Assistant professor Physiology 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 : 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) 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: 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:

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

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)

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

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

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

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

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

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

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

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

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