Chapter 16
Immunity to Microbes
Important General Features of Immunity to Microbes

Defense against microbes is mediated by the effector mechanisms of
innate and adaptive immunity

The immune system responds in specialized and distinct ways to different
types of microbes to most effectively combat these infectious agents

Survival and pathogenicity of microbes in a host are critically influenced
by the ability of the microbes to evade or resist the effector mechanisms
of immunity

Many microbes establish latent, or persistent, infections in which the
immune response controls but does not eliminate the microbe and the
microbe survives without propagating the infection

Tissue injury and disease may be caused by the host response
 IMMUNITY TO EXTRACELLULAR BACTERIA
Immunity to Extracellular Bacteria
Innate Immunity to Extracellular Bacteria

Principal mechanisms of innate immunity to extracellular bacteria are
complement activation, phagocytosis, and the inflammatory response

Toll-like receptors (TLRs) of phagocytes participate in the activation of
the phagocytes as a result of encounter with microbes

Cytokines also induce the systemic manifestations of infection, including
fever and the synthesis of acute-phase proteins
Adaptive Immune System to Extracellular Bacteria
Injurious Effects of Immune Responses

Principal injurious consequences of host responses to extracellular
bacteria are inflammation and septic shock

Septic shock is a severe pathologic consequence of disseminated infection
by gram-negative and some gram-positive bacteria

TNF is the principal cytokine mediator of septic shock, but IFN-γ and lL12 may also contribute
Bacterial Super -Antigen

Staph. Aureus (SEA-E), TSST, Mycoplasma (Exotoxins), Streptococci
(Endotoxins)

Entrotoxin bind to the Vβ region of TCR and MHC class II
Polyclonal activation of T cells by bacterial superantigens
Immunity to Intracellular Bacteria
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Innate and Adaptive Immunity to Intracellular Bacteria
Cooperation of CD4+ and CD8+ cells in Defense
Against Intracellular Microbes
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T Cells and Cytokines Role in Infection Outcome
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Immunity to Tb

Mycobacteria are slow-growing, aerobic , facultative intracellular bacilli
whose cell walls contain high concentrations of lipids

BCG ( bacillus Calmette-Guerin) used as a vaccine against Tb

CD4+ T cells, IFNγ, TNF

DTH & Granuloma & Caseous necrosis

PPD (purified protein derivative)
Mechanisms of Immune Evasion by Bacteria
Immunity to Fungi

Fingi infection called mycoses are important causes of morbidity and
mortality in humans

Compromised immunity is the most important predisposing factor
(opportunistic infection)

The principal mediators of Innate Immunity are neutrophils and
macrophages (neutropenia)

Phagocytes and dendritic cells sense fungal organisms by TLRs and
lectin-like receptors called dectins

Neutrophils presumably liberate fungicidal substances, such as reactive
oxygen species and lysosomal enzymes, and phagocytose fungi for
intracellular killing

Cell-mediated immunity is the major mechanism of adaptive immunity
against fungal infections

Histoplasma capsulatum, C. neoformans
facultative intracellular parasite

Many extracellular fungi elicit strong TH17 responses

Individuals with defective TH17 responses are susceptible to chronic
mucocutaneous Candida infections
and Pneumocystis jiroveci
Immunity to Viruses

Viruses are obligatory intracellular microorganism

Cytopathic effect of viruses

Innate immunity to viruses:


Antiviral state by IFN type I

NK cell-mediated killing
Adaptive immunity to viruses:

Antibodies
 CTL & cross priming
Innate and Adaptive Immune Responses to Viruses
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Innate and Adaptive Immune Responses to Viruses
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Mechanisms of Immune Evasion by Viruses
Immunity to parasites

Parasitic infection such as protozoa, helminths, and ectoparasites (ticks
and mites)

Innate immunity to parasites:
 to protozoa and helminths is phagocytosis but may resist


activate the alternative pathway of complement
Adaptive immunity to parasites:
 to protozoa is macrophage activation by Th1 cell-derived cytokines
 to helminths is Th2 cells and IgE and activation of eosinophils then secrete
MBP that is severe toxin for helminths

Tissue injury after Adaptive immune responses (as fibrosis)
Immune Responses to Disease-Causing Parasites
Mechanisms of Immune Evasion by Parasites
STRATEGIES FOR
VACCINE DEVELOPMENT

The birth of immunology as a science dates from Edward Jenner's
successful vaccination against smallpox in 1796

The success of active immunization in eradicating infectious disease is
dependent on numerous factors:


Vaccines are effective if the infectious agent does not establish latency, if it does
not undergo much or any antigenic variation, and if it does not interfere with
the host immune response
limited to human hosts, and do not have animal reservoirs
Vaccines
Adjuvants and Immunomodulators

Most adjuvants elicit innate immune responses, with increased expression
of costimulators and production of cytokines such as IL-12 that stimulate
T cell growth and differentiation

Heat-killed bacteria are powerful adjuvants that are commonly used in
experimental animals with severe local inflammation

Several are in clinical practice, including aluminum hydroxide gel (which
appears to promote B cell responses) and lipid formulations that are
ingested by phagocytes

IL-12 incorporated in vaccines promotes strong CMI

plasmid DNA has intrinsic adjuvant-like activities, and it is possible to
incorporate costimulators (e.g., B7 molecules) or cytokines
Passive Immunization

Passive immunity is short-lived because the host does not respond to the
immunization and protection lasts only as long as the injected antibody
persists

In the clinical situation, passive immunization is most commonly used for
rapid treatment of potentially fatal diseases caused by toxins, such as
tetanus, and for protection from rabies and hepatitis

Passive immunization does not induce memory, so an immunized
individual is not protected against subsequent exposure to the toxin or
microbe