Dr.Mohammed Sharique Ahmed Quadri Assistant professor Physiology بسم الله الرحمن الرحيم 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 (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)

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 now-activated 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