2. Immunology Review Part One Immune Responses

3. Innate Immunity First line of defense in preventing foreign substances from entering body. Available at birth (innate or natural). Generalized, nonspecific reaction.

4. Innate Immunity No prior exposure to foreign substance required. Response doesn’t change with further exposure. Influenced by: –Age –Stress –Fatigue –Nutritional status

5. Elements Of Innate Immunity Skin Tears, saliva, secretions Mucus Chemicals pH Normal flora Temperature Cough Reflex Toll-like receptors Phagocytes Inflammation

6. Phagocytosis Monocyte, macrophage, eosinophil or neutrophil drawn in to area by chemotactic factors such as complement or cytokines. Receptors on phagocyte make contact with foreign material. –May be enhanced by CRP, complement or antibodies. (Opsonins) Phagocyte engulfs foreign material to form phagosome. Phagosome merges with granules in cytoplasm. Granules contain chemicals that digest foreign material. Waste material is expelled from phagocyte (exocytosis).

7. Inflammation Capillaries dilate and blood accumulates in the affected area, leading to redness and increased temperature. Fluid accumulates, causing edema. Phagocytes migrate into the tissue and destroy foreign invaders.

8. Cells Alive! To see the interaction between elements of innate immunity, please go to http://www.cellsalive.com/ouch1.htm http://www.cellsalive.com/ouch1.htm View “Anatomy of a Splinter”.

9. Acquired (Adaptive) Immunity Forms only after exposure to foreign substance. Response is specific to the foreign stimulus. Recognizes self vs. non-self. Displays memory. 2 forms: –Cell mediated –Humoral

10. Cell Mediated Immunity

11. Controlled by T lymphocytes. –Influence other parts of the immune system (including the humoral response) through the release of cytokines. Responsible for such processes as delayed hypersensitivity, transplant immunity, and tumor rejection.

12. Cell Mediated Process Foreign matter is broken down into smaller peptides. Peptides combine with the Major Histocompatibility Complex (MCH) antigens.

13. Major Histocompatibility Complex Found on the membrane of every nucleated cell. Three classes: –I (A, B, C loci) –II (DR, DQ, DP loci) –III (complement, Tumor Necrosis Factor [TNF]) MHC Class I and II antigens each have an antigen binding groove which carries foreign peptides.

14. Major Histocompatibility Complex Class I Class II Antigen Binding Groove

15. Pathogen Recognition MHC Class I antigens are found on almost every nucleated cell in the body These antigens bind peptides that are produced within the cell –Tumors, viruses, intracellular bacteria –These peptides are termed endogenous antigens

16. Pathogen Recognition MHC Class II molecules are found on monocytes, macrophages, dendritic cells, and B lymphocytes. –Termed Antigen Presenting Cells (APC) Class II molecules bind foreign peptides that come from bacteria, virus, or parasites that have been ingested by the APC. –Termed exogenous antigens

17. Pathogen Recognition T cells possess receptors (TCR) that recognize foreign antigen when it is bound to MHC antigen. –T cytotoxic lymphocytes (T c cells) interact with Class I antigens. –T helper lymphocytes (T H cells) interact with Class II antigens. TCR is coupled to CD3. CD3 signals the interior of the T cell that antigen is present. T cell then secretes cytokines that effect surrounding cells. Some T cells mature into memory T cells. These assist with rapid recognition of the foreign antigen the next time it is encountered, thus speeding up the immune response.

18. T Lymphocyte Subsets T helper cells (T H ) –Make up 2/3’s of the T lymphocyte population –CD4 positive –React with MHC class II proteins –Stimulate both the cytotoxic and the humoral responses T cytotoxic cells (T C ) –CD8 positive –React with MHC class I proteins

19. Cytotoxic T Cells T C cell recognizes the foreign peptides associated with the Class I MHC antigen. –Recognition via the TCR and CD8. T C produces perforin, a protein that causes disruption of the membrane of the affected cell. The affected cell dies by apoptosis. –Cell fragments into smaller particles. –Fragments are engulfed by phagocytes. Cytokines TNF and interferon are released by the T C to prevent spread of virus. –May injure healthy tissue.

20. Cells Alive! Please go to http://www.cellsalive.com/ctl.htm http://www.cellsalive.com/ctl.htm View “The Cytotoxic T Lymphocyte”.

21. Humoral Immunity

22. Major cell involved is the B cell. Develops into plasma cells and memory cells. Influenced by T helper cells.

23. The Humoral Process Foreign antigen is introduced to host. Antigen Presenting Cells (APCs) process antigen into peptide fragments, then present it to the T H lymphocyte. –Dendritic cells and macrophages function as APCs –Foreign peptides bind to MHC Class II antigens The T H recognizes the foreign antigen through its T Cell Receptor (TCR) and CD4.

24. The Humoral Process The B cell has also recognized the foreign antigen via the B cell receptor (BCR), and processed the foreign antigen. –Foreign peptide is then expressed on the surface MHC class II molecules. T H recognizes that the peptide seen by its TCR and the peptide presented by the B cell are the same. T H releases cytokines to stimulate B cell.

25. The Humoral Process B cells divide into plasma cells or memory cells. –Plasma cells produce and secrete antibody. –The antibody produced is specific for one antigenic determinant! –Memory cells recall previous encounter with foreign antigen. Persist in circulating lymphocyte pool for months up to years.

26. Cells Alive! Please go to http://www.cellsalive.com/antibody.htm http://www.cellsalive.com/antibody.htm View “Making Antibodies”.

27. The Humoral Process Signals from the T H influence the class of antibody produced by the B cell and the ability to switch immunoglobulin classes. –Interleukins –Transforming growth factor IgM is the first immunoglobulin produced. Most B cells switch from IgM production to IgG, the most prevalent immunoglobulin.

28. Primary vs. Secondary Humoral Response First exposure to antigen Second & subsequent exposures to the same antigen IgM IgG

29. Primary Response First time the host encounters the foreign antigen. Latency period: Lag time between exposure to antigen and production of antibodies. IgM is the main class of antibody (immunoglobulin) produced. –Some IgG is made.

30. Primary Response Concentration of antibody (titer) is relatively low. Antibody titer drops off quickly.

31. Secondary Response Also called the anamnestic or memory response. A repeat encounter with the same foreign antigen. Usually takes a smaller dose of antigen to stimulate the response. Memory cells hasten the immune response.

32. Secondary Response IgG is the primary immunoglobulin produced. –Some IgM is also made. Response is faster. Antibody titer is higher. Antibody detectable for a longer period of time.

33. Secondary Response Faster, Higher, Stronger, Longer

34. This concludes “Immunology Review, Part One: Immune Responses” Please complete the exercise “Comparing Immune Response Mechanisms”