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T LYMPHOCYTES

بسم الله الرحمن الرحيم. T LYMPHOCYTES. Dr. Shaikh Mujeeb Ahmed Assistant professor Physiology Al Maarefa College . T (thymic) Lymphocytes. Lymphocytes migrate from bone marrow to the thymus for preprocessing to form “T” lymphocytes Preprocessing in the thymus :

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T LYMPHOCYTES

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  1. بسم الله الرحمن الرحيم T LYMPHOCYTES Dr. Shaikh Mujeeb Ahmed Assistant professor Physiology Al Maarefa College

  2. T (thymic) Lymphocytes • Lymphocytes migrate from bone marrow to the thymus for preprocessing to form “T” lymphocytes • Preprocessing in the thymus : • Cells divide rapidly - each thymic lymphocyte developing specific reactivity for one antigen • End result: thousands of T lymphocytes each with different specific reactivities for different antigens • Insuring that each T lymphocyte will not react with the body’s own antigens (self antigen) • Then the preprocessed cells leave thymus to lymphoid tissues • Most preprocessing of T lymphocytes occurs prior to and completely after birth

  3. T Lymphocytes • Carry out cell-mediated immunity • Clonal and antigen specific – acquire receptors in the thymus • T cells are activated for foreign attack only when it is on the surface of a cell that carries foreign and self antigens • Learn to recognize foreign antigens only in combination with a person’s own tissue antigens • A few days are required before T cells are activated to launch a cell-mediated attack

  4. The T cell System • Exposure to specific antigen causes marked reproduction in specific T lymphocytes • Memory T cells are created (T-lymphocyte memory cells) • Mature T-cells have T cell receptors which have a very similar structure to antibodies and are specific to one antigen. • T cells respond to antigens only when they are bound to MHC proteins on the surface of antigen-presenting cells (macrophages, B lymphocytes, dendritic cells)

  5. T Lymphocytes • 2 main types of T cells • CD8 cells (cytotoxic, or killer T cells) • Destroy host cells harboring anything foreign • CD4 cells (mostly helper T cells) • Modulate activities of other immune cells • Secrete chemicals that amplify the activity of other immune cells • Β-cell growth factor • T-cell growth factor (interleukin 2) • Macrophage-migration inhibition factor • CD4+CD25+T cells / Suppressor T- cells( regulatory T cells)

  6. Cytotoxic T Cells • Direct attack (killer cells) • Secrete perforins (punch holes in cells) • Releases toxic substances directly into cells • Kills multiple cells • Important in destroying virus infected cells

  7. Types of T Lymphocytes: Helper T cells • Most numerous • Formlymphokines (IL-2, 3, 4, 5, 6) • Regulatory functions of lymphokines: • Stimulation of B cell growth and differentiation • Activation of the macrophage system • Positive feedback effect on the helper cells • They help in the functioning of Cytotoxic T – cells. HIV virus destroys these cells & hence both the types of immunity are lost.

  8. Suppressor T Cells • Capable of suppressing actions of cytotoxic and helper T cells • Prevent excessive damage to the body tissue – Immune tolerance • Known as regulatory T cells

  9. Antigen Presentation • T-Lymphocytes respond only to antigens presented to them by antigen-presenting cells • Macrophages can be antigen-presenting cells • As macrophage engulfs and ingests microbe, it digests the microbe into antigenic peptides • Antigenic peptides bind to a MHC molecule which transports the bound antigen to the cell surface where it is presented to passing lymphocytes • Antigen-presenting macrophages secrete interleukin • Enhances differentiation and proliferation of now-activated T-cell clone

  10. Self-antigens( major histocompatibility complex/MHC) • Plasma membrane-bound glycoproteins called MHC molecules • Synthesis is directed by group of genes called major histocompatibility complex (MHC) • Exact pattern of MHC molecules varies from one individual to another ( BIOCHEMIAL FINGER PRINTS/ “MOLECULAR IDENTIFICATION CARDS). FUNCTIONS: - Directing response of T-lymphocytes - Rejection of transplanted tissue

  11. Immune System Tolerance of Self-Antigens • Tolerance refers to preventing the immune system from attacking the person’s own tissues • Mechanisms involved in tolerance • Clonal deletion: is a process by which B cells and T cells are deactivated after they have expressed receptors for self-antigens and before they develop into fully immunocompetent lymphocytes • Clonal anergy:lack of reaction by the body's defense mechanisms to foreign substances, and consists of a direct induction of peripheral lymphocyte tolerance. • Receptor editing:occurs during the maturation of B cells is an attempt to change the specificity of the antigen receptor of self reactive immature B-cells • Inhibition by regulatory T cells (T cells suppressor) • Immunological ignorance: Anatomical barriers can separate the lymphocytes from the antigen e.g BBB • Immune privilege:

  12. Autoimmune Diseases • Arise from loss of tolerance to self-antigens • e.g. multiple sclerosis, rheumatoid arthritis , myasthenia gravis • Causes : • Exposure of normally inaccessible self-antigens sometimes induces an immune attack against these antigens • Normal self-antigens may be modified by factors such as drugs, environmental chemicals, viruses, or genetic mutations so that they are no longer recognized and tolerated by the immune system. • Exposure of the immune system to a foreign antigen structurally identical to a self-antigen • May be related to pregnancy, arising from lingering fetal cells in the mother’s body after the pregnancy

  13. Immune Diseases • Due to abnormal functioning of the immune system • 2 general ways • Immunodeficiency diseases • Too little immune response • Examples • severe combined immunodeficiency • AIDS • Inappropriate immune attacks • Too much or mistargeted immune response • Categories of inappropriate attacks • Autoimmune responses • Immune complex diseases • Allergies

  14. Hypersensitivity • When an immune reaction results in considerable damage to the body its called hypersensitivity. • Four types • Type I hypersensitivity (Anaphylaxis) • Type II hypersensitivity (antibody mediated cytotoxicity) • Type III hypersensitivity (immune complex disorder) • Type IV hypersensitivity (delayed type of hypersensitivity)

  15. Type I hypersensitivity (Anaphylaxis) • Mast cell degranulation • Ig E response • eg. • Allergic rhinitis • Eczema • Acute urticaria • Occurs within minutes • Mediators • Histamine • Slow reacting substance of anaphylaxis (SRS-A) • Its called Atopy

  16. Type II hypersensitivity (antibody mediated cytotoxicity) • Immune reaction that damages antigen bearing cells • Example – incompatible blood transfusion

  17. Type III hypersensitivity (immune complex disorder) • When antigen antibody complexes are deposited in normal tissues of the body where they fix complement. • Complement activation damages the surrounding tissue cells. • Damage of “innocent bystanders” • eg. A form of glomerulonephritis

  18. Type IV hypersensitivity (delayed type of hypersensitivity) • Its mediated by macrophages that have been activated by T cells. • Hypersensitivity starts after several hours and peak at 48 to 72 hrs. • Characteristically associated with granuloma formation • eg. Hypersensitivity to tuberculin which is present in M. tuberculosis

  19. VACCINE • Vaccine (vaccinus – pertaining to cows) • By Edward Jenner for small pox. • Act on the principle of “mock” infection • Types of Vaccines • Live, Attenuated Vaccines • Inactivated Vaccines • Subunit Vaccines • Toxoid Vaccines • Live, attenuated vaccines - Measles, mumps, rubella, polio • Inactivated or killed vaccines- Cholera, flu, hepatitis A • Toxoid vaccine - Diphtheria, tetanus

  20. measles الحصبة Mumps النكاف Tetanus الكزاز Diphtheria الخناق Tuberculosis مرض السل Hepatitis التهاب الكبد Polio شلل الأطفال

  21. Mechanisms of Immunity: A Summary • Recognition of an antigen as foreign – accomplished by macrophages and helper T-cells • Foreign antigen is phagocytized by a macrophage • Macrophage presents antigen material on its cell membrane • Helper T-cell is exposed to this part of the macrophage membrane and becomes sensitized • Once an antigen has been recognized, the activated helper T cells initiate one or both immune mechanisms. • Cell Mediated Immunity • Humoral Immunity

  22. Antigen macrophage Processed Antigen cytotoxicT cell (-) T helper cell (-) T memory cell T Suppressor cell Lymphokines IL2 IL3 IL4 IL5 IL6 B memory cell B cell Plasma cell Antibodies

  23. Β versus T Lymphocytes

  24. References • Human physiology by Lauralee Sherwood, seventh edition • Text book physiology by Guyton &Hall,11th edition • Text book of physiology by Linda .s contanzo,third edition

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