Introduction to Immunology BIOS 486A/586A

1. 0 Introduction to ImmunologyBIOS 486A/586A Kenneth J. Goodrum,Ph.D. Department of Biomedical Sciences Ohio University 2005

2. 0 Definition of Immunity • Protection against disease, usually infectious disease, mediated by a collection of molecules, cells, and tissues collectively called the immune system. In a broader sense, immunity refers to the ability to respond to foreign substances, including microbes or molecules.

3. 0 Immunogen/Antigen • Definition: a substance which induces an immune response • Properties • Foreign (not a shared human molecule) • Large (>10 Kda), complex molecule • Biodegradable (not inert) • Examples: infectious microorganisms, allergens, any large complex biomolecule

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5. 0 Cells of the Immune System • White Blood Cells (derived from precursor cells in the bone marrow) • phagocytes (granulocytes, monocytes/macrophages) • lymphocytes (B and T) • natural killer cells

6. 0 Immune Cells

7. 0 Immune cells

8. 0 Immune Cells

9. 0 Left: Light photomicrograph of a lymphocyte in a stained smear of peripheral blood. Right: Electron micrograph Fig 1.5

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11. 0 Immune System-Lymphoid tissues • Lymphocytes mature in the primary lymphoid organs • bone marrow or thymus • Secondarylymphoid organs trap antigen to allow initiation of immune responses and sustain recirculating lymphocytes • bone marrow, thymus, spleen, lymph nodes, mucosal-associated lymphoid tissue

12. 0 Foreign substances in tissue fluids (lymph) or in blood are carried via lymphatic or blood vessels to lymphoid organs for interaction with lymphocytes Fig 1.7

13. 0 Lymphocytes circulate between blood and lymph and between various lymphoid organs to insure that the appropriate immune cell contacts an immunogen regardless of where it enters the body.

14. 0 Lymph nodes filter immunogens from the lymph, and the resident lymphocytes proliferate in response to immunogens.

15. 0 Principles of Immunity • Each lymphocyte generates a unique antigen receptor by DNA rearrangement of its receptor genes • B cell antigen receptor =antibody • T cell antigen receptor =T cell receptor • Lymphocytes proliferate in response to antigen in secondary lymphoid tissues generating effector cells and memory • Clonal expansion [clone = single cell]

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18. Immune Response 0 Thymus Bone marrow stem cells Blymphocytes Tlymphocytes immunogen Clonal selection, expansion (proliferation), differentiation in lymphoid organs Cytotoxic functionexpressed (immunogen-specific)andcytokinesproduced(immunoregulatory factors) plusmemory T cells Antibody production(immunogen specific) plusMemory B cells Elimination of immunogen and long term immunity

19. 0 Principles of Immunity • Activation of specialized antigen-presenting cells is a necessary first step for induction of adaptive immunity • Dendritic cells • Lymphocytes activated by antigen give rise to clones of antigen-specific cells that mediate adaptive immunity • Clonal selection

20. T cells are activated by foreign peptides trapped and displayed by dendritic cells in lymph nodes. B cells directly bind immunogens and proliferate with the help of T cell-derived growth factors. 0

21. 0 Each lymphocyte has a single antigen-specificity mediated by a cell surface antigen receptor. Amino acid variability (variable structural regions) in the actual antigen binding sites explains the different antigen binding specificities between any 2 different B cells.

22. On first contact with a new immunogen, immune responses are delayed, small, and short-lived. (Primary responses are therapeutic). On secondary contact with the same immunogen (boost), responses are rapid, large, and long-lived (Secondary responses are prophylactic). 0 Fig 1.20

23. 0 Protective mechanisms of antibodies. B cells secrete their antigen receptor as a soluble molecule (antibody). Antibody recognizes and binds the immunogen resulting in direct neutralization of toxicity or infectivity; promotes phagocytosis and digestion of the antigen directly or via serum complement activation. Fig. 1.24

24. 0 Protective mechanism of T cells. Cytotoxic T cells recognize foreign antigens on self cells (such as on virus-infected or tumor cells) and mediate direct lysis and cell death of the altered self cells. Fig 1.25

25. 0 Protective mechanisms of T cells. Activated T helper cells secrete soluble protein factors (cytokines) that enhance the innate antimicrobial functions of phagocytes allowing an infected phagocyte to more easily kill an intracellular microbe. Fig 1.26

26. 0 Effect of immunizations on incidence of infectious diseases.

27. 0 Consequences of normal or deficient immune responses.