Practical Applications of Immunology

1. 18 Practical Applications of Immunology

2. Vaccine History • Variolation: Inoculation of smallpox into skin (18th century). • Vaccination: Inoculation of cowpox into skin. • Herd immunity results when most of a population is immune to a disease.

3. Principal Vaccines Used in the United States to Prevent Bacterial Diseases in Humans • DtaP • Diphtheria: Purified diphtheria toxoid • Pertussis: Acellular fragments of B. pertussis • Tetanus: Purified tetanus toxoid • Meningococcal meningitis: Purified polysaccharide from N. meningitidis • Haemophilus influenzae type b meningitis: Polysaccharides conjugated with protein • Pneumococcal conjugate vaccine: S. pneumoniae antigens conjugated with protein

4. Principal Vaccines Used in the United States to Prevent Viral Diseases in Humans • Smallpox: Live vaccinia virus • Poliomyelitis: Inactivated virus • Rabies: Inactivated virus • Hepatitis A: Inactivated virus • Influenza: Inactivated or attenuated virus • Measles: Attenuated virus • Mumps: Attenuated virus • Rubella: Attenuated virus • Chickenpox: Attenuated virus • Hepatitis B: Antigenic fragments (recombinant vaccine)

5. Monoclonal Antibodies (Mabs) • Alemtuzumab: For leukemia • Infliximab: For Crohn’s disease • Rituximab: For non-Hodgkin’s lymphoma • Trastuzumab: Herceptin for breast cancer • Basiliximab and daclizumab: Block IL–2, immunosuppresives for transplants • Palivizumab: Treatment of RSV

6. Monoclonal Antibodies Figure 18.2

7. Monoclonal Antibodies • Immunotoxins: Mabs conjugated with a toxin to target cancer cells. • Chimeric mabs: Genetically modified mice that produce Ab with a human constant region. • Humanized mabs: Mabs that are mostly human, except for mouse antigen-binding. • Fully human antibodies: Mabs produced from a human gene on a mouse.

8. Precipitation Reactions • Involve soluble antigens with antibodies. Figure 18.4

9. Agglutination Reactions • Involve particulate antigens and antibodies. • Antigens may be • On a cell (direct agglutination). • Attached to latex spheres (indirect or passive agglutination). Figure 18.5

10. Antibody Titer • Is the concentration of antibodies against a particular antigen. Figure 18.6

11. Viral Hemagglutination • Hemagglutination involves agglutination of RBCs. • Some viruses agglutinate RBCs in vitro. Figure 18.8

12. Viral Hemagglutination-Inhibition • Hemagglutination involves agglutination of RBCs. • Some viruses agglutinate RBCs in vitro. • Antibodies prevent hemagglutination. Figure 18.9b

13. Neutralization Reactions • Eliminate the harmful effect of a virus or exotoxin. Figure 18.9b

14. Complement Fixation Test Figure 18.10 (1 of 2)

15. Complement Fixation Test Figure 18.10 (2 of 2)

16. Fluorescent Antibody Techniques (Direct) Figure 18.11a

17. Fluorescent Antibody Techniques (Indirect) Figures 18.11b, 3.6b

18. Enzyme-Linked Immunosorbent Assay(Direct ELISA) Figure 18.14a

19. Enzyme-Linked Immunosorbent Assay (Indirect ELISA) Figure 18.14b

20. Serological Tests Figure 18.13

21. Serological Tests • Direct tests detect antigens (from patient sample). • Indirect tests detect antibodies (in patient′s serum).

22. Serological Tests • Agglutination: Particulate antigens • Hemagglutination: Agglutination of RBCs • Precipitation: Soluble antigens • Fluorescent-antibody technique: Antibodies linked to fluorescent dye. • Complement fixation: RBCs are indicator. • Neutralization: Inactivates toxin or virus. • ELISA: Peroxidase enzyme is the indicator.

23. Question 1 • Patient’s serum, influenza virus, sheep RBCs, and anti-sheep RBCs are mixed in a tube. • Influenza virus agglutinates RBCs. • What happens if the patient has antibodies against influenza virus?

24. Question 2 • Patient’s serum, Chlamydia, guinea pig complement, sheep RBCs, and anti-sheep RBCs are mixed in a tube. • What happens if the patient has antibodies against Chlamydia?

25. Disorders Associated with the Immune System • Harmful immune responses • Allergies • Transplant rejection • Autoimmunity • Superantigens cause release of cytokines that cause adverse host responses. • Immunodeficiencies

26. 19 Disorders Associated with the Immune System

27. Hypersensitivity Reactions • Response to antigens (allergens) leading to damage. • Require sensitizing dose(s).

28. Type I (Anaphylactic) Reactions • Involve IgE antibodies. • Localized: Hives or asthma from contact or inhaled antigens. • Systemic: Shock from ingested or injected antigens. Figure 19.1a

29. Type I (Anaphylactic) Reactions • Skin testing • Desensitization Figure 19.3

30. Type II (Cytotoxic) Reactions • Involve IgG or IgM antibodies and complement. • Complement activation causes cell lysis or damage by macrophages.

31. ABO Blood Group System Table 19.2

32. Hemolytic Disease of the Newborn Figure 19.4

33. Drug-induced Thrombocytopenic Purpura Figure 19.5

34. Type III (Immune Complex) Reactions • IgG antibodies and antigens form complexes that lodge in basement membranes. Figure 19.6

35. Type IV (Cell-Mediated) Reactions • Delayed-type hypersensitivities due to TD cells. • Cytokines attract macrophages and initiate tissue damage. Figure 19.8

36. Autoimmune Diseases • Clonal deletion during fetal development ensures self-tolerance. • Autoimmunity is loss of self-tolerance.

37. Autoimmune Diseases • Type I — Due to antibodies against pathogens. • Type II — Antibodies react with cell-surface antigens. • Type III (Immune Complex) — IgM, IgG, complement immune complexes deposit in tissues. • Type IV — Mediated by T cells.

38. Reactions Related to the Human Leukocyte Antigen (HLA) Complex • Histocompatibility antigens: Self antigens on cell surfaces. • Major histocompatibility complex (MHC): Genes encoding histocompatibility antigens • Human leukocyte antigen (HLA) complex: MHC genes in humans

39. Diseases Related to Specific HLAs Table 19.3

40. HLA Typing Figure 19.9

41. Reactions to Transplantation • Transplants may be attacked by T cells, macrophages, and complement-fixing antibodies. • Transplants to privileged sites do not cause an immune response. • Stem cells may allow therapeutic cloning to avoid rejection.

42. Grafts • Autograft: Use of one's own tissue. • Isograft: Use of identical twin's tissue. • Allograft: Use of tissue from another person. • Xenotransplantation product: Use of non-human tissue. • Graft-versus-host disease can result from transplanted bone marrow that contains immunocompetent cells.

43. Immunosuppression Prevents an Immune Response to Transplanted Tissues • Cyclosporine suppresses IL-2. • Mycophenolate mofetil inhibits T cell and B cell reproduction. • Sirolimus blocks IL-2.

44. The Immune System and Cancer • Cancer cells possess tumor-specific antigens. • TC cells recognize and lyse cancer cells. • Cancer cells may lack tumor antigens or kill TC cells. Figure 19.10

45. Immunotherapy • Treatment of cancer using immunologic methods. • Tumor necrosis factor, IL-2, and interferons may kill cancer cells. • Immunotoxins link poisons with an monoclonal antibody directed at a tumor antigen. • Vaccines contain tumor-specific antigens.

46. Immune Deficiencies • Congenital: Due to defective or missing genes • Selective IgA immunodeficiency • Severe combined immunodeficiency • Acquired: Develop during an individual's life, due to drugs, cancers, and infections. • Artificial: Immunosuppression drugs. • Natural: HIV infections.