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Unit 2 seminar: Adaptive immunity T & B lymphocytes

Unit 2 seminar: Adaptive immunity T & B lymphocytes. Reminders: -Use references in discussion and be sure to rephrase information in your own words -Evaluate the quality of reference materials before using. T lymphocytes (T cells). Develop in the thymus

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Unit 2 seminar: Adaptive immunity T & B lymphocytes

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  1. Unit 2 seminar:Adaptive immunityT & B lymphocytes Reminders: -Use references in discussion and be sure to rephrase information in your own words -Evaluate the quality of reference materials before using

  2. T lymphocytes (T cells) • Develop in the thymus • Stem cells from bone marrow migrate to thymus in fetal life • Early thymocytes develop from stem cells in the thymus cortex • Late thymocytes develop from early thymocytes in the thymus medulla • T cells develop from late thymocytes in the medulla • Maturation and release occurs along with the training to differentiate self from non-self • Positive selection • Negative selection (apoptosis)

  3. T cells - TCR complex • TCR ( T Cell Receptor complex) • T cell receptor- antigen specific - • Has 2 chains - a & b • Has constant and variable domains • Structure like immunoglobulin light chain • CD3 receptor- carries signal from the cell membrane to the cell cytoplasm • CD4 or CD8 receptors- determine the function of T cell

  4. T cell receptor • Antigen specific receptor on T cell • Heterodimer (a &b) chains- • Two external domains each- Ca, Cb , Va and Vb • a transmembrane segment • Cytoplasmic extension

  5. CD receptors • T cell differentiation markers (CD= Cluster of Differentiation) • Mature T cells- 4 important types • CD2, CD3, CD4 and CD8 • CD2- Present on all peripheral T cells • receptor for attachment to cells • CD3 - Associated with TCR • consists of 5 molecules (g,d,e and two z) • Transduces signals across the membrane.

  6. CD receptors ( Contd.) • CD4 receptors • present mainly on T helper cells • Interact with MHC class II antigens • target for HIV ( AIDS virus) • CD8 receptors • present mainly on T-cytotoxic and T suppressor cells • recognize MHC class I antigen

  7. Other accessory molecules of T cells • CD 28- Costimulation- signal transduction • CTLA-4:Signal transduction • LFA-1: Adhesion • VLA-4: Adhesion

  8. T cell accessory molecules (Fig 5-3 B)

  9. Antigen doesn’t bind directly to TCR.T cell receptor and CD receptor work together to interact with peptide (from antigen processing) and MHC molecules

  10. T cell - subtypes • T helper/inducer cells ( TH) • T suppressor cells ( Ts) • T cytotoxic cells (CTL or Killer cells) • T cells involved in Delayed type of hypersensitivity( T DTH ) • T memory cells ( Usually a subset of T helper cells)

  11. T helper/inducer cell • CD4 receptor • Function- • Recognize antigen epitope in conjunction with MHC class II antigen • Reacts with IL1 (interleukin-1) from macrophages • Produces IL2 and expresses IL2 receptors • Is activated by IL2 • Stimulate B cell growth and differentiation with a variety of lymphokines.

  12. T suppressor cell • Has CD8 receptors • Function- • Interacts with MHC class I receptors on the cells • Inhibits and regulates B cell differentiation into plasma cells • Activated by products of T helper cells , IL2.

  13. T cytotoxic cells (Tc) • Killer cells • Possess CD 8 receptors • Function • Cell mediated cytotoxicity • Develop after IL2 activation • require MHC class I receptors for recognition of foreign antigen

  14. TDTH- Delayed Type of Hypersensitivity • Possess CD4 receptors • Require lymphokines for their activation ( IL1, IL2 and g interferon) • Function • Immunity against • Fungi • Mycobacterium leprae • Chronic infections • Delayed type of hypersensitivity • Major component of granulomatous lesions.

  15. B lymphocytes • Develop from stem cells in Bone marrow • Unique S-Ig receptor for antigen ( can be of any type of Ig) • Differentiate into Plasma cells for production of antibodies. • Receptors- Surface Immunoglobulin • 100,000 copies per cell • undergoes capping and endocytosis after combining with antigen

  16. Plasma cell • Terminally differentiated B cells • Ovoid shape eccentric spoke-wheel nucleus • Intensely basophilic cytoplasm • Average life span less than 4 days • Mostly present in lymphoid tissues • Produce only one type of antibody

  17. Normal circulation of lymphocytes and other immune cells • Lymphocytes and macrophages do circulate through different organs. Lymphocytes are the only cells allowed in the CNS • But they tend to localize back into the sites they originated from, with the help of lymphocytic homing molecules or vessel addressins

  18. Points to discuss • Definition • Types of cytokines • Sources of cytokines • Chemokines • Interferons • Interleukins • Tumor Necrosis Factors • Cytokine receptors • Therapeutic applications of cytokines

  19. Cytokine- Definition & General properties • Cytokines are low molecular weight proteins which act as intercellular communication molecules. • They mostly act in autocrine and paracrine manner. A few may act in an endocrine manner. • They are produced mainly by immune system cells but can also be produced by many other cells.

  20. Types of cytokines • Most of these are generally called cytokines • If they are produced by lymphocytes predominantly, they are sometimes referred to as Lymphokines • If they are produced by monocytes predominantly, they are sometimes referred to as Monokines

  21. Types of cytokines • Chemokines- involved in chemotaxis • Interferons- Inhibitory factors • Interleukins- Mostly cell messenger function • Tumor necrosis factors- mainly apoptosis signals or cell lytic function • Colony stimulating factors (CSFs) • Sometimes interleukins and CSFs are included in a broader family of hematopoietins

  22. Chemokines • Chemokines- The cytokines which aid in chemotaxis of phagocytes mainly. • Examples • IL8, TNF-alpha - for neutrophils • MIP-beta : for macrophages

  23. Interferons • 3 types • Alpha IFN & Beta IFN - secreted by leukocytes , fibroblasts and other cells infected by a virus • make the host cells resistant to viral invasion and inhibits viral multiplication • Gamma IFN - secreted by lymphocytes to activate the macrophages to enhance intracellular killing.

  24. Interleukins • So far IL 1 to IL 25 have been significantly characterized. Many more are being investigated. • A few key interleukins are IL1, IL2, IL4 and related interleukins. • Many of these can induce acute phase reactants from liver

  25. Interleukin 1 • Secreted mainly by macrophages, also by endothelium and epithelial cells • Endogenous pyrogen- fever –signals hypothalamus • Lymphocyte proliferation and activation • Expression of selectins by endothelial cells and increased adhesion of leukocytes

  26. Interleukin 2 • Secreted by activated lymphocytes (TH1) • autocrine and paracrine action • T helper cell proliferation • T cytotoxic cell activation & proliferation • Natural Killer cell activation

  27. Interleukin 4 family(IL4,5,10,14) • Secreted by T lymphocytes and mast cells • Predominant in TH 2 responses • Stimulate IgE production (esp. IL 5) • involved in allergic phenomena

  28. Interleukin 6 • Secreted by activated T cells, monocytes, fibroblasts and endothelial cells • Progenitor cell stimulation • Platelet production • Immunoglobulin production in B cells.

  29. Tumor necrosis factors • TNF alpha- • Secreted by macrophages, lymphocytes and other cells • Chemotactic for neutrophils • Inflammation and fever • Cytotoxic for some tumor cells • TNF beta- • T lymphocytes (esp. T cytotoxic cells) and natural killer cells • Cytotoxic for target cells

  30. Cytokine receptors • Many different types • One receptor can interact with many different cytokines • One cytokine can interact with different receptors • when a cytokine attaches to a receptor it will induce intracellular messenger which in turn can induce gene transcription change.

  31. Examples of Cytokine receptors • Interleukin receptors e.g. IL2R • TNF receptor family • Interferon receptor family • Immunoglobulin family • Chemokine receptor family.

  32. Therapeutic uses of cytokines • Receptor antagonists- antibodies or mimic molecules- rheumatoid arthritis e.g Enbrel, Remicade • Interferons- Hepatitis B, C, Kaposi’s sarcoma, Multiple sclerosis, melanoma • Colony stimulating factors- After bone marrow transplants

  33. Development of T Lymphocytes (Fig 4-13)

  34. T cell receptor (Fig. 4-5)

  35. Recognition of a peptide epitope nestled in MHC class I molecule by TCR

  36. Maturation of lymphocytes (Fig 4-8)

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