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Transcript
T LYMPHOCYTES Dr.Mohammed Sharique Ahmed Quadri 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 : – 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 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 The T cell System • Exposure to specific antigen causes marked reproduction in specific T lymphocytes • Memory T cells are created (Tlymphocyte 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 antigenpresenting cells (macrophages, B lymphocytes, dendritic cells) 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) 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 Types of T Lymphocytes: Helper T cells – Most numerous – Form lymphokines (IL-2, 3, 4, 5, 6 and BCSF, BSDF) – 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. 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 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 nowactivated T-cell clone 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 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 – Clonal anergy – Receptor editing – Inhibition by regulatory T cells – Immunological ignorance – Immune privilege 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 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 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 Β versus T Lymphocytes 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