UNIT II

Mechanism of Infection &

Inflammation
TALHA LODHI BSN (RCN), ISLAMABAD

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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

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Cont.…..

■ Differentiate the vascular and cellular phases of

inflammatory response
■ Differentiate between chronic and acute
inflammation.

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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

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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,).
■ Decline stage (Subsidence of symptoms)
■ The recovery stage (symptoms have
disappeared, tissue heal and the body regains
strength).

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The Incubation Stage
■ The incubation period is the phase during which
the pathogen begins active replication without
producing recognizable symptoms in the host.
■ The incubation period may be short, as in the
case of salmonellosis (6 to 24 hours), or
prolonged, such as that of hepatitis B (50 to 180
days) or HIV (months to years).
■ The duration of the incubation period can be
influenced by additional factors, including the
general health of the host, the portal of entry,
and the infectious dose of the pathogen.

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Prodromal Stage
► The hallmark of the prodromal stage is the initial
appearance of symptoms in the host, although
the clinical presentation during this time may be
only a vague sense of malaise.
► The host may experience mild fever, myalgia,
headache, and fatigue.
► These are constitutional changes shared by a
great number of disease processes.
■ The duration of the prodromal stage can vary
considerably from host to host.

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The Acute Stage
► This is the period during which the host
experiences the maximum impact of the
infectious process corresponding to rapid
proliferation and dissemination of the pathogen.
► During this phase, toxic byproducts of microbial
metabolism, cell lysis, and the immune response
mounted by the host combine to produce tissue
damage and inflammation.
► The symptoms of the host are pronounced and
more specific than in the prodromal stage.

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The Convalescent Stage
► This is characterized by the containment of
infection, progressive elimination of the
pathogen, repair of damaged tissue, and
resolution of associated symptoms.
► Similar to the incubation period, the time
required for complete convalescence may be
days, weeks, or months, depending on the type
of pathogen.

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The Resolution Stage
■ The resolution stage is the total elimination of a
pathogen from the body without residual signs or
symptoms of disease.

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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.

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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.

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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.

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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.

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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.

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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.

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 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.

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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).

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Why Cardinal signs ?

■ CALOR = Increase blood flow, elevated cellular metabolism

■ RUBOR = Increase blood flow, vasodilation
■ TUMOR = Vasodilation, extravasations of fluid, cellular influx
Elevated cellular metabolism

■ DOLOR = Release of cellular mediators, cellular influx,

Elevated cellular metabolism

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Local effects of inflammation
- 4 cardinal signs of inflammation
• Redness (rubor) – from increased blood supply
• Heat (calor) – from increased blood supply
• Swelling (tumor) – from increased permeability & increased
proteins in interstitial fluid
• Pain (dolar) – from chemical mediators
- Also get inflammatory exudate
• Serous – from allergic reactions & burns
• Purulent – from infections
- May lead to abscess
Systemic effects of inflammation
- General malaise
- Fatigue
- Headache
- Fever
• Caused by pyrogens (chemicals released from phagocytes)
• Beneficial
- Inhibits growth of pathogens
- Enhances repair process via increased metabolic rate

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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.

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Physiological mechanism involved in
the production of cardinal signs

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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.

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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.

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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.

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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.

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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
(1) Margination and adhesion to the endothelium,

(2) Transmigration across the endothelium,

■ Chemotaxis, and activation

■ Phagocytosis

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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.

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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.

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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.

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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.

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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

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Purpose of inflammation

■ To limit the spread of pathogens and ultimately

destroy them.
■ To remove the debris of damage tissue.
■ To initiate tissue repair.

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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
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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.

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Causes

■ Persistent infections
■ Prolonged exposure to toxic agents
■ Chronic inflammation following acute
inflammation.
■ Reccurrent attacks of acute inflammation

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