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

2. 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. 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

5. 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. Immune Cells

7. Immune cells

8. Immune Cells

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

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

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

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

15. 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]

16. Fig 1.14

17. Fig. 1.15

18. Immune Response Bone marrow stem cells Thymus  lymphocytes T lymphocytes immunogen Clonal selection, expansion (proliferation), differentiation in lymphoid organs Antibody production (immunogen specific) plus Memory B cells Cytotoxic function expressed (immunogen-specific)and cytokines produced(immunoregulatory factors) plus memory T cells Elimination of immunogen and long term immunity

19. 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.

21. 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. Fig 1.20 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).

23. 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. Fig 1.25 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.

25. Fig 1.26 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.

26. Effect of immunizations on incidence of infectious diseases.

27. Consequences of normal or deficient immune responses.