Medical Technology Department, Faculty of Science, Islamic University-Gaza MB M ICRO B IOLOGY Dr. Abdelraouf A. Elmanama Ph. D Microbiology 2008 Chapter 19 Disorders Associated with the Immune System

2008 Disorders Associated with the Immune System Infection and immunosuppression are failures of the immune system. Superantigens cause release of cytokines that cause adverse host responses. Allergies and transplant rejection are harmful immune reactions

2008 Response to antigens (allergens) leading to damage Require sensitizing dose(s) Hypersensitivity Reactions

2008 Involve IgE antibodies Localized: Hives or asthma from contact or inhaled antigens Systemic: Shock from ingested or injected antigens Type I (Anaphylactic) Reactions Figure 19.1a

2008 Skin testing Desensitization Type I (Anaphylactic) Reactions Figure 19.3

2008 Involve IgG or IgM antibodies and complement Complement activation causes cell lysis or damage by macrophages Type II (Cytotoxic) Reactions

2008 ABO Blood Group System Table 19.2

2008 Hemolytic Disease of the Newborn Figure 19.4

2008 Drug-induced Thrombocytopenic Purpura Figure 19.5

2008 IgG antibodies and antigens form complexes that lodge in basement membranes. Type III (Immune Complex) Reactions Figure 19.6

2008 Delayed-type hypersensitivities due to T D cells Cytokines attract macrophages and initiate tissue damage Type IV (Cell-Mediated) Reactions Figure 19.8

2008 Clonal deletion during fetal development ensures self- tolerance Autoimmunity is loss of self-tolerance Autoimmune Diseases

2008 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 Autoimmune Diseases

2008 Histocompatibility antigens: Self antigens on cell surfaces Major histocompatibility complex (MHC): Genes encoding histocompatibility antigens Human leukocyte antigen (HLA) complex: MHC genes in humans Reactions Related to the Human Leukocyte Antigen (HLA) Complex

2008 Diseases Related to Specific HLAs Table 19.3

2008 HLA Typing Figure 19.1

2008 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. Reactions to Transplantation

2008 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 Grafts

2008 Cyclosporine suppresses IL-2 Mycophenolate mofetil inhibits T cell and B cell reproduction Sirolimus blocks IL-2 Immunosuppression prevents an immune response to transplanted tissues

2008 Congenital: Due to defective or missing genes Selective IgA immunodeficiency Severe combined immunodeficiency Acquired: Develop during an individual's life, due to drugs, cancers, infections Artificial: Immunosuppression drugs Natural: HIV infections Immune Deficiencies

2008 Cancer cells possess tumor-specific antigens T C cells recognize and lyse cancer cells Cancer cells may lack tumor antigens or kill T C cells The Immune System and Cancer Figure 19.11

2008 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 Immunotherapy

2008 Acquired Immunodeficiency Syndrome (AIDS) 1981In U.S., cluster of Pneumocystis and Kaposi's sarcoma in young homosexual men discovered. The men showed loss of immune function. 1983Discovery of virus causing loss of immune function.

2008 Acquired Immunodeficiency Syndrome (AIDS) Figure 19.12a

2008 Crossed the species barrier into humans in Africa in the 1930s Patient who died in 1959 in Congo is the oldest known case Spread in Africa as a result of urbanization Spread in world through modern transportation and unsafe sexual practices Norwegian sailor who died in 1976 is the first known case in Western world The Origin of AIDS

2008 HIV Infection Figure 19.12b

2008 HIV Infection Figure Retrovirus penetrates host cell. Virion penetrates cell and its DNA is uncoated The new viral DNA is tranported into the host cell’s nucleus and integrated as a provirus. The provirus may divide indefinitely with the host cell DNA DNA Transcription of the provirus may also occur, producing RNA for new retrovirus genomes and RNA that codes for the retrovirus capsid and envelope proteins. 4 Mature retrovirus leaves host cell, acquiring an envelope as it buds out. 5 Capsid Reverse transcriptase Virus Two identical + stands of RNA DNA of one of the host cell’s chromosomes Provirus Host cell Reverse transcriptase Viral RNA RNA Viral proteins Identical strands of RNA

2008 HIV Infection Figure 19.13

2008 HIV Infection Figure 19.14

2008 Category AAsymptomatic or persistent lymphadenopathy Category BPersistent Candida albicans infections Category CClinical AIDS. CMV, TB, Pneumocystis, toxoplasmosis, Kaposi's sarcoma The Stages of HIV Infection

2008 The Stages of HIV Infection Figure 19.15

2008 Some Common Diseases Associated with AIDS Table 19.5

2008 Seroconversion takes up to 3 months HIV antibodies detected by ELISA HIV antigens detected by Western blotting Plasma viral load is determined by PCR or nucleic acid hybridization Diagnostic Methods

2008 HIV survives 6 hours outside a cell HIV survives >1.5 days inside a cell Infected body fluids transmit HIV via: Sexual contact Breast milk Transplacental infection of fetus Blood-contaminated needles Organ transplants Artificial insemination Blood transfusion HIV Transmission

2008 Modes of HIV Transmission Figure 19.17

2008 U.S., Canada, western Europe, Australia, northern Africa, South America Injecting drug use, male-to-male sexual contact Sub-Saharan Africa Heterosexual contact Eastern Europe, Middles East, Asia Injecting drug use, heterosexual contact AIDS Worldwide

2008 AIDS Worldwide Figure 19.16

2008 HIV-1 is the most common. It has 11 clades: 90% of U.S. infections caused by clade B Clade C predominates in sub-Saharan African Clades B, C, & E are in south and southeast Asia HIV-2 is seen in western Africa Clades

2008 Use of condoms and sterile needles Health-case workers use universal precautions Wear gloves, gowns, masks, goggles Do not recap needles Risk of infection from infected needlestick injury is 0.3% Prevention of AIDS

2008 Whole-cell Salmonella with gp120 gene Subunit vaccine using gp120 expressed in Saccharomyces Canarypox virus with HIV capsid protein genes Naked DNA consisting of tat (transcription factor) or gag (capsid protein) genes Vaccines in Clinical

2008 Nucleotide Reverse Transcriptase Inhibitors Non- Nucleoside Reverse Transcriptase Inhibitors Protease Inhibitors Virus decoys Chemotherapy

2008 Combinations of nucleoside reverse transcriptase inhibitors + Non-nucleoside reverse transcriptase inhibitor or Protease inhibitor Highly Active Antiretroviral Therapy (HAART):