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Adaptive Defenses T Lymphocytes

Adaptive Defenses T Lymphocytes. T lymphocytes constitute the " cellular " arm of acquired/specific immunity T lymphocytes play a central role in controlling the acquired immune response

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Adaptive Defenses T Lymphocytes

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  1. Adaptive DefensesT Lymphocytes • T lymphocytes constitute the "cellular" arm ofacquired/specificimmunity • T lymphocytes play a central role in controlling the acquired immune response • Serve as crucial effector cells through antigen specific cytotoxic activity and the production of soluble mediators calledlymphokines(thecytokinesproduced by lymphocytes)

  2. Adaptive DefensesT Lymphocytes • There are two major subsets of T lymphocytes that differ ineffector function, MHC restrictionandaccessory moleculeusage • helper T cell (CD4+Tcells) • cytotoxic T cell (CD8+Tcells)

  3. Adaptive DefensesLymphocyte Functions • T cells • secrete lymphokines (cytokines) • help activate T cells • cause T cell proliferation • activate cytotoxic T cells • stimulate leukocyte production • stimulate B cells to mature • activate macrophages • secrete toxins that kill cells • secrete growth-inhibiting factors • secrete interferon • cellular immune response

  4. Adaptive Defensescytokines (Lymphokines) • Cytokines are basically polypeptide hormones • The term is often used to denote those molecules which are the products of cells of the immune system or which act upon such cells • In common with other hormones, cytokines exert their effects by binding to specific cell-surface receptors which signal to their target cells

  5. Adaptive Defensescytokines (Lymphokines) • Cytokinesact at very low concentrations • They are short-lived and may act locally, either on other cell types (paracrine)or on the same cell type (autocrine), or systemically (endocrine)

  6. Adaptive DefensesAntigen presentation • T cells must see antigen in the form of peptides bound to self MHC molecules • Class I MHC is adapted for mainly antigenes produced inside the cells • Class II MHC is specially adapted to present extracellular antigens

  7. Adaptive DefensesAntigen presentation • Three sets of cells can present antigens to T lymphocytes, which are named Antigen Presenting Cells (APCs) • APCs are Dendritic cells, activated Macrophages or B cells, which have both clas I and class II MHC

  8. Adaptive DefensesAntigen presentation • Most real antigen presentation situations require the binding to a receptor which triggers endocytosis • This receptor can be for complement or the Fc of IgG or it can be an innate, carbohydrate receptor on macrophages/dendritic cells. • In normal situations the critical antigen presenting cell (APC) is the dendritic cell

  9. Adaptive DefensesAntigen presentation • The role of dendritic cells is to act as antigen sensors • They recognize antigen via their innate (carbohydrate or complement) receptors • These receptors can trigger activation (upregulation of antigen presenting and accessory functions) and migration from the peripheral tissue to the lymph node via the afferent lymphatics

  10. Adaptive DefensesAntigen presentation • Within the lymph node the antigen presenting DC can interact with the many T cells constantly trafficking through. • Interact with MHC/peptide – TCR • The principal one which concerns us is the association of theCD28moleculeon the T cell with either of 2 ligandsB7.1 (CD80)andB7.2(CD86)molecule on the dendritic cell.

  11. Adaptive DefensesAntigen presentation • These molecules are termedaccessory moleculesand we know that the CD28 molecule delivers an essentialsecond signalto the T cell without which the T cell does not become activated (indeed it becomes unresponsive)

  12. CYTOKINES, T CELL SUBSETS • CD4+ helper T cells are capable of differentiating from an initial common state (TH)into 2 apparently distinct types called TH1and TH2. • These subtypes differ in their cytokine secretion

  13. CYTOKINES, T CELL SUBSETS

  14. CYTOKINES, T CELL SUBSETS • The commitment of TH0cells to become TH1 or TH2is influenced by cytokinessecreted by the 2 subtypes themselves and by macrophages , NK cells and mast cells as shown in the following diagram

  15. CYTOKINES, T CELL SUBSETS

  16. CYTOKINES, T CELL SUBSETS AND Ig ISOTYPE REGULATION • The outcome of this differentiation switch is to activate 2 different pathways of immunity which are associated with different antibody isotypes • The TH1pathway is essentially cell mediated immunity, with the activation of macrophages, NK cells, cytotoxic T cells and a prolonged inflammatory response • The cytokines secreted by TH1cells also boost production of IgG2a antibody production in mice

  17. CD4 T cell APC Th1 CD8 T cell Macrophage Adaptive Defenses Cellular Immunity Pathogens IFN-γ Cytotoxic activity IFN-γ Promastigotes Amastigotes

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