1. Chapter 16
Immunity to Microbes

2. 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

5. IMMUNITY TO EXTRACELLULAR BACTERIA

6. Immunity to Extracellular Bacteria

7. 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

8. Adaptive Immune System to Extracellular Bacteria

9. 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 lL- 12 may also contribute

10. Bacterial Super -Antigen
Staph. Aureus (SEA-E), TSST, Mycoplasma (Exotoxins), Streptococci (Endotoxins)
Entrotoxin bind to the Vβ region of TCR and MHC class II

11. Polyclonal activation of T cells by bacterial superantigens

12. Immunity to Intracellular Bacteria
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13. Innate and Adaptive Immunity to Intracellular Bacteria

14. Cooperation of CD4+ and CD8+ cells in Defense
Against Intracellular Microbes
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15. T Cells and Cytokines Role in Infection Outcome
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16. 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)

17. Mechanisms of Immune Evasion by Bacteria

19. Immunity to Fungi

20. 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)

21. 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

22. Cell-mediated immunity is the major mechanism of adaptive immunity against fungal infections
Histoplasma capsulatum, C. neoformans and Pneumocystis jiroveci facultative intracellular parasite
Many extracellular fungi elicit strong TH17 responses
Individuals with defective TH17 responses are susceptible to chronic mucocutaneous Candida infections

23. Immunity to Viruses

24. Antiviral state by IFN type I
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

25. Innate and Adaptive Immune Responses to Viruses
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26. Innate and Adaptive Immune Responses to Viruses
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27. Mechanisms of Immune Evasion by Viruses

30. Immunity to parasites

31. to protozoa and helminths is phagocytosis but may resist
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)

32. Immune Responses to Disease-Causing Parasites

33. Mechanisms of Immune Evasion by Parasites

34. STRATEGIES FOR VACCINE DEVELOPMENT

35. 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

36. Vaccines

37. 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

38. 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