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TORTORA FUNKE CASE ninth edition MICROBIOLOGY an introduction 18 Part A Practical Applications of Immunology PowerPoint® Lecture Slide Presentation prepared by Christine L. Case Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Monoclonal Antibodies Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.2 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Precipitation Reactions Involve soluble antigens with antibodies. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.4 Agglutination Reactions Involve particulate antigens and antibodies. Antigens may be On a cell (direct agglutination). Attached to latex spheres (indirect or passive agglutination). Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.5 Antibody Titer Is the concentration of antibodies against a particular antigen. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.6 Viral Hemagglutination Hemagglutination involves agglutination of RBCs. Some viruses agglutinate RBCs in vitro. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.8 Viral Hemagglutination-Inhibition Hemagglutination involves agglutination of RBCs. Some viruses agglutinate RBCs in vitro. Antibodies prevent hemagglutination. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.9b Neutralization Reactions Eliminate the harmful effect of a virus or exotoxin. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.9b Complement Fixation Test Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.10 (1 of 2) Complement Fixation Test Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.10 (2 of 2) Fluorescent Antibody Techniques (Direct) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.11a Fluorescent Antibody Techniques (Indirect) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figures 18.11b, 3.6b Enzyme-Linked Immunosorbent Assay (Direct ELISA) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.14a Enzyme-Linked Immunosorbent Assay (Indirect ELISA) Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.14b Serological Tests Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 18.13 Serological Tests Direct tests detect antigens (from patient sample). Indirect tests detect antibodies (in patient′s serum). Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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? Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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? Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Disorders Associated with the Immune System Harmful immune responses Allergies Transplant rejection Autoimmunity Superantigens cause release of cytokines that cause adverse host responses. Immunodeficiencies Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings TORTORA FUNKE CASE ninth edition MICROBIOLOGY an introduction 19 Part A Disorders Associated with the Immune System PowerPoint® Lecture Slide Presentation prepared by Christine L. Case Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Hypersensitivity Reactions Response to antigens (allergens) leading to damage. Require sensitizing dose(s). Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Type I (Anaphylactic) Reactions Involve IgE antibodies. Localized: Hives or asthma from contact or inhaled antigens. Systemic: Shock from ingested or injected antigens. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 19.1a Type I (Anaphylactic) Reactions Skin testing Desensitization Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 19.3 Type II (Cytotoxic) Reactions Involve IgG or IgM antibodies and complement. Complement activation causes cell lysis or damage by macrophages. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings ABO Blood Group System Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Table 19.2 Hemolytic Disease of the Newborn Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 19.4 Drug-induced Thrombocytopenic Purpura Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 19.5 Type III (Immune Complex) Reactions IgG antibodies and antigens form complexes that lodge in basement membranes. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 19.6 Type IV (Cell-Mediated) Reactions Delayed-type hypersensitivities due to TD cells. Cytokines attract macrophages and initiate tissue damage. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 19.8 Autoimmune Diseases Clonal deletion during fetal development ensures self-tolerance. Autoimmunity is loss of self-tolerance. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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 Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Diseases Related to Specific HLAs Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Table 19.3 HLA Typing Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 19.9 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 19.10 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 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. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings