Module 6

• Solutions to the anticipatory problem of immunity

  Intrinsic defenses

  Innate Immune System

  Adaptive Immune system
• Intrinsic defenses


  - First line, always active

  - No specificity

  - No memory
• Innate Immune System


  - rapid response

  - limited specificity due to limited number of germline encoded PRRs

  -No memory
• Adaptive Immune System


  -Slower response

  -Very high specificity due to generation of diversity in individual lymphocyte clones

  -memory response generated
• Adaptive Immunity


  Cell mediated

  humoral
• Humoral Immunity


  B cells

  Helper T cells (CD4+)

  antibodies
• Cell Mediated Immunity


  Cytotoxic T cells (CD8+)

  Helper T cells (CD4+)
• Adaptive Immune cells


  The components of the adaptive immune system are lymphocytes and their products
• True


  Both b and T cells express very specific receptors that usually recognize only one epitope per cell
• B cell effector function


  Antibody production
• T cell effector function

  Helper or cytotoxic T cells
• Antigen


  Any molecule that can be specifically recognized by the adaptive elements of the immune system
• Antigenicity


  Ability to stimulate an immune response
• Epitope


  Part of the antigen that is recognized by the immune system
• Primary Antibody Response


  - first time antigen is encountered

  -initial lag phase

  -IgM early and often mostly

  -Relatively low total antibody

  -typically short lived, declines
• Secondary antibody response


  -subsequent encounters with previously seen antigen

  -rapid response

  - Mostly IgG

  - greater total antibody production

  - longer lived (months-years)
• Hypersensitivity


  Immune response with an inappropriate or overzealous response
• Type I (Immediate) Hypersensitivity


  Immune mechanism: IgE

  Antigen: Allergens
• Type II (antibody mediated) hypersensitivity


  Immune mechanism: IgM, IgG

  Antigen: Cell or ECM antigens
• Type III (immune complex) hypersensitivity


  Immune mechanism: IgM, IgG

  Antigen: Soluble antigens
• Type IV (cell mediated) hypersensitivity


  Immune mechanism: T lymphocytes

  Antigen: Cell-associated and some soluble antigens
• Urticaria


  Hives
• Angioedema


  Facial swelling
• Anaphylaxis


  Type I hypersensitivity on a systemic scale
• Respiratory anaphylaxis


  Rapid decrease in blood pressure

  bronchoconstriction

  pulmonary edema

  cows, horses, humans
• Visceral anaphylaxis


  Rapid constriction in abdominal vasculature leads to rapid decrease in blood pressure

  dogs, cats, pigs
• Atopy


  hypersensitive or allergic state involving an inherited predisposition
• Superantigen T cell activation

  No processing by APC required

  MHC-II positive cells required but not antigen restricted

  Massive proportion of T cells activated

  not well regulated
• Autoimmune disease


  The immune system mistakenly targets the own host's cells and tissues
• Tolerance


  Unresponsiveness to an antigen induced by exposure to that antigen
• Self tolerance


  Normal individuals are tolerant to their own antigens
• Central tolerance


  Primary lymphoid tissues, deletion of self-reactive lymphocytes
• Peripheral tolerance


  Secondary lymphoid tissues, induced lack of activation of self-reactive lymphocytes (anergy) or apoptosis of self-reactive lymphocytes that encounter self antigens
• True


  Failure of self tolerance leads to autoimmune disease
• General mechanisms of failure of tolerance

  Genetic susceptibility

  activation of autoreactive T cells

  exposure off hidden antigens/epitopes
• Failure of self-tolerance genetics


  Evidence for genetic susceptibility

  - clusetering in families

  -higher concordance in monozygotic twins

  -higher prevalence in specific ethnic groups
• True


  Most autoimmune diseases are polygenic
• True


  Infectious agents can induce loss of self-tolerance by several mechanisms
• Failure of self-tolerance - immune dysregulation

  Central tolerance is inefficient, autoreactive immune cells are largely, but not entirely eliminated
• Mechanisms of autoimmune damage


  Circulating autoantibodies, t lymphocytes, non-specific