1
UNIT II
Mechanism of
Infection &
Inflammation
Ashfaq Ahmad Sahil
Lecturer INS-KMU
2
Objectives
At the end of this unit each learners will be able to:
Describe the stages of an infectious disease after
the point at which the potential pathogen enters the
body.
List the systemic manifestation of infectious
diseases
Discuss the purpose of inflammation
Describe the physiological mechanism involved in
the production of five cardinal signs of inflammation
3
Cont.…..
Differentiate the vascular and cellular phases of
inflammatory response
Differentiate between chronic and acute
inflammation.
4
Inflammation
Inflammation is a protective response intended to
eliminate the initial cause of cell injury, remove the
damaged tissue, and generate new tissue.
It accomplishes this by diluting, destroying, or
otherwise neutralizing the harmful agents.
It then sets the stage for the events that will
eventually heal and reconstitute the damaged
tissue.
Thus, inflammation is intimately interlinked with the
repair processes that replace damaged tissue or fill
in the residual defects with fibrous scar tissue.
5
Inflammation
Inflammation is the reaction of vascularized tissues to injury.
It is characterized by the elaboration of inflammatory
mediators and the movement of fluid and leukocytes from
the blood into the extravascular tissues.
This response localizes and eliminates microbes, foreign
particles, and abnormal cells and paves the way for repair of
the injured tissue.
Inflammatory conditions are commonly named by adding the
suffix -itis to the affected organ or system.
For example, appendicitis refers to inflammation of the
appendix, pericarditis to inflammation of the pericardium,
and neuritis to inflammation of a nerve.
6
Cardinal signs of
inflammation
In the first century AD, the Roman physician Celsus
described the local reaction of injury in terms that
are now known as the cardinal signs of
inflammation.
These signs are rubor (redness), tumor (swelling),
calor (heat), and dolor (pain).
In the second century AD, the Greek physician
Galen added a fifth cardinal sign, functio laesa (loss
of function).
7
Acute inflammation
Acute inflammation is of relatively short duration,
lasting from a few minutes to several days, and
is characterized by the exudation of fluid and
plasma components and emigration of
leukocytes, predominantly neutrophils, into the
extravascular tissues.
8
9
Physiological mechanism
involved in the production
of cardinal signs
10
Vascular Stage
The vascular changes that occur with
inflammation involve the arterioles, capillaries,
and venules of the microcirculation.
These changes begin almost immediately
after injury and are characterized by
vasodilation and changes in blood flow
followed by increased vascular permeability
and leakage of protein-rich fluid into the
extravascular tissues.
11
Cont….
Vasodilation, which is one of the earliest
manifestations of inflammation, follows a transient
constriction of the arterioles, lasting a few seconds.
Vasodilation first involves the arterioles and then
results in opening of capillary beds in the area.
As a result, the area becomes congested, causing
the redness (erythema) and warmth associated with
acute inflammation.
Vasodilation is induced by the action of several
mediators, most notably histamine and nitric oxide.
12
Cont…..
Vasodilation is quickly followed by increased
permeability of the microvasculature, with the
outpouring of a protein rich fluid (exudate) into the
extravascular spaces.
The loss of fluid results in an increased
concentration of blood constituents (red cells,
leukocytes, platelets, and clotting factors),
stagnation of flow, and clotting of blood at the site of
injury.
This aids in localizing the spread of infectious
microorganisms.
13
Cont….
The loss of plasma proteins reduces the
intracapillary osmotic pressure and increases
the osmotic pressure of the interstitial fluid,
causing fluid to move into the tissues and
produce the swelling (i.e., edema), pain, and
impaired function that are the cardinal signs
of acute inflammation.
The exudation of fluid into the tissue spaces
also serves to dilute the offending agent.
14
15
Cellular Stage
The cellular stage of acute inflammation is marked
by changes in the endothelial cells lining the
vasculature and movement of phagocytic leukocytes
into the area of injury or infection.
The sequence of events in the cellular response to
inflammation includes leukocyte
Margination and adhesion to the endothelium,
Transmigration across the endothelium,
Chemotaxis, and activation
Phagocytosis
16
Margination, Adhesion, and
Transmigration.
During the early stages of the inflammatory response,
cross-talk between the blood leukocytes and the
vascular endothelium defines a definite inflammatory
event and ensures secure adhesion and arrest of the
leukocytes along the endothelium.
As a consequence, the leukocytes slow their migration,
adhere tightly to the endothelium, and begin to move
along the periphery of the blood vessels.
This process of leukocyte accumulation is called
margination.
17
Cont…..
The subsequent release of cell communication
molecules called cytokines causes the endothelial cells
lining the vessels to express cell adhesion molecules,
such as selectins, that bind to carbohydrates on the
leukocytes.
This interaction, which is called tethering, slows their
flow and causes the leukocytes to move along the
endothelial cell surface with a rolling movement, finally
coming to rest and adhering strongly to intercellular
adhesion molecules (ICAMs) on the endothelium.
18
Cont……
The adhesion causes the endothelial cells to
separate, allowing the leukocytes to extend
pseudopodia and transmigrate through the
vessel wall and then, under the influence of
chemotactic factors, migrate into the tissue
spaces.
19
Chemotaxis
Chemotaxis is the dynamic and energy-directed
process of directed cell migration.
Once leukocytes exit the capillary, they wander
through the tissue guided by a gradient of secreted
chemoattractants, such as chemokines, bacterial and
cellular debris, and protein fragments generated from
activation of the complement system
Several immune (e.g., macrophages) and nonimmune
cells secrete these chemoattractants to ensure the
directed movement of leukocytes to the site of
infection.
20
Leukocyte Activation and
Phagocytosis
During the next and final stage of the cellular
response, monocytes, neutrophils, and tissue
macrophages are activated to engulf and
degrade the bacteria and cellular debris in a
process called phagocytosis
21
22
Purpose of inflammation
To limit the spread of pathogens and ultimately
destroy them.
To remove the debris of damage tissue.
To initiate tissue repair.
23
Inflammatory mediators
Plasma-derived:
Complement, kinins, coagulation factors
Cell-derived:
Preformed, sequestered and released (mast cell
histamine)
Synthesized as needed (prostaglandin)
24
25
Possible outcomes of acute
inflammation
Complete resolution
Little tissue damage
Capable of regeneration
Scarring (fibrosis)
In tissues unable to regenerate
Excessive fibrin deposition organized
into fibrous tissue.
Abscess formation occurs with some
bacterial or fungal infections
Progression to chronic inflammation
26
27
Chronic inflammation
Chronic inflammation is of a longer duration
(lasting for days to years) in which
inflammation, tissue injury and attempts at
repair coexist in varying combinations.
28
Causes
Persistent infections
Hypersensitivity diseases/ Immune mediated
inflammatory diseses
Prolonged exposure to toxic agents
Chronic inflammation following acute
inflammation.
Reccurrent attacks of acute inflammation
29
Morphology
Mononuclear cells infiltration
Proliferative changes and attempts at healing
Tissue destruction or necrosis
30
Mechanisms of macrophage
accumulation during Chronic
Inflammation
Continued recruitment of monocytes from
the circulation
Most important source for macrophages
Local proliferation of macrophages from
the blood stream
Immobilization of macrophages within the
site of inflammation
Cytokines and oxidized lipids can
cause immobilization
31
Consequences of
impaired inflammation
Defective inflammation Excess Inflammation
↑ susceptibility to Allergies
infection Important in
Delay in wound • Cancer
healing • Atherosclerosis
Tissue damage
• IHD
32
Infectious disease
The invasion of the human body by
microorganisms can produce harmful and
potentially lethal consequences.
The consequences of these invasions are
collectively called infectious diseases
33
Stages of an infectious
disease
The incubation stage (silent stage-- the
pathogen has gained entry into the host and
starts replicating).
The prodromal stage (appearance of S/S ).
The peak/ clinical stage (the disease reaches its
highest point of development,).
The recovery stage (symptoms have all but
completely vanished; pathogen has been mostly
eliminated)
34
Systemic Manifestations of
Infection
Under optimal conditions, the inflammatory
response remains confined to a localized area.
In some cases, however, local injury can result in
prominent systemic manifestations as inflammatory
mediators are released into the circulation.
The most prominent systemic manifestations of
inflammation include the acute-phase response,
alterations in white blood cell count (leukocytosis or
leukopenia), and fever.
35
Acute-Phase Response
The acute-phase response, which usually begins within
hours or days of the onset of inflammation or infection,
includes changes in the concentrations of plasma
proteins, skeletal muscle catabolism, negative nitrogen
balance, elevated erythrocyte sedimentation rate, and
increased numbers of leukocytes.
These responses are generated by the release of
cytokines, particularly IL-1, IL-6, and TNF-α.
These cytokines affect the thermoregulatory center in the
hypothalamus to produce fever, the most obvious sign of
the acute phase response.
36
Cont…
Other manifestations of the acute-phase
response include anorexia, somnolence, and
malaise, probably because of the actions of IL-1
and TNF-α on the central nervous system.
The metabolic changes, including skeletal muscle
catabolism, provide amino acids that can be used
in the immune response and for tissue repair.
37
White Blood Cell
Response
Leukocytosis, or increased white blood cells, is
a frequent sign of an inflammatory response,
especially one caused by bacterial infection.
The white blood cell count commonly
increases from a normal value of 4000 to
10,000 cells/μL to 15,000 to 20,000 cells/μL in
acute inflammatory conditions.
38
Cont….
Bacterial infections produce a relatively selective
increase in neutrophils (neutrophilia), whereas
parasitic and allergic responses induce
eosinophilia.
Viral infections tend to produce a decrease in
neutrophils (neutropenia) and an increase in
lymphocytes (lymphocytosis).
A decrease in white blood cells (leukopenia)
may occur with overwhelming infections or an
impaired ability to produce white blood cells.
39
40
41
