abdomen, Pelvis, Perineum

1.How is the process of the descent of the testes?

Anterior abdominal wall layers: skin superficial fascia: camper (fatty)- scarpa external
oblique  internal oblique  transversus abdominis  transversalis fascia  extraperitoneal
connective tissue  parietal peritoneum.

Testis develops in the posterior extraperitoneal tissue near the kidney then testis migrates
downward into the scrotum (derives from the invagination of skin + scarpa which changed its
name into dartos fascia). In the order, the testis in the extraperitoneal tissue  deep inguinal
ring (transversalis fascia) and covered by internal spermatic cord pass under the transverses
abdominis muscle  internal oblique muscle and covered by cremasteric muscle and fascia
which is derived from the falx inguinalis (conjoint tendon) of internal oblique muscle 
external oblique muscle and covered by the external spermatic fascia which is derived from the
external oblique fascia  dartos fascia + skin (scrotum)
In conclusion, the testis will be covered by 3 layers (internal spermatic fascia , cremasteric
muscle+ fascia, external spermatic fascia). The cremasteric muscle regulates the temperature
for the testis by moving it upward or downward to the body.

2.What are the differences between indirect inguinal hernia and direct inguinal hernia?
Both emerge from the superficial inguinal ring. The indirect inguinal hernia follows the same
pathway with the descent of the testes so it is covered by 3 layers (external spermatic fascia,
cremasteric muscle+ fascia, internal spermatic fascia), lateral to the inferior epigastric artery,
and could be palpated in the 1/3 distal of inguinal ligament remarking the deep inguinal ring
(drawing imaginary line between the SIAS and pubic tubercle) when patient asked to cough.
However, the direct inguinalis hernia emerges from the weak area (Hasselbach’s Triangle) in the
superficial fascia through the superficial inguinal ring, so it is only covered by the external
spermatic fascia. The indirect inguinal hernia is the most common and occurs in the children
and young adult.

The Hasselbach’s triangle has the border as following:

-Lateral border: inferior epigastric vessels
-Medial border: rectus abdominis muscle
-Inferior border: inguinal ligament

3.How to distuingish femoral hernia and inguinal hernia?

Femoral hernia is below the inguinal ligament.

4.What are the differences between gonad development in the female and male?

In male, the testes are sliding down into the scrotum guided by the evagination of parietal
peritoneum (processus vaginalis). The testes are moving downward with the gonadal artery
(testicular artery) in the spermatic cord. The processus vaginalis will be obliterated before birth
and becomes tunica vaginalis. An incomplete fusion of the processus vaginalis will result in the
accumulation of serous fluid called hydrocele, while the failure of fusion will lead to the idirect
inguinal hernia.

In female, the ovaries stay in the place and only the round ligament of the utery will pass
through the inguinal canal and extend between the uterus and labia majora.

5.What are the differences between vitelline fistula and meckel diverticulum?

Vitelline duct is the connection between the gut tube and umbilical cord that would be fused
afterbirth. The persistent vitelline duct will form fistula with the manifestation meconium
passing through the umbilicus. The meckel diverticulum occurs when the vitteline duct
incompletely fused and formed the diverticle. The most common location of the diverticle is 2
feet from the ileocecal junction, 2 inches long, and appear in 2% of population (rule of 2). It is
usually asymptomatic, but it will be inflamed if it contains ectopic gastric secreting acid. The
manifestations are painless rectal bleeding and black starry stool (melena).

6.How are the divisions of the primitive gut tube?

Remember that every regions have different arterial blood supply, innervations, and
relationship to the mesentery. The celiac, superior mesenteric artery, and inferior mesenteric
artery supply the foregut, midgut, and hindgut respectively.

Note that, duodenum and transverse colon get dual blood supplies. So, the boundary between
the foregut and midgut is somewhere between the second part (ampulla vater) and third part
of duodenum. While the boundary between the midgut and hindgut is somewhere between the
2/3 proximal transverse colon and 1/3 distal transverse colon. Thus, the collateral circulation
could also be found in this boundary.

Spleen is not in the table because it develops from the mesoderm and gets the blood supply
from the celiac artery.

7.What are the rules of the gut development that we should remember?
The retroperitoneal organ is covered by the parietal peritoneum, while the gut tube is
surrounded by the visceral peritoneum so it’s called peritoneal (intraperitoneal) organ.

Dorsal mesentery is the connection between the retroperitoneal organ and the gut tube, while
ventral mesentery is the connection between the gut tube and the body wall. The artery, vein,
and nerve come along the mesentery.
8. How is the development of the liver?

-The second part of duodenum invaginates into the ventral mesentery. Then, the ventral
mesentery enlarges and becomes the hepatic diverticulum liver, gall bladder, biliary duct.
The ventral mesentery changed its name into the lesser omentum (connecting the liver with the
gut tube, specifically the common bile duct with the second part of the duodenum), the visceral
peritoneum (covering the liver), and falciform ligament (connecting the liver into the body
wall).

9. How is the development of the pancreas?

The pancreas develops from the ventral pancreatic bud (head and uncinate processus) and
dorsal pancreatic bud (neck, body, and tail) then the ventral pancreatic bud rotates around the
duodenum to reach dorsal mesentery and fuses to become one pancreas with 2 ducts draining
into the duodenum.

10. Why does polyhydramnion occur in the annular pancreas?

The defect in the rotation of the ventral and dorsal pancreatic bud form the ring around the
duodenum and obstruct the duodenum. Therefore, the fetus couldn’t swallow the the amniotic
fluid and result in the polyhydramnion. On the other hand, the pancreas divisum (the buds
don’t fuse) will cause the dorsal pancreatic duct too small accumulation of the much fluid 
pancreatitis.

11.How is the development of the spleen?

The stomach invaginates and forms the dorsal mesogastrium (dorsal mesentery). The spleen
develops from the dorsal mesogastrium, so the spleen derives from the mesoderm. The dorsal
mesogastrium then changed its name into splenorenal ligament (the spleen artery passes
through it), visceral peritoneum of spleen covering the spleen, and gastrosplenic ligament.
12. What happens after 90 degree rotation of the foregut and what do clinical issues correlate
to it ?

In the week 6-10, the 90 degree rotation will change the position of the ventral mesentery
(liver)  right and dorsal mesentery (spleen)  left.

Then this rotation will divide the peritoneal cavity into the lesser sac (extending vertically into
the transverse colon) and the greater sac (extending vertically into the pelvic). The epiploic
foramen (foramen of winslow) provides an access from the greater sac into the lesser sac but it
not surgically accessible. In the free edge of the lesser omentum, there are 3 important
structures: common bile duct, proper hepatic artery, and portal vein cause the epiploic foramen
doesn’t become the surgical access. However, if there’s bleeding of the liver, we might stop the
bleeding by grabbing the lesser omentum.

In relation with the sac, the perforation in the anterior wall of the stomach will cause the
hypogastric pain, while the perforation in the posterior wall will cause the epigastric pain. By
saying that, the lesser sac (omental bursa) is a potential where we cand find blood if there’s
perforation in the posterior wall of stomach.

13. What happens after 270 rotation of the midgut and what do clinical issues correlate to it?
During week 6-10, the midgut herniates into the umbilical cord as it rotates and becomes
longer so it needs larger space. The rotation is 270 degrees counterclockwise around the axis of
the superior mesenteric artery. This rotation will cause the jejunum in the left, ileum and cecum
in the right, and the transverse colon has the U inverted shape.

Around week 12, the midgut loops should go back into the abdominal cavity. If it doesn’t go
back, it will result with the omphalocele. The herniated viscera contained the shiny sac of
amnion at the base of umbilical cord. While the gastroschisis occurs when the abdominal
viscera herniate through the defect of abdominal wall and contact directly with the amniotic
fluid. This is a defect in the closure of lateral body folds and the weakness of the anterior wall,
usually in the right of the umbilicus. Both can be detected by the increasing level of AFP in
mother’s blood serum.

14.What are the layers of GI tract from the innermost to the outermost?
-Mucosa: contains of the epithelial, lamina propria (location of blood supply and gut associated
lymphoid tissue), and muscularis mucosa
-Submucosa: contains of the connective tissue meissner plexus
-Muscularis externa: contains the smooth muscle (circular and longitudinal) and responsible for
the peristaltis. This is the location of the auerbach plexus.
-Serosa: composed of mesothelium and loose connective tissue.
The thick of each layer varies among the GI track based on its function.

15. How is the innervation of the GI tract?

The GI tract has intrinsic innervations which is controlled by the Auerbach and Meissner plexus.
This intrinsic innervations are being modulated by the parasympathetic (to increase the
peristaltis) and sympathetic (to decrease the peristaltis) pathway as the extrinsic innervations.

16.How do we distinguish each part of the GI tract?

-Esophagus: nonkeratinized stratified squamous epithelium, has the skeletal muscle in the
muscularis externa in the upper third, and smooth muscle in lower part.
-Stomach: simple columnar epithelium, has rugae (shallow pit)and gastric pit penetrating the
entire the mucosa. The transition between the pits and glands remark the isthmus, where we
could find the stem cells. The stomach has various cells: the mucous cells (secrete mucous),
chief cells (dark staining in the microscope, secrete pepsinogen that should be activated by HCl
and lipase), parietal cells (secrete HCl and intrinsic factor for the absorption of vitamin B 12),
and enteroendocrine (secrete the variety of peptide hormones as the signals for the intestine
such as gastrin in the pyloric).
-Small intestines: function for absorption so they have villi, plicae, and crypts of Lieberkuhn.
 Duodenum: has abundant of brunner glands in the submucosa which discharge the alkaline
secretion to neutralize the acid chime from the stomach. The other cells are the goblet cells
(secrete acid glycoproteins that protect mucosal linings), paneth cells in the crypts of
Lieberkuhn (contains granules secreting lysozime to kill the pathogen), enteroendocrine cells
(secreting the cholecystokinin and secretin).
Jejunum: has the best developed plica and the same cell types like the duodenum.
Ileum: aggregation of lymph nodules called Peyer’s patches with M cells to endocytose and
transport antigen from the lumen to lymphoid cells, number of villi < jejunum.
Large intestine: villi <<, crypts +, has the taenia colli (3 longitudinal bands) except the appendix,
and mainly contains of mucous-secreting and absorptive cells to lubricate the stools.

17. What are the kinds of the salivary glands?

-The parotid glands are entirely serous salivary glands and drain into the Stensen’s ducts.
-The submandibular glands contribute to 70% of saliva, predominantly serous cells, and drain
into the Wharton’s duct.
-The sublingual glands are also mixed, but predominantly mucous cells.
The mucous cells are pale staining under the microscope because the contains are washed
away.

18.How is the structure of the liver?

The liver consists of the lobule with hexagon shape. Each lobule consists of hepatic sinusoid
(unusual capillaries) where the Kupffer cells patrol the space of Disse between the hepatocytes
and blood. The ito cells (stellata cells) also live in the space of Disse and are involved in storage
of fat soluble vitamins (mainly vitamin A). When stimulated during the liver injury, the ito cells
can produce type I collagen and lead to the scarring (cirrhosis). Every hepatocyte produces the
bile and drains into the bile canaliculi  peripherally into the biliary duct. While the hepatic
artery and portal vein drain centrally into the central vein.

2
1

1: most susceptible to the necrosis and mostly involved in the metabolism of drug, lipid, and
alcohol
2.transitional zone
3.mainly synthetic activity: glycogen + plasma protein

EPIDEMIOLOGY AND BIOSTATISTICS

02.01- Epidemiology: Epidemiologic Measures
1. What are the differences between endemic, epidemic, pandemic, and hyperendemic?
-endemic: the usual = expected rate of disease over time
-epidemic: excess of the expected rate, occur in larger geogprahic
-pandemic: worldwide epidemic
-hyperendemic: endemic but relative higher than usual (but still in the expected rate)
The result is presented as the rate, usually per 100,000 people (>40-50/100,000 people aren’t
acceptable) and for vital statistics usually per 1,000 persons.

2.What are the differences between incidence and prevalence?

Incidence= new cases in the D-1 calculation (new cases/ number of persons exposed to risk of
becoming new cases during this period). Attack rate is part of incidence for calculating the
food-borne illness and presented in the percentage: number of people with disease/ total
number exposed people.

Prevalence=All cases, except people who are death before D-1 (all of cases at given point/ total
population at risk). It can be divided into the point (particular time, ex: 1/1/2017) and period
prevalence. Point gives snapshot view to determine whether the outbreak is occurring.

The relationship between them: Prevalence= Incidence x Duration (PID)

IR (1/1/2006-1/1/2007)= 4/6
PR (1/1/2006-1/1/2007)= 7/9
Point prevalence (1/1/2007)= 4/6

3. A population at risk is composed of 100 medical students. 25 medical students develop symptoms
consistent with infectious diarrhea confirmed by laboratory testing to be campylobacter. If 12 students
developed campylobacter in September, and 13 students in October, what is the incidence of
Campylobacter in these two months?
Firstly, determining the denominator: use average method= average number of monthly students x
number of months
Average number= at risk population at beginning+ at risk population at the end x # P(number of months)
2
=(100+75/2) x 2= 175
Incidence rate= 25/175= 0,14 cases per student month

BIOCHEMISTRY

04.01-

MEDICAL GENETICS

05.01-Single Gene Disorders

1. The autosomal dominant disorder, neurofibromatosis, type I (NFI), consists of growth of
neurofibromas in skin, café -au-lait spots, hamartomas on iris of eye (Lisch nodules), CNS
tumors, and cancer of the nervous system or muscle. This is an example of what characteristic
of autosomal dominant disorders?
Pleiotropy exists when a single disease-causing mutation affects multiple organ system, such as
Marfan syndrome (gene defect in chromosome 15 encoding fibrillin, autosomal dominant)
involves 1 structural protein. Other example that doesn’t involve the structural protein is the
cystic fibrosis (CFTR gene on chromosome 7).

2. A child has severe neurofibromatosis type I (NF1). Her father is phenotypically normal, Her
mother seems clinically normal with the exception of several large café -au-lait spots and a few
Lisch nodules. What is the best explanation for these findings?
Variable expression refers to when the effect of a mutated gene for a dominant disease may be
severe in one member of the family and mild in another. Other example is hemochromatosis.
Enviromental influences also play role in which the female with hemochromatosis has milder
symptoms because of loss of iron from the menstrual period.

3. Which of the following terms best describes the situation in which two different diseases,
sickle cell anemia and thalassemia, are both caused by mutations in the same gene (beta-
globin)?

Allelic heterogeneity refers to the situation when there are different mutations within the
same locus leading to multiple mutant alleles, usually results in the variable expression. Other
example is Tay Sach disease (illustrating the alternative splicing, insertion 4 nucleotide 
frameshift mutation), G6PD gene differs from people in French or Saudi.

4.How to distinguish the pattern of the inheritance?

-Dominant vs recessive: disease exists in generation to generation vs skipped generation
-X-link vs autosomal: no male to male transmission vs male to male transmission +
-Mithocondrial: no male to male transmission, only affected female could inherit the disease to
all the children.
The most common question: recognize mode of inheritance, predict recurrence risk, and
identify carriers (obligate).
5. What is the probability that the fetus suffers from albino?

II-1 is an albino, so his genotype is aa, since albinism is inherited as an autosomal recessive.
Since II-1 is an albino, both I-1 and I-2 are heterozygous for the trait. Given I-1 and I-2’ s
genotypes, there are three possible genotypes for their children, AA, Aa, and aa. These
genotypes occur in a 1:2:1 ratio. The phenotype of II-3 is normal, hence he cannot have aa as
his genotype. Of the remaining three possibilities, two are carriers, and one is homozygous
normal. Hence, the probability that II-3 is a carrier is 2/3 and the probability that he is
homozygous normal is 1/3.
II-4 is an albino, so her genotype can be set as aa.
Overall, the probability that III-1 will be aa is the following:
The P(III-1) is aa = P(II-3 is Aa/A) P(II-3 passes a to IV-1)
= (2/3)(1/2)
= 2/6=1/3

6. In the pedigree below, individuals II-2 and II-3 are monozygotic twins. II-2 is normal, but II-3 is
affected with hemophilia A, as is her brother, II-1. Which of the following causes is the most
likely explanation for this disparity?

Hemophilia A is an X-linked trait. Since normal females have two copies of the X chromosome,
they require two copies of the mutation to express the disease. However, because X
inactivation is a random process, a heterozygous female will occasionally express an X-linked
recessive mutation because, due to random chance, a majority of the X chromosomes carrying
the normal allele have been inactivated. These females are called manifesting heterozygotes. If
they have at least a small population of active X chromosomes carrying the normal allele, their
disease expression will be milder than that of an affected male.

7.What are the diseases showing the autosomal dominant inheritance?

-Familial hypercholesterolemia (LDL receptor deficiency), Huntington disease,
neurofibromatosis type I, marfan syndrome (defect of fibrillin), acute intermittent porphyria
(most cases). Most of the cases, the genotype is Aa because the homozygote would be die
before mating age.

8. Both familial hypercholesterolemia (LDL receptor deficiency) and marfan syndrome are
autosomal dominant diseases. However, why does familial hypercholesterolemia result in the
decrease number of the receptor, but Marfan result in abnormal protein?
Supposed the cell needs 100 copies of an enzyme to function. Both genes needed to express
protein, in which each gene makes 50 enzyme so the result is deficiency of the receptor. In the
dominant negative phenotype like in the Marfan Syndrome, both normal and mutant gene
produce 100 protein but the mutant protein antagonize the normal protein. Therefore, the
fibrillin will bind to the elastin in the Marfan Syndrome.

9.What are the diseases showing the autosomal recessive inheritance?

-Sickle cell anemia, cystic fibrosis, PKU (defect of phenylalanine hydroxilase), Tay Sachs disease
(hexoaminidase A deficiency). The consanguinity is typically found in the pedigree.
From this figure, the probability of IV-1 being carrier is 2/3=0,67%. Besides that, if the question
states that the probability of father of being carrier 1/10, mother of being carrier 1/10, so the
probability for having the affected child: 1/10x 1/10x1/4=1/400.

10.Why is the heterozygous individual not affected in the autosomal recessive disease?
Supposed the cell needs 100 copies of an enzyme to function. Each gene makes 100 enzymes
(more than enough), so the mutant gene which produces misfolded protein doesn’t affect.

11.What are the diseases showing X-linked recessive diseases?

Duchenne muscular dystrophy, Lesch Nyhan syndrome (HGPRT deficiency), G6PD deficiency,
hemophilia A and B, red-green color blindness, Menke’s disease, ornithine transcarbamoylase
deficiency, SCID (IL receptor gamma chain deficiency).

From this pedigree, we can see the disease skips generation, no male to male transmission,
mostly affect male, and the carrier must be female (mother of affected son or daughter of
affected father).
12.What is the definition of X inactivation?
X inactivation occurs early in the female embryo with random, fixed, and incomplete and form
the barr bodies. In a cell, all X chromosomes but one are inactivated by the lyonization (the
cytosine methylation). Therefore, the barr bodies are mostly abundant in the trisomy XXX.

Example: Lesch-Nyhan Syndrome (carrier female) ½ cells make HGPRT and other X-
chromosome (mutant allele) is off, while ½ cells make mutant enzyme and other X-
chromosome (good allele) is off.

13. Genetic mosaicism is the presence of 2 or more cell lines with different karyotypes in an
individual. Why does it happen?
-The mitotic nondisjunction

14.What are diseases showing X-linked dominant inheritance?

Fragile X syndrome and hypophosphatemic rickets (vitamin D resistant rickets)

15. Heteroplasmy is variable proportions of mitochondria DNA (encodes 22 tRNAand 2 rRNA) in

a given cell results in variation in the severity of expression of mitochondrial diseases. What are
the diseases showing the mitochondrial inheritance?
-The tissues mostly affected are the cells with the big amount of mitochondria: muscle and
neuron. The diseases are Leber hereditary optic neuropathy (defect of oxidative
phosphorylation), MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke like
episodes due to tRNA leu defect), myoclonic epilepsy with ragged red muscle fibers (tRNA lys
defect).

16. A child has severe neurofibromatosis type I (NF1). Her father is phenotypically normal, Her
mother seems clinically normal with the exception of several large café -au-lait spots and a few
Lisch nodules. What is the best explanation for these findings?
Variable expression refers to when the effect of a mutated gene for a dominant disease may be
severe in one member of the family and mild in another.

17. Prader-Willi syndrome (PWS) usually results from an interstitial deletion as biomolecular
causes involving the paternal copy of chromosome subregion 15q11-q13. Which of the
following is the best explanation for this?
Prader-Willi syndrome (PWS) is caused by the loss of active genes in a specific region of
chromosome 15. The hallmark of this disease is hyperphagia and obesity. People normally have
two copies of this chromosome in each cell, one copy from each parent. However, some genes
in this region of the chromosome are active only when they are inherited from a person's
father. PWS occurs when the region of the paternal chromosome 15 containing these genes is
missing, and the genes on the maternal chromosome are imprinted (turned off). Most cases of
Prader-Willi syndrome are not inherited. The genetic changes occur as random events during
the formation of gametes or in early fetal development. Affected people typically have no
history of the disorder in their family.
While the Angelman syndrome, the hallmark is puppet-like posture of limbs and happy
disposition due to the imprinting of paternal chromosome and deletion gene in maternal
chromosome.
18. A novel genetic disease is found to exhibit a gradually decreasing age of onset with each
generation. Which of the following types of mutation is likely to be responsible for this genetic
disorder?
Genetic mutations involving trinucleotide repeats often show signs of anticipation, in which the
age of onset of disease occurs earlier in life with each generation. This occurs primarily because
of gradual expansion in trinucleotide repeats after each round of replication.
19. Mutations in proteins involved in collagen synthesis can result in a genetic disease
characterized by an increased propensity for bone fractures. This may occur, for example, from
a mutation in collagen itself, in enzymes involved in selected hydroxylation of prolines and
lysines, or in those required for glycosylation of hydroxylysine residues. This phenomenon may
be referred to as which of the following?
Locus heterogeneity refers to a single disease phenotype caused by mutations in different loci.
The example described involves osteogenesis imperfecta, in which errors in collagen synthesis
lead to a defect in bone formation, resulting in an increased likelihood of suffering from
fractures.

20. The patient with the mutant gene will result with no pathology is known as incomplete
penetrance, occur most commonly in the autosomal dominant inheritance. How do we
determine the degree of penetrance?
Degree of penetrance= #individuals showing disease
# known to have defective gene

From the figure above, the degree of penetrance= 6/7= 86%.

Someone who inherits 1 mutant allele and 1 normal allele needs secondary hit mutation in the
somatic cell to set off the disease, example: retinoblastoma, HNPCC, hemochromatosis
(autosomal recessive), BRCA 1 or BRCA 2 in breast cancer.

21.What are the diseases with delayed age of onset?

-acute intermittent porphyria, Huntington disease, hemochromatosis, and familial breast
cancer.

22.Besides the imprinting, the Prader-Willi and Angelman syndrome also shows the uniparental
disomy. Why?
-It happens when two copies of the same chromosome derived from the same parent.
Paternal disomy (lack of maternal chromosome)= Angelman syndrome, maternal disomy (lack
of paternal chromosome)= Prader-Willi syndrome.
05.02-Population Genetics
1. In an isolated Honduran village, the prevalence of deafness due to an autosomal recessive
gene is approximately 1/400. A man suffering from this disease will have what probability of
having a child with this disease?
Since the prevalence of deafness in this population is 1/400, which = q2, the frequency of the
recessive allele must be about 1/20. The carrier frequency is then about 2 × 1/20 × 19/20 = 2pq,
which is about 1/10. For this man to transmit the disease to his offspring, he must marry either
another homozygote (for which the probability of having a child with the disease will be 100%)
or a heterozygous carrier (for which the probability drops to 50%). However, because there are
so many more carriers, we can assume the likelihood of this man marrying a heterozygote and
then having a diseased child to be 1/10 × 50%, which equals 1/20.

2. A 9-year-old girl suffers from a genetic deficiency in which there is almost no detectable
expression of the LDL receptor. Both of her parents suffer from a milder form of the disease
with high levels of serum cholesterol and must take atorvastatin to maintain their health. The
child, however, must undergo a plasmapheresis procedure twice a week to remove the excess
cholesterol in her blood. Most children with this disease will suffer from atherosclerosis and
coronary artery disease early in life. The occurrence of this severe phenotype is 1 in 1 ×
106. What is the approximate prevalence of people with the LDL-receptor phenotype found in
this patient's father or mother?

Familial hypercholesterolemia, a genetic disease characterized by a deficiency in LDL-receptor

expression, is an autosomal dominant illness. The patient described, however, suffers from a
severe homozygous version. Because the prevalence of homozygotes is 1/(1 × 106) = p2, the
prevalence of the diseased allele is 1/1,000 = p. The patient's parents must both be
heterozygotes, the prevalence of which would be 2p for dominant diseases, which is 1/500.

3. The allele frequency of Tay-Sachs disease is 1/60 for Ashkenazi Jews. What is the
approximate Tay-Sachs disease carrier frequency in this population?
When q is very small, p could be considered as 1. The carrier frequency is 2pq, so the carrier
frequency is 2(1) (1/60) = 1/30. The prevalence of Tay Sachs in Ashkenazi Jews is
1/60x1/60=1/3600.

4. For the ABO blood group in a given population, the allele frequencies are:
A = 0.30 (p)
B = 0.10 (q)
O = 0.60 (r)
What percent of the population will have type B blood?
Both genotype BB (q2) and genotype BO (2qr) will have the type B phenotype. The percentage
of people with BB blood is q2 = (0.1)(0.1) = 0.01 x 100 or 1%. The percentage of people with BO
blood is 2qr = 2(0.1)(0.6) = 0.12 x 100 or 12%. Overall the percentage of people with type B
blood is 1% + 12% =13%.
5.Cystic fibrosis is an autosomal recessive disorder caused by a defect in the cystic fibrosis
transmembrane conductance regulator (CFTR) protein. In the United States, 1 out of every 25
Caucasians carries a disease causing allele. If two American Caucasians with no family history of
the disease produce a child, what is the probability that the child will be affected?
The statement that one out of every 25 American Caucasians carries a disease causing allele,
tells us that 2pq is 1/25. So, the probability that two individuals from the population with no
family history produce a child with the disease is 2pq x 2pq x 1/4 = 1/25 x 1/25 x 1/4 = 1/2500.

6. In an isolated Icelandic population, one in ten males has red-green colorblindness. What is
the frequency of affected females in this population?
Color blindness is an X-linked recessive trait. Since males have only one copy of the X
chromosome, when a gene is located on the X chromosome, the Hardy Weinberg equations for
the genotype frequencies is different for males and females. When the incidence of an X-linked
recessive disease in males is given, this frequency is equal to q, the frequency of the recessive
allele in the population. In males, the equation p + q = 1 is the equation that expresses both the
allele frequencies and genotype frequencies. In females, the allele frequencies equation is p + q
=1, while the genotype frequencies equation is p2 + 2pq + q2=1. In this problem, the frequency
of colorblindness in males is 0.1. This means that q = 0.1. Using the female equation for
genotypic frequency, the prevalence of colorblindness among females in the population is q 2 =
1/100.

7.The prevalence of thalassemia in the Eastern region of Saudi Arabia is 145/10000. What is
the chances of marrying someone who is carrier in this region?
q2=145/10000 so q=0,12
2pq=2x1x0,12=0,24=24%

8. A woman with cystic fibrosis marries her first cousin. Their shared grandparent had a brother
who died of cystic fibrosis. What is the risk that their first child will have CF?

The woman received one of her cystic fibrosis alleles from a grandparent that she shares with
her first cousin. The probability that this common grandparent gave the allele to her cousin’ s
parent is 1/2. The probability that the cousin received the allele is 1/2. If the cousin is a carrier,
the probability that they would produce an affected child is 1/2. So the overall probability that
the first child will be affected is equal to the following:
P(woman is cc) P(cousin is Cc) P(affected child)
(1) [(1/2)(1/2)](1/2) = 1/8

9. Sickle cell anemia is a potentially lethal genetic disease that severely limits the ability of the
red blood cells to carry oxygen. However, in areas where falciparum malaria is prevalent, the
sickle cell allele is maintained because individuals who are heterozygous for the sickle-cell trait
are more likely to survive malaria than those who are homozygous normal. This situation
illustrates which of the following concepts

Heterozygous advantage is the situation in which the heterozygous genotype for a particular
gene has a higher relative fitness that either homozygote genotype. In African populations
where malaria caused by Plasmodium falciparum is prevalent, fatalities in homozygotes for the
sickle cell trait are offset by the survival advantage of heterozygotes bearing one copy of the
sickle cell allele over those who are homozygous for the normal allele.

10. The Afrikaner population of Dutch settlers in South Africa is descended mainly from a few
colonists. Today, the Afrikaner population has an unusually high frequency of the gene that
causes Huntington disease, because those original Dutch colonists just happened to carry that
gene with unusually high frequency. Which of the following genetic terms best describes this
situation?’

The founder effect occurs when a small population of individuals colonizes a new place, and
remains genetically isolated. If one or more of the founders is carrying a rare allele, it may
become much more abundant within this population due to intermarriage.

11. Almost all affected individuals with Duchenne muscular dystrophy (DMD) die without
reproducing. Given the selection against the DMD phenotype, the allele should eventually
disappear from a population. However the allele frequency stays constant. Which of the
following is the best explanation for this phenomenon?
DMD is caused by a defective gene located on the X chromosome that is responsible for the
production of dystrophin. The dystrophin gene is the largest gene yet found in humans,
spanning approximately 2.3 megabases. The vast majority of mutations of the dystrophin gene
are deletions caused by unequal crossing over during meiosis. This mutation rate is very high,
so mutation replaces the DMD alleles lost when affected individuals die before reproducing. In
fact, about 1/3 of all DMD cases each generation result from new mutations during meiosis in
the mother.

12. What are the factors responsible for genetic variation among population?
-Mutation: new mutation would change q.
-Natural selection: promote survival or fertility (fitness)
-Genetic drift: allele frequency change caused by small population size involved the founder
effect and new mutation.
-Gene flow: exchange of genes among previously separated populations, example: sickle cell
disease in US vs Africa the intermarriage between black and white American the change of
prevalence in each population.
-Consanguinity: unrandom mating  increase the risk of genetic disease. Statistically, siblings
share ½ of their gene, first cousins share 1/8 of their genes, second cousins share 1/32 of their
genes.

05.03-Cytogenetics
1.Cytogenetics is study of microscopically observable alterations in the chromosomes. The
alterations could be numerical (mostly caused by nondinsjunction) and structural. In the cell
cycle, where could we see the two pairs of sister chromatids?
-End of S phase, all G2 phase, and beginning M phase. Every cell that have finished Sphase will
be 4 N.

2.Based on the relative position of the centromere, the chromosomes are classified into
metacentric, submetacentric, and acrocentric chromosome. What are the acrocentric
chromosomes?
-The centromere is far toward one end: 13,14,15, 21, and 22.

3. What are the examples of numerical chromosome abnormalities?

-autosomal aneuploidies:
Down syndrome trisomy (47, XY/XX, +21). The Down syndrome patient will increase the
likelihood for congenital heart defects, Alzheimer, and acute lymphoblastic leukemia.
Edwards syndrome, trisomy 18 (47, XY/XX, +18): clenched fist, rocker bottom feet, low set
ears, and micronanghtia.
Patau syndrome, trisomy 13 (47, Xy/XX, +13): cleft lip/ palate, microphtalmia, microcephaly,
cardiac and renal defects.
Other trisomies are lethal, whereas all monosomies are lethal.
-sex chromosome aneuploidies:
Klinefelter syndrome 47, XXY
Turner syndrome 45, XO monosomy (some others are 46, XX or 47, XXX) show mosaicism.
The patient will increase the likelihood to have coarctatio aorta.

4.The most common cause of aneuploidies is the nondisjunction. How does it occur?
5.The structural chromosome abnormalities could produce the balanced alteration (90%)
without gaining or losing of genetic material or unbalanced alteration (10%) with gaining or
losing of genetic material. What will happen if there’s alteration in the germline or somatic cell?

Those that happen in germline will result in no pathology in the individual but can be
transmitted to the offspring, whereas those that happen in somatic cell can cause cancer.

6.What are the differences between alternate vs adjacent segregation?

The adjacent segregation: chromosomes from adjacent quadrants (next to each other) enter a
gamete.

The alternate segregation: chromosomes from alternate (diagonally opposed) quadrants enter
a gamete.

7.Two chromosomes are almost identical but not the sequence because of mutation in the SNP
and STRP. The normal crossover between homologous chromosome will result with no
pathology. What is the example of the disease in which the unequal crossover between two
homologous chromosome resulting with pathology?

Unequal crossover of chromosome 16= α thalassemia.

8.In the reciprocal translocation, the genetic material is exchanged between non-homologous
chromosome. Why does the adjacent segregation produce most likely loss of pregnancy?

The adjacent segregation unbalanced alteration  pregnancy loss, alternate segregation 

still have 2 copies of gene no pathology if occurs in the germline (=reciprocal translocation
carrier). The carriers typically identified during evaluation for recurrent pregnancy loss or
infertility or after the diagnosis of fetus/ child with an unbalanced translocation.

9.What are the important examples which the translocations cause the cancers?
-Chronic myelogenous leukemia: abl x bcr t (9:22)=Philadelphia chromosome results in a
continuously active tyrosine kinase. Normally, this receptor is inactive and requires hormone to
be active. Treatment: imatinib (Gleevec) that blocks tyrosine kinase receptor.
-Burkitt lymphoma: t (8:14) specific transcription factor which is C-myc (protooncogene)
regulates the expression of 15% of all genes after binding with the enhancer. This is C-myc is
then degraded by the ubiquitin chromosome (t ½=30 min). Translocation between chromosome
8 and 14 results in heavy chain gene near C-myc inhibits the ubiquination and leads to
stabilization. Treatment: methotrexate.
-AML:M3: t (15:17) translocation between chromosome 15 and 17 disrupts retinol receptor
gene. Retinol is hormone with zinc finger class receptor but the gene is defect. Treatment: all
trans retinoic acid (ATRA) the hormones could attach with the receptor to cause myeloblast
(basically immortal) to differentiate into the neutrophils (lifespan 2 days)  So the cells could
die.
-Follicular lymphoma: t(14:18) bcl 2 that inhibits apoptosis.
-Mantle cell lymphoma: t (11:14)  cyclin D.

10.The Robertsonian translocations occur only in the acrocentric chromosomes

(13,14,15,21,22) and involve the loss of two short arms (not having important genes) followed
by the fusion of long arms. In the Down syndrome, 95% due to nondisjunction, 4% due to
Robertsonian translocation, and 1% due to mosaicism. However, the recurrence of having baby
with Down syndrome is bigger than the nondisjunction. Why?

45,XY,-14,-12, +t(14q; 21 q)
The adjacent segregation produces unbalanced genetic material most likely loss of
pregnancy.

11.Deletion occurs when chromosome loses some its genetic information. It could occur in the
middle of chromosome which is known as interstitial deletion (chromosome 15: Prader Willi/
Angelman syndrome) or in the end of chromosome which is known as terminal deletion
(chromosome 5 involved in the development of the larynx: Cri du chat syndrome).
Based on the structural size, what are the other examples of the deletion?
-Microdeletion: deletion is so small that requires FISH technique to identify. It includes Di
George syndrome (chromosome 22), wilms tumor (WAGR), Williams syndrome (chromosome
7), and alpha thalassemia (chromosome 16).
-Chromosomal deletion: Turner’s syndrome
-Single gene deletion: Prader-Willi and Angelman syndrome that occur in the q arm
chromosome 15.
-Codon deletion: cystic fibrosis
-Nucleotide deletion: Duchenne’s muscular dystrophy (most of the time this mutation is lethal).

12.The isochromosome results from the p or q arms stucked together. In the Turner syndrome,
50% have 45, XO (monosomy due to nondisjunction), 20% have mosaicism (45 XO and 46 XX
cells due to the nondisjunction in the mitosis after birth), and structural alteration
(isochromosome, 46 X,i (Xq)). How do we identify the isochromosome in the Turner syndrome?
- The size of an X is larger than another.

13.How do we interpret the Trisomy 21 from FISH?

A probe that is specific for chromosome 21 will hybridize in 3 places in patient with trisomy 21.
However, the fetus could still have a chromosome abnormality, such as a deletion or
rearrangement, which was not detected with this FISH study. Therefore, the study has not ruled
out a chromosomal abnormality.

14.How do we interpret the Philadelphia chromosome from the spectral kariotyping?

Every chromosome is painted with different color. This allows the ready visualization of
chromosome rearrangements such as small translocation.

05.04-Genetics of Common Diseases

1.What are the key features of oncogene and tumor suppressor genes?
Example: retinoblastoma is autosomal dominant, heterozygous with 90% penetrance  first hit
inherited  second hit changes the function of Rb as tumor suppressor gene  cancer +

Other tumor suppressor genes: BRCA 1 and 2 (breast cancer in 5-10%, most cases due to
multiple somatic mutation), Li-Fraumeni syndrome (p53), p 16 (melanoma), and APC (colon
cancer).

2. Although various genetic and environmental factors predispose individuals to pyloric

stenosis, the disease affects males almost five times more often than it does females. Which of
the following relatives, if affected, would pose the highest risk for an individual to develop this
disease?
The recurrence risk of a multifactorial disease like pyloric stenosis is increased if the relative is
closer and if the affected individual is a member of the less commonly affected sex (i.e.,
female). The closest female relative in this case is the mother, who shares about 1/2 of a
person's genetic makeup. The brother also shares the same amount of genetic material but is a
male.

3.An 80-year-old man is brought to his physician by his family after he exhibits some signs of
confusion, problems with language, short-term memory loss, and personality changes. No one
in the family, however, has any history of dementia. Which of the following genes is most likely
involved in this patient's condition?
The patient's condition is a classic presentation of Alzheimer disease. However,
although BAPP and presenilin are involved in familial forms of this disease, only APOE is
involved in sporadic, late-onset cases, such as the one presented here.

4. The numbers below show the percent of children in different groups that have a disease.
Which of the following diseases would have the greatest genetic contribution?

The disease with the highest genetic contribution must show the greatest percent difference
between children of affected parents with children of normal parents. This is best determined
by simply comparing the percentage of children of affected parents raised by normal parents
(column 3) with the percentage of children of normal parents raised by normal parents (column
1). Based on the data shown, disease A shows a 8-fold greater risk in children of affected
parents than normal parents (8 vs 1).
5.What are the factors influencing the recurrence risk?
-Increase as number of affected relatives increases
-Increase as severity of disease expression increases
- Recurrence risks increase if the affected proband (the first family identified to have a disease)
is a member of the less commonly affected sex since an affected individual of the less
commonly affected sex will be, on average, higher on the liability distribution.
-Decrease very rapidly for more remotely related relatives
-Increase as prevalence of the disease increases in a population

6.Concordance rate calculates the chance of twins to get the same disease: 1 in monozygotic
and 0.5 dizygotic twins. If the number of concordance rate is not as expected, what does it
mean?
It means the disease is multifactorial, as the concordance rate >>  gene involvement >>

05.05-Gene Mapping
1. To determine whether a new genetic marker may be used to predict an autosomal dominant
disease phenotype, the following LOD scores were calculated for various recombination
frequencies, as shown below:

Which of the following conclusions may be drawn from these results regarding the linkage
between the disease locus and the genetic marker?
A LOD score of 3 normally denotes a 1,000-fold likelihood that two loci are linked at that
distance, whereas a score of 2 denotes a 100-fold likelihood that they are linked, and a -2 score
denotes a 100-fold likelihood that they are not linked. In this case, although no conclusion may
be drawn for statistical linkage (LOD >3), it does suggest that there is some likelihood (about
100-fold more) that they are linked at a distance of 20 cM apart. We cannot determine whether
the actual location falls somewhere before or after 20 cM unless a higher LOD score is
determined at a recombination frequency between 0.10 and 0.20 or between 0.20 and 0.40.

2. Marfan syndrome (M) is an autosomal dominant trait with complete penetrance, and the
Marfan allele is completely dominant to the normal allele, m. The Marfan locus is located 20 cM
away from an RFLP with two forms, A and B. An affected man has the linkage phase shown
above. With respect to these two loci, which of the following is the approximate correct ratio of
the four types of gametes from this individual?
The loci are located 20 centimorgans apart. During gametogenesis, 20% of the time, a
recombination event occurs between the two loci producing recombinant gametes. The two
types of recombinant gametes occur at equal frequency (0.1). 80% of the time nothing
happens, and two types of parental gametes are produced at equal frequency (0.4). This gives
the approximate ratio of gametes as 4:4:1:1.
4.The results of linkage analysis for microsatellite S1 and the neurofibromatosis type 1 (NF-1)
locus are shown above. Based on the data given, what is the approximate genetic distance
between microsatellite S1 and the NF-1 locus?

The LOD score (Z) is the statistical test used to determine if two loci are linked. Data from LOD
scores are additive between different families, so the problem of small sample size is
eliminated. By convention, if the LOD score is equal to or greater than 3, meaning that the odds
of linkage are 1000:1, the loci are considered to be linked. A LOD score of -2 (100:1 odds against
linkage) is taken to be proof of independent assortment. The highest LOD value over three is
considered to be the actual recombination frequency between the 2 loci, which .15=15
centimorgans.

5.Osteogenesis imperfecta is a rare autosomal dominant. A, B, C and D represent allele

II-1 received a chromosome from I-1 with A linked to osteogenesis imperfecta. The
chromosome that he received from I-2 had C linked to the normal allele. The only child to
receive a recombinant chromosome in the third generation is III-3. He received A linked to the
normal allele. This combination would only be seen if a recombination event occurred between
the RFLP and the locus for osteogenesis imperfecta during meiosis I in II-2.
6.What are the differences between the DNA polymorphism?

Both RFLP and VNTR require restriction endonuclease enzyme.

7. Linkage means the likelihood the two alleles are inherited together. The closer the two
alleles, the lower recombination frequency and vice versa. How do we interpret the
recombination frequency?
The linkage is measured by centimorgan. 1 cM=1% recombination frequency= 1 million base
pairs. The actual linkage in the population is stated by LOD (log of the odds) score. LOD score
>3= linkage = 1000 times more likely that the gene and marker are linked at that distance than
unlinked. LOD score < -2= nonlinkage = 100 times more likely that the gene and the marker are
unlinked than linked at that distance. While the LOD score between -2 amd 3 is indeterminate (
not enough data to interpret).

05.06-Genetic Diagnosis
1.What are the tests classified into the direct and indirect?

Direct test= examine the mutant allele directly, while indirect test= use linked markers to detect
the individual in the family (pedigree) has inherited the disease-causing mutation. ASO (allele-
specific oligonucleotide) uses 2 different probes (10-20 nucleotides) to detect 1 normal allele
and 1 mutant gene. Sometimes, RFLP could be used for direct test if the mutation hits the
palindrome.
2. Familial breast cancer is a genetic disease that can arise from a number of different
mutations in the BRCA1 and BRCA2 genes. Considering the diversity in the types of mutations,
what is the best tool for genetic testing of this disease?

Due to the diversity in types of mutations affecting BRCA1 and BRCA2, the optimal method for
genetic testing would require direct sequencing of the gene. ASO, PCR, and RFLP analysis
require a common mutation, such as C282Y in hemochromatosis.

3.The most common genetic cause for hemochromatosis is the C282Y mutation in
the HFE gene. Using allele-specific oligonucleotide probes on dot blots, the presence of the
mutated allele can be detected. In the couple whose results are shown above, what is the
probability that their next child will suffer from this disease?

According to the genetic test, both parents are heterozygous carriers of the mutant alleles.
Their offspring will therefore have a 1 in 4, or 25%, chance of developing the disease.

4.Indirect genetic analysis uses genetic markers closely linked to the disease locus to identify
the presence of the disease. Which of the following is a major advantage of indirect genetic
diagnosis?

A major advantage of indirect genetic testing is the ability to test for several types of mutations
with a single test because no specific mutation is being screened for. However, it has many
disadvantages, including the need for family information, the likelihood of recombination
producing errors, and the fact that the genetic markers may not be informative.

5.Duchenne muscular dystrophy is an X-linked recessive disorder characterized by generalized

muscle weakness and muscle wasting

Given the pedigree information, the unknown individual is an AB carrier female with
band A corresponding to the presence of the diseased allele, and band B corresponding
to the normal allele. Since II-2 has an affected brother with band A and an affected son
with band A, she inherited the A band linked to the DMD allele from her mother. Her
father, I-1, gave her the other X chromosome, which had a normal DMD allele and band
B. This is supported by her daughter, III-2, carrying band B.

6. Fabry disease is caused by an α -galactosidase A deficiency. It is characterized by skin

lesions, lens and cornea opacities, painful neuropathies, and vascular disease of the
kidney and heart. It exhibits an X-linked recessive inheritance pattern. II-2 and II-3
present for genetic counseling. They have a healthy daughter, and II-2 is pregnant with
their second child. An RFLP is located 1 cM from the α -galactosidase A locus, and the
haplotypes of each individual are given beneath their symbols. Which of the following is
the best conclusion about the third generation?
The allele for Fabry disease is linked to the C form of the RFLP in I-1. He passes this
chromosome to his daughter II-2. Since the RFLP is 1 cM from the locus for Fabry disease, the
recombination frequency between the two loci is 1%. 99% of the time, if II-2 contributes the B
form, it is linked to a normal allele. 1% of the time, the B form is linked to the disease allele due
to recombination between the loci. Likewise, 99% of the time, if II-2 contributes the C form, it is
linked to the Fabry allele, and 1% of the time the C form is linked to the normal allele due to
recombination. III-1 is AB. Most likely, she inherited a normal allele at the Fabry locus from her
mother. III-2 is C. Most likely he received the Fabry allele from his mother and will be affected.

7.The Huntington disease is autosomal disease with the trinucleotide expansion. The DNA will
get longer for the subsequent generation. The figure below shows the pattern of DNA of
myotonic dystrophy. What do we expect from this figure?

The 10 kb and 9 kb are normal base pairs. As the generation grows, the length of DNA gets
longer (III-1). This phenomenon is known as an anticipation.

8. A woman had a previous child with Down syndrome by her first husband. She is remarried,
and recently discovered that she is pregnant and about 4 weeks' gestatation. She is interested
in learning as quickly as possible if this fetus is affected with Down syndrome as well. What is
the earliest test that she could undergo that would tell her with certainty if the fetus has Down
syndrome?
Among the various methods for prenatal genetic testing, the earliest is CVS, which can be
performed at 10-12 weeks' gestation. Amniocentesis can be taken around 16 weeks' gestation.
Preimplantation is available even earlier but only for in vitro fertilization. The optimal timing of
a second trimester ultrasound screening for fetal anomalies is from 16 to 20 weeks, and the
results will not give a definitive answer.

9. What is a major disadvantage of relying on a chorionic villus sample for diagnosis of a genetic
disorder?

Placental mosaicism refers to differences between individual cells in the placental tissue itself.
The villi are of fetal, not maternal, origin and can be sampled even before amniocentesis.
However, placental mosaicism may contribute a small possibility of diagnostic error.

IMMUNOLOGY

06.01- The Immune System

1.What are differences between innate versus adaptive immunity?

The T cells are better to turn themselves off.

2.What is the timeline of the immune response to the acute infection?

Innate immune response would be the first immune response to eliminate the pathogen. Once,
it can’t overcome the pathogen, it will induce the primary adaptive immune response in 1-2
weeks. The T and B cells from the adaptive immune response will undergo the apoptosis after
pathogen has been cleared or proliferate into the memory cells. The second re-exposure to the
antigen will induce the robust response in the shorter period which is 1-3 days.
The antigen’s threshold to activate the immune response depends on the pathogenicity and
immune status of individual.

3.What is the difference between the cytokine and chemokine?

Cytokine is the secreted proteins to tell other cells to change their behavior, then chemokine is
chemical to change the direction of other cells.

06.02- Ontogeny of The Immune System

1. Where are the sites of the hematopoeisis during the development?
In the fetus, the hematopoeisis takes place in the yolk sac  liver  spleen. After birth, it will
take place in the distal long bones  axial skeleton in the adult. Hematopoiesis could go back
into the liver and spleen if there’s fibrosis in bone marrow.

2.How is the ontogeny of immune cells from the multipotent stem cells into the lymphoid stem
cell?
Multipotent stem cells in the bone marrow have CD34 as the marker in the surface and
differentiate into various cells in response to the different cytokine.

Multipotent stem cell that receives the signal of IL-7 (usually in response to viral infection) will
undergo the differentiation into lymphoid stem cell and gives rise into:
-Natural Killer: kill virally infected cells and tumor cells. The markers are CD 16 and CD 56.
-T progenitor: has the surface marker CD 3 and differentiate into Thelper cell (CD4) and
Tcytotoxic (CD8) in the thymus.
-B progenitor: has the surface markers CD 19, CD 20, and CD 21 and develops in the bone
marrow. When it circulates in the bloodstream to seek the antigen, it can turn into the plasma
cell.

3.How is the ontogeny of immune cells from the multipotent stem cells into the myeloid stem
cell?

Multipotent stem cell that receives signal of GM-CSF and IL-3 (usually in response in the
bacterial, fungal, or parasitic infection) will differentiate into:
-Granulocyte/ monocyte progenitor: monocyte  macrophage, neutrophil, and dendritic cell.
All of these cells are phagocytic.
-Eosinophil progenitor: receiving the signal from IL-5 and turns into the eosinophil.
-Basophil progenitor: basophil  mast cell
-Megakaryocyte: receiving the signal from thrombopoietin. When megakaryocyte in the bone
marrow receives the signal of IL-11, it will turn into the platelet (thrombocyte) in the
bloodstream.
-Eryhtroid progenitor: receiving the signal from erythropoietin. It will turn into the RBC. The
erythroid progenitor can be infected by parvovirus B19, while the RBCs couldn’t be infected
since they don’t have organelles and nucleus.

4. What is the reference for the leukocyte differential count in the bloodstream?
Cell type Adult reference (%) Clinical Correlate
Neutrophil (PMN) 50-70 Bacterial and fungal infection,
acute inflammation
Band cells=immature neutrophils 0-5 Leukemia
Lymphocytes 20-40 Viral infection, chronic
inflammation
Monocytes 5-10 Doesn’t give much information
unless the pathogen is known
Eosinophils 0-5 Extracellular infection (parasitic),
hypersensitivity type 1 (allergy)
Basophils <1 Extracellular infection (parasitic),
hypersensitivity type 1 (allergy)
Mnemonic: Never Let Monkey Eat Banana
5.What are the key points to differentiate the leukocyte under microscope preparation?
First, look the nucleus, cytoplasm, and size of the cell. The key features of the cells are
described below:
-Neutrophil: segmented and lobular nuclei (3-5 lobes), pink cytoplasm, size>RBC
-Lymphocyte: the nucleus is very large and centrally located, cytoplasm is small, and size= RBC
-Plasma cell: clock faced=small eccentric nucleus, intensely staining golgi apparatus in the
cytoplasm, size > RBC
-Natural killer: nucleus is large, large cytoplasmic granules, size > RBC
-Monocyte: bean or kidney shaped nucleus, agranulocyte, size> RBC
-Macrophage: found in the tissue, agranulocyte, with vacuoles and vesicles in the cytoplasm,
size > RBC
-Dendritic cell: found in the epithelial and lymphoid tissue, cytoplasm with stellata projection,
size > RBC
-Eosinophil: bilobed=headphone shaped nucleus, pink cytoplasm with granules, size > RBC
-Mast cell:found in the adjacent to the blood vessel small nucleus, blue cytoplasmic with
granule, size > RBC. Major secretion is histamine that is activated by the tissue damage. The
histamine increases the vasodilation in arteries, permeability in the capillaries and venules,
peristaltic movement in the GI tract, and bronchoconstriction in bronchus.
-Basophil: densed nucleus and large blue cytoplasmic granules, size> RBC.

06.03- Lymphocyte Development and Selection

1. How is the structure of the immunoglobulin?
The immunoglobulin has 2 identical halves, each composed of heavy and the light chain. The 2
halves are held by disulfide bond and form the variable region. This variable region has the N-
terminal end and serves as the antigen binding site. This antigen binding is very specific and
unique among cells and it’s called idiotype (remember Ig and T cell receptor has 1 idiotype).

The hinge region is composed by the heavy chains held together with disulfide bonds and
permits the mobility so the two identical idiotypes could move apart or closer.
The constant region of the heavy chain in B cells will determine the isotype: IgG, IgA, IgM, IgE,
IgD. Therefore, the isotype of Ig is always 5. However, in the naïve or mature B cells which
haven’t been exposed to the antigen only IgM and IgD are produced. In the light chain, the
constant region will determine kappa or lambda.
The valency is number of combining site/molecule, thus the valency of IgM is 2x5=10 and the
dimer IgA=2x2=4.

2.What are the differences between B and T signal transduction?

In the B cells, there are pairs of Igα and Igβ (the invariant chains) when there’s antigen
binding give signal transduction  proliferation and differentiation of B cells. There are also
co-receptors CD 19, CD 21 (receptor for EBV infection, and opsonins C3b and C3d could bind to
it), and CD 81 (receptor for hepatitis C and Plasmodium vivax). These co-receptors will lower
the threshold for B cell activation. This Ig is ultimately modified to be secreted antibody.

While in the T cells, the receptor consists of β and α chain and both form variable and constant
region. Therefore, T cell receptor only has 1 idiotype, 1 valency, and 1 isotype. Besides that, it
doesn’t have hinge region so it’s very rigid and only recognized antigen presented by MHC
peptide complex. The signal transduction is multichain structure which is called CD3 and it has
long tail structure to transduce the signal into the cytoplasm.

3.How do the T and B cells generate the receptor diversity?

-Firstly, the heavy chain (=β chain in T cell) is composed first encoded by paternal or maternal
gene (only one gene is expressed due to the allelic exclusion. If both are inactive, the cells will
undergo the apoptosis). The sequences of the gene rearrangement are: DJ  V/DJ producing
the diversity of heavy chain variable domains. Then, this DNA is being transcripted into the
mRNA which joins this variable domain sequence to µ or ð constant region.
-Second, the light chain (=α chain in T cell) is composed. The sequences of the gene
rearrangement: VJ producing diversity of light chain in the variable domains  kappa or
lambda are added to the constant domain in the B cells.
-The recombinase enzyme (RAG 1 and RAG 2) is responsible for this gene rearrangement.
-The junctional diversity is driven by Tdt (terminal deoxyribonucleotidyl transferase) which
randomly inserts the bases in the heavy chain of B cell and both αβ chain of T cell. If Tdt doesn’t
work, it will increase the susceptibility of infection and cancer. Therefore, Tdt is used as a
marker for early stage T and B cell development in ALL.

4.What are the clinical outcomes of the failed gene rearrangement?

5.How is the B lymphocyte development?

The B cells develop in the bone marrow. They develop from lymphoid stem cell (CD 34, IL7) 
pro-B cell that undergoes Ig heavy chain gene rearrangement (rag expression +, Tdt +)  pre-B
cell that undergoes Ig light chain gene rearrangement and has marker cytoplasmic µ (rag
expression+) immature B cell has the surface IgM+ and circulates to the periphery mature
B = naïve B cell that has surface IgM and IgD  activated B cell when it’s exposed to the antigen
differentiate into the majority plasma cell (cytoplasmic Ig+) and small group of memory B cell
(surface IgG+, IgA+, IgE+). From the pro B cell differentiation of activated B cell (plasma or
memory cell), they all have MHC II, CD 19, CD 20, CD 21, and CD 40 (for the T cell activation).

6.How is the selection of B cells?

The B cells whose have too great affinity will undergo apoptosis (clonal deletion) in the bone
marrow. Sometimes, some self-reactive B cells release into the periphery and they express high
levels of IgD, so they become inactive (clonal anergy). IgD doesn’t have function, except during
the development of B cell.

7.How is the T lymphocyte development?

The T lymphocyte progenitor=pre-tymic=double negative cells (don’t have CD4/CD8) will go the
thymus, the second primary lymphoid organ. In the cortex, they undergo the gene
rearrangement to compose αβ chain express the CD4 and CD8, so they are called now as
double positive cells. In the medulla, the T cells are directed to express only CD4 (if they bind to
MCH class II) or CD8 (if they bind to MHC class I), so they are called as single positive.
8.How is the selection of the T cell lymphocyte?
The stroma cells of thymus express both MHC class I and MHC class II that present the self-
peptide antigen. The positive selection will select the T cells which can bind to the MHC to
survive, if they can’t bind then it will undergo the apoptosis. Next, in the negative selection, T
cells with high affinity will undergo apoptosis, while T cells with low affinity will survive.

9. What are the differences between MHC class I and II?

MHC= HLA. MHC class I consists of HL-A, HL-B, HL-C, while the MHC class II consists of HL-DM
(for loading the peptide into the surface of MHC), HL-DP, HL-DQ, HL-DR. Both MCH are
expressed in codominant fashion and encoded by chromosome 6.

Their structures are different. MHC class I has the small peptide binding group, while the MHC
class II has large peptide binding group. Besides that, MHC class I is expressed by all the
nucleated cells (included macrophage, dendrytic, and B cells), while MHC class II mostly
expressed only by macrophage, dendrytic, and B cells.
06.04- Periphery: Innate Immune Response
1.How does the innate immune response recognize the pathogen?
The phagocytic cells (monocyte/macrophage, neutrophils, and dendritic cells) recognize the
pathogens via shared molecule. They have pattern recognition receptors (PRRs) that recognize
pathogen-associated molecular patterns (PAMPs, such as lipopolisaccharide) or damage-
associated molecular patterns (DAMPs).

2.How is the inflammosome being produced during the innate immune response?
The innate signals from toll like receptor on the phagocytic cells activates the pro IL β gene
transcription  pro IL 1β.
The binding of pathogen with the NRLP-3 (sensor) + adaptor+ procaspase-1 NLRP3
inflammosome  activation of caspase-1 (protease)  cleave the pro IL 1 β IL 1 β and IL 18
(family of IL-1 and acts together with the IL 12) which are potent inflammatory cytokines 
acute inflammation.

3.What are the types of the innate immune system receptors?

-Toll like receptors located in the extracellular eradicate the bacterial, while the receptors
located intracellular eradicate the viral infection.
-Unmethylated CpG oligonucleotide : the residual of bacterial that hasn’t been cleared or
intracellular bacteria

3.How do the mutations in innate immune receptor manifest into the disease?

-The absence of TLR is caused by loss of function mutation so the phagocytes couldn’t recognize
the intracellular and extracellular pathogen. The individual will tend to the recurrent and severe
bacterial infection such as pneumonia.
-The gain of function mutation will produce large number of inflammosome that will lead to the
excess inflammation, such as: gout, atherosclerosis, and type II diabetes.

4.What are the pathways for macrophage activation?

Classical M1 Alternative M2
Induced by innate immunity (TLRs, IFN Induced by IL-4, IL-13
gamma)
Phagocytosis, initiate inflammatory response Tissue repair and control of inflammation
Relate to TH 1 Relate to TH2

5.How is the collaboration of macrophages and NK cells?

6. Every acute inflammation will produce cytokines: IL1, IL6, TNF α and chemokines: IL8 and
IL12. What are their specific functions?
-IL 1: endogenous pyrogen and increases the expression of ICAM
-IL-6: synthesis of acute phase protein in the liver
- TNF α: responsible to induce cachexia
-IL-8: induce adherence to endothelium, chemotaxis for neutrophil, extravasation
-IL-12: induce the production of IFN-γ from the NK cells.
Besides that, IL1, IL6, TNF α will cause the vasodilation in the arterioles, extravasation and
increased vascular permeability in venules, and increased vascular permeability in the
capillaries.

7.The complement system is set of proteins produced by the liver and released into the
bloodstream. It has 2 pathways related to innate immune response (alternative pathway which
occurs immediately by binding to the LPS or polisachharide of gram negative bacteria and
mannose-binding pathway which is activated in 6-24 hours by the binding of lectin with
pathogen’s carbohydrate). Regardless of the pathway, what are the major functions of the
complement?

1: related to hypersensitivity type 1

2.related to opsonization and hypersensitivity type 3
3: related to the formation of membrane attack complex. It is extremely important in
eradicating Neisseria which has poli-O-saccharide. The absence of C5B and C9 will make
individual prone to the recurrent neisseria infection.

8.How do the phagocytes extravasate into the site of inflammation?

Step 1. Rolling: binding between E-selectin in the endothelium X mucin-like CAM. The blood
flow in the area will cause the cell to detach and reattach repeatedly.
Step 2. Activation by chemo-attractans: the chemokines released by macrophage such as IL-8
will induce the conformational change of integrin on the surface of the phagocyte.
Step 3. Arrest and adhesion: interaction between the integrin X igCAM mediates the tight
binding of the leukocytes.
Step 4.Transendothelial migration: the phagocyte extends pseudopodia through the vessel
wall and extravasates into the tissue.
9.The leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disease. The patients
suffer chronic and recurrent bacterial infection, the absence of abscess and pus formation, and
have the history of omphalitis (delayed separation of umbilical cord). Why?
-LAD is caused by the absence of CD18 (the common β2 chain of integrin). Therefore, the
phagocytes couldn’t undergo the adhesion and and migrate into sthe site of inflammation.

10.What are the important chemoattractive molecules?

11.How does acute inflammatory response occur?

-Tissue damage or bacteria will activate the complement pathway  produce C5a bind the
mast cell  release histamine (short lived) to increase the vascular permeability 
prostaglandin + leukotrienes (long lived) to increase the vascular permeability facilitate the
migration pf the monocyte, neutrophil, or lymphocyte
-Tissue damage or bacteria will also activate the macrophage  release IL-1+ IL-6+ TNF-α
(which increase the expression of E selectin), IL-8( which increases the expression of integrin),
and prostaglandin+leukotriene (increase the vascular permeability).

12. How is the process of phagocytosis?

In the area of antigen entry, phagocyte extends pseudopodia to engulf the attached material 
fusion of pseudopodia to form the phagosome  fusion of phagosome with a lysosome 
phagolysosome  digestion  exocytosis of digested contents  spill out the debris into the
environment= neutrophil extracellular trap (NET)  to trap bacteria and tissue damage if ROS
get released.

13.How is the process of opsonization?

Both macrophages and neutrophils have Fc receptor (=Fcγ) to bind the antibody (IgG) and
certain complement (C3b). This binding will enhance the adherence and phagocytosis of the
antigen.

14.The phagocytosis involves intracellular killing which is oxygen dependent or oxygen

independent killing (lysozyme, defensin, lactoferrin, and hydrolytic enzymes). The defect in the
oxygen independent killing will be asymptomatic, while the defect in the oxygen dependent
killing will cause patient more susceptible to catalase- positive organism infection (extracellular
bacteria and fungi). Why?
The oxygen dependent killing is the process of activation:
-NADPH oxydase: reduces oxygen  superoxide anion hydroxyl radical and hydrogen
peroxide which are microbicidal. The intracellular bacteria such as Mycobacterium, Lysteria,
Legionella could escape from this killing process.
-Myeloperoxidase (the back up enzyme when there’s defect of NADPH oxydase): lysosome acts
on hydrogen peroxide and chloride ions to produce hypochlorite (=Bleach). The prion could
escape from this killing process.
In the defect of NADPH oxydase, catalase- positive organism (Staphylococcus, Serratia,
Klebsiella, Aspergillus) could reduce the H2O2 which is the substate for myeloperoxydase as the
back up enzyme. Eventhough the macrophages fail to kill the pathogen, they will form
granulomatous to wall the pathogen. Therefore, this disease is known as chronic granumatous
disease.
The failure of oxygen radical generation could be easily detected by nitroblue tetrazolium
reduction with the formazan positive (purple blue) indicates the normal cell.

15. The innate immune response to viruses involves the interferons and natural killer cells. How
do these two major mechanisms occur?
-Any cells that are virally infected will produce IFN α and IFN β. These interferons which are not
virus-specific will temporarily shut down viral protein synthesis by activation of an RNA
endonuclease (digest viral and host RNA cell damage ) and phosphorylation of protein kinase
(inactivates eIF2 inhibiting viral protein synthesis).
-Natural killer cells employ 2 categories of receptor killer activating receptor (KAR: NKGD2)X
stress molecule (=MIC protein from the infected cells) and killer inhibitory receptor (KIR) X
HLA-E(= MHC class I). IFN-α, IFN-β, and IL-12 increase the NK activity by producing the perforin
(forming pores on the cells) and granzyme ( inducing caspace-lipase apoptosis). As long as, KAR
binds to the HLA-E, the cells won’t be killed.
16. What are therapeutic use of interferons?
-Interferon α: treatment for Hepatitis B and C, hairy B cell leukemia, CML, and Kaposi sarcoma (
HHV-8).
-Interferon β: multiple sclerosis to lengthen the period of remission and reduce relapses.
-Interferon γ: CGD induce the activation of macrophage and inflammatory response.

06.05- Secondary Lymphoid Tissue: Innate Meets Adaptive Immune Response

1. The spleen and lymph nodes are secondary lymphoid tissue. How do the dendritic cells
present the antigen into the secondary lymphoid tissue?
Only dendritic cells that could leave the site of injury by expressing CCR7 (induced by
chemokine from endothelium) and enter the lymph nodes via HEV  paracortex lymph node.
The other way is the pathogen or protein could be drained to the lymphatic drainage via
afferent lymphatic  lymph node which is surrounded by fibrous capsule subcapsular
sinus outer cortex (rich of B cell)  follicles (rich of B cell) inner medulla (activated cells
and memory cells) + medullary sinus  efferent lymphatic.
T cells are in the paracortex area. Both T and B cells are still naïve.

In the spleen, dendritic cells enter through the spleen artery  central arteriole 
periarteriolar lymphoid tissue (PALS)  vascular sinusoid  venules collect blood into the
splenic vein portal circulation. Marginal zone is B cell rich area, while PALS is T cell rich area.
The germinal center is the ring of proliferating lymphocyte and site for isotype switching,
somatic hypermutation, and the B cell differentiation into the plasma or memory cells.
2.What are the differences between MHC I and II peptide loading?
The exogenous pathway for MHC II loading: MHC class II is made in the ER and inactivated by
the invariant chain (Ii) and CLIP (class II invariant chain peptide) golgi apparatus  when
there is phagolysosome contained of the antigen, the invariant chain will be released from the
MHC class II HLA-DM helps loading the peptide into the binding groove of MHC class II. The
defect in this pathway will cause MHC II deficiency  defect of B cell, dendritic, and
macrophage cells SCID.

The endogenous pathway for MHC I loading: this pathway to eradicate all the intracellular
pathogen for example virus  synthesized viral protein targeted by ubiquitin and degraded
in proteasome into the smaller peptide because MHC class I has smaller binding groove  this
peptide is transported into the ER by TAP (transporter of antigen processing) through tapasin
(tunnel-like) bind to MHC class I golgi apparatus  forming the vesicles  attach on the
cell surface. The defect of TAP will cause patient becomes susceptible to intracellular infection
and tumor.
3.What are co stimulary molecules for MHC class II?

The first signal, is the binding of MHC class I/II to the T cell receptor followed by the second
signal from the binding between the B7 (B7.2) on dendritic cell with CD28 on the T cell.The
dendritic cells are the most profilic APC because they constitutively express the co-stimulatory
molecules needed to activate the T cells. The macrophages don’t have high level of MHC when
are inactive (lack of first signal), while B cells don’t have the secondary signal when are inactive.

4.How do the proteasome inhibitors work in treating the cancer?

The oncogenic cells are overly active with the higher protein synthesis. Protease inhibitors will
produce an accumulation of p53 as well as other regulatory proteins that lead to cell death via
apoptosis. The examples of this drug are: bortezomib (multiple myeloma and mantle cell
lymphoma) and carfilzomib (multiple myeloma).

5.What is the definition of cross presentation (cross priming)?

Besides expressing MHC class II on its surface, dendritic cell also recognizes the viral infected
cell by binding to the MHC class I and ingests this cell. Therefore, the dendritic cell could be the
APC by expressing the MHC class I to the CD8+ T cell.
06.06- Secondary Lymphoid Tissue: B and T Lymphocyte Activation
1. How does the activation of helper T cell by the macrophage occur?

-First signal: The binding of MHC class II with the TCR is stabilized with CD4. The macrophage
produces the inflammatory cytokines (IL-1, IL-6, TNF-α, IL-12) that induce the transformation of
TH1. CD3 acts as the transduction signal.
-Second (costimulatory) signal: recognition of B7.1 (=CD 80) or B7.2 (=CD86) on the
macrophage with the CD 28 on TH1.
-Later, the TH1 expresses the IgCAM binding with the integrin and CD40L binding with CD40-L
on the macrophage. These bindings to enhance activation of TH1.
-TH1 also produces an autocrine IL-2 to induce self-proliferation and expansion, IFN-α that
hyperactivates the macrophage  increase the ability to kill and produce more inflammatory
cytokines.
-In the end of adaptive response, TH1 should turn themselves off in which the CTLA-4 (the off
switch) competitively binds to the B7 receptor.

2. What is the clinical use of the CTLA-4?

CTLA-4 is important immunoregulatory molecule expressed by TH and Treg to downregulate
the immune response by binding competitively to B7-1 and B7-2 on APCs.
Agonists CTLA-4 will inhibit inflammation, while antagonist CTLA-4 will induce the
inflammation.

3.How do the superantigens induce T cell activation and proliferation?

The staphylococcal enterotoxins, toxic-shock syndrome-1 (TSST), and streptococcal pyogenic
exotoxins are the superantigens. They can cross-link the variable-β domain in the T cell receptor
with an α-chain of class II MHC molecule with the absence of antigen-speficic recognition in the
MHC class II groove. The manifestation could occur in the patient with the neglected surgical
tampons.

4.How is the development Th subsets?

-The type of antigen or pathogen determines the production of cytokine being produced by
Th0 Th1/Th2/Th 17 by activation transcription factor produce different cytokines  induce
different functions.
-Activation of each subset will inhibit the activation of another subset.
-Th 17 is new subset of Th that is responsible for killing the extracellular bacterial + fungal
infection, and abscess formation. Th17 leads to recruitment of neutrophil, while IL-22 decreases
the vascular permeability to inhibit the spread of pathogen.
-Delayed type hypersensitivity (type IV) is induced by Th1 and Th17. Thus, the cytokines IL-4, IL-
10, TGF β could suppress it.
-Type I hypersensitivity is induced by activation of Th12. Thus, the IFNγ could suppress it.

5.Why do T reg cells prevent the autoimmunity?

T reg cells actually inhibit Th1 cell function by secreting IL-10. This IL-10 has been shown critical
in prevention of autoimmunity. They also express CD 25 and transcription factor FoxP3.
6. What are the differences between tuberculoid vs lepramatous leprosy?
-Tuberculoid: strong Th1, granulomatous +
-The lepramatous: Th2 response is turned on and the cell-mediated response is decreased 
mycobacteria multiply inside macrophages  acid fast bacilli +.

7.Why is only IgM found in the full blown AIDS patient?

-The AIDS patient is lack of TH2 cells which are responsible for thymus-dependent activated B
lymphocytes no isotype switching activation of B cells only via thymus-independent IgM.

8.What are the major differences between thymus- independent (TI) and thymus- dependent
(TD) antigen activated B lymphocyte?
-TI: the antigen could be carbohydrate, polysacharride, lipid  generate weak response, no
memory cells, only produce IgM
-TD: the antigen should be peptide so Th1 could recognize it generate strong response,
memory response +, produce different isotype through isotype switching, undergo affinity
maturation.

9. How is the process of TD-antigen activated B lymphocytes?

This process occurs in the spleen or lymph node.

B lymphocytes activated TD antigens are released in 2 subsequent waves:

1st wave: producing plasma cells with IgM leave the secondary lymphoid tissue
2nd wave: producing plasma cells with IgG remain in the follicles of secondary lymphoid tissue
and clonal expansion  produce germinal center where the affinity maturation and isotype
switching occur.
10. What is the affinity maturation?
During the intense proliferation of B cells, DNA polymerase could make mistake leads to single
point mutation in the variable region (idiotype)  increase the affinity to the antigen  it’s
called somatic hypermutation. Over time, the cells with the higher affinity will predominate in
the germinal center through the clonal selection which produce the antibody with the high
affinity to the antigen, this process is know affinity maturation.

11.What is the isotype switching?

B lymphocytes receive the cytokine signals from T lymphocyte  the heavy chain of constant
domain undergoes the DNA rearrangement (DNA to be looped out, excised, and degraded) 
the combination of new constant region domain with the idiotype  isotype switching from
IgM in the mature B cell into the IgG, IgA, or IgE.

06.07- Humoral Immunity

1. Why is the IgM has the highest avidity, but the lowest affinity?

-The avidity= valency in which the IgM is the pentamer and the valency is 10. However, the IgM
never undergoes affinity maturation since it’s the antibody that is firstly produced (primary
isotype).

2.The CD40L defect causes hyper IgM which is known as X-linked hyper-IgM syndrome. Why?

The CD40L is the costimulatory molecule on the surface of the T cells that binds with the CD40
on the B cells. This is the second signal that will induce the proliferation and clonal expansion of
B cells (TD). Thus, the patient is failed to make other isotypes (low IgG, IgA, IgE). The B cells only
undergo the TI activation and result in hyper-IgM. There are also auntoantibodies toward
neutrophils, platelets, and red blood cells. Lymphadenopathy is not found because the B cells
fail to make germinal center. The children with this disease tend to suffer from the recurrent
respiratory infection, especially Pneumocystic jirovecii.

3.What are the unique factoids about IgG compare to IgM?

-It has the lower avidity (2), but the higher affinity compared to the IgM. Besides that, the IgG is
the only Ig that can across the placenta. It has 4 isotypes: Ig1 (the highest amount), Ig2, Ig3, Ig-
4. Both act in complement activation. However, the complement needs to IgGs and only 1 IgM
to be activated.
4.What are the unique factoids about IgA?

It is dimer Ig (secretory form) and mostly produced the submucosa than in the lymph nodes and
spleen (mucosal-type antigen). It has 2 subisotypes, IgA-1 (serum IgA with monomer) and IgA-2
(secretory in the mucosa). It functions as neutralizing antibody by inhibiting the binding of
toxins or pathogens to mucosa, especially in the mucosal-associated lymphoid tissue. IgA dimer
produced by the plasma cells  bound to the J chain poly-Ig receptors (like transportation) on
the basolateral side of the epithelia  endocytosed  released into the lumen bound to a
secretory piece (residue of the receptor) that protects the IgA from breaking down by IgA
protease and helps attachment of the IgA to the mucin in the mucosa.

5.What are the biologic functions of the antibody isotype?

06.08- Cell Mediated Immunity
1.Cell mediated immunity is dictated by the Th1 response and is mediated via macrophages and
CD+8 T cell to kill obligate and facultative intracellular. Why are the macrophages best effector
mechanism to eradicate Mycobacteria infection?
-The macrophages  produce IL-12  activate TH-1produce IFN-γ hyperactivate
macrophages (M1) to be “crazy” killers and protect themselves better against the
Mycobacteria. This process is also known as delayed type hypersensitivity that could lead to
granuloma formation.

2.How is the activation of the cytotoxic T lymphocytes?

CTL is capable of differentiation and cloning by themselves in the presence of appropriate MHC
class I non-self peptide. The CD8+ cells are stronger if being activated by T-helper by production
of IL-2. CTLs kill the target (the intracellular pathogen and tumor transformation) in 4 phases:
attachment to the target cell (mediated by TCR, CD8, LFA-1 integrin)  activation of
cytoskeletal rearrangement to concentrate granules into the target cells  exocytosis of
granule contents (perforin and granzymes)  detachment from the target cell. CTLs have CD
markes on the surface:CD8, CD3, TCR, CD2.
The Fas/FasL interaction is less time consuming than perforin and granzymes. Fas is being
expressed by the target cell. This binding will lead cell to the apoptosis.

3.A final mechanism of cytotoxicity which bridges humoral and cell-mediated effector systems
in the body is antibody-dependent cell-mediated cytotoxicity (ADCC). How does this mechanism
work?
-All of cytotoxic potential cells (NK cells, macrophages, neutrophils, and eosinophils) have
membrane receptor Fc region of IgG (=CD16). The IgG will bind to the Fc receptor and allow the
cytotoxic cells to kill the target cells by secreting lytic enzymes, tumor necrosis factor, and
perforin/ granzymes. In this process, the target cell is being killed without expression of MHC
class I.
06.09- Immunodiagnostics
1.What is the meaning of allotype?
The allelic difference in the same antibody isotypes that differ between people because the
alleles are inherited from both parents. Therefore, a patient receiving pooled gamma globulins
might react to these allotypic differences in the constant regions which may result in type III
hypersensitivity.

2.Papain and pepsin are proteolytic enzymes that cleave the antibody. The cleavage from
papain will not result in agglutination, while the cleavage from the pepsin will result in
agglutination. Why?
The papain will cleavage above the disulfide bond that holds the heavy chains together and
result in separated Fab (fragment antigen binding) and Fc (fragment crystallizable). While the
pepsin, it cleaves the constant region of the heavy chain and remains 2 antigen binding sites
that are still held together.

3.Why is the HBsAg not detectable in the window period of Hepatitis B infection?

The window period shows the equivalence zone where all of the antigen is complexed with
antibody (immune complex reaction between HBBsAg X HBsAb). Therefore, HBcAb is used to
detect hepatitis B infection in the window period.

4.What is the difference between the monoclonal and polyclonal antiserum?

Polyclonal antiserum represents many different clones of B cells that are making antibodies to
many different epitopes on an antigen, it can be derived from natural response against specific
infection. On the other hand, monoclonal antiserum is one clone of B cells with specificity for
the exact same epitope on the antigen.
5.What are the differences between direct vs indirect serologic tests?
The direct serologic test is for detecting the unknown antigen (the qualitative result), while the
indirect serologic test is for detecting the antibody in the patient’s serum (qualitative or
quantitative result). The indirect tests are generally more specific resulting in fewer false-
positives. Coombs, ELISA, and fluorescent antibody could be used for the direct or indirect
tests.

6.What are the differences between direct and indirect Coombs test?
The direct coombs test is for detecting the maternal anti- Rh antibody that is already bound
with the RBC of the baby or antibody bound on the RBCs in patient with autoimmune hemolytic
anemia.

While the indirect cooms test is for detecting the maternal anti-Rh antibody (IgG) in the
maternal serum which can be transferred via placenta to the baby or for diagnosis of
transfusion reaction.
7.In the ABO testing, we develop the antibody which doesn’t cross-react with our blood. The
antigens are the glycoprotein molecules on the red blood cells in response to similar molecules
express on the intestinal flora. What are the results of agglutination test for blood typing?

8.What is the test to detect the presence of Pneumococcus, Haemophilus, Meningococcus, and
Cryptococcus in the CSF?
Latex bead test agglutination which the antibodies against these organisms are conjugated to
the latex beads. The presence of the organisms will agglutinate and form lattice-like
presentation.

9.Fluoroscent antibody (FA) test is divided into direct (DFA) and indirect (IFA). What are the
major differences between them?
The DFA is used to detect antigen in the tissue by using specific fluorescent- labeled antibody
against the Ag. This test is used to diagnose respiratory syncytial virus, herpes simplex 1 and 2,
rabies in animal tissues, and Pneumocystis infections. While IFA is used to detect antibodies in
the patient by adding the test antigen and anti human gamma globulin labeled with
fluorescent, especially autoantibodies in various autoimmune diseases.
10. How is the interpretation of ELISA in HIV infection?
If the patient has p24 Ag in the serum, the substrate will change the color. This test can be also
used for the detecting the presence of hormones, drugs, antibiotics, serum proteins, infectious
diseases antigens, and tumor markers.

11.How is the interpretation of fluorescence activated cell sorting (FACS)?

Figure 1. Quadrant 1: CD3+, CD 8-= T helper cells, 2: CD3+, CD8+= T cytotoxic, 3=CD8+,CD3-= no
T lymphocyte maturation in the absence of CD3, 4: CD3-, CD8-= other cells.
Figure 2. 1: CD3+, CD4-= T cytotoxic cells, 2: CD3+, CD4+= T helper cells, 3:CD 3-, CD 4+= no
population cells found, 4: CD3-, CD4-= other cells.
Figure 3. 1: CD 3+, CD 20-= T CD 4+/ CD 8+ cells, 2: CD 3+, CD 20+= this type of cells is
unexisted, 3: CD3-, CD 20+=B cells, 4: CD 3-, CD 20-= other cells. Based on this figure, quadrant
1 would be empty in the Di George syndrome, quadrant 2 will be empty in the
agammaglobulinemia, and quadrant 1,2,and 3 would be empty in the SCID.
06.10- Immunizations
1.What are the differences between primary vs secondary immune response?

2.What are the side effects of passive immunotherapy?

-Systemic anaphylaxis especially for the patient with selective IgA deficiency, serum sickness
(hypersensitivity type III) due to activation of complement-activating immune complexes.

3.What are the types of vaccine?

-Live vaccine: the best vaccine to induce humoral and cellular immunity. Typically, the first dose
to give the immunity, while the second dose to ensure the seroconversion. Attenuated that is
recommended in the US: MMR, VZV, rotavirus, and influenza (now preferred the killed one).
Other vaccines that are given under special circumstances are polio (sabin), small pox, and
yellow fever. The only non-attenuated live vaccine is adenovirus type 4 and 7 given to US
military to prevent pneumonia.
-Killed vaccine: predominantly induce humoral immunity and require several doses. RIP-A
rabies which is the only vaccine given after exposure, influenza, polio (salk), and hepatitis A.
-Toxoid vaccine: made from exotoxin that prevents disease not the infection. The different of
DTaP and DTP is the DTap containing acellular pertussis (filamentous hemagglutinin).
-Polysaccharide vaccine: this vaccine only induces the formation of IgM because there’s no
involvement of T cell activation. Therefore, it has been replaced by the conjugate vaccines. The
only available vaccine is PPSV23 for the prevention of S. pneumonia, indicated for adults > 65
y.o., splenectomy, and COPD.
-Conjugate vaccine: capsular polysaccharide conjugated with the protein in order to induce T-
cell dependent immune response. Common Be Honest (conjugate: Haemophillus influenza type
B, Streptococcus pneumonia (PCV 13 for pediatric), and Neisseria meningitides (type B is the
most common but the capsule is not immunogenic. The available vaccine is against Y, W-135, C,
A).
-Component vaccine: the protein from the virus that is grown in the yeast. The available
vaccines are HBV, HPV (the new regimen is gardasil 9: contain serotypes
6,11,16,18,31,33,45,52,and 58).

4.Why is the live vaccine not given to the immunocompromised people?

-The live vaccine which is attenuated could revert back to a virulent form. Therefore, it is not
recommended for HIV or pregnant women whose the immune system is compromised to
prevent fetus rejection.

5. Why is the live attenuated vaccine is given after the children > 12 months old?

The baby acquires the passive immunity (IgG) from the mother in the end of first trimester. The
level of the maternal IgG starts to decline in the 6 months old and disappear in the 12-15
months old. Thus, the live vaccine is recommended after 12 months old so the maternal IgG
couldn’t neutralize the antigen. Besides that, it’s the reason why the primary immunodeficiency
starts to show up after 6 months old. Since the 12 months- old infants only have IgA 20% of
adult, the colostrums from the breastfeeding is very important.

06.11- Primary Immunodeficiency

1.What are the defects of phagocytic cells?
2.What are the defects of humoral immunity?
3.What are deficiencies in the complement?

*C1-INH is the molecule to turn the complement off. The defect of this molecule will lead to the
overuse of C1, C2, or C4 and result in edema at mucosal surface. While the C3 is used for
immune complex clearance and opsonization, the defect of the C3 will make individual
susceptible for recurrent bacterial infections and immune complex disease.

4.What are the defects of T lymphocytes and severe combined immunodeficiencies?

-In the Digeorge syndrome, the failure of formation of 3rd and 4th pharyngeal pouches  thymic
aplasia (thymic shadow -) and parathyroid aplasia hipocalcemia.

-The most common cause of SCID is IL 2 defect (50% cases) the failure of proliferation and
clonal expansion of T cells. In the vignette, the manifestation of SCID could be followed with
this lab results: T -, B+/-, and NK +/-.

06.12- Hypersensitivity and Autoimmune Disease

1. How is the process of type I hypersensitivity?
-This type 1 hypersensitivity is mediated by IgE (produced by B cells) that attached on the mast
cells. This IgE is normal protective response against the helminthes. This is also involved in the
allergic rhinitis, systemic anaphylaxis, food allergens, wheal and flare (in vivo skin testing), and
asthma. This reaction occurs immediately after second exposure and releases the preformed
mediators. After 4-6 hours later, arachidonic acid cascade releases the mediators that is known
as late phase reaction which is more potent and last longer.
2.What are the major differences between type II and type III hypersensitivity?
Both involve the IgG and IgM. In the type II hypersensitivity, antibody (autoantibodies towards
the antigen that cross react with self-tissue in most cases) against the cell or extracellular
matrix is specific to the tissue and not usually systemic. While in the type III hypersensitivity,
the immune complexes circulate and lodged in the small vasculature. In the comparison, the
biopsy of the kidney in Goodpasture syndrome (type II hypersensitivity) results in the smooth
ribbon like-pattern (right pic), while the lupus nephritis results in lumpy bumpy appearance due
to formation of immune complex (left pic).

3.What are the diseases reflecting the type II hypersensitivity?

It can be divided into the cytotoxic and non-cytotoxic. In the cytotoxic, the complement and or
ADCC is activated and cause the lysis of the cells. In the non-cytotoxic, there’s no involvement
of the complement or ADCC, thus the binding of the antibody alters the cell function.
3.What are the diseases reflecting the type III hypersensitivity?

*Arthus reaction is the only localized reaction (like wheal and flare) due to the immune
complexes.
4.What are the diseases reflecting the type IV hypersensitivity?
The tissue injury is elicited by CD4+, Th1, Th17, CD8+ CTL which activate macrophages, recruit
neutrophil, and induce inflammation.

5.How is the mechanism of the body to prevent autoimmunity?

The 3 mechanisms involved in the peripheral tolerance are anergy, deletion, and suppression. B
cells that recognize self-antigen will become anergic by expressing high levels of IgD on their
surface. While the T cells become anergic as the result of breakdown in either TCR signaling or
the binding of an inhibitory receptor, CTLA-4 or PD-1. Besides that, T regs secrete IL-10 and
TGF-beta will inhibit the activation of lymphocytes, macrophage, and dendritic cells. CTLA-4 is
expressed at high levels on Tregs which binds to the and sequester the costimulatory molecule
B7 which would otherwise be used to activate T lymphocyte.

6.What are the examples of HLA-linked immunologic diseases?

06.13- Transplantation

1.What are types of graft tissue?

-Autologous (auografts): from self to self , example: coronary bypass and skin graft. The only
transplantation that doesn’t require immosuppressant therapy.
-Isograft (syngeneic graft): transplantation between genetically identical invidual like
monozygotic twins.
-Allogeneic grafts: transplantation between genetically different members of the same species.
-Xenogeneic grafts: transplation between different species, example: pig heart valves into
human.

2.What mediators that increase the susceptibility of cells in the graft to MHC-restricted killing?
Interferon α,β, γ and TNF α, β increase expression of class I MHC molecules in the graft, and
IFN-γ increases the expression of class II MHC molecule.

3.Hyperacute graft rejection is very rare because of cross-matching blood. However, why does
it occur within minutes to hours?
The pre-formed antibodies (acquired from the transfusion, multi-parity, or previous organ
transplant) activate the complement (type II hypersensitivity) and clotting cascade resulting in
the thrombosis and ischemic necrosis. In the biopsy, more neutrophils are found in the tissue.

4.What is the mechanism involved in the acute (occurs within days to weeks) and accelerated
acute graft rejection (occurs within days)?
Both involve CD4+ and CD8+ T cells as well as antibodies. This reaction is similar with the
primary immune response. Thus, more lymphocytes are found in the biopsy in the acute. The
accelerated acute graft rejection occurs earlier because the reactivation of T lymphocytes that
have been sensitized during the first graft.
5.The cause of chronic rejection (occurs within months to years) is unclear, thus makes it
difficult to treat. What would happen in the blood vessels of transplanted organ?
-This reaction is predominantly T cell mediated and displays chronic DTH reaction. There’s
vessel wall proliferation leads to the vessel occlusion.

6. Why do the rash, jaundice, diarrhea, and gastrointestinal hemorrhage occur in the graft-
versus-host disease?
In the bone marrow transplant, the patient should undergo radiation targeted high replication
cells in the skin, mucosa, GI tract, hepatocytes, and bone marrow  inflammation 
presenting the MHC-bearing cells. Then, any mature T cells remaining in the bone marrow
inoculums can attack this MHC bearing cells and results in various symptoms. Little rejection
could be beneficial because of killing the cancer cells.

7.What are monoclonal antibodies used in the treatment and prevention of graft rejection
(combined with the classic therapies: corticosteroid, cyclosporine A, rapamycin, etc)?
8. What are the tests performed for tissue typing?

A one-way mixed lymphocyte response is performed to assess differences between donor and
recipient at the MHC class II loci.
An agglutination test is used to test ABO blood group compatibility. Cross-matching refers to
the mixing of recipient serum with donor lymphocytes to identify any unidentified preformed
antibodies that could cause hyperacute graft rejection. The microcytotoxicity test is used to
assess MHC class I haplotypes. All of the tests mentioned are part of the general process of
tissue typing.

MICROBIOLOGY

07.01- General Microbiology

1.A patient suffers from endocarditis and the serial blood cultures are taken. The result is
Staphylococcus epidermidis. How do distinguish whether it’s the causal organism or
contaminant?
If the Staphylococcus epidermidis only exists in one blood culture, it’s most likely contaminant.
However, if it exists in more than 2 blood cultures, it’s most likely the causal organism.

2.What are the important pathogenicity among organisms?

-Colonization: adherence medited by the techoid acid for gram positive and LPS (lipid A) for
gram negative, pili/ fimbriae (E.coli causing UTI), adhesions, IgA protease (breaking down the
IgA in the mucosa). Partial adherence is mediated by production of biofilms (S. epidermidis, S.
mutans, P. aeruginosa).
-Avoiding the immediate destruction by host defense mechanism: The capsules: Some Killers
Have Pretty Nice Capsules (Streptococcus pneumonia, Klebsiella pneumonia, Haemophilus
influenza, Pseudomonas aeruginosa, Neisseria meningitides, Cryptococcus neoformans), and
IgAprotease
-Hunting and gathering needed nutrients: siderophose to steal and import iron
-Antigenic variation: Neisseria gonorhoeae,Trypanosoma brucei+gambiense, Borrelia
recurentis, Enterobacteriaceae
-Ability to survive intracellularly: Mycobacterium (inhibits the fusion of phagolysosome),
Listeria (inhibits the phagosome and polymeraze actin  invade the neighboring cells), Yersinia
pseduotuberculosis (invasin to allow organism to bind and invade non-phagocytic cells)
-Type III secretion system: tunnel made by Yersinia,P. aeruginosa, Chlamidya to transport
toxin.
-Inflammation or immune mediated damage: cross reaction of bacteria induced antibodies X
tissue antigen (rheumatic fever and post-streptococcal glomerulonephritis), granuloma
formation (Mycobacterium, Chlamidya causing PID)
-Physical damage: swelling from the infection (meningitis), blocking the bile duct (Ascaris)

3.What are the differences between the exotoxin and endotoxin?

The septic shock with gram negative as the causal organism, the major pathogenicity is the LPS
(lipid A portion).

4.What are the toxins inhibiting protein synthesis?

-Corynebacterium diphteriae (diphtheria toxin target epithelium/heart/nerves) and
Pseudomonas aeruginosa (exotoxin A target liver) : both inactivate eEF-2 by ADP rybosil
transferase  inhibit protein synthesis
-Shigella dysenteriae and EHEC: both interfere with 60S ribosomal protein  inhibit protein
synthesis.

5.Why does Clostridium botulinum toxin causing the flaccid paralysis, while the Clostridium
tetani toxin causing the tetani?
6.The superantigens can induce cytokine storm. What are the organisms producing the
superantigen?

7.What are the organisms producing the toxin which acts as cAMP inducer?

8.The cytolysins work by punching hole on the cells leading to the cell death. What are the
organisms producing the cytolysins?
07.02- Medically Important Bacteria
1.Bacillus and Clostridium produce the spore in the extreme environment. Why is the spore
difficult to be eradicated?

2.Bacterial growth has 4 phases: lag, log, stationary, and death. What is the best phase to give
antibiotic?
-Log phase because the bacteria is growing very rapidly in this time.

3.What are types of special media to grow the organism?

MacConkey’s agar as the selective media will select certain types of bacteria: only gram
negative could grow, as the differential media will differentiate the properties that bacteria has,
for example: lactose fermenter will change the color into pink (differentiate between E. coli and
Shigella).
EMB: to grow the gut flora bacteria, used for the feces contaminated water e.g.E.coli produce
metallic green color.
Buffer Charcoal Yeast Extract (BCYE): Legionella causing pneumonia
Chocolate agar (heated blood agar to release the substrate to be used by bacteria that couldn’t
lyse the red blood cells): Neisseria, Haemophillus (need factor X and V to grow)
TCBS (sucrose medium): Vibrio  Will produce orange color.

4.Based on the oxygen requirement, what are the classifications of the organism?
-Obligate aerob (non-fermenter): Mycobacterium, Pseudomonas, Bacillus
-Microaerophilic: Campylobacter, Helicobacter
-Obligate anaerob( fermenter, lack SOD) : Actinomyces, Bacteroides, Clostridium
-Facultative anaerob: most of enteric organism (mostly glucose fermenter)

5.Based on the gram stain, how do we classify the bacteria?

-Gram positive coccus: Staphylococcus, Streptococcus, Enterococcus
-Gram negative coccus: Moraxella, Neisseria
-Gram positive rod: Bacillus, Clostridium, Corynebacterium, Listeria (BC2L)
-Gram negative rod: others

6. Cultures of the skin taken from a child with impetigo grow out gram-positive cocci. What is
the most appropriate next step in the diagnostic process?

The catalase test is the most important test to distinguish between the gram-positive cocci of
the genera Streptococcus and Staphylococcus. The CAMP test is used to distinguish
between Streptococcus pyogenes and S. agalactiae. The coagulase test is used to
identify Staphylococcus aureus specifically. The ELEK test is used to distinguish between normal
flora diphtheroids and the pathogen Corynebacterium diphtheriae. The oxidase test is the major
test that distinguishes between the gram-negative bacilli,
with Campylobacter and Vibrio testing positive and the Enterobacteriaceae testing negative.
7.What are important features related to S. aureus?
-Gram positive, catalase +, coagulase +, beta hemolytic, manitol fermenter, forming yellow
colony
-Presdiposing factor for infection: surgical packing/ tampons, intravenous drug user, severe
neutropenia, chronic granulomatous disease, cystic fibrosis
-Pathogenesis: toxic shock syndrome-1 (superantigen), enterotoxin (A-E preformed in food) ,
exfoliatin (involved in scalded skin syndrome), protein A binds Fc component of IgG (inhibiting
phagocytosis)

-Diseases: Staphylococcal food poisoning is most commonly associated with salty foods such as
ham, potato salad, and custard pastries (2-6 hours after ingesting food), infective endocarditis,
toxic shock syndrome, impetigo, osteomyelitis (the most common cause in the children, unless
in the patient with sickle cell anemia, Salmonella would be the most common cause), septic
arthritis, pneumonia (salmon-colored sputum).
-Treatment: self limiting for gastroenteritis, nafcillin/oxacillin (drug of choice), vancomycin (for
MRSA), quinupristin/dalfopristin (for VRSA)

8. How do we differentiate between Staphylococcus epidermidis and Staphylococcus

saprophyticus?
Both are gamma hemolytic (no hemolysisis). Staphylococcus epidermidis is novobiocin sensitive
causing endocarditis in IV drug user and infection related to cathehter and prosthetic device
(biofilm producer), while the Staphylococcus saprophyticus is novobiocin resistant causing
honeymoon cystitis.

9. A patient isolate is analyzed with the following results: What would be the next step in
laboratory diagnosis?

The isolate is a gram-positive coccus that is catalase negative, so it belongs to the

genus Streptococcus. It is alpha hemolytic, which means that it could be either the viridans
group or Streptococcus pneumoniae. The distinction between them is made on the basis of
optochin sensitivity or resistance.

10. What are important features related to Group A Streptococcus (S. pyogenes)?
-Gram +, catalase -, beta hemolytic, bacitracin sensitive, PYR +
-Pathogenicity: M protein antiphagocytic associated with rheumatic fever (type II
hypersensitivity) and acute glomerulonephritis (type III hypersensitivity). Spreading factors:
hyaluronidase (hydrolyzes connective tissue causing necrotizing fasciitis), streptokinase
(breaking down the clot), and exotoxins A-C (superantigen and cause of rash in the Scarlet
fever)
-Diseases: pharingitis (exudates), scarlet fever (sandpaper rash and hand+soles desquamation),
impetigo (honey-crusted lesion), rheumatic fever (ASO> 1/200, required antibiotic at least for 5
years post acute rheumatic fever), acute glomerulonephritis.
-Diagnosis/ treatment: rapid strep test (ELISA), drug of choice beta lactam or macrolide (if
penicillin allergy)
11.What are important features of Group B Steptococcus (S. agalactiae)?
-Gram +, catalase -,beta hemolytic, bacitracin resistant, CAMP + (secreting polypeptide factor
that enhances Beta hemolysis  arrowhead formation when is cultured with S. aureus)
-Pathogenicity: capsule; beta hemolysin and CAMP factor
-Diseases: the most common cause of neonatal septicemia and meningitis (because it’s normal
flora of vagina in the 15-20% women administered antibiotic during delivery)
-Treatment: beta lactam with aminoglycoside or cephalosporin (most common drug for
meningitis).

12.What are the important features of Streptococcus pneumonia?

-Gram +, catalase -, alfa hemolytic (greenish color colony), optochin sensitive, lancet-shaped
diplococcic surrounded by halo (=capsule), bile soluble
-Presdiposing factor; influenza/ measles infection, COPD, CHF, alcholosism, asplenia (prone to
capsular infection organism)
-Pathogenecity: polysaccharide capsule, IgA protease, techoid acid, pneumolysin O (damaging
epithelium of respiratory tract and inhibiting complement)
-Diseases: the most common cause of adult meningitis and community pneumonia (rusty
sputum), the most common cause of sinusitis and otitis media in children.
-Diagnosis/ treatment: latex particle agglutination (mostly used), Quellung reacting (antibody
specific to capsule  swelling of the capsule). Beta lactam (drug of choice), cephalosporin,
macrolide.

13.What are the important features of Streptococci viridians (S. sanguis, S. mutans)?
-Gram +, alfa hemolytic, PYR negative, optochin resistant, bile insoluble
-Pathogenicity: normal flora of human oropharynx  dextran (biofilm) mediated adherence on
to teeth
-Diseases: dental caries, subacute endocarditis (especially for patient with non-sterile dental
procedure), colon cancer (S. gallolyticusi)
-Treatment: penicillin G with aminoglycoside for endocarditis

14. How is the pneumococcus serotyped?

The streptococci are grouped with the C carbohydrate, Streptococcus pyogenes is serotyped
with the M protein, and because pneumococcus is not groupable, it is serotyped by analysis of
its capsular polysaccharide.
15.What are the important features of Enterococcus faecalis/ faecium?
-Gram +, catalase -, PYR negative, black colony on bile esculin agar
-Diseases: UTI related to the catheter (most commonly unresponsive to the antibitotic),
endocarditis in the prostethic valves
-Treatment: beta lactam or gentamicin as prophylaxis prior to intestinal or urinary tract
manipulation.
16.What are the important features of Bacillus antrachis?
-Gram positive, boxcar like, spore forming rods, potential biowarfare agent
-Anthrax toxin consisiting of lethal factor (killing cell), edema factor ( increasing cAMP
swelling), and B factor (mediate binding to the cell)
-Diseases: cutaneous anthrax (edematous + black eschar), pulmonary life threatening
pneumonia (wool sorter’s disease) with mediastinal widening in the X ray might be fatal if not
treated in 48 hours because the bacteria starts to produce toxin when given antibiotic 
toxin released  toxemia.
-Treatment/ prevention: ciprofloxacin or doxycycline, toxoid vaccine (AVA for military),
raxibacumab for prophylaxis

16. What are the important features of Bacillus cereus?

-Gram + rod, spore forming, foodborne, associated with fried rice in the Chinese food
restaurant
-Toxin: emetic (preformed toxin) fast onset in 1-6 hours= S. aureus, diarrheal toxin (produced in
vivo) late onset in 18 hours  increasing cAMP watery diarrhea= E. coli, but self limiting.

17.What are the important features of Clostridium tetani?

-Gram +, large, spore forming (tennis racket shaped), anaerob, associated with the puncture
wound/ human bite
-Pathogenicity; spore producing tetanospasmin  carried intra-axonally into the CNS 
inhibiting the release og GABA and glycine at spinal synapse  excitatory is unopposed 
extreme musle spasm (started with the lockjaw)
-Treatment/ prevention: hyperimmune human globulin to neutralize the unbound toxin,
diazepam, antibiotic (metronidazole/penicillin), toxoid vaccine (booster every 10 year for low-
risk patient). In an unresponsive patient or one who is unfamiliar with his vaccination history,
the vaccine should be administered, and antitoxin antibodies (tetanus immune globulin) should
be administered around the wound site.
18. What are the important features of Clostridium botulinum?
-Gram +, spore forming, anaerobic, related to the foodborne/ traumatic implantation,
producing toxin A-B polypeptide neurotoxin and coded for by a prophage absorbed by gut 
carried by blood to the peripheral synapse  inhibiting the release of acetylcholine flaccid
paralysisis.
-Different cause leading to the diseases

-Symptoms are various

-Treatment/ prevention:

Note: antibiotic is not required for adult botulism because the cause of the disease is the toxin.
Toxin is heat labile (inactivated in 600C for 10 minutes). The most common form of botulism in
the US is floppy baby botulism.

19. What are the important features of Clostridium prefringens?

-Gram +, large rod, spore forming, anaerobic, nonmotile, stormy fermentation (in milk media),
double hemolysis (in blood agar).
-Produce cytolysin toxin  alfa toxin (phospholipase C)= lecithinase that could be identified by
nagler reaction=egg yolk plate in which the lecithinase activity is shown in the absence of
antitoxin damaging the cell  gas gangrene=myonecrosis. Enterotoxin=E. coli  watery
diarrhea.
-Treatment/ prevention: debridement+ delayed closure+ hyperbaric chamber+ penicillin/
clindamycin (gangrene), self-limiting (food poisoning).

20. What are the important features of Clostridium difficile?

-Gram +, sporeforming, anaerobic, normal flora in the GI tract and grow rapidly after
administration of broad spectrum antibiotic (cephalosporin, clindamycin, ampicillin,
amoxicillin) producing toxin A (enterotoxin damaging mucosa) and B (cytotoxic)
-Disease: pseudomembranous colitis (yellowish plaque in the colon).
-Diagnosis/ treatment: identify toxin in the stool, stop the antibiotic for the mild case,
adimistering metronidazole (for severe case), fecal transplant to re-grow normal flora in the
chronic infection, isolated symptomatic patient to prevent nosocomial infection.

21. What are the important features of Lysteria monocytogenes?

-Gram +, small rod, facultative intracellular, beta hemolytic, thumbling or actin jet motility (to
move to the neighboring cell without being detected by the immune system), related with
unpasteurized milk, cold growth (deli meat, softcheese, cabbage, hotdog)
-Pathogenicity: hemolysin alfa and beta, listeriolysin O
-Disease: listeriosis in the pregnant woman can lead to sepsis and miscarriage  across the
placenta  neonatal disease: granulomatosis infantisepticum with disseminated
granulomatosis=non-caseating (early onset) and meningitis with septicemia 2-3 weeks after
birth due to fecal exposure (late onset). Listeria meningitis in the immunocompromised patient
(patient with renal transplant and cancer).
-Diagnosis/ treatment: blood/ CSF culture at 40C, wet mount of CSF thumbling motility,
ampicillin+ gentamicin.

22.What are important features of Corynebacterium diphteriae?

-Gram +, club shaped (V/L) / Chinese-letter shaped, aerobic, black colony on tellurite medium,
not invasive but toxin (A-B component  inhibiting eEF-2 protein synthesis inhibitor)
produced by beta prophage goes systemic.
-Disease: diphtheria (dirty gray pseudomembranous+ bull neck), laryngeal obstruction,
recurrent laryngeal palsy, myocarditis, lower limb polyneuritis, renal failure
-Diagnosis/ treatment: to distinguish Diphteria and diphteroid as normal flora  perform Elek
test  put the antitoxin on the filtering paper  forming arc precipitin line (+), ELISA (gold
standard), PCR. Treatment: erythromycin, penicillin+ aminoglycoside for 4-6 weeks for
endocarditis, and toxoid vaccine DTaP.

23.What are the important features of Actinomyces israelii?

-Gram +, branching, anaerobic, non-acid fast staining, endogenous infection (part of normal
flora: human gingival crevices + genital tract in female invasive in oxygen deprivation tissue)

-Disease: actinomycosis in the some regions: cervicofacial (lumpy jaw, not painful), cervix,
abdominal, thoracic, CNS (solitary brain abscess, while nocardia forms multiple foci), draining
abscesses with sulfur granules (hard yellow microcolonies)
-Diagnosis/ treatment: gram stain branching bacilli with sulfur granule+ molar tooth colony
(diagnostic). Penicillin IV + metronidazole (drug of choice).

24.What are the important features of Nocardia?

-Gram +, filaments breaking up into rods, aerobic, partially acid fast stain, no toxin, exogenous
(traumatic implantation/ airborne).
-Disease: cavitary bronchopulmonary nocardiosis (diffuse pneumonia with cavitation in IC
patient, mostly caused by Nocardiosis asteroids) may spread to the brain and causes multi
foci brain abscess, cutanoeus/ subcutaneous abscesses with sulfur granules (mycetoma, mostly
caused by Nocardia braziliensis)
-Diagnosis/ treatment: culture from sputum/ pus, sulfonamide/ TMP-SMX

25.What are the important features of Mycobacterium tuberculosis?

-Gram +, acid fast rod, obligate aerob, facultative intracellular, cell wall contain of mycolic acid,
slow growing in the Lowenstein-Jensen faster growing in the broth with palmatic acid,
producing niacin+ heat-sensitive catalase, transmission respiratory droplet.
-Pathogenesis; sulfatide (important factor to avoid phagosome-lysosome fusion by producing
sulfuric acid  low pH  survive in the macrophage), cord factor strongly correlated with
pathogenicity (=trehalose dimycolate inhibiting leukocyte migration and disrupting
mithocondrial respiration), tuberculin (surface protein along with mycolic acid inducing CMI
 DTH IV) .
-Disease: primary tuberculosis (Ghon focus (bacteria in the alveolar macrophage)  Ghon
complex (spreading the lymph node))  outcome: infection resolved, granuloma formation,
disease, reactivational TB (erosion of granuloma systemic).
-Diagnosis/ treatment: sputum staining (auramine-rhodamine positive green fluorescent
acid fast stain), PPD skin test (positive >= 5 in IC patient, >=10 mm in high risk population, >= 15
mm in low risk population)  exposure + not necessarily active infection. Treatment in the first
2 months (HRZ) + in the next 4 months (HZ). Prevention is given to the PPD + and chest X ray +
 isonizid for 6-9 months.
-In the AIDS patient, CD4 > 200 cell/mm3 TB.

26. What are the important features of Mycobacteriaa other than tuberculosis?
-Mycobacterium kansasii (photochromogen +) + avium intracellulare (non-chromogenic) 
presentation similar with TB but infect patients with CD4 < 50 cell/mm3.
-Mycobacterium marinum  fish tank grnauloma in the fish tank enthusiast.
-Mycobacterium ulceransi buruli ulcer from wound contamination.
- Mycobacterium scrofulaceum  solitary cervical lymphadenitis in kids from contaminated
water sources.

27. What are the important features of Mycobacterium leprosii?

-Gram +, acid fast stain, obligate intracellular, grow in the cold temperature, transmission via
armadillo in texas and Lousiana+ nasal discharge from the patient.
- Disease: tuberculoid (low number of bacteria, strong CMI to wall of bacteria granuloma
formation nerve damage and loss of sensation, fewer lesion, lepromin test +), leprosy (high
number of bacteria, weak CMI  Overgrowth bacteria nerve damage +numerous lesion +
leonine facies, lepromin test -)
-Diagnosis/ treatment: punch biopsy from nasal scraping, acid fast stain, lepromin skin test.
Treatment included dapsone+ rifampin, additional clofazimine in leprosy, and dapsone for close
family contact as prevention.

28. How do we distinguish Neisseria meningitides and Neisseria gonorrhea?

-Both gram -, diplococcus, oxidase +, beta lactamase, grow in the Thayer- Martin agar
(=selective media which is made from the chocolate agar with the antibiotic)

29.What are the important features of Neisseria meningitides?

-Large capsule (B is the most important not too immunogenic), ferment maltose, normal flora in
the nasopharynx, transmission respiratory droplet (especially in the person living in the
dormitory).
-Pathogenicity: LPS (endotoxin), overproduction of outer membrane containing endotoxin
facilitate the entry into the meninges and septic shock in meningococcemia, capsule, pili
and outer membrane protein to invade and colonize, IgA protease, deficiency of complement
factor C5-C8 for MAC(recurrent Neisseria infection)
-Disease: meningitis with rash that is generally petechial (differ from S. pneumonia),
Waterhouse-Friderichsen syndrome (adrenal crisis hypovolemia  death in 10-12 later)
-Diagnosis/ treatment: gram stain of CSF and latex agglutination. Treatment ampicillin and
cefotaxime (neonates and infant), cefotaxime/ ceftriaxone with or without vancomycin
(children and adult). Prevention vaccination and rifampin/ciprofloxacin for the close contact.

30.What are the important features of Neisseria gonorrhea?

-Pathogenicity; antigenic variation in pilli, outer membrane (OMP 1 for serotyping and OPA)
-Disease: urethritis (yellowish purulent), endocervicitis, PID, ophtalmia, gonococcal pharyngitis
(the most common cause in the sexually active adult).
-Diagnosis/ treatment: intracellular gram-negative diplococci, culture in Thayer-Martin (oxidase
+, non-maltose fermenter). Ceftriaxon (drug of choice), would be better choice if given along
with doxycycline for the test of C. trachomatis, erythromycin ointment or silver nitrate to
prevent neonatal ophtalmia.

31.What are the important feature of Moraxella catarrhalis?

-Gram-, diplococcus, transmission via respiratory droplet
-Disease: sinusitis + otitis media (3rd common cause after S. pneumonia and non-typeable H.
influenzae), bronchitis+ bronchopneumonia in COPD
-Treatment: amoxicillin+ clavulanate, second or third cephalosphorin, TMP-SMX

32.What are the important features of Pseudomonas aeruginosa?

-Gram -, rod, oxidase + (differ from the enteric bacteria), catalase +, aerobic nonfermenting,
pyocyanin (blue-green) appearance , grape like odor, capsulated, transmission via water
aerosol/raw vegetable/ flower
-Pathogenicity: capsule/ slime layer (most important), LPS (inhibiting eEF2)
-Disease: hot tub folliculitis (2nd common cause after S. aureus), eye ulcer, cellulitis in burn
patient  septic shock, pneumonia and septicemia in neutropenia patient, CGD, echtyma
gangrenosum, UTI related with cathether, recurrent pneumonia with high slime production in
CF patient.
-Diagnosis/treatment: gram stain+ culture, piperacillin/ ticarcillin, aminoglycoside

33.What are the important features of Legionella pneumophilla?

-weakly gram -, pleomorphic rod, require cysteine and iron in charcoal yeast extract, water
organism (air conditioning/ river stream), non-human to human transmission, facultative
intracellular  granuloma
-Disease: smoker> 55 yo+ alcoholic, renal transplant patient atypical pneumonia= legionnaire
(followed by mental confusion and diarrhea), Pontiac fever (pneumonitis)
-Diagnosis/ treatment: direct fluorescent antibody by Dieterle silver stain 4x increase of titer,
urinary antigen test. Treatment: FQ/ azithromycin/ rifampin. Decontamination of air-
conditioner cooling tank routinely as prevention.

34.What are the important features of Francisella tularensis?

-Gram -, small rod, facultative intracellular in reticuloendothelial cells granuloma, zoonosis
(rabbit, deer) transmitted by the tick bite (Dermacentor) ulceroglandular disease, aerosol
from skinning rabbit  pneumonia, undercooked rabbit  typhoidal tularemia, potential
biowarfare agent
-Disease: tularemia (high in Arkansas and Missouri).
-Diagnosis/ treatment: serodiagnosis/DFA, streptomycin, live attenuated vaccine for high risk
people.

35.What are the important features of Bordetella pertussis?

-Gram -, small rod, strict aerob, capsulated, reservoir vaccinated human.
-Pathogenicity: filamentous hemagglutinin (for attachment  damage the cilia whooping
cough blood shot eye), pertussis toxin (increasing cAMP  efflux ion and water+
lymphocytosis promotion islet activation inducing hypoglycemia, block immune effector
cells, increase histamine sensitivity ), adenylate cyclase toxin+tracheal cytotoxin  damage
respiratory epithelium.
-Disease:
Catarrhal stage with unspecific symptoms but the best bacterial culture. The convalescence
state is the time for the complication development.
-Diagnosis/ treatment: nasopharyngeal aspirate  grow the culture in the Bordet Gengou or
Regan Lowe, DFA from nasopharyngeal smear, PCR, serology (best used for the middle of the
paroxysmal stage on). Treatment is erythromycin for 2 weeks. The vaccine DTaP for prevention.

36. What are the important features of Brucella?

-Gram -, rods, aerobic, zoonosis, facultative intracellular, potential biowarfare (causing the
disease very quickly), transmission via unpasteurized dairy products (high in California and
Texas, and travel to Mexico) and direct contact with animal in the slaughterhouse.
-Brucella abortus (cattle) ,Brucella melitensis (goat), Brucella suis (pig)
-Pathogenicity: endotoxin, facultative intracellular  granuloma
-Disease: brucellosis (undulant fever, profuse sweating), chronic brucella (related to the B.
melitensis, cyclic form depression and profuse sweating)
-Diagnosis/ treatment: serum agglutination test. Treatment rifampin+doxycycline (adult),
rifampin+ cotrimoxazole (children), vaccinate cattle/ high risk human+ pasteurize goat milk.

37. What are the important features of Campylobacter jejuni?

-Gram -, curved rods, “gulls wings’, oxidase +, microaerophilic, grow at 420C (campy medium or
skirrow), transmission via contaminated poultry, acid tolerant

-Pathogenesis: low infectious disease invade mucosa bloody diarrhea

-Disease: gastroenteritis (the most common in the US) which is generally self-limiting  could
develop GBS (antibody for bacteria cross reacts with nerve tissue), reactive arthritis (HLA B 27)
-Diagnosis/ treatment; skirrow agar, fluid and electrolyte replacement, erythromycin/ FQ in IC
patients

38. What are the important features of Helycobacter pilorii?

-Gram -, spiral with flagella, oxidase +, urease + (important virulence factor), microaerophilic,
fecal-oral/oral-oral via human
-Disease: duodenal ulcer+chronic gastritis  increase gastric adenocarcinoma (type 1
carcinogen) and B cell lymphoma/ MALT-oma (resolved during treatment H. pylori)
-Diagnosis/ treatment; biopsy with culture (gold standard), urease breath test. Treatment is
multidrug: amoxicillin+ omeprazole+ clarithromycin for 10-14 days.

39. What are the important features of Vibrio cholera?

-Gram -, curved rod, oxidase +, grow in TCBS  orange , L tor serotype (predominant now),
shooting star motility, reservoir human colon, transmission fecal oral (require high dose), acid
sensitive
-Pathogenesis: cholera enterotoxin (=E.coli) ADP ribosylates (GS alpha) increase cAMP
-Disease: rice water stools
-Diagnosis/ treatment: culture stool on TCBS, oxidase +. Treatment: fluid and electrolyte
replacement, doxicycline/ ciprofloxacin.

40.What are the important features of V. parahaemolyticus and V. vulnificus?

41.How do we distinguish Enterobacteriaceae?

-Gram – rod, facultative anaerob, ferment glucose, oxidase – (differ from diarrhea causing
organisms such as Pseudomonas, Campylobacter, Vibrio), catalase + (in CGD), antigen O-body,
H-flagella, K-capsular, Vi-virulence, grow in the EMB or MacConkey agar (lactose fermenter:
pink colony)
42.What are the important features of E.coli?
-Gram -, rod, oxidase -, lactose fermenter, transmission in the endogenous, fecal oral, maternal
fecal flora, bovine fecal contamination and apple juice from fallen apple.
-Disease: UTI (the most common cause), neonatal septicemia and meningitis (K1 serotype
capsule+endotoxin), gastroenteritis (PITcH: EPEC, EIEC similar to shigellosis, ETEC, EHEC: the
most common).
*ETEC has 2 enterotoxin: LT  ADP ribosylation of Gs increasing cAMP watery diarrhea,
ST stimulating guanylate cyclase  watery diarrhea.
*EIEC watery diarrhea with pus, 10% progress on to dysentery.
*EHECO157: H7 (the most common type), has plasmid-associated verotoxin=shiga like toxins
(inhibiting protein synthesis) causes mild diarrhea to hemorrhagic colitis (bloody stool
without fever and PMN because of non-inflammatory disease)  hemolytic uremic syndrome
(contraindicated for antibiotic) in kids< 5 yo. Diagnosis: sorbitol Mc-Conkey colorless colony
to differ it from the normal flora E.coli
*EAEC: the fimbriae forms stack brick layer biofilm persistent diarrhea
-Treatment: ciprofloxacin (for UTI), ceftriaxone (meningitis and septicemia), rehydration + TMP-
SMX to shorten the duration of the disease (ETEC), Fluoroquinolone (EIEC)

43. A fecal specimen from a patient with inflammatory diarrhea is cultured on agar media, and
gram-negative bacilli are grown. What is the first diagnostic test that should be ordered to
distinguish between the various gram-negative rods that cause diarrhea?
The oxidase test is the major test that distinguishes between the gram-negative bacilli,
with Campylobacter and Vibrio testing positive and the Enterobacteriaceae testing negative.
This test depends on flooding test colonies with phenylenediamine. If cytochrome c oxidase is
being produced, black colonies will result. Within the Enterobacteriaceae, differential media
distinguish between lactose fermenters and non lactose fermenters. A test with fibrinogen
describes the coagulase test, which is diagnostic for Staphylococcus aureus. A test with
hydrogen peroxide describes the catalase test, which distinguishes between the gram-positive
cocci. Tests with specific antisera are commonly used to serotype organisms within a genus or
species.
44. What are the important features of Klebsiella pneumonia?
-Gram -, rod, oxidase -, lactose fermenter, normal flora in the respiratory tract
-Pathogenesis: capsule + endotoxin
-Disease: pneumonia with currant jelly sputum (not foul smelling differ from aspirate
pneumonia) in alcoholic patient, UTI, Septicemia
-Diagnosis/ treatment: culture and lactose fermenterpink colony=E.coli but Klebsiella is
indole negative.

45.What are the important features of Shigella?

-Gram -,rods, oxidase -, nonlactose fermenter, nonmotile, acid resistant require small
number to cause the disease
-Pathogenesis: endotoxin, shiga toxin (inhibiting protein synthesis), invading M cell to avoid
immune system  polymerize actin jet trails very shallow ulcers.
-Disease: enterocolitis / shigellosis (watery diarrhea followed by the bloody diarrhea), common
in the children in the day care HUS
-Diagnosis/ treatment: isolation of stool during illness and culture on selective media. Fluid
and electrolyte replacement, antibiotic (In severe cases)

46.What are the important features of Yersinia pestis?

-Gram -, small rod, facultative intracellular, bipolar staining, coagulase +, reservoir rodents
(prairie dogs, chipmunks, squirrel), vector flea, potential biowarfare agent, zoonosis in US
desert Southwest (common area for infection of Coccidis and Hantavirus)
-Pathogenesis: coagulase (coagulate the content of the gut  regugirgated by animal 
contagious), F1 envelope inhibits phagocytosis
-Disease : bubonic plague (rapidly increasing fever, conjunctivitis, regional buboes) and
pneumonia plague (highly contagious)
-Diagnosis/ treatment: serodiagnosis/ direct immunofluorescence, safety pin staining.
Treatment is aminoglycoside and killed vaccine as prevention for high risk population.

47.What are the important features of Yersinia enterocolitica?

-Gram -, rod, motile at 250 C cold growth (=Listeria), zoonotic, unpasteriuzed milk and pork,
prominent in Nothern Climates (Michigan, Scandinavia)
-Pathogenesis:endo/exotoxin, multiple in the cold
-Disease: bloody diarrhea (very young children) ,enterocolitis (adult) and pseudoappendicitis
(both)
-Diagnosis/ treatment: stool culture, 250C, cold enrichment. Treatment supportive care, FQ/
cephalosporin for IC patient.

48.What are the important features of Proteus?

-Gram -, rod, enterobacteriaceae, non-lactose fermenting, urease + kidney stone formation
(staghorn calculi), petrichious flagella  swarming (highly motility) aid entry into the bladder
-Disease: Proteus mirabilis (90% infection) UTI and septicemia, Proteus vulgaris
-Diagnosis/ treatment: culture of blood or urine in Mc Conkey agar. Treatment: FQ, TMP-SMX,
cephalosporin.

49. What are the important features of Salmonella ?

-Gram -, rod, flagella + motile, non-lactose fermenter, H2S producer, > 2400 serotypes (based
on O antigen), acid sensitive (need large number to cause infection), fecal oral transmission,
reservoir poultry/ turtle/ snakes
-Pathogenesis: infection begion in the ileocecal region constipation (1st symptom), host cell
membrane “ ruffle” from Salmonella contact, reach basolateral side of M cell mesenteric
lymph node+ blood (first septicemia) go to the liver, gallbladder and spleen manifesting with
fever (secondary septicemia). Besides that, S. typhi lives in the macrophage intracellularly and
killing resistance due to defensin. At 1 week, 80% positive blood culture + 25% rose spot  at
week 3: 85% stool culture positive.
S. enteridis and S. typhimurium (the most common cause in the US)  invasive  inflammatory
diarrhea (the second most common cause after Campylobacter )
-S. cholerasuis, S. paratyphi, S. enteric  septicemia
-Disease: typhoid fever complication (thrombophlebitis, pneumonia, necrosis peyer patches,
cholecystitis). Osteomyelitis in the sickle cell anemia caused by S. typhi, S. dublin, S. cholerasuis,
S. paratyphi.
-Diagnosis/ treatment: culture from blood, urine, bone marrow, biopsy from rose spot, culture
on Hektoen agar  black colony= H2S producer. The Widal test is an agglutination test that
allows for the detection of envelope (O), flagellar (H), and capsular (Vi) antigens of the
subspecies of Salmonella enterica. Treatment: FQ or cephalosporin. Attenuated oral vaccine,
parenteral heat killed+ ViCPS polysaccharide capsular vaccine as prevention.

50. What are the important features of Haemophillus ?

-Gram -, rod, encapsulated, grow on the chocolate agar (require heme and NAD), grow in the
blood agar closed to S.aureus satellite phenomenon
-Pathogenesis: capsule (type B), IgA protease
-Disease: meningitis (unvaccinated children ages 3 months -2 years), otitis media+bronchitis in
smokers with COPD+ pneumonia+ epiglottitis with drooling (non-typeable H. influenza)
H. ducreyii  chancroid
-Diagnosis/ treatment: blood or CSF culture on chocolate agar, latex particle agglutination,
DNA probe (for H. ducreyi). Treatment : cephalosporin for meningitis, azythromycin/ceftriaxon/
ciprofloxacin for chancroid. Conjugate vaccine as prevention and rifampin in the unvaccinated
children.

51. What are the important features of Gardnerella ?

-Gram -, pleomorphic rods, facultative anaerob, catalase -, oxidase -.
-Disease: polymicrobial infection  bacterial vaginosis (thin grayish discharge  frothy odor)
-Diagnosis/ treatment: pH> 4.5, clue cells on vaginal saline smears, whiff test. Treatment:
metronidazole and clindamycin.

52. What are the important features of Pasteurella multocida ?

-Gram -, small rod, Cat –bite wound
-Pathogenesis: endotoxin, capsule
-Disease: cellulitis (rapidly spreading)
-Treatment: amoxicillin-clavulanate

53. What are the important features of additional organisms associated with animal/ human
bites ?

54. What are the important features of HACEK group (Haemophilus aphrophilus,
Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens,
Kingella kingae)?
-All part of normal flora in the human oropharynx
-The most common cause of gram negative associated with subacute endocarditis in the non-IV
drug user. Kingella kingae could cause septic arthritis in children.
-Difficult to diagnose and treat with third generation cephalosporin/ FQ.

55.What are the important features of Bacteroides fragilis?

-Gram -, rod, anaerob, endogenous from bowel defect (surgery, trauma, cytotoxic drug use)
-Pathogenesis: capsule and modified LPS with reduced endotoxin activity.
-Disease: septicemia, peritonitis, abdominal abscess (rare less frequent due to prophylaxis
antibiotic)
-Diagnosis/ treatment: gas chromatography+ biochemical test. Treatment: metronidazole,
clindamycin.

56.What are the important features of Treponema pallidum?

- Poorly stained gram -, spiral shaped, axial filament=endoflagella=periplasmic flagella, obligate
pathogen can’t be cultured, transmitted sexually or cross placenta, endarteritis resulting in
lesions  strong tendency to chronicity.
-Disease:

-Diagnosis/ treatment: The fluorescent treponemal antibody-absorption test (FTA-ABS) is the

only test on the list that is specific for syphilis. It detects specific antibodies that bind to the
treponemes. The automated reagin test (ART), rapid plasma reagin (RPR), and venereal disease
research lab (VDRL) tests are all nonspecific antibody tests that depend on the detection of
antibodies elicited during infection and which bind to mammalian cardiolipin. Treatment
benzathin penicillin with side effect Jarisch-Herxheimer reaction.

57.What are the important features of Borrelia burgdorferi?

-Gram -, spirochetes, microaerophilic, reservoir (mice and deer), vector Ixodes tick
-Pathogenesis: tick bites  organism spreads to the heart, joint (migratoryarthritis), CNS via
bloodstream
-Disease: initial symptoms: bull’s eye rash (annular lesion, white in the central with the red
around), flu like illness, arthralgia bells palsy, severe headache, arryhtmia, myocarditis,
pericarditis (develop in the one to several weeks)  migratory arthritis (immune complex)
occur in the late onset (months to years)
-Diagnosis/treatment: serodiagnosis/ ELISA (many false positive and negative), western blot for
confirmation. Treatment: doxycycline/ clarithromycin/ azythromicin for primary, ceftriaxone for
secondary, doxycycline or ceftriaxone for arthritis.
-Other species Borrelia recurrentis causing relapsing fever (due to antigenic variation).
Treatment is doxycycline.

58. What are the important features of Leptospira?

-Gram -, spirochetes with tight terminal hooks in fark field microscopy, zoonosis, transmission
via contaminated water with animal urine, highest incident in Hawaii
-Disease: leptospirosis (swineherd’s disease, mud/ swamp disease) with flu like illness+ GI tract
symptom (Weil disease) complication is hepatitis.
-Diagnosis/ treatment: serodiagnosis (agglutination test). Treatment: doxycycline/ penicillin.

59. What are the important features of Chlamydiaceae?

-Not seen in gram stain, obligate intracellular bacteria (macrophage) because cannot make ATP,
elementary (has the protein for the attachment =infectious form, extracellularly)/ reticulate
body ( replication form intracellularly), muramic acid in the cell wall.
-Chlamydia trachomatis: damage of epithelial cells granulomatous reaction. Serotypes D-K
(the most common cause of bacterial STD in the US) + inclusion conjunctivitis in the neonates.
Serotype L1,2,3 cause lymphogranuloma venereum (swollen lymph nodes, not common in the
US). Serotype A,B, Ba, C cause trachoma (not common in the US) follicular conjunctivitis
scarring of cornea blindness.
-Diagnosis/ treatment: DNA probe and PCR (good modality), gram stain would result in high
PMN without bacteria, serodiagnosis (DFA/ ELISA). Treatment: doxycycline/ azithromycin.
60. How do we distinguish between C.Pneumoniae and C. Psittaci?

61. What are the important features of Rickettsia?

-Poor stain gram -, bacilli, aerobic, obligate intracellular (unable to make sufficient ATP for
independent existence), Rickettsia prowazekii transmitted via human body louse, Rickettsia
rickettsii transmitted via dermacentor tick (=Francisella tularensis) with reservoir rodents and
dogs.
-Pathogenesis: invade endothelial cells  vasculitis in many organs including brain, liver, lung,
kidney, GI tract, and skin.
-Disease: Rocky Mountain Spotted Fever (emergency case), prevalent in East Coast (Oklahoma,
Tenesse, North and South Carolina) especially in the North Carolina. Symptoms are headache,
fever, maculopapular petechial rash started in the wrist and ankle  trunk (=centripental).
-Diagnosis/ treatment: serological IFA (>4x titer), Weil-Felix test (not used anymore).
Treatment is doxycycline.
62. What are the important features of Ehrlichia?
-Gram -, obligate intracellular bacteria of mononuclear or granulocytic phagocytes, prevalent in
the area and vector are similar with Lyme disease  co-infection with Lyme disease (fever
much higher).

E. phagocytophila= Anaplasma phagocytophylum

-Disease: similar to RMSF without rash, leukopenia+ thrombocytopenia, mulberry like
structures inside infected cells.
-Diagnosis/ treatment: Giemsa stained blood film, IFA, PCR. Treatment is doxycycline.

63. What are the important features of Mycoplasma?

-Smallest free extracellular, no cell wall but has sterol, require cholesterol, fried egg colonies
-Mycoplasma pneumonia : the most common cause walking pneumonia (in children and young
adult) with dry hacking cough and pharyngitis. The pathogenesis is inhibition of ciliary action.
Diagnosis is positive cold agglutinin. Treatment non- beta lactam: azythromycin, erythromycin,
clarithromycin.
-Ureaplasma urealyticum: normal flora in the sexually active young adult (if it’s found in the
children indicating sexual abuse), urease +. The diseases are urethritis, prostatitis, and renal
calculi. Treatment is erythromycin or tetracycline.

07.03- Microbial Genetic/ Drug Resistance

1.What are the differences between bacterial chromosome, plasmid, and bacteriophage?
-Bacterial chromosome: one chromosome, circular organized into loops, around 2000 genes,
contain all essential genes
-Plasmid: extrachromosomal genetic element, circular, small, replicate autonomously, carry
genetic for fertility, antibiotic resistance, and bacterial exotoxin, contain non-essential genes
for bacterial life.
-Bacteriophage: stable piece of bacteriophage DNA, generally repressed temperate phage
(=lysogenic conversion).
2.How is the process of homologous recombination?
It’s the process of gene exchange between homologous DNA mediated by the recA+, example
a-b- X a+b+  size of chromosome stays the same.

3.How is the process of site-specific recombination?

-It’s the integration of one DNA molecule into another DNA molecule, no homology+ DNA lost,
requires restriction endonuclease. The major roles are integration of fertility factor, temperate
phage, and movement and insertion of transposon.

4.Bacteria is asexual, thus producing the progeny which is identical with the parent. In order to
get new genetic combination, the bacteria undergo transformation, conjugation, and
transduction. How do we distinguish between those 3 processes?

-transformation: the competent bacteria takes up linear DNA from the environment and
incorporate it into the DNA by rec A+. H. influenza, S. pneumonia (increase the pathogenicity of
the capsule) , Bacillus, Neisseria are capable of natural transformation.

-conjugation: gene transfer by direct cell to cell contact via sex pili, require fertility factor (F+
into the F-, or high frequency recombination (HfR) into the F-), require homologous
recombinase for integrating bacterial genes. In the conjugal crosses, F+ transfers small piece of
plasmid into the F- then will change the recipient into the F+. In the Hfr conjugation, the
plasmid is inserted into the chromosome (donor) transfer to F- requiring longer time 
integrate the DNA with Rec A the recipient stays F-.

-transduction: transfer of bacterial DNA with phage vector. Generalized transduction occurs
when the phage randomly grabs the bacterial DNA and mistakenly packaged in assembly
process all genes have the equal chance to be transduced, it could happen in the lytic and
temperate phage. Specialized transduction occurs as a result of excision error, it could happen
only in the temperate phage.
The phage has the specific site to integrate the DNA. If the repressor gets damaged by UV,
alkylating agent, or cold then the phage will undergo the lytic cycle, this process is known as
induction. The phage mistakenly excises the bacteria DNA and transfers it into another bacteria
by inserting it into the specific site (between bio and gal region). Some toxin productions which
are mediated by the phage: COBEDS (cholera toxin, O antigen of Salmonella, Botulinum toxin,
Eryhtrogenic exotoxin of S. pyogenes, Diphteria toxin, Shiga toxin).

The summary table is below

5. In which of the following DNA transfer mechanisms can the statistical probability of gene
transfer and stabilization be used as a measure of genetic distance?
In Hfr conjugation and specialized transduction, the success with which a particular genetic trait
is transferred and stabilized in the recipient cell is directly proportional to the genetic distance
between that gene and a particular locus on the chromosome. In the case of the Hfr transfer,
the proximity to oriT is the determining factor. In the case of specialized transduction, it is the
proximity to the insertion point of the viral genome that determines the likelihood of transfer.

6. The figure below is a genetic map of an Hfr bacterium. Which gene is most likely to be
transferred stably to an F- cell?
The episomal (plasmid origin) DNA in the figure lies between the indicated insertion sequences
(IS). The transfer to an F- cell will begin with oriT and proceed in this case counterclockwise, so
after oriT, B (from the episome) will cross the conjugal bridge next, then the first half of the
insertion sequence, and then chromosomal allele D. Since there is no homology in the F- cell for
the episomal DNA, and the linear piece will have to be recombined in the recipient cell by
homologous recombination, D is the only allele that can be stably transferred to the recipient
cell.

7. What is the most rapid and effective means of transfer of drug resistance in gram-negative
bacteria?

R factors are multiple drug-resistance plasmids that are capable of mediating conjugation.
When they are transferred, the bacterium receiving the plasmid receives multiple drug
resistances in a single conjugative event. None of the other transfer mechanisms listed are
nearly as rapid and efficient as this one.
In the Hfr conjugal transfer, a few chromosomal genes may be transferred to the recipient. In
generalized and specialized transduction, a few chromosomal genes may be transferred using a
virus vector. In transformation, chromosomal genes from dead cells may be acquired following
homologous recombination
8.What are the mechanisms of drug resistance?
-Intrinsic: normal anatomy or physiology of bacteria that make them resistant to the drug’s
action, e.g.: Mycoplasma lacks of peptidoglycan  resistant to the penicillin.
-Chromosome-mediated: genes modify the receptor of the drug so the drug can no longer bind
 low-level drug resistance (ex: MRSA and S. pneumonia)
-Plasmid-mediated: often genes code for enzymes that modify the drug, especially R factors
which are conjugative plasmid carrying genes for drug resistance located between tra and ori T
region transmitted via conjugation. Multiple drug-resistance plasmids arise by integration of
jumping gene which is called gene cassettes/ integrons/ transposons. Examples: S. aures
acquires gene for Vancomycin resistant from enterococcus via transposon on a multi-drug
conjugative plasmid. While Neisseria gonorrheae lost tra region (but still has oriT) and requires
the tra region from other bacteria in order to transfer the drug resistance gene, this process is
known as non-conjugative plasmid.

9. What are the examples of plasmid mediated drug resistance?

10. How do we perform antibiotic susceptibility testing?

-The Kirby-Bauer test is a screening technique that determines the resistance or sensitivity of a
bacterial isolate against large numbers of antibiotics simultaneously.Determination of colony
formation is used to initially isolate a bacterial organism and determine the effects of individual
drug therapies.
-The E-test is a variation of the Kirby-Bauer using a specific drug that achieves a slightly more
quantitative result.
-The MBC, or minimal bactericidal concentration, of a drug is the amount of that specific drug
that is required to kill that organism. It’s given to the immunocompromised patient.
-The MIC, or minimal inhibitory concentration, is the minimum amount of a specific drug that is
required to inhibit the growth of an organism. It’s given to the immunocompetent patient to
induce immune response.

07.04- Medically Important Viruses

1.How is the process of viral replication?
RNA viruses replicate in the cytoplasm, while the DNA viruses replicate in the nucleus except
poxvirus.

The fusion protein on the surface of virions is associated with the fusion of cellular membranes
and promotes the production of multinucleated giant cells, or syncytia, example: Herpesvirus.
Hemagglutinin (H) molecules bind to sialic acid residues on cells and promote entry into the
cell. Neuraminidase (N) cleaves the sialic acid residues and promotes virus release from the cell.
The matrix (M) protein stabilizes the viral envelope, and the polymerase (P) is carried inside the
nucleocapsid in cases in which the virus life cycle requires a different enzyme from those
available in the cell.

2.How is the process of macromolecular synthesis of viruses?

3.Why do only naked viruses infect the GI tract?
-The naked viruses are more sturdy and insensitive to the stomach acid, heat, detergents, and
alcohol, example: rotavirus, poliovirus, Norwalk.

4.What is the vaccination strategy for the naked and enveloped virus?
-Antibody for the naked virus and CMI for the enveloped virus.

5.What are the patterns of viral infection?

6.In the viral infection, age is very important to determine the diagnosis. What are the most
common viral infections based on the age?
-The dash line resembles the infection of RSV (bronchiolitis) and parainfluenza virus (croup)
which may cause serious diseases in the children but only cause the common cold in the adults.
-Rotavirus is the most common virus causing the diarrhea in children, while the Norwalk virus is
the common cause in the adults.
-The adolescence when they start to be sexually active, there are some sexually transmitted
diseases starting to appear such as HSV 2, HIV, and hepatitis.

7. How do the IFN α and β prevent the viral infection?

The infected cells produce IFN α and β as the signal for the uninfected cells to inhibit protein
synthesis by:
-activation of RNA endonuclease which digests viral RNA
-activation of protein kinase that inactivates eIF2 inhibiting viral protein synthesis.

Thus, when the virus infects the other cells, they can’t replicate. The IFNs do not act directly
and species specific(not-virus specific).

8. What are the differences between hepatitis viral infection?

-Both hepatitis A and E are fecal-oral transmission and naked viruses but hepatitis E is more
virulent and cause severe disease in the pregnancy.
-Hepatitis D (delta) could only cause the disease if co-infection with hepatitis B  fulminant
hepatitis with high mortality rate.
-Both hepatitis B and C are parenteral-sexually transmitted diseases  cirrhosis and
hepatocellular carcinoma. However, hepatitis C has more tendency to be chronic.

9. How do we interpret the serology markers for hepatitis B?

-HBsAg is the surface antigen on HBV, found in the large amount during acute infection, and
continued presence > 6 months marking chronic infection.
-HBsAb is the antibody made against HBsAg. It indicates the immunity status and recovery of
the disease.
-HBcAg is the core antigen and positive in the acute and chronic infection, so it couldn’t be the
marker to differentiate acute and chronic infection.
-HBcAb is the antibody made against HBcAg and first antibody to appear. IgM HBcAb (+) is the
best indicator for the recent infection.
-HBeAg is the second core antigen and important factor of high transmissibility (correlates with
the viral replication and infectivity). If the HBsAg (+)> 6 months and HBeAg (+) chronic active
infection.
-HBeAb is the antibody made against the HBeAg and important factor of low transmissibility. If
the HBsAg (+)> 6 months and HBeAb (+) chronic infection.

The window period (=zone of equivalence when all antibodies bind to the antigen), the markers
that can be used are anti-HBc and anti-HBe.
10. What are the characteristics of DNA viruses?
Mnemonic: Pardon Papa As He Has Pox (parvovirus, papillomavirus, polyomavirus, adenovirus,
hepadnavirus, herpes, poxvirus).

11.What are the important features of Parvovirus (B19)?

-Small ssRNA virus, naked, icosahedral, transmitted via respiratory route, fomites and vertical
transmission.
-Pathogenesis: infect the erythroid progenitor mild anemia, but can lead aplastic crisis in the
sickle- cell anemia.
-Disease: fifth disease/ erythema infectioum/ slapped cheeks (fever, indurated facial rash, and
arthralgia, myocarditis, in the fetus can cause severe anemia, hydrops fetalis, CHF, and
spontaneous abortion especially in the mother with update vaccine (since there’s no vaccine for
B19). However in the mother with incomplete vaccine status, rubella infection could be the
more common cause.
-Diagnosis/ treatment: serology/ molecular analysis, supportive care.

12. What are the important features of papillomaviridae?

-dsDNA, naked, consisting of HPV, BK, and JC
-HPV: cause cutaneous wart, genital wart (serotype 6 and 11), and cervix cancer ( serotype 16,
18, 31, and 35 produce E6 and E7 protein inhibit tumor suppressor gene p53 and RB).
Diagnosis is the finding of koilocytic cells from the pap smear (enlarged nucleus with the
perinuclear cytoplasm vacuolization ), in situ DNA probes, or PCR.

Treatment is cidofovir, surgical (cryotherapy, laser therapy, excisional), podophylin,

trichloroacetic acid, 5-fluoroacil, immune-mediated (imiquimod and interferon alpha), and
vaccine Gardasil/ Cervarix for preventing cervix cancer.
-Polyomaviridae: BK and JC viruses infect the immunocompromised patient.
13.What are the important features of adenovirus?
-dsDNA, naked, icosahedral, has penton fiber acting as hemagglutinin and are toxic to the cells,
cause lytic in the permissive cells (virus could replicate) and oncogenic in the nonpermissive
cells (virus couldn’t replicate).
-Disease: acure respiratory disease+ pneumonia (serotype 4,7,21), pharyngoconjunctivitis
(swimming conjunctivitis), acute hemorrhagic cystitis (bloody urine and painful in young boys
age 5-15, differential diagnosis: PSGN), gastroenteritis (serotypes 40 and 41, not the most
common), myocarditis.
-Diagnosis/ Treatment: serology/ ELISA, supportive care.

14.What are the important features of herpesviridae?

-large dsDNA, enveloped, icosahedral, intranuclear inclusion bodies, latency (+). Herpesviruses
are the only family of viruses that captures their envelope from the nuclear membrane of the
infected cell.

-HSV: forming vesicles (=dew drop on the rose), treatment: acyclovir, famcyclovir, valacyclovir
(inhibit the thymidine-kinase, the enzyme for viral protein synthesis).
HSV 1 (above the waist infection) gingivostomatitis and latent in trigeminal ganglion cold
sore in reactivation, keratoconjuctivitis (dendritic ulcers), meningoencephalitis (the most
common cause of viral meningitis  reactivation cause cause the encephalitis in temporal
lesion).
HSV 2 (below the waist infection) genital infection with ulcerated lesion and giant
multinucleated cells with Tzank smear ( latency in the sacral nerve ganglia genital herpes in
reactivation), neonatal herpes (disseminated wilth liver involvement, meningoencephalitis,
vesicles on the skin, mouth, and eyes).
The replication of Herpes is below:
Herpes viruses assembly the structural protein in the nucleus. Then, adding some glyproteins
on the surface so the virus could exocytose from the cells.

-Varicella Zoster: transmission via respiratory droplet and skin contact (less frequent). 1st
viremia infect spleen and liver  2nd viremia cause the skin rash and latent in the dorsal root
ganglia. The diseases are the chicken pox (asynchronous rash= different lesion at the same
time, while the smallpox has the same lesion) and shingles (reactivation), giant cell pneumonia
as complication. Diagnosis is Tzank smear. Treatment is oral acyclovir, IV acyclovir (in the
immunocompromised), and aspirin contraindicated that can cause Reye syndrome. The
prevention is live attenuated vaccine and varicella zoster IG in IC patients.

-EBV: infect B cells by binding to the CD 21  non-specific proliferation of B cells 

heterogenous  heterophile antibodies (+) and production of atypical reactive T cells (Downey
cells). Latency + in the B cells. The diseases are mononucleosis or kissing disease (very fatigue,
lymphadenopathy, splenomegaly that can be ruptured due to contact sport),
lymphoproliferative disease (when T cells can’t control the B-cell growth in IC patient), hairy
oral leukoplakia, malignancies (Burkitt lymphoma, nasopharyngeal ca, and Hodgkin
lymphoma). The Burkitt lymphoma is a result of the transpositional mutagenesis when
translocation juxtaposes the c-myc oncogene to a very active promoter such as one for an
immunoglobulin gene.
Diagnosis is the heterophile antibody (+) , serology, Downey cells (atypical T cells react to the
RBC) and increased monocytes in the blood smear, epstein barr nuclear antigen indicating
transformed cells.
Treatment is supportive care or acyclovir in the IC patient.

-CMV: latency in mononuclear cell, heterophile negative, owl eye inclusion. CMV is the most
common in uteroinfection in the US  blue berry muffin baby, mental retardation,
pneumonitis. The second common cause of mononucleosis. In the transplant patient and AIDS
patient, CMV causes the interstitial pneumonitis and CMV retinitis.

Treatment is supportive care and ganciclovir/ foscarnet/ human immunoglobulin in the IC

patients.

-HHV 6 and 7:transmitted via respiratory droplet and replicate in the blood mononuclear cells
cause roseola with extremely high fever that can induce seizure (3-5 days) lacy body rash
when afebrile.

-HHV 8: cause Kaposi sarcoma, turn on VEGF so should be differed from bacillary angiomatosis.

15.What are the important features of Poxviruses?

-Large dsDNA, complex morphology, replicate in the cytoplasm (because it has ‘complete
package’ in its envelope)
-Variola (small pox): classic pocks, has been eradicated, transmission respiratory tract
lymphatics viremia  dermal tissues and internal organ  vesicles from face to the trunk.
Diagnosis is the found of Guarnieri bodies (intracytoplastic). Treatment is supportive care and
live attenuated vaccine (vaccinia).
-Molluscum contagiosum:umblicated- wart like tumors, transmission via direct contact and
fomites, replication in the dermis. Diagnosis eosinophilic cytoplasmic inclusion bodies.
Treatment is self limiting in the healthy person, ritonavir + cidofovir in IC patients.

16.What are the general features of RNA viruses?

-All RNA viruses are single stranded (except reo), negative sense RNA viruses carry an RNA-
dependent RNA polymerase to make the template, virion-associated polymerase (carried by
reo, arena, and retro), most are enveloped (except HPCR: hepevirus, picorna with major
members, calici, reo), segmented viruses (ROBA: reo, orthomyxo, bunya, arena).
17. What are the members of positive sense RNA viruses?

Mnemonic: Call Henry Pico and Flo To Come Righthaway

Mnemonic: PEE Co Rn A Viruses (Polio, Entero, Echo, Coxsackie, Rhino, Hep A)
-Positive-sense RNA viruses, which are capable of direct translation from their genome. Once
they have created their first RNA-dependent RNA polymerase, they can then produce the
complementary strand (negative-sense RNA) and can amplify the speed of their life cycle by
producing multiple copies of the genomic RNA.

18.What are the important features of Calicivirus?

- positive sense ssRNA, naked, icosahedral
-Norwalk virus:cause watery diarrhea (the most common non-bacterial diarrhea in the US),
related to the cruise ships. Treatment is self-limiting and the prevention is handwashing.

19.What are the important features of Picornavirus?

-Pico (small), + sense RNA, naked, icosahedral, divided into 3 genera enteroviruses ( not cause
diarrhea but transmitted fecal oral), rhinoviruses (not stable under acidic condition, growth at
cold  chicken soup makes patient feel better because of inhaling the steam of the soup,
common infect in the summer and fall), herparnavirus.
-Enteroviruses: Coxsackie A causes 3 major diseases: hand foot mouth disease, herpeangina,
and aseptic meningitis. Coxsackie B is the most common cause of myocarditis in the healthy
young adult and Bornholm disease (intercostals pain like devil’s grap). D68 causes the motor
neuron disease with the flaccid paralysis and becomes outbreak in the Colorado, transmitted
via fecal oral/ respiratory, and potential spread to CNS.
20. What are the important features of Flaviviridae?
-positive sense RNA, enveloped, icosahedral, arthropod-borne (arboviruses) except for hepatitis
C.
-West nile viruses entered US in the 1999 and causes fatal disease in the elderly.
-The best prevention for yellow fever is the vaccination.
-Zika virus is transmitted via mosquitp, vertical, and sexual. It can cause the congenital disease
resulting with microcephaly and fetal demise.

21.What are the important features of Togaviridae?

-positive sense RNA, enveloped
-To distinguish rubella (German/ 3 –day measles) and measles (7-day measles): the macular
rash in the rubella started in the face and spread to the whole body+lymphadenopathy, while
the rash in the measles started in the ear and below the neck and spread to the face and whole
body+more serious clinical presentation.

22.What are the important features of Coronaviridae?

-positive sense RNA, enveloped, the second common cause of common cold in the spring and
winter.
-SARS-COV: history of travel to the endemic area (China and Canada) atypical pneumonia, show
interstitial infiltrate and patchy distribution in the chest X ray. Treatment is supportive,
ribarivirin/IFN promising.
23.What are the important features of retroviridae?

-P24 is the first protein to be detected in the HIV patient.

-Nef is responsible for the virulence of HIV. The deleted of this factor could lengthen the
survival rate of patient.
-The replication of the virus: binding of gp120 (determining the tropism of the virus) and CD4
and coreceptor CCR5 enable virus fusion via gp41 ssRNA is transcripted into dsDNA by
reverse transcriptase  into the nucleus integrate the genom and viral dsDNA via integrase
 provirus  uncleaved (genomes) and cleaved (for protein synthesis and cleavage) leave
the host cell by forming the cell membrane from host cells.
-Homozygous mutation of CCR5 (the coreceptor for HIV infection) = immune, heterozygous
CCR5 mutation= slow progression.
-The infection of Herpes could be worse because of the latency of the virus.

-Diagnosis: screening test is ELISA, confirmatory test is nucleic acid test (NAT). RT-PCR is used
for counting viral load and PCR for detecting HIV infection in the infant. The progression of the
disease is CD4:CD8 (normal 2:1).
-Treatment: combination of 2 RT and 1 protease inhibitor.

24. What are the groups of negative-stranded RNA viruses?

-All are enveloped, allhave virion-associated polymerase and all helical nucleocapsids except:
orthomyxovirus (linear and 8 segmented= ortho, replicate in the nycleus and cytoplasm),
bunyavirus (circular), and arenavirus (one-negative strand).
-The major difference between (+) and (-) standed RNA virus that (-) stranded carries their own
RNA-dependant RNA polymerase.
-Life cycle: fusion with cell membrane  (-) strand is transcripted by RNA-dependendant RNA
polymerase  (+) stranded RNA that is translated for protein synthesis and as a template for
producing the genome  assembly  virus budding from the cell membrane.

Mnemonic: Pain Results From Our Bunion Always

25.What are the important features of measles?

-H-glycoprotein and F protein, transmission via human respiratory tract, ability to form giant
cell
-disease: measles started with 3Cs (coryza, conjunctivitis, and cough)with photophobia, koplik
spot, maculopapular rash from ears down, giant cell pneumonia (= Warthin-Finkeldey cells).
Complication is subacute sclerosing panencephalitis.

-diagnosis/ treatment: serology and treatment is supportive. The prevention is MMR (live
attenuated vaccine).

26. What are the important features of mumps?

-transmission via respiratory droplet, lytic, has H and F protein
-disease : uni-/bilateral lymphadenopathy with serious complication for male is orchitis,
pancreatitis, and meningoencephalitis.
-diagnosis/ treatment: serology (ELISA, IFA), treatment supportive, and MMR for prevention.

27. What are the important features of other Paramyxoviruses?

-Human metapneumovirus is the other common cause of common cold in children besides
rhinoviruses and coronaviruses.

28. What are the important features of rhabdoviridae?

-bullet-shaped, the most common reservoir in the USA is raccoon followed by bats, foxes, and
skunks, transmission via bite or contact with rabid animal.
-pathogenesis: bind to peripheral nerve to Nicotinic acethylcholine receptor or indirectly into
the muscle  retrograde axoplasmic transport to dorsal root ganglia and soinal cord  brain
 fatal.
-disease: rabies with hallucination, hydrophobia, disorientation, seizure.
-diagnosis/ treatment: negri bodies post mortem, PCR/ DFA (late), if symptoms + none
treatment, post-exposure 1 dose of human rabies Ig+ vaccination (killed vaccine) in the site of
injury and other side of body (0,3,7,14,28) to induce immune system.

29.What are the important features of filoviridae (Ebola and Marburg)?

-Outbreak in the US laboratory, transmitted via direct contact from secrete of death person,
reservoir is bats, very virulence.
-disease: non-specific flu like illness, Gi problem, rash and meningoencephalitis, may cause
massive hemorrhage from all orifices (mouth, ears, nose).
-diagnosis/ treatment: rapid antigen test for screening, RT-PCR for confirmation. Treatment is
symptomatic.

30. What are the important features of influenza virus (orthomyxoviridae)?

-transmission via respiratory droplet and contact, could undergo antigenic drift and shift
because of segmented, consists of A(human and animal), B (human), C, has 2 glycoproteins on
envelope for determining serotype: HA=hemagglutinini (binds to syalic acid and allow virus to
get into the cell) and NA=neuraminidase (liquefies the mucus so the virus could move easily and
clip the newly made virus that stucked on the cell membrane).
-antigenic drift because the misproof-reading of RNA polymerase antigenicity  epidemic.
-antigenic shift occurs when coinfection of 2 different strains  rearrange of the segment 
produce new strain of virus  pandemic (worldwide infection).
-disease: fever, bronchiolitis, croup, otitis media (in kids), secondary infection such as
pneumonia in hospitalized patient  cause of death, can lead to Reye syndrome/ GBS
-diagnosis/ treatment: serology, clinical symptoms and season (peak in the flu season).
Treatment: -dine (amantadine and rimantadine) to inhibit viral uncoating and –ivir (inhally
zanamivir or orally osetlamivir) to inhibit neuraminidase. Prevention is killed vaccine.

31. What are the important features of Hantavirus (sin nombre) as family of bunyaviridae?
- four corners disease (Colorado, New Mexico, Arizona, Utah), transmission via rodent
excrement in the rainy season.
-disease: pulmonary syndrome with massive pulmonary edema and effusion, leg muscle cramp,
and hypotension death.

32.What are the important features of arenaviridae?

-virions have a sandy appearance (arena appearance) because the virus takes the
ribosomewhen getting out the cells, causes lymphocytic choriomeningitis virus (LCMV) and
lassa fever virus.

33.What are the important features of reoviridae?

-double stranded RNA, segmented, rotavirus virus is the common cause of diarrhea in young
children. The prevention is orally live attenuated vaccine.

34.What are the important features of the prion diseases?

-Infected protein which causes slow progression disease, diffential diagnoses are measles SSPE,
AIDS dementia, and progressive multifocal leukoencephalopathy.

35.What are the types of viral genetics?

-phenotypic mixing: two viruses in the same cell could produce the mixture phenotypic
progeny.

-phenotypic masking: two viruses in the same cell could produce the progeny with other
capsid.

-complementation: two defective genes complement each other to infect cells but produce the
same progeny with the parents.
-genetic reassortment: antigenic drift (minor changes) and shift

07.05- Medically Important Fungi

1.What are the important features of general fungi?
-Eukaryotic= human (has true nucleus, 80 S ribosome, mithocondria), cell wall made from
chitin, glucan, and mannan, has major membrane sterol which is ergosterol (target of drug),
heterotrophic (requires carbon), saprophytic (lives in dead organism), and parasitic.

2.Histoplasma, blastomyces, coccidiodes, and sporothrix are classified as dimorphic fungi. Why?
-They are able to convert from mold in the cold (250C) to yeast form in 370C.
*mnemonic: Body Heat Changes Shape

3.What are the important features of Malassezia furfur?

-superficial infection,normal skin flora (lipophilic yeast), grow in the moist and warm condition.
-Disease; pytiriasis/ tinea versicolor, fungemia in premature infant
-Diagnosis/ treatment: KOH mount (meatball and spaghetti hyphae/ bacon and eggs), coppery
orange fluorescence under Wood Lamp. Treatment is tropical selenium sulfide.
4.What are the important features of dermatophytes infection?
-Cutaneous infection that can cause inflammation (little inflammation=human to human
infection, high inflammation is from animal), consist of 3 genus, may disseminate in IC patients.
-Microsporum (infect hair and skin), Epidermophyton (infect skin and nail), Tricophyton (infect
hair, nail, and skin) manifestation: tinea capitis, tinea barbae, tinea corporis, tnea cruris, tinea
pedis, and tinea unguium.
-Diagnosis/ treatment: microsporum will fluoresce with bright yellow-green under Wood lamp,
KOH mount to find arthroconidia and hyphae. Treatments are topical imidazole/ tofnaltate,
oral imidazoles or griseofulvin.

5.What are the important features of Sporothrix schenkii (subcutaneous mycoses)?

-Dimorphic, hyphae with rosettes and sleeves of conidia, cigar yeast form (hyphae form is
important to diagnose patient), related with traumatic implantation especially gardener, florist,
and basket weaver.
-Disease: sporotrichosis (rose gardener disease) subcutaneous and lymphocutaneous lesions
and pulmonary sporotrichosis in urban alcoholic (alcoholic rose-garden-sleeper disease).
-Diagnosis/ treatment: cigar shaped yeast from skin and sputum, CXR for pulmonary
sporotrichosis is cavitary lesion in the upper lobe. Treatment is itraconazole+ potassium iodide
in milk for sporotrichosis, and itraconazole and amphotericin B for the pulmonary
sporotrichosis.

6.What are the important features of Histoplasma capsulatum?

-Endemic region: Eastern Great Lakes, Ohio, Missisipi, Missouri River beds, related to bird or bat
feces, chicken farmer, spelunking cave, commonly affect newcomers.
-Environment form: hyphae with microconidia and tuberculate macroconidia. Tissue form is
mall intracellular yeast with narrow neck on bud and no capsule. Facultative intracellular
parasite in RES cells.
-Disease: asymptomatic, pneumonia with flu-like symptom (not response to antibiotic remarks
fungal infection), hepatosplenomegaly, mucocutaneous lesion in disseminated infection
common in IC patients.
-Diagnosis/ treatment: sputum cytology and blood culture (can be found in the circulating
monocyte).Treatment itraconazole for mild and amphotericin B for severe.

7.What are the important features of Coccidioides immitis?

-dimorphic fungi (arthroconidia as hyphae and spherules with endospores in tissue form),
endemic region Desert Southwest; Southwestern US (Southern California especially San
Joaquin Valley), Arizona, New Mexico, Texas, Nevada.

-Disease:Valley fever (asymptomatic to self-resolving pneumonia), desert bumps (erythema

nodosum with arthritis as good prognosis, eosinophilia, fatigue syndrome), tend to disseminate
in the third semester of pregnancy, mucocutaneous lesion and meningitis in disseminated
infection common in IC patients.
-Treatment: itraconazole or amphotericin B.

8.What are the important features of Blastomyces dermatidis?

-Broad base budding yeast (mnemonic: BBB= blastomyces, broad based, budding), double
refractile cell wall, associated with rotting wood, endemic regions are Upper Great Lakes, Ohio,
Missisipi River Beds, Southeastern/ Eastern seaboard of the US and Northern Minnesota into
Canada.

-Disease: blastomycosis, acute and chronic pulmonary infection (=less likely Histoplasma and
Coccidiodes)
-Diagnosis/ treatment: itraconazole or amphotericin B.

9.What are the important featurs of Aspergillus fumigatus as opportunistic fungi?

-Generally acute angles with 450 septate hyphae, monomorphic

-Disease: allergic bronchopulmonary aspergillosis/ asthma, fungus ball in preformed lung

cavities, and the most severe is invasive aspergillosis in severe neutropneia, CGD, CF, and burn
(invades tissues causing infarcts and hemorrhage, pneumonia or meningitis via nasal
colonization, and cellulitis in burn patients).
-Treatment: voriconazole for invasive and aspergilloma, glucocorticoid and itraconazole for
ABPA.

10.What are the important features of Candida albicans as opportunistic fungi?

-Normal flora, form germ tubes (in the image) in serum at 370 C, form pseudohyphae and true
hyphae when invading tissue (nonpathogenic Candida do not)
-Diagnosis/ treatment: KOH mount and culture lab. Treatment is imidazole and nystatin, and
amphotericine B or fluconazole for disseminated.

11. What are the important features of Cryptococcus neoformans as opportunistic fungi?
-monomorphic, encapsulated yeasts, associated with pigeon dropping
-Disease : the most common cause of meningitis in AIDS patient
-Diagnosis/ treatment: detect capsular antigen in CSF by latex particle agglutination, india ink,
cultures (urease + yeast). Treatment amhotericine B and flucytosine  then fluconazole when
afebrile and culture negative.

12.What are the important features of zygomycophyta (Mucor, Rhizopus, Absidia)?

-Broad ribbon like, non-septate with branching 900 degree.
-Disease: rhinocerebral infection characterized with pranasal swelling, necrotic tissue,
hemorrhagic exudates from nose and eyes could disseminate into brain especially in
leukemic and ketoacidotic patient high fatality rate. Black pus from sinusitis.
-Diagnosis/ treatment: debridement necrotic tissue and amphotericin B.

13. What are the important features of Pneumocystic jirovecii?

-Obligate extracellular parasite, silver stained cysts in tissues

-Disease: pneumonia in AIDS ( CD4<50)/ IC patients, malnourished babies, premature infant

with non-productive sputum. Serum leaks into alveoli  exudate with foamy or honey comb
appearance on H and E stain.
-Diagnosis/ treatment: silver stain cyst in bronchial lavage/ biopsy, patchy infiltrative (ground
glass appearance) in X-ray. Treatment is TMP-SMX, dapsone for moderate to severe.

07.06- Medical Parasitology

1.What is general classification of protozoans?

2.What is general classification of metazoans?

3.What are the important features of Entamoeba histolytica?

-Cyst in the environment and transmission form, trophozoite as invasive form, fecal oral, water,
fresh fruit and vegetables, common in Hispanic immigrant.

-Disease: dysentery inverted flask-shaped in the large intestine blood and pus in the stool 
can extend into peritoneum, liver (serious complication: liver abscess), lung, brain, heart. The
symptoms of liver abscess are right upper abdominal pain with elevated liver enzyme. Other
disease is pseudoappendicitis.
-Diagnosis/ treatment: trophozoite or cyst in stool, sometimes with RBC inside cell, serology
(nuclei have sharp central karyosome and fine chromatin “spokes”). Treatment is
metronidazole followed by iodoquinol.
4.What are the important features of Giardia lamblia?
-The most prevalent enteric parasite, waterborne outbreak, fecal-oral transmission, cyst is
transmission form.
-Disease : giardiasis ( a fatty and foul smelling diarrhea)  ventral sucking disk attaches to
lining of duodenal wall malabsorption in the duodenum and jejunum.
-Diagnosis/ treatment: cyst or trophozoite in the stool, antigen test (replacing string test),
“falling leaf” motility. Treatment is metronidazole.

5.What are the important features of Cryptosporidium sp?

-most common in AIDS/ IC patient, transmission via cysts in undercooked meat and
contaminated water.
-Disease: cause cryptosporidiosis which is persistent watery diarrhea in AIDS patient
-Diagnosis/ treatment: acid fast round oocyst in the stool and found dots (cyst) in the biopsy.
It’s self limiting disease in healthy people but very difficult to treat in AIDS patient. The drugs of
choice are nitrozoxanide, puromycin, or azythromicin.

6. What are the important features of Isospora belli?

-Oocyst ingestion, fecal oral transmission
-Disease: = giardiasis, cause persistent watery diarrhea in AIDS patient/ transient diarrhea in
healthy patient.
-Diagnosis/ treatment: acid fast and elliptical oocyst in stool (2 sporocysts; each has 4
sporozoites). Treatment is TMP-SMX or pyrimethamine/ sulfadiazine.

7. Both Cyclospora cayetanensis and microsporidia cause transient diarrhea in AIDS patient but
not as common as Cryptosporidium and Isospora. What are the differences between those two?
-Transmission form: oocyst in Cyclospora and spore in microsporidia.
-Diagnosis/ treatment: both acid fast, but microsporidia could be gram stained as well.
Treatment for Cyclospora cayetanensis is TMP-SMX.

8.What are the important features of Trichomonas vaginalis?

-transmission is trophozoite, sexually, fomites (from shared towel)
-Disease: trichomoniasis with yellow green malodorous discharge, inflammation + 
strawberry cervix appearance.
-Diagnosis/ treatment: motile trophozoite in methylene blue wet mount. Treatment is
metronidazole.

9. A man experienced the altered smell after diving in fresh water about a month ago.
Naegleria is suspected because it could stick to cribiform plate and enter the brain. What are
the important features of Naegleria?

10.A myopia- woman suffered keratitis. She always uses the contact everyday. A week later,
she died because of encephalitis. From the brain biopsy, found star-shaped cysts that indicates
the Acanthamoeba infection. What are the important features of it?

The cyst attaches to epithelial cornea (stromal ring in eye) optic nerve  brain.

11.What are the important features of Plasmodium?

-P. vivax: benign tertian with 48 hour fever spikes, schuffner’s dot, hypnozoite +(requires
primaquine for liver stage + chloroquine)
-P. ovale: manifestation= P. vivax,oval-shaped, hypnozoite + (requires primaquine for liver
stage+ chloroquine)
-P.malariae: =quartan, 72 hour fever spike, bar and band form, rosette schizonts,
recrudescence + (recurrence of the symptoms with low level of organism), treatment is
chloroquine.
-P. falciparum: =malignant tertian, irregular fever spike, multiple ring form+ banana shaped
gamete, chloroquine resistance becomes problem.
-Hbs heterozygote patient has protection towards P. falciparum, duffy blood group antigen is
receptor for P.vivax, and other abnormal Hb (thalassemia) are indigestible to all malarial
species.

12.What are the important features of Trypanosoma cruzii?

-Trypomastigote in the blood with flagellum and undulating membrane, amastigote in the
tissue, reduviid bug (=kissing=cone bug) as vector for transmission, reservoirs are cat, dog,
armadillo, and poverty housing, associated with Latin America.
-Disease: chagoma (swelling in the bite lesion), toxic megacolon, chagas disease with Romana
sign (swelling around the eye) as the early sign  cardiac, muscle, liver, brain are often
involved. About ½ million Amerucans are infected  increase risk for transfusion transmission.
-Diagnosis/ treatment: blood films to find trypomastigote, xenodiagnosis (uninfected cone bug
bites the patient assess the trypomastigote under microscope). Treatment is benzimidazole/
nifurtimox.

13. Both Trypanosoma brucei gambiense and rhodesiense cause African sleeping sickness. What
are the important features related those two?
-Transmission from trypomastigote in the saliva of Tsetse fly, show antigenic variation.
-Diagnosis/ treatment: find trypomastigote in blood smear, high immunoglobulin in CSF.
Treatment is suramin (acute) and melarsoprol (chronic).

14. All of Leishmaniasis are intracellular parasite, transmitted by sandfly bite and treated by
stibogluconate sodium. What are the differences between them?
-Leishmania donovani causes Kalazar (visceral leishmaniasis) with hepatosplenomegaly and
lymphadenophaty, no trypomastigote, only amastigotes found in the macrophages, bone
marrow, liver, and spleen. It is also common in the Middle East and Central Asia.
-Leishmania (15 different species) cause cutaneous leishmaniasis with ulceration skin sore with
spontaneously healing. Diagnosis is found of amastigotes in the macrophage.
-Leishmania braziliensis causes mucocutaneous leishmaniasis  disseminating to hard and soft
palate  restructuring of the face. Diagnosis is same as above.

15.The patient with bull eye lesion who’s treated with doxycycline showed no improvement,
and he started to complain about malarial-like symptom. It indicates the Lyme disease with
Babesia co-infection. What are the important features of Babesia?
-Transmission via Ixodes tick bite, coinfection with Borrelia
-Disease: babebiosis (malaria-like) with hemolytic
-Diagnosis/ treatment: Giemsa stain of thin smear or hamster inoculation, maltese cross
(tetrad in RBC= multicross like). Treatment is clindamycin+ quinine.

16.What are the important features of Toxoplasma gondii?

-Cats as definitive host, pork as the first common vector in US, transmission via oocyst.
-Ingested oocyst  tachyzoite (trophozoite-like) in the small intestine  encyst bradyzoite as
the immunity develops in the skeletal muscle  turns back to tachyzoite in IC patients.
-In healthy individual:commonly asymptomatic, non-specific flu like illness with
lymphadenopathy and fever, heterophile-negative mononucleosis.
-In pregnant patients: primary infection in pregnancy  transplacental  severe congenital
infections (intracerebral calcifications, chorioretinitis, hydro-or microcephaly or convulsion).
Later infection transplacental  progressive blindness in the child later in life.
-In AIDS patients: leading cause of focal AIDS patient with ring-enhancing lesion (majority case
is reactivation of encyst bradyzoite). The toxoplasmosis is also found in the deficiency of T cell
such as chemotherapy, lymphoma, and transplant patients.
-Diagnosis/ treatment: serology. Treatment is pyrimethamine and sulfadiazine.

17.What are the important features of trematodes infection?

-= fluke, hermaphroditic and have operculated eggs except for Schistosoma, snail as the
intermediate host
-Schistosoma mansoni +japonicum :=intestinal schistosomiasis, penetrating skin from
contaminated water cyst  mesentery veins  eggs (with spike in Mansoni) cause
granuloma in liver  hepatomegaly in chronic disease. Diagnosis is egg in the stool and
treatment is praziquantel.

-Schistosoma haemotobium: =vesicular schistosomiasis, contact with water and skin

penetration terminal spike egg mature in bladder veins  chronic infection has high
association with bladder carcinoma in Egypt and Africa. Diagnosis is the egg in the stool.
Treatment is praziquantel.

-Non-human schistosomiasis: swimmer’s itch (dermatitis). Treatment is trimeprazine, calamine,

and sedative.
-Clonorchis sinensis: =Chinese fluke disease, related to raw fish consumption, cause wserum like
sickness and bile duct obstruction. Diagnosis is operculated egg (circle on the edge). Treatment
is praziquantel.
-Fasciola hepatica = sheep liver fluke, ingestion of aquatic plants, cause night sweat+ fever.
Diagnosis and treatment are the same.
-Fasciolopsis buski: =giant intestinal fluke, ingestion of aquatic plants and water chestnut,
reservoir pigs, dogs, and rabbits, cause abdominal pain and diarrhea. Treatment and diagnosis
are the same as above.

-Paragonimus westermanii: lung fluke, associated with raw crabs and crayfish, disease can
mimic TB with bloody tinged sputum.

18.Taenia saginata (beef tapeworm) and Taenia solium (pork tapeworm) are both intestinal
tapeworms caused by ingestion of cysticerci. Both could be diagnosed by finding of proglottids
or eggs in the feces and treated by praziquantel. However, cysticercosis from Taenia solium
infection could lead more serious complication. Why?
- Cysticercosis occurs after ingestion of eggs from contaminated water, vegetation, or food. In
this case, humans act as intermediate host, autoinfection (+). The eggs then develop into the
larva and migrates into the eye, heart, lung, and brain (lead to adult-onset epilepsy). Biopsy is
needed for diagnosis and sometimes requires the surgery to remove it.

19. Diphyllobothrium latum (fish tapeworm) is transmitted by drinking pond water

contaminated with larvae (in crustacean) or eating the raw pickled fish containing a
sparganosis. This infection could cause megaloblastic anemia. Why?
-This intestinal tapeworn could inhibit absorption of B12  megaloblastic anemia. The biopsy
and the finding of proglottids or eggs in feces are required for diagnosis. The treatment is
praziquantel.
20.What are the differences between Echinococcus granulosus and Echinococcus multilocularis
infection?
- Echinococcus granulosus has intermediate host herbivores and definitive host is carnivores
and sheep raising area. While Echinococcus multilocularis has intermediate host rodents and
definitive host caninens and cats (most common in Northern Area).
-Both transmitted by ingestion of eggs  hydatid cyst in liver and lung (where cysts containing
brood capsules develop)  rupture of cyst  anaphylactic shock. More severe in Echinococcus
multilocularis because of exogenous budding of cysts (cyst metastasis).
-Both are diagnoses by imaging or serology. The treatment is albendazole (for E.granulosus) and
surgical resection (for E.multilocularis).

21.Enterobius vermicularis is the most frequent helminth parasite in the US. What are the
important features of it?
-Transmission via eggs adult form in the intestine  laying egg in the perianal at night 
perianal itching and very contagious, autoinfection (+).
-Disease: pinworms
-Diagnosis/ treatment: sticky swab of perianal area, ova have flattened side with larvae inside.
Treatment is pyrantel/ mebendazole/ albendazole, and treat all family.

22.What are the important features of Trichuris trichiura (=whipworm)?

-Transmission via ingestion of eggs
-Disease: cecum, appendicitis, and rectal prolapsed.
-Diagnosis/ treatment: barrel-shaped eggs with bipolar plugs in stools. Treatment is
albendazole.
23.What are the important features of Ascaris lumbricoides?
-The most common helminth worldwide infection, the largest roundworm, transmission via
eggs.
-Disease : ingest eggs  larva migrate through lung could manifest as Loeffler pneumonitis
(cough) get mature in small intestine  may obstruct intestine or bile duct gangrenese
necrosis.
-Diagnosis/ treatment: bile stained knobby eggs or adults. Treatment is supportive therapy
during pneumonitis, surgery for ectopic migrations, mebendazole.

24. What are the important features of Toxocara canis or cati?

-Transmission via eggs ingested from handling puppies or cats or from eating dirt (pica)
-Disease: visceral larva migrans  larvae wabder aimlessly until they die  massive
inflammation.

-Diagnosis/ treatment: history/ serology. Most of the cases are self-limiting and treatment is
mebendazole or surgery to remove the worms.

25. What are the important features of Necator americanus or Ancylostoma duodenale (human
hookworm)?
-Transmission via penetration of filariform larva through intact skin of bare foot.
-Disease: lung migration  pneumonitis, bloodsucking  anemia.
-Diagnosis/ treatment: occult blood fecal, eggs (oval, transparent with 2-8 cell stage visible
inside)/ larvae in the stool. Treatment mebendazole and iron therapy.
26. Ancylostoma braziliense and caninum are the cat and dog hookworm. What are the
differences between those two with human hookworm?
-The filariform larva penetrates intact skin but cannot mature and only migrate into the skin.
The disease is cutaneous larva migrans with intense skin itching. The treatment is thiabendazole
and topical corticosteroid.

27.What are the important features of Strongyloides stercoralis ?

-Same as above that filariforn larva penetrates intact skin, autoinfection ( infection can be
amplified in the human host without a new external source of contamination).
-Disease: threadworm strongyloidiasis with early signs are pneumonitis, abdominal pain, and
diarrhea. While the late signs are the malabsorption, ulcer, and bloody stool.
-Diagnosis/ treatment: larva in stool/ serology. Treatment is thiabendazole.

28. What are the important features of Trichinella spiralis?

-Related to bear hunting and consumption of viable encysted larvae in meat.
-Disease: trichinosis larvae encyst in muscle  fever, myalgia, splinter hemorrhage,
eosinophilia.
-Diagnosis/ treatment: muscle biopsy, steroid for severe symptoms+ mebendazole
(albendazole).

29.What are the important features of Wuchereria bancrofti and brugia?

-Transmitted by mosquito, causes elephantiasis (lymphedema), microfilariae in blood+
eosinophilia for diagnosis, diethylcarbamazine+ivermectin+ surgery for treatment.

30.Both Loa-loa (African eye worm) and Onchocerca volvulus (river blindness) infect the eyes.
What are the important features of those two?
-Both could manifest as calabar swelling.
-Loa-loa: pruritus, not painful, transmitted by Chrysops or mango flies. Diagnosis is microfilariae
in blood and eosinophilia, DEC and surgical for treatment.
-Onchocerca volvulus: itchy leopard rash, chorioretinitis, transmitted by blackflies. Diagnosis is
skin snips. Treatments are DEC/ ivermectin and surgical removal.

31.What are the important features of Dranunculus medinensis (guinea worm, fiery serpent)?
-Transmitted by drinking water with infected copepods.
-Disease: creeping eruptions, ulcerations, rash
-Diagnosis/ treatment: increased IgE. The treatment is albendazole and slow-cautious worm
removal with stick to avoid worm damage that can induce anaphylactic.

PHYSIOLOGY
08.01-Fluid Distribution and Edema
1.The body consists of 2/3 intracellular fluid and 1/3 extracellular fluid in which the
compartment is separated by semipermeable membrane. The osmotic gradient is required to
allow the water movement from the higher concentration of the water to the lower one. What
is the definition of the effective osmole?

-The molecules that create the osmotic force so the solute doesn’t easily cross the membrane.
Example: plasma protein is effective osmole for the vascular compartment, while the natrium is
the effective osmole for the extracellular compartment.

2.What are the normal ranges of extracellular solutes?

3.The normal osmolality for the plasma is 275-295 mOsm/kg and the normal osmolar gap is ≤
15 . What is the clinical correlate for osmolar gap calculation?

Na is doubled because for every positive charge, there is a negative charge.

4.The alteration of the intracellular compartment is the result of the alteration of the
extracellular compartment. The alteration is shown through Darrow-Yannet diagram. How do
we interpret this figure?

The effect: blood pressure ↓, RAAS ↑, ADH ↑

5.How do we interpret this figure?

-Loss of hypotonic urin from diabetes insipidus (DI) could result in this figure. The causes of DI
could be central (neurogenic) with decreased ADH, or nephrogenic with decreased sensitivity
of renal nephron.
The effect: blood pressure ↓, RAAS ↑, ADH ↑

6. How do we interpret this figure?

-If there’s an increase of ECF, think first about the increase of Na. However, it could be the
initial effect of hyperglycemia too.
- The effect: blood pressure ↑, RAAS ↓, and ADH ↔ (difficult to predict)

7. How do interpret this figure?

-Both compartments go up so we don’t develop the edema.
-The effect: blood pressure ↔, RAAS ↓, ADH ↓

8. How do we interpret this figure?

-Infusion with saline and colloid (dextran, plasma with protein) could expand the entire ECF.
-The effect: blood pressure ↑, RAAS ↓, ADH ↓
-Pathology: ↑ aldosterone in the Conn syndrome.

9.How do we interpret this figure?

The loss of salt and water in the extracellular component could be caused by waterhouse-
friederichson syndrome, primary adrenal insufficiency=aldosterone deficiency, and Addison’s
disease.

10. Why does the osmolality need to be constant?

-To control ICF and blood pressure

11. Why does the surgery increase the ADH?

-The CRH increases which is induced by stress related surgery  Angiostensin II and ADH
increase.

12. How does our body regulate the volume?

-Plasma angiostensin II and plasma K increase  release of aldosteron from zona glomelurosa
 ↑ absorption of Na and ↑ secretion of K  to maintain extracellular volume.

-1% change of osmolality detected in the hypothalamus and 10% change of volume detected in
the carotid  release of ADH (=arginine vasopression) act in the V2 cells on the collecting
causing water reabsorption and also act in the V1 cells on the arteriolar causing the
vasoconstriction. Thus, the release of ADH is influenced by the increase osmolality and
decrease blood pressure/volume.

-Juxtaglomerular complex senses hypotension via β2 receptor (= decrease perfusion to the

kidney) + decrease sodium to the macula densa + sympathetic stimulation via β1 receptor 
release of renin change angiostensinogen into angiostensin 1 angiostensin 2 by ACE in the
lung aldosterone (water and Na retention)

13.What are the influencing factors for absorption and filtration?

The filtration is mainly influenced by hydrostatic pressure of the plasma, and absorption is
mainly influenced by the oncotic pressure of the plasma. The oncotic pressure in the
interstitium doesn’t play important role because the lymphatic removes the leaked protein.

14. Why do the increased hydrostatic pressure of plasma and decreased of oncotic pressure of
plasma cause the pitting edema?
-Both could cause the movement of the water into the interstitial and leave indentation of the
skin after the pressure. The causes are heart failure, liver failure, and nephritic syndrome.

15. Why do the inflammation and change of the vascular anatomy result in the non-pitting
edema?
-The increased of interstitial oncotic pressure caused by the thyroid dysfunction (elevated
mucopolysaccharides in the interstitium) could act as an osmotic agent resulting in fluid
accumulation  non-pitting edema. The mediators of inflammation such as bradykinin, TNF
alpha, histamine, and cytokine could increase the capillary permeability  non-pitting edema.
At last, the lymphedema can produce a non-pitting edema because of the rise in interstitial
oncotic pressure.

16. What are the differences between cardiogenic and non-cardiogenic pulmonary edema?
-Cardiogenic PE: Left ventricular failure backward flow to the left atrial  ↑venous pressure
 ↑ capillary pressure  fluid accumulation in the interstitial  marked by elevated
pulmonary wedge pressure.
-Non-cardiogenic PE=ARDS: direct injury of the alveolar epithelium or capillary endothelium
↑ capillary permeability  fluid accumulation in the interstitial and decreased lung compliance
due to the decreased surfactant marked by normal or low pulmonary wedge pressure.

17. What are the tracers used to measure various compartments?

08.02-Excitable Tissue
1.What are the 5 key principles of excitable tissue?
-membrane potential (Em): separation of charge across the membrane of excitability tissue at
rest.
-electrochemical gradient: combination of electrical gradient (charges repel opposite attract)
and chemical gradient (high to flow).
-equilibrium potential: the membrane potential that puts an ion in electrochemical
equilibrium Em towards equilibrium of most permeable (conductance) ion. EK+ -95 mV, ECl -
76 mV, E Na+ +70 mV, E Ca2+ +125 mV.
-conductance: = permeability
-net force (driving force): resting membrane potential-equilibrium potential. The greater net
force, the further from the equilibrium.

2.What are the types on ion channels?

-Ungated (leak) that always open, voltage-gated, and ligand gated. NMDA receptor has both
voltage and ligand-gated channel.
The ligand is the aspartate and glutamate. The functions of the receptor are for the pain and
memory. NMDA blocker is ketamine and PCP.

3.Why does the hyperkalemia cause the depolarization, while the hypokalemia cause the
hyperpolarization?

Hyperkalemia: concentration gradient decreases  positive charge stays in the cells 

depolarization.
Hypokalemia: concentration gradient increases  positive charge leaves the cells 
hyperpolarization.

4.How do voltage-gated (Fast) Na channels work?

-closed : low Na conductance

-open (activated state= m gate): depolarization  open the gate  high conductance of Na
more depolarization. This gate is blocked by Ca2+.
-inactivated (=h gate): the positive membrane potential  inactivation gate is closed
repolarization turn back into the closed state.
5.Hyperkalemia increases the neuronal excitability. However, the chronic hyperkalemia will
decrease it. Why?
-Hyperkalemia keeps cell depolarized, so overtime the fat Na channel is unable to transition
back to the closed state and locked in the inactivated state.

6.How does the action potential occur?

The threshold stimulus (or summation of subthreshold stimulus)  opening of Fast Na channels
 depolarization action potential turn back to inactivated state opening K channels  K
moves into the equilibrium to cause repolarization  act slower causing
hyperpolarizationback to rest membrane potential.

Blockade of sodium channels would reduce height of the action potential. Increased potassium
conductance would cause the resting potential to be more negative and possibly decrease the
slope of the upstroke of the action potential; increased sodium conductance would depolarize
the resting potential. Stimulation of the sodium-potassium pump would hyperpolarize the cell.

7.What are the differences between absolute and relative refractory periods?
- The absolute refractory period is the period when the action potential couldn’t be
regenerated by second stimulus regardless the strength of stimulus. It determines the
maximum frequency of action potentials. For example, the cells have absolute refractory
periods every 10 ms so the maximum frequency of action potential is 1000/10= 100. The cause
of this period is the opening or inactivated fast Na gate.
-The relative refractory period is the period when second action potential could be
regenerated by the greater threshold stimulus.

8.What are the factors influencing conduction velocity of action potential?

-The velocity is directly related to cell diameter and myelination (=insulation). Alpha motor
neuron has more rapid velocity.

9.Both multiple sclerosis and Guillain-Barre are demyelinating diseases. MS manifest as spastic
paralysis (=UMN loss inhibition of alpha motor neuron), while the GBS (=LMN peripheral
lesion because of blockage of conduction in the alpha motor neuron). Why does it happen?
-Loss of myelin results in current leakage across the membrane not enough current reaching
fast Na+ channels  can’t reach the threshold depolarization.

10.How does synaptic transmission occur in NMJ?

The action potential opens Ca2+ voltage gated channel (+125 mV) in the presynaptic
membrane influx of Ca  release of vesicles containing Ach  bind to non-specific Na-K
ligand gated ion channel (Nm receptor) in the sarcolemma (=postsynaptic membrane)  Na
has greater net force than K so Na moves inward the cell  depolarization (occurs if it’s over
the subthreshold=end plate potential) 1 action potential on the nerve causes 1 action
potential on the skeletal muscles to induce contraction under the normal circumstances
acetylcholinesterase breaks down the Ach  choline (re-uptake to presynaptic membrane)
and acetate.

11.The decreased neuronal excitability could manifest as weakness, ataxia, hyporeflexia,

paralysis, and sensory deficit. What are the causes of decreased neuronal excitability?
-Ion disturbances: hypokalemia (hyperpolarization), chronic hyperkalemia (inactivated Na+
channel), hypercalcemia (blocks Na+ channel).
-Demyelination/ loss of neurons: GBS, ALS, aging
-Toxins/ drugs: local anesthetics (caine drugs ), tetrodotoxin (TTX), saxitoxin (STX)  block fast
Na+ channels  preventing action potential.
-Neuromuscular junction: depolarizing Nm blocker (succhynilcholine), non-depolarizing Nm
blockers (rocuronium, atracurium), Lambert Eaton (autoimmune disease where antibodies
block voltage gated Ca2+ channels in the presynaptic membrane), myasthenia gravis
(autoimmune disease where antibodies block Nm receptor in the postsynaptic membrane),
botulinum toxin (protease that destroys protein needed for fusion and release of synaptic
vesicles).

12.The clinical signs of increased neuronal excitability could initially include hyperreflexia,
spasms, muscle fasciculations, tetany, tremors, parasthesia, and convulsions. However, the
toxic level can drive into complete paralysis and death. What are the causes of increased
neuronal excitability?
-Ion disturbances : acute hyperkalemia (depolarization), hypocalcemia.
-Demyelination/ loss of neurons: MS
-Toxins/ drugs: ciguatoxin (CTX: fish) and batrachotoxin (BTX: frogs)  block inactivation of fast
Na+ channels  longer duration of action potential, 3-4 diaminopyridine  longer opening of
presynaptic voltage gated Ca2+ channels  longer depolarization.
-NMJ: AChE inhibitors (physostigmine could cross blood brain barrier, neostigmine,
pyridostigmine), organophospate, latrotoxin that opens presynaptic Ca2+ channels and resulting
in excess Ach release.

13. What are the differences between excitatory postsynaptic potential and inhibitory
postsynaptic potential?
-Excitatory postsynaptic potential increased excitability of the postsynaptic neuron as the
result of the increased Na+ g. The important receptors are:

 Nicotinic: Ach bind to the receptors NM and Nn (the blockers: hexamethonium and
mecamylamine)
 Non-NMDA: aspartate and glutamate as endogenous ligands
 NMDA: amino acids

-Inhibitory postsynaptic potential decreased excitability of the postsynaptic neuron as the

result of increased Cl – g (equilibrium=- 76mV). The important receptors are:

 GABA A&C: GABA as endogenous ligand

 Glycine: the most predominant in the ventral horn of the spinal cord. The tetanus toxin
inhibits the release of the glycine.

14.