Immunity

1. Immunity Innate & Adaptive

2. Immunity • Innate: response to attack is always the same • Mechanical mechanisms • Chemical mediators • Cellular response • Inflammatory response • Adaptive:response to attack improves with each exposure • Specific • Has memory

3. Innate immunity • Mechanical mechanisms • Skin & mucus membranes form physical barriers to prevent entry • Tears, saliva, urinewash away pathogens from surface or body or dilute invading army of pathogens

4. Innate immunity • Chemical mediators: Some prevent entry to cells, kill bacteria, or produce inflammation • Complement proteins • ~ 20 in plasma • normally inactive; activated by combining with parts of bacterial cells or antibodies • Leads to chain rxn activation of neighboring compliments & inflammation, phagocytosis, or lysis

5. Innate immunity • Chemical mediators • Interferons protect against viral infection • Virus-infected cells place interferons on their surface (SOS signal) • These bind to neighboring cells & stimulate neighbors to produce antiviral proteins • Intiviral proteins inhibit production of new viral RNA • Some interferons activate macrophages and NKC

6. Innate immunity • Cellular mechanisms • WBC & derivatives are most important cellular components • Attracted to invading bacteria and microorganisms through chemotaxis • Phagocytic cells (who are these?) • Inflammatory cells (…and these?) • Natural Killer Cells (NKC)

7. White Blood Cells

8. Innate immunity • Phagocytic cells • Neutrophils • Small; first to enter infected tissue from blood; ingest, then die --> pus accumulation • Macrophages • Monocytes leave blood & enlarge; arrive after neutrophils; do most eating & cleanup • Also hang out at “entry points” (gate-keepers)

9. Innate immunity • Natural Killer Cells (NKC) • 15% of all lymphocytes are NKC • Recognize tumor cells or virus-infected cells (generalist killers) • No memory; non-specific • Kill via chemical release (cell membrane lysis)

10. Innate immunity • Inflammatory cells: activated through innate or adaptive immunity; release histamine & pyrogens • Basophils • Motile WBC; enter infected tissue • Mast cells • Non-motile; Located in lymph organs at “points of entry” • Eosinophils • Release enzymes that reduce inflammation (control)

11. Inflammation is useful! • Localinflammation: Redness, heat, swelling • caused by increased blood flow & vascular permeability • Chemicals and swelling activate pain receptors • Systemic inflammation • Red marrow increases neutrophil production • Pyrogensstimulate fever by increasing heat production & conservation • Vascular permeability increases

12. Adaptive immunity • Lymphocytes • Origin & development • Activation & multiplication • Antibody-mediated • Cell-mediated

13. Adaptive immunity • Antigens stimulate adaptive immune response • Self • Foreign • MHC molecules display antigens • Lymphocytes • Origin & development • Activation & multiplication • Types of Adaptive Immunity • Antibody-mediated • B cells; produce cells that make antibodies • Cell-mediated • T cells; cytotoxic & helper T cells

14. Antigens • Foreign • Components of bacteria, viruses, and their chemical byproducts • Pollen, animal hair, foods produce allergic response (overreaction of immune system) • Self • Produced by our bodies • Recognize tumor antigens

15. B & T-cells (Lymphocytes) • Contain antigen receptors in their cell membranes • We each have thousands of different populations of B & T-cells, each with unique antigen receptors • Cells are stimulated by binding of antigens to their unique receptors

16. Bone marrow Stem cell Thymus Via blood Immature lymphocytes Antigen receptor Antigen receptor B cell T cell Via blood Lymph nodes, spleen, and other lymphatic organs Final maturation of B and T cells in lymphatic organ Cell Development • Red marrow produces: • Pre B-cells: released into bloodstream • migrate to lymph organs • Pre T-cells: migrate to thymus & mature there • Mature T-cells migrate to lymph organs

17. Activation & multiplication • Macrophages present antigens • Phagocytize invaders, process & display antigens (with help of MHC molecules) • MHC/Antigen complex binds to receptors on B or T-cells • T-cells auto-stimulate • Produce cytokines (peptides; e.g. interleukin) that up-regulate growth & division

18. B cell activation • Antibody-mediated • B-cells can also phagocytize & process antigens • same antigen that stimulated a Th • Th binds to B-cell • Interleukins are produced • stimulate B-cell division & proliferation • Daughter (plasma) cells produce antibodies

19. Effects of Antibodies • Direct • Antibodies bind antigens = inactivation • Indirect • Activate Complement cascade • Inflammation (mast cells and basophils release histamine) • Chemotaxis (attracts white blood cells) • Phagocytosis or lysis (macrophage eats antibody & antigen

20. Binding of antibodies to antigens inactivates antigens by Agglutination of microbes Activation of complement system Precipitation of dissolved antigens Neutralization Complement molecule Bacteria Virus Antigen molecules Bacterium Foreign cell Hole Leads to Enhances Cell lysis Phagocytosis Macrophage

21. Antibody production • Differs following first and second exposure to antigen • First exposure = primary response • B-cells bind antigen; produce plasma cells (produce antibodies) and memory B-cells • Response time = 3-14 days; disease symptoms develop; SLOW

22. Primary immune response Antigen receptor (antibody on cell surface) 1 Fig. 24-7aa-1 B cells with different antigen receptors

23. Primary immune response 2 Antigen molecules Antigen receptor (antibody on cell surface) 1 Fig. 24-7aa-2 B cells with different antigen receptors

24. Primary immune response 2 Antigen molecules Antigen receptor (antibody on cell surface) 1 Fig. 24-7aa-3 B cells with different antigen receptors First exposure to antigen 3 Cell activation: growth, division, and differentiation

25. Primary immune response 2 Antigen molecules Antigen receptor (antibody on cell surface) 1 Fig. 24-7aa-4 B cells with different antigen receptors First exposure to antigen 3 Cell activation: growth, division, and differentiation Antibody molecules 4 Endoplasmic reticulum First clone Plasma (effector) cells secreting antibodies

26. Primary immune response 2 Antigen molecules Antigen receptor (antibody on cell surface) 1 Fig. 24-7aa-5 B cells with different antigen receptors First exposure to antigen 3 Cell activation: growth, division, and differentiation Antibody molecules 4 5 Endoplasmic reticulum First clone Plasma (effector) cells secreting antibodies Memory cells

27. Antibody production • Differs following first and second exposure to antigen • Second exposure = secondary response • Memory cells quickly induce plasma cells to produce antibodies • Time to antibody production is reduced • More plasma cells & antibodies produced • RAPID response, no disease symptoms = immunity

28. Fig. 24-7aa-6 Antigen molecules Second exposure to same antigen 6 Antibody molecules Secondary immune response (May occur long after primary immune response.) Endoplasmic reticulum Second clone Plasma (effector) cells secreting antibodies Memory cells

29. Second exposure to antigen X, first exposure to antigen Y Secondary immune response to antigen X Fig. 24-7b First exposure to antigen X Antibody concentration Primary immune response to antigen Y Primary immune response to antigen X Antibodies to Y Antibodies to X 7 28 42 49 0 14 21 35 56 Time (days)

30. Cell-mediated immunity • Cytotoxic T cells (Tc) • Effective against viruses, bacteria • Infected cells display antigens, and Tc binds to MHC/antigen combo • Stimulates production of more Tc • Costimulation by Th which were stimulated by macrophage display of antigens

31. Fig. 24-11b Humoral immune response (secretion of antibodies by plasma cells) B cell Self-nonself complex Interleukin-2 stimulates cell division T cell receptor 6 5 3 Interleukin-2 activates B cells and other T cells 2 Helper T cell 7 4 Cell-mediated immune response (attack on infected cells) Cytotoxic T cell Antigen-presenting cell Binding site for antigen Interleukin-1 stimulates helper T cell Binding site for self protein

32. Fig. 24-12-1 Cytotoxic T cell binds to infected cell 1 Self-nonself complex Foreign antigen Infected cell Perforin molecule Cytotoxic T cell

33. Fig. 24-12-2 Perforin makes holes in infected cell’s membrane and enzyme enters Cytotoxic T cell binds to infected cell 2 1 Self-nonself complex Hole forming Foreign antigen Infected cell Perforin molecule Enzyme that can promote apoptosis Cytotoxic T cell

34. Fig. 24-12-3 Infected cell is destroyed Perforin makes holes in infected cell’s membrane and enzyme enters Cytotoxic T cell binds to infected cell 2 3 1 Self-nonself complex Hole forming Foreign antigen Infected cell Perforin molecule Enzyme that can promote apoptosis Cytotoxic T cell

35. Show “Immune Response”Mcgraw Hill

36. Humoral immune response (secretion of antibodies by plasma cells) B cell Self-nonself complex Interleukin-2 stimulates cell division T cell receptor Macrophage Microbe 6 5 3 Interleukin-2 activates B cells and other T cells 1 2 Helper T cell 7 4 Self protein Cell-mediated immune response (attack on infected cells) Antigen-presenting cell Cytotoxic T cell Antigen from microbe (nonself molecule) Interleukin-1 stimulates helper T cell Binding site for antigen Binding site for self protein Th stimulate both immune responses

37. Acquiring Adaptive immunity

38. Antigens, Antibodies & Vaccines • Inject host with inactive or attenuated virus (usually bits & pieces akaantigens) • Host immune cells grab antigens & stimulate other cells (B cells) to engineer antibodies to bind to antigens

39. Antigens, Antibodies & Vaccines • B cells “remember” how to make this antibody forever • On subsequent infection, live virus is mobbed by antibodies, targeted for termination and eaten by macrophages