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Immunology molecular medicine 3

Immunology molecular medicine 3. Conleth Feighery. Learning objectives. T cell binding to APC essential for T cell stimulation T cell cytokines – determine their effect APC use pattern recognition receptors The structure of the T cell receptor. CYTOKINES.

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Immunology molecular medicine 3

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  1. Immunology molecular medicine 3 Conleth Feighery

  2. Learning objectives • T cell binding to APC essential for T cell stimulation • T cell cytokines – determine their effect • APC use pattern recognition receptors • The structure of the T cell receptor

  3. CYTOKINES Cells of the immune system ‘talk’ to each other by producing cytokines - like ‘text messages’ informing cells what their function should be!

  4. CD4+ T cells - MHC II interaction T h APC cytokines

  5. CD4+ T cells interact with APC and other cells by releasing cytokines. APC also release cytokines. T h APC cytokines The type of cytokines that are released are crucial to the type of immune response which results

  6. Cytokine products of cells T h APC CD28 B7 IL-1 IL-2

  7. Cytokine product of cells T h APC CD28 B7 IL-1 IL-2 Cells interact through the production and release of cytokines - these bind to cells and affect their function

  8. Cytokine products of cells T h APC IL-1 Receptors - cytokines bind to specific cell receptors IL-2

  9. Cytokines • Small protein molecules c. 20,000 aa • Specific types produced by different cells • Bind to cells and affect cell function • Some are called “interleukins” or IL

  10. IL-1 helps T cell activation T h APC IL-1 produced by APC

  11. T cell co-stimulation Essential to T cell activation, division and replication

  12. Activation of T cells • Requires 2 signals • Signal 1 - TCR, MHC, antigen • Signal 2 - CD28 binding to B7 • Both signals must be from the same APC • ONLY now can T cell proliferation start

  13. CD4+ T cells - activation requires 2 signals CD4 T h APC B7 CD28 T cell receptor binding to antigen = signal 1 CD28 binds to B7 = signal 2

  14. Stimulated T cell - IL-2 produced CD4 T h APC IL-2 receptor B7 CD28 IL-2 IL-2 binds to receptor on cell - causes cell growth, division

  15. IL-2 required for T cell growth T h APC CD28 B7 IL-2

  16. CTLA-4 - negative signal CD4 T h APC B7 CTLA-4 T cell receptor binding to antigen = signal 1 CTLA-4 binds to B7 - inhibits stimulation

  17. T cell cytokines affect B cells B T h IL-4,5,6

  18. T cell cytokines affect B cells B T h IL-4, 5 and 6 all involved in B cell stimulation and Ig production IL-4, IL-5, IL-6

  19. Lymph node - cartoon Alberts et al. T cell activation takes place in lymph node tissue T cell help for B cells takes place in lymph. follicles

  20. Lymph node - histology Lymphoid follicles

  21. Interferon gamma helps kill intracellular infections T h MO TB IFN-g activates macrophage killing mechanisms Interferon - gamma IFN-g

  22. T cytotoxic cell - recognition of antigen, role of CD8 CD8 virus T cytx APC Target cell MHC I T cytotoxic cell reacting with virus antigen presented by MHC class I molecule

  23. CD8+ T cells can kill target cells by inserting a ‘perforating hole’ in the cell, through which enzymes enter, damaging the cell CD8 TARGET CELL T cytx APC • perforin • enzymes

  24. T cytotoxic cell - cytolytic mechanism Lytic granules virus Granules - content perforin, enzymes T cytx APC Target cell perforin Enzymes, water, salts

  25. Pattern recognition receptors TOLL Stimulus APC Various stimuli bind to receptors on APC and influence APC reaction

  26. Pattern recognition receptors Toll-like receptors Stimulus B7 Different cytokines APC Various stimuli bind to receptors on APC and influence APC reaction

  27. APC –effect on T cell response Stimulus TH 1 IFN-g TH 2 APC IL-4 T reg IL-10

  28. APC - effect on T cell response Stimulus TH 1 IFN-g TH 2 IL-4 APC T reg IL-10

  29. Cytokines and T cells • Depending on the antigen, APC may produce different sets of cytokines • These cytokines determine the type of T cell that proliferates • Different types of T cells produce specific sets of cytokines

  30. Structure of molecules of IS • T cell receptor or TCR • MHC class I • MHC class II • Antibody molecules Knowledge of these structures is helpful in understanding how immune system functions

  31. TCR - alpha, beta chains constant region variable region alpha chain beta chain variable region

  32. T cell receptor structure Alberts et al.

  33. TCR - gamma, delta chains constant region variable region gamma chain delta chain variable region

  34. Immunoglobulin super-family Alberts et al. Many molecules in the immune system have an Ig-like structure and hence, belong to the “Ig superfamily”.

  35. MHC I and II structure Alberts et al.

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