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Immunity to Infection 101

Immunity to Infection 101. Why do you need a “course” in Immunology in order to understand parasitology? Because parasites invest a great deal of energy in avoiding the host immune response. Trypanosoma brucei. Trypanosoma cruzi. Crash course in Immunology: Major points:

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Immunity to Infection 101

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  1. Immunity to Infection 101

  2. Why do you need a “course” in Immunology in order to understand parasitology? Because parasites invest a great deal of energy in avoiding the host immune response

  3. Trypanosoma brucei

  4. Trypanosoma cruzi

  5. Crash course in Immunology: Major points: The immune system is a complex but understandable network of cells and secreted factors. This system is most easily understood by breaking it down into it component parts – keeping in mind that the parts are work together. The immune system has choices; an effective response to a pathogen requires that the immune system make the correct choices. Pathogens, including parasites, invest a great deal of energy in avoiding the host immune response.

  6. Defining characteristics of Immune System • Discriminates between self and non-self • Essentially unlimited capacity to respond specifically to non-self • Remembers non-self and responds more vigorously on subsequent encounters Immune system is probably evolved to deal with infections, to rid the body of infectious agents, and to prevent reinfection. Pathogens that it cannot get rid of are trouble.

  7. Immune system: Components Innate: macrophages: phagocytosis complement-mediated lysis skin, mucosa: barrier NK cells: altered or missing MHC neutrophils, eosinophils, mast cells dendritic cells Adaptive: T cells and B cells dependent on innate to get activated but are much more complex in part because of specificity

  8. Innate Immunity innate immunity is the initial response to microbes that prevents infections and in some cases eliminates pathogens the effector mechanisms of innate immunity are often used to eliminate microbes even in the adaptive response (innate often the first AND the end responders/effectors) innate immunity stimulates and directs adaptive responses

  9. Epithelial Barriers e.g. gamma/delta T cells, NK-T cells

  10. Exceptions – dead or dying cells

  11. Features of Innate Immune Recognition components of the innate immune response recognize structures unique to microbes and required for their survival (molecular patterns; pathogen associated molecular patterns = PAMPs) these “pattern recognition receptors” (PRR) of innate system are germ-line encoded (therefore not variable)

  12. Trinchieri and Sher Nature Reviews Immunology7, 179–190 (March 2007) | doi:10.1038/nri2038

  13. Phagocytosis

  14. Effector functions of macrophages

  15. Role of innate immune responses in defense 1. Local reaction to infection - inflammation - to bring effectors to the sites of infection 2. Systemic: endocrine actions of cytokines (e.g. fever, increased leukocyte production) note: both responses can be damaging Role of innate immune responses in stimulating adaptive responses activate and direct T cell and B cell response provide the “second signals” (pathogens which fail to activate innate responses generate poor acquired response)

  16. Innate and adaptive responses to intracellular pathogens

  17. Exceptions – dead or dying cells

  18. Phases of an adaptive immune response Proliferation

  19. Types of Adaptive Immunity

  20. cellular and humoral adaptive immunity humoral immunity: initiated by antigen recognition by B cells, mediated by antibodies and effective against extracellular pathogens or their (toxic) products cell-mediated immunity: initiated by antigen recognition by T cells, mediated by T cells and other downstream effectors (e.g. macrophages), effective against intracellular pathogens (also important in transplant rejection and tumor immunity)

  21. Effector functions of antibodies

  22. Overview of Immune Responses in vivo

  23. B Menu F

  24. IgA transport in the gut

  25. Effector function of antibodies Review points antibodies are produced by B cells and plasma cells and perform their effector functions at sites distant from their production - systemic prior antigen exposure results in the activation of long-lived plasma cells that continue to produce antibodies for many years, and memory cells which can be reactivated for increased production upon re-exposure.

  26. cellular and humoral adaptive immunity humoral immunity: initiated by antigen recognition by B cells, mediated by antibodies and effective against extracellular pathogens or their (toxic) products cell-mediated immunity: initiated by antigen recognition by T cells, mediated by T cells and other downstream effectors (e.g. macrophages), effective against intracellular pathogens (also important in transplant rejection and tumor immunity)

  27. Types of CMI: Different types of microbes elicit distinct T cell responses 1. T cell mediated macrophage activation (Th1 and CD8+ T cells): activation of phagocytes to kill vaculolarized microbes. Cytokine production recruits cells (monocytes) and activates them in the site of infection. Final effector is macrophage. DTH 2. Cytolytic T lymphocyte (CTL): lysis of cells with cytosolic pathogens: - final effector is the CTL itself. Purpose is to destroy cells harboring intracellular microbes - viruses, bacteria, protozoans. Cytokines production also important in many cases. 3. Th2 cells: response to helminth parasites: - especially mast/basophil and eosinophil mediated responses (allergy) 4. NK cell response - especially early in viral and other infections - role in destruction of infected cells prior to expansion of CTL. Also important in destruction of target cells which have down-regulated class I MHC.

  28. Antigens must be “presented” to T cells

  29. Pathways for Class II and Class I presentation of antigens

  30. Two of the primary differentiation pathways of naïve CD4+ T cells: Th1 and Th2 Signature Th2 cytokines (IL-4) Signature Th1 cytokine Although chronically stimulated T cells tend to have this simplified dichotomy, actually much more complicated – CD4 T cells are much more heterogeneous than just Th1/Th2

  31. Differentiation of Th1 and Th2 cells The Th1/Th2 fate is determined by stimuli present early during the activation of naïve T cells Mice lacking IL-12, IL-12R, or Stat 4 fail to make Th1 responses – amplification loop

  32. Th1 and Th2 cells determine outcome of infection

  33. Reciprocal regulation of Th17 versus Tr/Treg

  34. CTL-mediated lysis (delivery of the “lethal hit”) Requires primed CD8 cell CD8, LFA-1 and TCR But no costimulation required Formation of immunological synapse

  35. Immunity to Microbes • Defense against microbes is mediated by innate and adaptive immunity • Response is specialized for particular pathogens • Survival of pathogens is dependent on immune evasion • Tissue injury may result from response to microbe

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