The Immune System

Emmanuel Kaitano
 Objectives

 Describe some of the mechanisms of

nonspecific and specific immunity .
 Describe the structure of antibodies and
the nature of antigens
 Describe innate and acquired immunity
and their examples
 Differentiate B cells and T cells
 The Immune Response

Immunity: “Free from burden”. Ability of

an organism to recognize and defend itself
against pathogens or antigen
Immune system:All structures and processes
that provide defense against potential
pathogens
 Categories of the immune system

1. Innate immune system (non-specific)

2. The adaptive immune system (specific)
 Innate immunity
Innate or Genetic Immunity: Immunity an
organism is born with.
 Genetically determined.
 Includes internal and external defenses
 External defenses: e.g. Epithelial
membranes act as barrier and their
secretions that have antimicrobial
effects.
 Internal defenses: e.g. phagocytosis
which at times act as both specific and
non-specific immunity
 Innate immunity cont’
Structure Function

External Skin Barrier to pathogen penetration, secretion of

lysozyme
Digestive tract Stomach acidity, normal flora of colon

Respiratory tract Mucous secretion, movement of mucus by cilia

movement, alveolar macrophages

Genitourinary Acidity of urine, lactic acid of vagina

tract
Internal Phagocytic cells Ingest and digest bacteria, denatured proteins, cellular
debris and toxins

Interferons Inhibit replication of viruses

Complement Promote destruction of bacteria, enhance

proteins inflammatory response
 Innate immunity cont’
Structure Function

Internal Endogenous Secreted by leukocytes and other cells,

pyrogen produces fever
Natural killer Destruction of viral infected cells, tumor
(NK) cells cells, mismatched transplant tissue cells

Mast cells Release of histamine and other mediators of

inflammation, release cytokines that
promote adaptive immunity.
Innate immune system: components of Blood

Complement proteins
Coagulation proteins
Extracellular
Cytokines

WBCs
 White blood cells (WBCs)
Macrophages

B-lymphocytes

T-lymphocytes

Natural killer(NK) cells

Mast cells
Activation of innate immune
system
 Innate immune system recognizes pathogen
associated molecular patterns (PAMPs) that
exist on pathogens e.g. lipopolysaccharides on
gram-negative bacteria.
 PAMPs recognized by pathogen recognition
receptors (PRR) on cells of innate immune
system
 Proteins for PRR encoded by genes inherited
through germ cells
 Example of pathogen PRR: Toll-like receptors,
NOD-like receptors
 Activation of innate immune
system
 Complement system:
 Integrates innate immune system and
adaptive immune system
 Proteins of blood plasma and other body
fluids that are activated when antibody
combine to antigen
 In activated state promote phagocytosis,
lysis of target cells, opsonization and
 Danger associated molecular patterns
(DAMPs): during necrosis (not apoptosis)
lead to local inflammation.
 Phagocytosis
 Three groups of phagocytic cells:
1) Neutrophils
2) Mononuclear phagocyte system: monocytes,
macrophages, dendritic cells, histocytes
3) Organ-specific phagocytes: In liver, spleen,
lungs, lymph nodes and brain. Include
Langerhans cells of epidermis, Kupffer
cells( Stellate macrophages) of liver,
microglia of brain, alveolar macrophages of
lungs
Phagocytosis cont’
 Fixed phagocytes:
 In liver, spleen and lymph nodes are
immobile in walls of sinusoids of the organs
 Remove pathogens, debris, foreign particles
from blood and lymph.
 Macrophages:
 Normally function to clear cellular debris
from apoptosis
 Produce pro-inflammatory cytokines,
( subclass chemokines) when their toll-like
receptors have received pathogenic signals
Phagocytosis cont’
 Chemokines attract neutrophils and monocytes by
chemotaxis to the site of infection.
 Monocytes can be transformed into macrophages to
escalate fight against infection
 Extravasation (diapedesis):
 Multi-step process in which signals between
leukocytes and endothelial cells allow neutrophils
and monocytes exit the blood vessels into
surrounding connective tissues
 Employed to fight spreading infection
Phagocytosis cont’
 Steps in phagocytic activity:
 Phagocytosis is triggered by receptors on
phagocytes that recognize complement
proteins on pathogens, microbial molecules,
antibodies.
 Microbe/foreign body is engulfed and
surrounded by a membrane to form a vacuole
 The vacuole fuses with lysosome that
contains a digestive enzymes which destroy
the microbe/foreign body.
Fever
 Part of non-specific body defense produced in
response to infection
 Hypothalamus controls the body temperature so that
it remains within 37 degrees Celsius.
 In response to endogenous pyrogen temperature
regulation is reset upward.
 In some infections endogenous pyrogen has been
identified as interleukin-1β
 Response to endogenous pyrogen causes increased
metabolic heat production by brown adipose tissue
and reduced heat loss by vasoconstriction.
Fever cont’
An endotoxin, LPS, in gram-negative cell wall of bacteria
stimulate monocytes and macrophages to release cytokines-
interleukin-1, interleukin-6 and tumor necrosis factor (TNF).
The cytokines lead to production of fever, increased sleepiness
and reduced plasma iron concentration.
Fever is produced in response to infection-reduce bacterial
activity
Low plasma iron concentration-reduce bacterial activity
Interferons
 Viral and bacterial nucleic acid in
infected cell stimulate the production of
STING
 STING:
 = stimulator of interferon genes
 Stimulates expression of interferon
genes
Alpha & beta interferon
 Produced by all cells in the body though
α-interferon is predominantly produced
by hematopoietic cells
 Protect other cells in their vicinity from
viral infections: viral replication is
inhibited.
 Alpha interferon used in treatment of
hepatitis C & B, Leukemia, viral genital
warts and Kaposi’s sarcoma
 Beta interferon is used to treat sclerosis
Gamma interferon
 Produced by lymphocytes and natural
killer cells (NKC)
 Used to treat chronic granulomatous
disease.
Local inflammation
 Inflammation: Complex biological
process by which body responds to
pathogens and irritants

 Associated with swelling of tissue

 Key player in innate immune response

 All roads lead to inflammation

Neutrophil
s Coagulation proteins

Monocytes /macrophages
Inflammation
C` proteins

NK cells

Cytokines /IFN
TLRs

Extracell
Cellular
ular
Inflammation and vascular changes
 Vasodilatation

 Increased capillary permeability

Normal blood vessel

Normal blood vessel Dilated blood vessel

Leaky blood vessel

Signs of inflammation
Vascular
changes
Vasodilat Capillary
ation permeability
Heat /
redness Swelling Pain

Temporary
Fever loss of
function
 Inflammation and innate immunity
Histamine

Pathogen
removal

+ Adaptive immune
response

Mast cells – similar to basophils in blood;

+
mast cells are present in tissues and release+
histamines
in response to wound / infection /irritant
Inflammatory mediators: prostaglandins, cytokines and chemokines
Summary: role of Inflammation in
innate immunity
 Initiation of phagocytosis – killing of pathogen

 Limiting the spread of infection

 Stimulate adaptive immune response

 Initiate tissue repair

The good and bad about inflammation

Acute /short- chronic /long-

term -Good term - Bad
Chronic inflammation = tissue
damage Normal tissue

 Chronic inflammation -
macrophages in the injured
tissue.

 Macrophages release toxins

(including reactive oxygen
Tissue : chronic inflammation
species or ROS) that injure
tissues

 chronic inflammation is
almost always accompanied
by tissue destruction.
Chronic inflammation and tissue
damage
Chronic
inflammation
Reduced tissue
function

Tissue
damage
Activation
of immune Killing of host
cells cells
Chronic inflammation and Cancer
RO
S
O2-
DNA
OH- Mutation

Cancer
Acquired Immunity
 Immunity that an organism develops
during lifetime.
 Not genetically determined.
 May be acquired naturally or artificially.
 Consider development of immunity to measles in
response to infection or vaccination.
 Read acquired immunity related to covid-19
infection.
Adaptive immunity
 Acquired by individuals due to prior exposure to a
specific pathogen
 This immune response is the function of
lymphocytes
 Immunological memory: ability of lymphocytes to
fight an infection with increased improvement due
to prior exposure.
 Trained immunity: some cells of innate immune
system such as natural killer cells exhibit
improvement during secondary exposure to a
pathogen.
Types of Acquired Immunity
I. Naturally Acquired Immunity: Obtained in
the course of daily life.
A. Naturally Acquired Active Immunity:
 Antigens or pathogens enter body naturally.
 Body generates an immune response to antigens.
 Immunity may be lifelong (chickenpox or mumps)
or temporary (influenza or intestinal infections).
B. Naturally Acquired Passive Immunity:
 Antibodies pass from mother to fetus via placenta
or breast feeding.
 No immune response to antigens.
 Immunity is usually short-lived (weeks to months).
 Protection until child’s immune system develops.
Types of Acquired Immunity (Continued)
II. Artificially Acquired Immunity: Obtained by
receiving a vaccine or immune serum.
1. Artificially Acquired Active Immunity:
 Antigens are introduced in vaccines (immunization).
 Body generates an immune response to antigens.
 Immunity can be lifelong (oral polio vaccine) or temporary
(tetanus toxoid).
2. Artificially Acquired Passive Immunity:
 Preformed antibodies (antiserum) are introduced into body
by injection.
 Snake antivenom injection from horses or rabbits.
 Immunity is short lived .
 Host immune system does not respond to antigens.
 Serum: Fluid that remains after blood has clotted
and cells have been removed.
 Antiserum: Serum containing antibodies to a
specific antigen(s). Obtained from injecting an
animal (horse, rabbit, goat) with antigen (snake
venom, botulism or diphtheria toxin).
 Serology: The study of reactions between
antibodies and antigens.
 Duality of Immune System
I. Humoral (Antibody-Mediated) Immunity
 Involves production of antibodies against foreign
antigens.
 Antibodies are produced by a subset of lymphocytes
called B cells as opposed to T cells.
 B cells that are stimulated will actively secrete
antibodies and are called plasma cells.
 Antibodies are found in extracellular fluids (blood
plasma, lymph, mucus, etc.) and the surface of B cells.
 Defense against bacteria, bacterial toxins, and viruses
that circulate freely in body fluids, before they enter
cells.
 Also cause certain reactions against transplanted
tissue.
Antibodies are Produced by B Lymphocytes
Antibodies are Proteins that Recognize Specific Antigens
Duality of Immune System (Continued)
II. Cell Mediated Immunity
 Involves specialized set of lymphocytes called T cells that
recognize foreign antigens on the surface of cells,
organisms, or tissues:
 Helper T cells
 Cytotoxic T cells
 T cells regulate proliferation and activity of other cells
of the immune system: B cells, macrophages,
neutrophils, etc.
 Defense against:
 Bacteria and viruses that are inside host cells and are
inaccessible to antibodies.
 Fungi, and protozoa
 Cancer cells
 Transplanted tissue
Cell Mediated Immunity is Carried Out by T Lymphocytes
 Antigens
 Most are proteins or large polysaccharides from
a foreign organism.
 Microbes: Capsules, cell walls, toxins, viral capsids,
flagella, etc.
 Nonmicrobes: Pollen, egg white , red blood cell
surface molecules, serum proteins, and surface
molecules from transplanted tissue.
 Lipids and nucleic acids are only antigenic when
combined with proteins or polysaccharides.
 Antigens
Epitope:
 Small part of an antigen that interacts
with an antibody.
 Any given antigen may have several
epitopes.
 Each epitope is recognized by a different
antibody.
 Haptens: small molecules that are not antigens but
become antigenic if they combine with proteins-
become epitopes.
Epitopes: Antigen Regions that Interact
with Antibodies
 Antibodies
 Proteins that recognize and bind to a particular
antigen with very high specificity.
 Made in response to exposure to the antigen.
 One virus or microbe may have several antigenic
determinant sites, to which different antibodies
may bind.
 Each antibody has at least two identical sites
that bind antigen: Antigen binding sites.
Antibodies (immunoglobulins)

Belong to the gamma-globulin fraction of

serum proteins
Y-shaped or T-shaped polypeptides

 2 identical heavy chains

 2 identical light chains
All immunoglobulins are not antibodies
Five kinds of antibodies

 IgG, IgM, IgA, IgD, IgE

IgG
 70-75% of total immuniglobulin
 Secreted in high quantities in secondary exposures
 Cross the placenta • 4-fold rise or fall
indicates active infection
 Major functions / applications
• A single positive
 neutralize microbes and toxins sample indicates past
 opsonize antigens for phagocytosis exposure
 activate the complement
 protect the newborn
IgM
 Secreted initially during primary infection
 Cannot cross the placenta
 Major functions / applications
•Presence in newborn
means infection
 secreted first during primary •Singlepositive sample in
exposure serum or CSF indicates
 activates the complement recent or active infection
 •Used to detect early
used as a marker of recent
phase of infection
infection
IgA
 Monomeric in serum
 Dimeric with secretory component in the lumen of
the gastro-intestinal tract and in the respiratory tract
 Major function / application
 neutralizes microbes and toxins
•Sero-diagnosis of
tuberculosis
•Synthicial respiratory
virus tests
IgD
 Monomeric
 Major functions / applications
 present on the surface of B lymphocytes
 functions as membrane receptor
 role unclear
 has a role in antigen stimulated lymphocyte differentiation
IgE
 Mediates type I hypersensitivity
 Monomeric
 Major functions / applications
 associated with anaphylaxis
 plays a role in immunity to Serodiagnosis of infectious and
non infectious allergies
helminthic parasites
(e.g., allergic
bronchopulmonary
aspergillosis, parasitic
diseases)
Sequential IgM-IgG humoral response

IgM
 produced as a first response to many antigens
 levels remain high transiently
IgG
 produced after IgM
 higher levels persist in small amounts throughout life
 produced in large amounts during secondary response
 persistence of antigen sensitive ‘memory cells’
after primary response
How Do B Cells Produce Antibodies?
 B cells develop from stem cells in the bone
marrow of adults (liver of fetuses).
 After maturation B cells migrate to lymphoid
organs (lymph node or spleen).
 Clonal Selection: When a B cell encounters an
antigen it recognizes, it is stimulated and divides
into many clones called plasma cells, which
actively secrete antibodies.
 Each B cell produces antibodies that will
recognize only one antigenic determinant.
Consequences of Antigen-Antibody Binding
Antigen-Antibody Complex: Formed when an
antibody binds to an antigen it recognizes.
Affinity: A measure of binding strength.
1. Agglutination: Antibodies cause antigens
(microbes) to clump together.
 Hemagglutination: Agglutination of red blood cells.
Used to determine ABO blood types and to detect
influenza and measles viruses.
 Immunoassays: antigen-antibody reactions for

diagnosis
2. Opsonization: Antigen (microbe) is covered with
antibodies that enhances its ingestion and lysis by
phagocytic cells.
 Immunological Memory
Antibody Titer: The amount of antibody in the
serum. Pattern of Antibody Levels During
Infection
Primary Response:
 After initial exposure to antigen, no antibodies are
found in serum for several days.
 A gradual increase in titer.
 Most B cells become plasma cells, but some B cells
become long living memory cells.
 Gradual decline of antibodies follows.
 Immunological Memory
(Continued)
Secondary Response:
 Subsequent exposure to the same antigen displays
a faster and more intense antibody response.
 Increased antibody response is due to the
existence of memory cells, which rapidly produce
plasma cells upon antigen stimulation.
Antibody Response After Exposure to Antigen
 T Cells and Cell Mediated Immunity
Antigens that stimulate this response are mainly
intracellular.
Requires constant presence of antigen to remain
effective.
Unlike humoral immunity, cell mediated immunity is
not transferred to the fetus.
Cytokines: Chemical messengers of immune cells.
 Over 100 have been identified.
 Stimulate and/or regulate immune responses.
 Interleukins: Communication between WBCs.
 Interferons: Protect against viral infections.

 Chemokines: Attract WBCs to infected areas.

 T Cells and Cell Mediated
Immunity
Cellular Components of Immunity:
 T cells are key cellular component of immunity.
 T cells have an antigen receptor that recognizes
and reacts to a specific antigen (T cell receptor).
 T cell receptor only recognize antigens combined
with major histocompatability (MHC) proteins on
the surface of cells.
 Clonal selection increases number of T cells.
 T Cells and Cell Mediated
Immunity
Types of T cells
1. T Helper (TH) Cells: Central role in immune
response.
 Most are CD4+
 Recognize antigen on the surface of antigen presenting

cells (e.g.: macrophage).

 Activate macrophages

 Induce formation of cytotoxic T cells

 Stimulate B cells to produce antibodies.

Types of T cells
2 Killer T cells
Destroy specific target cells that are identified
by specific antigens on their surface .It
involves secretion of certain molecules at the
region of contact
3 Suppressor T cells-Decreases the activity of
B and killer T cells and together with helper
T cells regulate immune responses
 HIV and Helper T cells

The HIV specifically attacks helper T

lymphocytes.
Helper T cells have particular antigen marker on
their surfaces known as CD4 antigen which can
be distinguished from a different antigen called
CD8 on suppressor and killer T cells. A person
with AIDS has a reduced number of CD4
indicating a reduction in helper T lymphocytes.
Failure of immune response

 Immune response helps individuals defend against

 microbes
 some cancers
 Immune response can fail
 hypersensitivity reactions
 immunodeficiency
Hypersensitivity reactions
 Cause cell damage through excessive immune
response to antigens
 Hypersensitivity
 overreaction to infectious agents
 Allergy
 overreaction to environmental substances
 Autoimmunity
 overreaction to self
Immunodeficiency
 Loss or inadequate function of various components
of the immune system
 Can occur in any part or state of the immune system
 physical barrier, phagocytes, B lymphocytes, T lymphocytes,
complement, natural killer cells
 The immuno-compromised host
 has an impaired function of immune system
 is at high risk of infection
Immunodeficiency
 Congenital (primary) immunodeficiency
 genetic abnormality
 defect in lymphocyte maturation

 Acquired (secondary) immunodeficiency

 results from infections, nutritional deficiencies or
treatments
 AIDS, chronic leukemia