1. 1 Immunity Chapter 35

2. 2 Edward Jenner’s Experiment Injected material from a cowpox sore into arm of healthy boy Six weeks later, injected material from smallpox sores Boy remained healthy French called Jenner’s procedure vaccination, which means “encowment”

3. 3 Louis Pasteur Developed immunization procedures for other pathogens Called them vaccinations in Jenner’s honor

4. 4 Robert Koch First to link a specific pathogen to a specific disease Injected blood from anthrax-infected animals into healthy animals Subject animals developed anthrax and had bacteria in blood When these bacteria were grown in lab, then injected, they caused anthrax

5. 5 Three Lines of Defense Barriers at body surfaces Nonspecific responses Immune responses

6. 6 Barriers at Body Surface Intact skin and mucous membranes Lysozyme Normal bacterial flora Flushing effect and low pH of urine

7. 7 Nonspecific Responses Lymph nodes trap and kill pathogens Natural killer cells attack a range of targets Inflammation

8. 8 Complement System Plasma proteins that take part in both specific and nonspecific response Activation of one triggers cascade of reactions that activate others CASCADE REACTION FORMATION OF ATTACK COMPLEXES LYSIS OF TARGET

9. 9 Acute Inflammation Nonspecific response to foreign invasion, tissue damage, or both Destroys invaders, removes debris, and prepares area for healing Characterized by redness, swelling, warmth, and pain

10. 10 Inflammation Mast cells release histamine Capillaries dilate and leak Complement proteins attack bacteria White cells attack invaders and clean up

11. 11 Immune Responses Directed against specific invaders Carried out by T cells, B cells, and macrophages Communication signals such as interleukins play a vital role

12. 12 Features of Immune System Immunological specificity –B and T cells zero in on certain kinds of pathogens; response is pathogen specific Immunological memory –Immune system recognizes and reacts swiftly to a pathogen it has “seen”

13. 13 Memory and Effector Cells When a B or T cell is stimulated to divide, it produces more than one cell type Memory cells are set aside for future use; they are the basis for immune memory Effector cells engage and destroy the current threat

14. 14 Key Component of Immune Response MHC markers Antigen-presenting cells Helper T cells Effector cytoxic T cells Natural killer cells B cells

15. 15 Overview of Interactions Naive helper T cell Naive B cell Antigen- presenting cell Activated helper T cell Effector B cell Naive cytotoxic T cell Effector cytotoxic T cell Antibody - mediated response Cell - mediated response

16. 16 B Cell Formation Derived from stem cells in bone marrow Acquire unique antigen-binding receptors in marrow Receptors interact with just one antigen Exposure to that antigen causes clonal selection –Division of cells specific for that antigen

17. 17 Clonal Selection of a B Cell antigen Only the B cell with antigen- receptor that matches antigen is stimulated to divide Mitosis yields many cells with that receptor

18. 18 Generating Receptor Diversity Antibody-coding gene recombines as B cell matures Produces variable transcripts that are translated to produce receptor portion of the antibody molecule transcription translation Similar process produces variable T cell antigen receptors

19. 19 Immunological Memory Memory cells specific for an antigen are quickly activated to divide upon subsequent exposure to that antigen effector cellsmemory cells naive T or B cell effector cellsmemory cells

20. 20 Lymphocyte Battlegrounds Lymph nodes filter antigens from body fluids Macrophages, dendritic cells, B cell and T cells in nodes and spleen mount a defense

21. 21 Antibody-Mediated Response Carried out by B cells Targets are intracellular pathogens and toxins Antibodies bind to target and mark it for destruction by phagocytes and complement

22. 22 Antibody Structure Antibody consists of four polypeptide chains Certain parts of each chain are variable; impart antigen specificity variable region of heavy chain antigen-binding site hinge region (flexible) variable region of light chain constant region of light chain

23. 23 Antibody- Mediated Response Naive B cell Antigen- presenting B cell Helper T cell Interleukins Memory B cell Effector B cell secretes antibodies Virgin B cell becomes antigen-presenting B cell Helper T cell binds to antigen-MHC complex on the B cell Interleukins stimulate B cell division and differentiation Effector cells secrete antibodies

24. 24 5 Classes of Immunoglobulins IgM are secreted first; trigger complement reactions, agglutination IgD function is not understood IgG activates complement; can cross placenta IgA associates with mucus-coated surfaces IgE triggers inflammation

25. 25 Cell-Mediated Response One macrophage Another macrophage interleukins Helper T cell Cytotoxic T cell Infected body cell Carried out by T cells Stimulated by antigen- presenting macrophages Main target is antigen- presenting body cells (cells with intracellular pathogens) or tumor cells

26. 26 Organ Rejection Cytotoxic T cells can contribute to rejection of transplanted tissue They recognize a portion of the donor cell’s MHC complex as self, view a portion as foreign Treat the combination as an antigen- MHC complex and attack donor cells

27. 27 Immunotherapy All body cells display fragments of proteins they are making bound to MHC on their surface In cancer cells, the fragment may be abnormal Immunotherapy uses this cue to attempt to destroy cancer cells

28. 28 Monoclonal Antibodies Manufactured antibodies against tumor- specific antigens First created by fusing antigen- producing B cells from mice with cells from B cell tumors Now made in genetically engineered cells

29. 29 Lymphokine-Activated Killers Lymphocytes are extracted from tumors Extracted cells are exposed to a lymphokine, an interleukin Large population of tumor-infiltrating, activated lymphocytes is then reinjected into patient

30. 30 Therapeutic Vaccines Researchers are genetically engineering tumor antigens to make them more obvious to the immune system The engineered antigen is used as a vaccine to activate the patient’s immune system against the tumor antigen

31. 31 Immunization Process that promotes immunity Active immunization - –Antigen-containing material is injected –Confers long lasting immunity Passive - –Purified antibody is injected –Protection is short lived

32. 32 Allergies Immune reaction to a harmless substance Genetic predisposition IgE responds to antigen by binding to mast cells and basophils These cells secrete the substances that cause symptoms

33. 33 Anaphylactic Shock A life-threatening allergic reaction Caused by the release of histamine by many mast cells and basophils Airways constrict and blood pressure drops as capillary permeability soars

34. 34 Autoimmune Disorders Immune system makes antibodies against self antigens Grave’s disease Myasthenia gravis Rheumatoid arthritis

35. 35 SCIDs Severe combined immunodeficiency Body’s ability to make lymphocytes is impaired or nonexistent High vulnerability to infection ADA deficiency is a heritable SCID Has been successfully treated using gene therapy

36. 36 AIDS Combination of disorders that follows infection with HIV Includes –Yeast (Candida) infections –Pneumocystis pneumonia –Karposi’s sarcoma

37. 37 HIV Replication (1) RNA retrovirus A protein (gp120) at virus surface binds to host cells with CD4 and chemokine receptors These receptors occur on helper T cells Once bound, RNA and viral enzymes enter the host cell

38. 38 HIV Replication (2) Viral RNA is reverse transcribed to DNA HIV DNA is called provirus; it inserts into host DNA The host cell makes copies of viral DNA and viral proteins that assemble to form new virus particles

39. 39 T Cell Decline Release of new viral particles kills the host T cell The body is constantly making new T cells, but cannot outpace the rate of destruction As infection proceeds, T cell numbers inevitably decline

40. 40 Effect of T Cell Decline CD4 helper T cells play a vital role in immune function They are required for both cell-mediated and antibody-mediated immunity Infected individual becomes vulnerable to other infections, which eventually result in death

41. 41 Transmission of HIV HIV does not live long outside human body Most often spread by exchange of bodily fluids with an infected person In the U.S., anal intercourse and needle sharing are main modes of transmission

42. 42 Transmission of HIV Less commonly transmitted by vaginal intercourse and oral sex Can travel from mothers to offspring during pregnancy, birth, or breast- feeding Not known to be transmitted by food, air, water, casual contact, or insect bites

43. 43 Treatment No cure Once HIV genes are incorporated, no way to get them out AZT, and other drugs slow the course of the disease and increase life span Researchers continue to develop drugs and to work toward an AIDS vaccine