1. BLOOD AND BODY DEFENCE Dr. Amel Eassawi Dr. Abdelrahman Mustafa 1

2. HMIM 224 L 9: T LYNPHOCYTE 2

3. OBJECTIVES 3 The student should be able to:  Identify the different types of T lymphocyte.  Discuss the functions of the different types of T lymphocyte.  Define the immune system tolerance.  Recognize the different types of hypersensitivity.  Define auto immune diseases and identify disease examples.  Discuss the different types of vaccines and identify examples for each type.

4. T LYMPHOCYTES Lymphocytes migrate from bone marrow to the thymus for preprocessing to form (thymic) “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. 4

5. 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. 5

6. 6 The T cell System

7. T LYMPHOCYTES 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). 7

8. 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). 8

9. T LYMPHOCYTES 9 T-Cell T-supressor T -helper T- ctotoxic T- memory Cell

10. 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. 10

11. 11 Cytotoxic T Cells

12. 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 and hence both the types of immunity are lost. 12

13. 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. 13

14. 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. 14

15. Plasma membrane-bound glycoproteins called MHC molecules. Self-antigens (Major Histocompatibility Complex). 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. MAJOR HISTOCOMPATIBILITY COMPLEX 15

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17. IMMUNE SYSTEM TOLERANCE 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. 17

18. 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. 18

19. 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 19

20. HYPERSENSITIVITY When an immune reaction results in considerable damage to the body its called hypersensitivity. Four types: 1. Type I hypersensitivity (Anaphylaxis). 2. Type II hypersensitivity (antibody mediated cytotoxicity). 3. Type III hypersensitivity (immune complex disorder). 4. Type IV hypersensitivity (delayed type of hypersensitivity). 20

21. TYPE I HYPERSENSITIVITY Type I hypersensitivity (Anaphylaxis): Mast cell degranulation. Ig E response. Examples: –Allergic rhinitis. –Eczema. –Acute urticaria. Occurs within minutes. Mediators. Histamine. Slow reacting substance of anaphylaxis (SRS-A). Its called Atopy. 21

22. TYPE II HYPERSENSITIVITY Type II hypersensitivity (antibody mediated cytotoxicity): Immune reaction that damages antigen bearing cells. Example – incompatible blood transfusion. 22

23. TYPE III HYPERSENSITIVITY 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”. Example:. Type of glomerulonephritis. 23

24. TYPE IV HYPERSENSITIVITY 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. Example: Hypersensitivity to tuberculin which is present in M. tuberculosis. 24

25. 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. Example: Measles, mumps, rubella, polio. Inactivated or killed vaccines. Example: Cholera, flu, hepatitis A. Toxoid vaccine. Example: Diphtheria, tetanus. 25

26. Mumps النكاف measles الحصبة Tetanus الكزاز Diphtheria الخناق Hepatitis التهاب الكبد Tuberculosis مرض السل Polio شلل الأطفال 26

27. MECHANISMS OF IMMUNITY 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. 27

28. T helper cell Suppressor T cell Plasma cell B cell cytotoxic T cell T memory cell B memory cell macrophage Antigen Processed Antigen Lymphokines IL2 IL3 IL4 IL5 IL6 Antibodies (-) 28

29. 29 Β versus T Lymphocytes

30. REFERENCES  Human Physiology, Lauralee Sherwood, seventh edition.  Text book Physiology by Guyton &Hall,11 th edition.  Text book of Physiology by Linda S. Contanzo, third edition.  Physiology by Berne and Levy, sixth edition. 30