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Topics. T cell mediated immunity Part II Effector T cells Binding and secretion of effector molecules CD8 T cell function CD 4 T cell function Cytokines T H 1 effector functions. Effector T cells. Adhesion molecules allow for longer cell-cell interaction

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  1. Topics • T cell mediated immunity Part II • Effector T cells • Binding and secretion of effector molecules • CD8 T cell function • CD 4 T cell function • Cytokines • TH 1 effector functions MICR 415 / 515 / 682

  2. Effector T cells MICR 415 / 515 / 682

  3. Adhesion molecules allow for longer cell-cell interaction • CD4 cells bind to target cells for a long time • CD8 T cells bind to targets cells for short periods, kills target cell, then detaches and binds to another cell MICR 415 / 515 / 682

  4. Binding leads to clustering of receptors • Polarization: • Reorganization of cortical actin cytoskeleton at site of contact • Reorientation of microtubule reorganizing center • Relocalization of Golgi apparatus • Exocytosis at site of contact (tight space) • Detachment x Fig 8.28 MICR 415 / 515 / 682

  5. Two types of effector molecules: • Cytotoxins • Cytokines Fig 8.28 MICR 415 / 515 / 682

  6. Cytotoxins • Soluble secreted factors • perforin • granzyme • Membrane associated factors • Fas Ligand MICR 415 / 515 / 682

  7. Cytokines • Small secreted soluble molecules that can change the behavior or properties of the cell itself or of another cell • Multiple effects in different types of cells • Synergism • Lymphocytes = lymphokines • T cell = Interleukines • Chemoattractants = chemokines • Studied by in vitro assays or gene disruption MICR 415 / 515 / 682

  8. Types of effector T cells CTL Cytotoxic T cells CD8 MHC I recognition Kill viral infected cells Kill Transformed cells Th1 CD4 MHC II recognition Activation of macrophages Th2 CD4 MHC II recognition Activation of B cells MICR 415 / 515 / 682

  9. Effector Molecules MICR 415 / 515 / 682

  10. CD8 T cells MICR 415 / 515 / 682

  11. The kiss of death MICR 415 / 515 / 682

  12. CTL effector molecules • Perforin: forms a pore in membrane • Granzymes: Serine proteases, activate apoptosis • Fas ligand: activates apoptosis • IFN-: inhibits viral replication, up-regulate MHC I expression, activates macrophages • TNF- TNF-: synergizes with IFN-, induce apoptosis MICR 415 / 515 / 682

  13. Cytotoxic T cells are selective MICR 415 / 515 / 682

  14. CD4 T cells TH 0 TH 1 & TH 2 MICR 415 / 515 / 682

  15. Differentiation of CD4 cells • Initial response mounted by the innate non-specific immune response is important in this process • Cytokines elicited by infectious agents • Molecules used for co-stimulation • Nature of MHC:peptide ligand MICR 415 / 515 / 682

  16. Main Th1 cytokines • IL-2 (Th 0, Th1, CTL) • Growth of T cells • Growth of NK cells • IFN- (Th1, CTL) • Increase MHC I & II • Inhibits Th2 cell growth • Activates macrophages • B cell differentiation, IgG2a synthesis • Activates NK cells Figure 8:31, appendix 2 MICR 415 / 515 / 682

  17. Main Th2 cytokines • IL-4 (Th2) • B cell activation and growth • Th2 growth and survival • Increase MHC II • IgG1, IgE • Decreases macrophage activation • IL-5 (Th2) • IgA • increase eosinophils • IL-10 (Th2) • Increase MHC II • Inhibit Th1 cell growth MICR 415 / 515 / 682

  18. other cytokines • IL-3 (Th1, Th2, CTL) • Stimulates hematopoiesis • TNF- (Th1, some Th2, CTL) • Activates macrophages (synergy with IFN-) • production of NO • GM-CSF (Th1, Th2, CTL) • Increase granulocyte production • Increase macrophage and dendritic cell production MICR 415 / 515 / 682

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  22. Th1 Th2 Anti-IL-4 IL-4 Resistant Susceptible Th 2 Th1 Susceptible Resistant Consequences of Th1 or Th2 Leishmania sp MICR 415 / 515 / 682

  23. Macrophage activation • Requires 2 signals: • IFN -gamma • CD40 or • membrane bound TNF alpha or beta • Stimulation via TCR triggers novo protein synthesis • Proteins are delivered to the site of contact by vesicles • Signals are delivered directly to that macrophage MICR 415 / 515 / 682

  24. Increase fusion of lysosomes and phagosomes to form phagolysosomes • Increase oxygen radicals and Nitric Oxide production • Increase expression of B7, CD40, MHC II & TNF receptors • Production of IL-12 (stimulates Th1 cells) • Recruitment of other cells • More effective killing • Better APC Activated macrophage MICR 415 / 515 / 682

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