Pathology of

Infections
 Learning
Objectives
• Characterize the agents of infectious
diseases
• Explain the mechanisms utilized by
infectious agents in disease causation
• Correlate clinical manifestations with
infectious agent characteristics
• Explain an infectious agent’s interaction
with the immune system
• Create a concept map to answer a
question/activity
 What are the major immune defense mechanisms
against pathogens?

Type of Infection Major Immune Defense Mechanism

Bacterial Antibody, immunocomplex, and
cytotoxicity
Mycobacterial DTH and granulomatous reactions
Viral Antibody (neutralization), CTL, and T DTH
Protozoal DTH and antibody
Parasitic worms Antibody (atopic, ADCC) and
granulomatous reactions
Fungal DTH and granulomatous reactions
 How is a typical infection handled by the
immune system?
Release of antigens that
trigger innate immune
response (nonspecific)
Complement components
and released chemokines
Pathogen encounters a attract phagocytes and
Breach of a microenvironment natural killer cells
mechanical suitable for replication
barrier
After 4-5 days antigen
specific lymphocytes (T & B
Within the first 4 hours undergo clonal expansion
preformed effector
molecules limit expansion

As the agent is cleared, residual

effector cells and antibodies are left
along with immunologic memory
How does the location
of the microorganism • Adapted from: Elsevier’s Integrated Review of
affect the immune Immunology and Microbiology, 2012
response?
How do bacterial infections interact with
the immune system?
• Adapted from: Elsevier’s Integrated Review of Immunology and Microbiology, 2012
 How do mycobacterial infections
interact with the immune system?
How do viral
infections interact • Adapted from: Elsevier’s Integrated Review of
with the immune Immunology and Microbiology, 2012
system?
How do parasitic
infections interact • Adapted from: Elsevier’s Integrated Review of
with the immune Immunology and Microbiology, 2012
system?
 How do fungal infections interact
with the immune system?
• Associated with depressed immune reactivity (delayed type)
• Cellular immunity: Most important factor
• Mononuclear infiltrate and granulomatous reactions
• Th1: protective via release of IFN-γ
• Th2 (IL-4 and IL-10) correlate with disease exacerbation and pathology
• General rule: Fungi resistant to antibody and CMI is needed for effective
resistance.
 What immune
deviation (split
tolerance)?

• Dominance of one immune response

mechanism over another for a specific antigen
• Tendency of certain individuals to develop IgE
instead of IgG
• Tendency to make strong cellular immune
response but weak antibody response to
certain antigens and vice versa
• Example: Leprosy
What immune deviation (split
tolerance)?
 In general, how do pathogens evade the
immune response?
Pathogen Evasion of Immune Responses
Mechanism Examples
Localization in protective niches Latent syphilis, tapeworm (Echinococcus)
Intracellular location Histoplasmosis, herpes virus, varicella,
HIV
Antigenic modulation Malaria, trypanosomiasis, relapsing fever
Preservation of receptor sites after Influenza virus
reaction with antibody
Immunosuppression Malaria, measles, HIV, tuberculosis
(anergy)
Inappropriate immune response (immune Lepromatous leprosy, chronic
deviation) mucocutaneous candidiasis
What are the mechanisms used by infectious
organisms to avoid immune defenses?
 How do bacteria
evade the
phagocyte-
mediated killing?

• Secrete toxins to inhibit

chemotaxis
• Contain outer capsules
that block attachment
• Block intracellular fusion
with lysosomal
compartments
• Escape from the
phagosome to multiply in
the cytoplasm
 How do viruses
subvert the
immune
responses?

• Virally encoded proteins

can:
• Block effector function of
antibody binding
• Block complement-
mediated pathways
• Inhibit activation of infected
cells
• Downregulate major
histocompatibility complex
class I antigens to escape
CTL killing.
 Key points about
major immune
defense
mechanisms against
pathogens
• The host defense is based
upon availability of resources
to combat a localized
pathogen.
• Virtually all pathogens have an
extracellular phase during
which they are vulnerable to
antibody-mediated effector
mechanisms and complement
components, macrophage
phagocytosis, and
neutralization responses.
 Key points about
major immune
defense mechanisms
against pathogens

• Intracellular agents usually

require T lymphocytes
(helper and cytotoxic) and
NK cells, as well as T-cell–
dependent macrophage
activation, to kill
organisms.
• Pathogens can damage
host tissue by direct and
indirect mechanisms.
 Key points about
major immune
defense mechanisms
against pathogens

• The main immune mechanisms

against pathogens are:
bacterial, antibody
(immunocomplex and
cytotoxicity);
mycobacterial, DTH and
granulomatous reactions; viral,
antibody (neutralization), CTL,
and T helper; protozoal, DTH
and antibody; parasitic worms,
antibody (atopic, ADCC) and
granulomatous reactions;
fungal, DTH and granulomatous
reactions.
 Key
points • The response to initial infection is divided
into phases.
•
about The first phase is an early innate and
nonspecific response, in which preformed
effector cells and molecules recognize
immune microorganisms.

deviation
 Key points
about immune
deviation
• The next phase is again
primarily a nonspecific
encounter with the
organism, characterized by
recruitment of professional
phagocytes and NK cells to
the site of infection.
• The final phase involves
antigen-specific cell (B and T
lymphocyte) effectors that
undergo clonal expansion;
these cells provide memory
responses in case of
reinfection.
 Key points about
evasion of immune
response

• Virtually all classes of infectious agents

have devised ways to avoid host
defenses.
• Mechanisms include inaccessibility in
protective niches, antigenic
modulation of surface molecules, and
release of factors to either suppress
the immune response or cause
immune deviation and ineffective
response to the agent.