MMI 301-Exam 2-Lecture 10: Innate Immunity

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MMI 301-Exam 2-Lecture 10: Innate Immunity
2013-10-25 16:48:06

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  1. Antigen
    • -molecule with ability to stimulate immune response
    • -i.e. foreign protein, polysaccharide, or lipid
  2. Epitope
    the part of an antigen that is bound by a specific antibody/T-cell receptor
  3. Cytokines
    -proteins used as signaling molecules or as chemoattractants for leukocytes
  4. Micro-Organism
    • -Local proliferation (Phagocytes, Complement lysis and metabolite transport blocked)
    • -Invasion (Antibody to aggressions, antibody to organism, complement lysis, phagocyte)
    • -Toxin production (antibody to toxin)
    • -Intracellular growth (Chronic infection) (Cell-mediated immunity)
  5. Cytokines and Chemokines (Interleukins)
    • -IL-6: proinflammatory, made in
    • response to bacterial products, Induces acute phase of response in liver,
    • promotes B-cell proliferation
    • -IL-12: Heterodimer of IL-12
    • alpha/beta, disulphide linked, promotes conversion Th0->Th1
    • -IFN-γ: Activates macrophages and T-cells, produces by Th1/NK cells
  6. Macrophages and Cytokines
    • -Important component of innate and adaptive immune response
    • -Important antibacterial phagocytic cell
    • -Produce IL-1, IL-6, IL-12, TNF-α/β and interferon-α
    • -Activation of acute-phase and inflammation responses
    • -Presentation of antigen to CD4 T cell
  7. T-cells Recognize Antigens in Presence of:
    MHC Class I/II
  8. B cells and T cells proliferate in response to
    Specific antigens
  9. Postulates of Lymphocyte Clonal Selection hypothesis
    • -Each lymphocyte bears a single type receptor of a unique specificity
    • -Interaction between a foreign
    • molecule with high affinity leads to lymphocyte activation
    • -Differentiated effector cells derived
    • from activated lymphocyte bear receptors of identical specificity to those of
    • parental cell from which that lymphocyte was derived
    • -Lymphocytes bearing receptors
    • specific for self molecules are deleted at an early stage in lymphoid cell
    • development and are therefore absent from the repertoire of mature lymphocytes.
  10. T-cell precursors/B-cell originate in
    Bone Marrow
  11. T cells selected for in
  12. Self-Tolerance
    • -In Thymic medulla
    • -Includes at least two cell populations
    • -Medullary thymic epithelial cells (mTECs): Delete self-antigens
    • -Haematopoietic antigen-presenting cells (APCs): Deletes but needs help
  13. Recognition of antigen bound MHC class II
    • -Along with a second signal from the APC
    • -Leads to conversion of Th0 cells to Th1 or Th2 effector cells:
    • -Pathogen binds APC
    • -Antigens fed to naïve T cell via MHC/TCR, naïve T cell become effector
    • -Cytokines released from APC go to effector
  14. Five Classes of Antibodies
    IgM, IgG, IgA, IgE, IgD
  15. IgM
    • Intravascular;
    • -complement activation, agglutination (5 IgGs)
    • -Mainly in bloodstream, B-cell
    • surface, responses to polysaccharides in bacterial surfaces
    • -First responder
  16. IgG
    • Intravascular Interstitial fluid,
    • Transplacental complement activation, Neutralization, opsonization, Immunity to neonate
    • -Bloodstream and extracellular, can get
    • to mucous membranes, most abundant
    • -Bulk of secondary response
  17. IgA
    • Luminal secretions, Breast milk
    • Neutralization at body surface,
    • Intestinal immunity in neonates (2 IgGs)
    • -Protects gut, respiratory tract, other
    • secretory surfaces such as tear ducts
  18. IgE
    • Subcutaneous Submucosal;
    • -Mast-cell sensitization, Eosinophil activation
    • -Mainly bound to mast cells, involved
    • in allergic response
  19. IgD
    • B-cell surface
    • -Not known (B-cellantigen receptor)
    • -Helps initiate B-cell response
  20. T-independent Response
    • -Does not require T-cells for B-cell proliferation
    • -Shorter lived/weaker response then T-dependent responses
    • -No isotype switching (get IgM)
    • -B-cells become plasma cells, release cytokines
  21. T-dependent Response
    • -Requires T-cells for B-cell proliferation
    • -T-cell signals using cytokines IL-2, IL-4, IL-5
    • -Get isotype switching to IgG, IgA, IgE
    • -Get stronger response and memory response
  22. Antibodies
    • -Binding to surface structures of bacteria (pili, lipoteichoic acid, capsule)
    • -Blocking of attachment
    • -Opsonization
    • -Promotion of complement action
    • -Promotion of clearance of bacteria
    • -Neutralization of toxins and toxic enzymes
  23. Candidates for Vaccination
    • -Causes significant illness
    • -Exists as only one Serotype
    • -Antibody blocks infection/systemic spread
    • -Organism does not have oncogenic potential
    • -Vaccine is heat-stable so can be transported to endemic areas
  24. What do Vaccine Do
    • -Neutralize toxins (diphtheria and tetanus)
    • -Prevent adherence (experimental cholera vaccine)
    • -Opsonize encapsulated organisms (pneumonia, influenza)
  25. Why Can Vaccines not work
    • -Pathogens rapidly change surface structure
    • -Immune responses can elicit damaging sequelae
  26. Properties of Good Vaccine
    • -Generate rapid memory response without disease symptoms
    • -Elicit strong response in vaccine (adjuvants)
    • -Correct immune response is elicited
    • -systemic vrs. mucosal
    • -antibody vrs. T cell
    • -reasonable cost
    • -safe
    • -Live vaccine better than inactivated
    • -Not storable, can be more volatile in response