* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download hypersensitivities ppt
Survey
Document related concepts
Sociality and disease transmission wikipedia , lookup
Complement system wikipedia , lookup
Monoclonal antibody wikipedia , lookup
DNA vaccination wikipedia , lookup
Hepatitis B wikipedia , lookup
Immune system wikipedia , lookup
Adaptive immune system wikipedia , lookup
Autoimmunity wikipedia , lookup
Adoptive cell transfer wikipedia , lookup
Sjögren syndrome wikipedia , lookup
Hygiene hypothesis wikipedia , lookup
Cancer immunotherapy wikipedia , lookup
Polyclonal B cell response wikipedia , lookup
X-linked severe combined immunodeficiency wikipedia , lookup
Molecular mimicry wikipedia , lookup
Innate immune system wikipedia , lookup
Transcript
Hypersensitivities, Infection, and Immune Deficiencies Chapter 7 Hypersensitivity • Altered immunologic response to an antigen that results in disease or damage to the host Hypersensitivity • Allergy • Deleterious effects of hypersensitivity to environmental (exogenous) antigens • Autoimmunity • Disturbance in the immunologic tolerance of self-antigens • Alloimmunity • Immune reaction to tissues of another individual Hypersensitivity • Characterized by the immune mechanism • Type I • IgE mediated • Type II • Tissue-specific reactions • Type III • Immune complex mediated • Type IV • Cell mediated Hypersensitivity • Immediate hypersensitivity reactions • Anaphylaxis • Delayed hypersensitivity reactions Type I Hypersensitivity • IgE mediated • Against environmental antigens (allergens) • IgE binds to Fc receptors on surface of mast cells (cytotropic antibody) • Histamine release • H1 and H2 receptors • Antihistamines Type I Hypersensitivity • Manifestations • Itching • Urticaria • Conjunctivitis • Rhinitis • Hypotension • Bronchospasm • Dysrhythmias • GI cramps and malabsorption Type I Hypersensitivity • Genetic predisposition • Tests • Food challenges • Skin tests • Laboratory tests • Desensitization • IgG-blocking antibodies Type I Hypersensitivity Type II Hypersensitivity • Tissue specific • Specific cell or tissue (tissue-specific antigens) is the target of an immune response Type II Hypersensitivity • Five mechanisms • Cell is destroyed by antibodies and complement • Cell destruction through phagocytosis • Soluble antigen may enter the circulation and deposit on tissues • Antibody-dependent cell-mediated cytotoxicity • Causes target cell malfunction Type III Hypersensitivity • Immune complex mediated • Antigen-antibody complexes are formed in the circulation and are later deposited in vessel walls or extravascular tissues • Not organ specific Type III Hypersensitivity • Immune complex clearance • Large—macrophages • Small—renal clearance • Intermediate—deposit in tissues Type III Hypersensitivity • Immune complex disease • Serum sickness • Arthus reaction Type IV Hypersensitivity • Does not involve antibody • Cytotoxic T-lymphocytes or lymphokine producing Th1 cells • Direct killing by Tc or recruitment of phagocytic cells by Th1 cells • Examples • Acute graft rejection, skin test for TB, contact allergic reactions, and some autoimmune diseases Allergy • Environmental antigens that cause atypical immunologic responses in genetically predisposed individuals • Pollens, molds and fungi, foods, animals, etc. • Allergen is contained within a particle too large to be phagocytosed or is protected by a nonallergenic coat • Original insult is apparent Autoimmunity • Breakdown of tolerance • Body recognizes self-antigens as foreign • Sequestered antigen • Self-antigens not normally seen by the immune system • Infectious disease • Molecular mimicry • Neoantigen • Haptens become immunogenic when they bind to host proteins Autoimmunity • Forbidden clone • During differentiation, lymphocytes produce receptor that react with self-antigens • Ineffective peripheral tolerance • Defects in regulatory cells • Original insult • Genetic factors Alloimmunity • Immune system reacts with antigens on the tissue of other genetically dissimilar members of the same species • Transient neonatal alloimmunity • Fetus expresses parental antigens not found in the mother • Transplant rejection and transfusion reactions Autoimmune Examples • Systemic lupus erythematosus (SLE) • Chronic multisystem inflammatory disease • Autoantibodies against: • Nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc. Autoimmune Examples • Systemic lupus erythematosus (SLE) • Deposition of circulating immune complexes containing antibody against host DNA • More common in females Systemic Lupus Erythematosus • Clinical manifestations • Arthralgias or arthritis (90% of individuals) • Vasculitis and rash (70%-80%) • Renal disease (40%-50%) • Hematologic changes (50%) • Cardiovascular disease (30%-50%) Systemic Lupus Erythematosus • Eleven common findings • Serial or simultaneous presence of at least four indicates SLE • Facial rash (malar rash), discoid rash, photosensitivity, oral or nasopharyngeal ulcers, nonerosive arthritis, serositis, renal disorder, neurologic disorder, hematologic disorders, immunologic disorders, and presence of antinuclear antibodies (ANA) Graft Rejection • Transplant rejection is classified according to time • Hyperacute • Immediate and rare • Preexisting antibody to the antigens of the graft • Acute • Cell-mediated immune response against unmatched HLA antigens Graft Rejection • Transplant rejection is classified according to time • Chronic • Months or years • Inflammatory damage to endothelial cells of vessels as a result of a weak cell-mediated reaction against minor HLA antigens Microorganism and Human Relationship • Mutual relationship • Normal flora • Relationship can be breached by injury • Leave their normal sites and cause infection elsewhere • Opportunistic microorganisms Stages of Infection • • • • Colonization Invasion Multiplication Spread Factors for Infection • • • • • • Mechanism of action Infectivity Pathogenicity Virulence Immunogenicity Toxigenicity Classes of Infectious Microorganisms • • • • • • • • Virus Chlamydia Rickettsia Mycoplasma Bacteria Fungi Protozoa Helminths Pathogen Defense Mechanisms • Surface coats • Inhibit phagocytosis, surface receptors to bind host cells, and toxins • Antigenic variation • Mutation • Antigenic drift • Recombination • Antigenic shifts • Gene switching Bacterial Virulence and Infectivity • Bacteria must have iron to multiply • Siderophores (iron receptors) • Presence of polysaccharide capsules • Suppression of complement activation • Bacterial proliferation rates can surpass protective response Bacterial Virulence and Infectivity • Toxin production • Exotoxins • Enzymes released during growth, causing specific responses • Immunogenic • Antitoxin production • Endotoxins • Lipopolysaccharides contained in the cell walls of gram-negative organisms • Pyrogenic effects Bacterial Virulence and Infectivity • Bacteremia or septicemia • Presence of bacteria in the blood as a result of a failure of the body’s defense mechanisms • Usually caused by gram-negative bacteria • Toxins released in the blood cause the release of vasoactive peptides and cytokines that produce widespread vasodilation Viral Infection and Injury • Obligate intracellular parasites • Dependent on host cells • No metabolism or incapable of independent reproduction • Permissive host cell • Virion binds to receptors on the plasma membrane • Usually a self-limiting infection • Spreads cell to cell Viral Replication • • • • • • DNA or RNA Single or double stranded Protein receptor-binding site Virus uncoats Most RNA viruses directly produce mRNA DNA “provirus” enters nucleus and is transcribed into mRNA Viral Replication • Translation of mRNA results in the production of viral proteins • New virions are released through budding • Viral DNA that is integrated in host cell DNA is transmitted to daughter cells by mitosis Cellular Effects of Viruses • Inhibition of host cell DNA, RNA, or protein synthesis • Disruption of lysosomal membranes • Promotion of apoptosis • Fusion of infected, adjacent host cells • Alteration of antigenic properties Cellular Effects of Viruses • Transformation of host cells into cancerous cells • Promotion of secondary bacterial infections Fungal Infection and Injury • Large microorganisms with thick cell walls • Eukaryotes • Exist as single-celled yeasts, multi-celled molds, or both Fungal Infection and Injury • Pathogenicity • Adapt to host environment • Wide temperature variations, digest keratin, low oxygen • Suppress the immune defenses Fungal Infection and Injury • Diseases caused by fungi are called mycoses • Superficial, deep, or opportunistic • Fungi that invade the skin, hair, or nails are known as dermatophytes • The diseases they produce are called tineas (ringworm) • Tinea capitis, tinea pedis, and tinea cruris Fungal Infection and Injury • Deep fungal infections are life threatening and are commonly opportunistic Clinical Manifestations of Infectious Disease • Variable depending on the pathogen • Directly caused by the pathogen or indirectly caused by its products • Fever • Resetting the hypothalamus • Exogenous pyrogens • Endogenous pyrogens Countermeasures • Vaccines • Induction of long-lasting protective immune responses that will not result in disease in a healthy recipient • Attenuated organism • Killed organisms • Recombinant viral protein • Bacterial antigens • Toxins Countermeasures • Antimicrobials • Inhibit synthesis of cell wall • Damage cytoplasmic membrane • Alter metabolism of nucleic acid • Inhibit protein synthesis • Modify energy metabolism Pathogenic Adaptations • Suppression of immune response • Antigenic changes • Development of resistance Immune Deficiencies • Failure of immune mechanisms of self-defense • Primary (congenital) immunodeficiency • Genetic anomaly • Secondary (acquired) immunodeficiency • Caused by another illness • More common Immune Deficiencies • Clinical presentation • Development of unusual or recurrent, severe infections • T cell deficiencies • Viral, fungal, yeast, and atypical microorganisms • B cell and phagocyte deficiencies • Microorganisms requiring opsonization • Complement deficiencies Primary Immune Deficiencies • Most are the result of a single gene defect • Five groups • B-lymphocyte deficiencies • T-lymphocyte deficiencies • Combined T and B cell deficiencies • Complement defects • Phagocyte defects B Lymphocyte Deficiencies • Hypogammaglobulinemia or agammaglobulinemia • Bruton agammaglobulinemia • Autosomal agammaglobulinemia • X-linked hyper-IgM syndrome • IgG subclass deficiency • Selective IgA deficiency • Common variable immune deficiency T-Lymphocyte Deficiencies • DiGeorge syndrome • Partial or complete absence of T cell immunity • Chronic mucocutaneous candidiasis Combined T and B Cell Deficiencies • Severe combined immunodeficiency (SCID) • Reticular dysgenesis (most severe form) • Adenosine deaminase (ADA) deficiency • X-linked SCID • JAK3 deficiency • IL-7 receptor deficiency • Purine nucleoside phosphorylase deficiency Combined T and B Cell Deficiencies • • • • • RAG-1 or RAG-2 deficiency Bare lymphocyte deficiency MHC class I and II deficiency Wiskott-Aldrich syndrome Ataxia-telangiectasia (AT) Complement Deficiencies • • • • • C3 deficiency Mannose-binding lectin (MBL) deficiency Properdin deficiency Factor I and factor H deficiency C9 deficiency Phagocytic Deficiencies • Severe congenital neutropenia • Cyclic neutropenia • Leukocyte adhesion deficiencies (LAD) • C3 receptor deficiency • Chédiak-Higashi syndrome • Myeloperoxidase deficiency • Chronic granulomatous disease Secondary Deficiencies • Also referred to as acquired deficiencies • Far more common than primary deficiencies Secondary Deficiencies • Causes • Normal physiology conditions • Psychologic stress • Dietary insufficiencies • Malignancies • Physical trauma • Medical treatments • Infections • Acquired immunodeficiency syndrome (AIDS) Acquired Immunodeficiency Syndrome (AIDS) • Syndrome caused by a viral disease • Human immunodeficiency virus (HIV) • Depletes the body’s Th cells • Incidence • Worldwide • 5 million per year • United States • About 31,000 cases per year Acquired Immunodeficiency Syndrome (AIDS) • Effective antiviral therapies have made AIDS a chronic disease • Epidemiology • Blood-borne pathogen • Increasing faster in women than men Acquired Immunodeficiency Syndrome (AIDS) • Pathogenesis • Retrovirus • Genetic information is in the form of RNA • Contains reverse transcriptase to convert RNA into double-stranded DNA • Integrase Human Immunodeficiency Virus (HIV) Human Immunodeficiency Virus (HIV) • Structure • gp120 protein binds to the CD4 molecule found primarily on the surface of helper T cells • CD4+ Th cells • Typically 800 to 1000 cells/mm3 • Reverses CD4/CD8 ratio Human Immunodeficiency Virus (HIV) • Structure • Co-receptors • CXCR4 and CCR5 • Strains can be selective for these receptors; influences the tropism of the target cells Human Immunodeficiency Virus (HIV) • Clinical manifestations • Serologically negative, serologically positive but asymptomatic, early stages of HIV, or AIDS • Window period • Th cells <200 cells/mm3 • Diagnosis of AIDS is made in association with various clinical conditions • Atypical or opportunistic infections, and cancer Human Immunodeficiency Virus (HIV) • Treatment and prevention • Highly active antiretroviral therapy (HAART) • Reverse transcriptase inhibitors • Protease inhibitors • New drugs • Entrance inhibitors • Integrase inhibitors • Vaccine development Graft-Versus-Host Disease (GVHD) • Immunocompromised individuals are at risk for CVHD • T cells in the graft are mature and capable of cell-mediated destruction tissues within the recipient • Not a problem if patient is immunocompetent Evaluation of Immunity • Complete blood count (CBC) with a differential • Subpopulations of lymphocytes • Quantitative determination of immunoglobulins • Subpopulations of immunoglobulins • Assay for total complement • Skin tests Treatment for Immunodeficiencies • • • • Gamma globulin therapy Transplantation or transfusion Treatment with soluble immune mediators Gene therapy