Cell Mediated Immunity

1. Cell Mediated Immunity

2. Cell Mediated Immunity (CMI) • Involves specialized set of lymphocytes called T cells that recognize foreign antigens on the surface of cells, organisms, or tissues: • T cells regulate proliferation and activity of other cells of the immune system: • B cells, macrophages, neutrophils, etc. • Defense against: • Bacteria and viruses that are inside host cells and are inaccessible to antibodies. • Fungi, protozoa, and helminths • Cancer cells • Transplanted tissue 2

3. Cell Mediated Immunity is Carried Out by T Lymphocytes 3

4. Antigens that stimulate cellular response are mainly intracellular. • Requires constant presence of antigen to remain effective. • Unlike humoral immunity, cell mediated immunity is not transferred to the fetus. • In addition to direct cytotoxicity, T cells produce cytokines that activate macrophages. Cytokines: • Chemical messengers of immune cells. • Over 100 have been identified. • Stimulate and/or regulate immune responses. • Interleukins: Communication between WBCs. • Interferons: Protect against viral infections. • Chemokines: Attract WBCs to infected areas. 4

5. T Cells and Cell Mediated Immunity Cellular Components of Immunity: • T cells are key cellular component of immunity. • T cells have an antigen receptor that recognizes and reacts to a specific antigen (T cell receptor). • T cell receptor only recognize antigens combined with majorhistocompatability (MHC) proteins on the surface of cells. • MHC Class I: Found on all nucleated cells. • MHC Class II: Found on phagocytes. • Clonal selection increases number of T cells. 5

6. Clonal selection of lymphocytes: 1) a hematopoietic stem cell undergoes differentiation and genetic rearrangement to produce 2) immature lymphocytes with many different antigen receptors. Those that bind to 3) antigens from the body's own tissues are destroyed, while the rest mature into 4) inactive lymphocytes. Most of these will never encounter a matching 5) foreign antigen, but those that do are activated and produce 6) many clones of themselves 6

7. T Cells Only Recognize Antigen Associated with MHC Molecules on Cell Surfaces 7

8. Types of T cells • T Helper (TH) Cells: • Central role in immune response. • There are three subpopulations of Th cells: • Th0(naïve) • Th1 (imflammatory) • Th2 cells(helper). • Most are CD4+ • Recognize antigen on the surface of antigen presenting cells e.g.: macrophage (MHC class II) • Activate macrophages • Induce formation of cytotoxic T cells • Stimulate B cells to produce antibodies.(helper) (inflammatory) 8

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10. Central Role of Helper T Cells 10

11. Types of T cells (Continued) • Cytotoxic T (Tc) Cells: • Destroy target cells. • CD8+ (CD4 -). • Recognize (MHC class I) antigens on the surface of all cells: • Kill host cells that are infected with viruses or bacteria. • Recognize and kill cancer cells. • Recognize and destroy transplanted tissue. • Release two types proteins: • perforinwhich forms pores in target cells, causing lysis of infected cells. • Granzymes (serine proteases) • Undergoapoptosiswhen stimulating antigen is gone. 11

12. Cytotoxic T Cells Lyse Infected Cells 12

13. Types of T cells (Continued) • Delayed Hypersensitivity T (TD) Cells: Mostly T helper and a few cytotoxic T cells that are involved in some allergic reactions and rejection of transplanted tissue. • T Suppressor (Ts) Cells: • may shut down immune response. • are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain: • immune system homeostasis and • tolerance to self-antigens. 13

14. Nonspecific Cellular Components 1. Activated Macrophages: (Stimulated phagocytes) • Stimulated by ingestion of antigen • Larger and more effective phagocytes. • Enhanced ability to eliminate intracellular bacteria, virus-infected and cancerous cells. 2. Natural Killer (NK) Cells: • Lymphocytes that destroy virus infected and tumor cells. • Not specific. Don’t require antigen stimulation. • Not phagocytic, but must contact cell in order to lyse it. 14

15. Relationship Between Cell-Mediated and Humoral Immunity 1. Antibody Production T-Dependent Antigens: • Antibody production requires assistance from T helper cells. • Macrophages ingest antigens and present them to TH cell. • TH cells stimulate B cells specific for that antigen to become plasma cells. • Antigens are mainly proteins on viruses, bacteria, foreign red blood cells, and hapten-carrier molecules. T-Independent Antigens: • Antibody production does not require assistance from T cells. • Antigens are mainly polysaccharides or lipopolysaccharides with repeating subunits (bacterial capsules). • Weaker immune response than for T-dependent antigens. 15

16. Humoral Response to T Dependent Antigens 16

17. Relationship Between Cell-Mediated and Humoral Immunity 2. Antibody Dependent Cell Mediated Cytotoxicity • Target cell is covered with antibodies, leaving Fc portion sticking outwards. • Natural killer and other nonspecific cells that have receptors for Fc region are stimulated to kill targeted cells. • Target organism is lysed by substances secreted by attacking cells. • Used to destroy large organisms that cannot be phagocytosed. 17

18. TCR • TCR is a heterodimercomposed of two transmembrane polypeptide chains, either: • aand b chains or • of g and d chains. • The abreceptors account for 90% of T-cell helper function and cytotoxicactivity. • The gd T cells receptors, its physiologic role is still unclear. • The biochemical signals that are triggered in T cells by antigen recognition are transduced not by the T cell receptor itself but by the invariant proteins called CD3 • CD3 are noncovalenlty linked to the antigen receptor to form the TCR complex.

19. TCR

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21. What are the similarities/differences betweenT-cell receptors and B-cell receptors? Similarities: 1.Both bind antigen 2.Both have their variabilities located in one part of the molecule that bind antigen (V-region) 3.Three dimensional structures are remarkably similar Differences: 1. Antibodies can be both soluble and membrane bound, TCR only membrane Bound 2. TCR has one binding site, Ab has two 3. TCR is shorter and wider than Fab portion of Ab. 4. B-cells/antibodies recognize circulating antibodies. T-cells require antigen to be presented by MHC-molecules 5. All energy of antigen-antibody focus on foreign antigens whereas a substantial fraction of the energy of the TCR-peptide-MHC is directed against self. 6. Antibodies have higher affinity than TCRs 20

22. Overview of the Immune Response 21