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Disorders of Immunity and Inflammation

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Information about Disorders of Immunity and Inflammation
Education

Published on October 15, 2008

Author: aSGuest1072

Source: authorstream.com

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Disorders of Immunity and Inflammation : Disorders of Immunity and Inflammation Hypersensitivity : Hypersensitivity Exaggerated Immune Response Hypersensitivity Types : Hypersensitivity Types Allergy Exogenous, non-human antigen Isoimmunity (alloimmunity) Exogenous, human antigen Autoimmunity Endogenous antigen Hypersensitivity Mechanisms : Hypersensitivity Mechanisms Type I: IgE mediated Type II: Tissue specific Type III: Immune complex mediated Type IV: Cell mediated Type I : Type I Immediate hypersensitivity IgE mediated Exogenous antigen Most (but not all) Allergies Type I: Mechanism : Type I: Mechanism Repeated antigen exposure causes increased IgE production IgE binds to mast cells Sensitization occurs Type I: Mechanism : Type I: Mechanism Antigen binds to IgE on mast cell membrane Mast cell releases histamine, chemotaxic factors Inflammatory response occurs Type I: Signs/Symptoms : Type I: Signs/Symptoms Clinical signs, symptoms = response to histamine release GI, skin, respiratory system High mast cells numbers Most sensitive Type I: Signs/Symptoms : Type I: Signs/Symptoms Histamine effects Vasodilatation Increased capillary permeability Non-vascular smooth muscle spasm Type I: Signs/Symptoms : Type I: Signs/Symptoms Skin: flushing, itching, edema, urticaria, hives Respiratory: bronchospasm, laryngospasm, laryngeal edema Cardiovascular: tachycardia, hypotension GI: nausea, vomiting, cramping, diarrhea Type I: Atopia : Type I: Atopia “Allergy prone” individuals Genetic predisposition More IgE More mast cell receptors for antibodies than normal Type I: Anaphylaxis : Type I: Anaphylaxis Severe, generalized Type I reaction Life-threatening Loss of airway Ventilatory failure Hypoperfusion Type II : Type II Tissue specific Reaction to tissue-specific antigens Causes target cell destruction, dysfunction Exogenous or endogenous antigen Type II : Type II Most commonly affected cells Red blood cells Thyroid cells Type II: Mechanisms : Type II: Mechanisms Antibody binds to cell membrane, triggers compliment-mediated lysis Examples Reaction to transfused blood Hemolytic disease of newborn Type II: Mechanisms : Type II: Mechanisms Antibodies promote target cell clearance by macrophages Type II: Mechanisms : Type II: Mechanisms Antibodies bind to target cells and cytotoxic T-cells Trigger release of toxins to destroy target cells Type II: Mechanisms : Type II: Mechanisms Antibody binds to cell membrane, causes alterations in target cell function Example: Graves' disease Antibody binds to thyroid cell membrane Mimics Thyroid Stimulating Hormone action Causes production of excessive amounts of thyroid hormone Results in common form of hyperthyroidism Type III : Type III Mediated by antigen/ antibody complex deposition in tissues Exogenous or endogenous antigen Type III: Mechanism : Type III: Mechanism Ag-Ab complex deposited in tissues Especially sensitive tissues are blood vessels, GI, respiratory system Causes complement activation, increased neutrophil activity Neutrophils have trouble digesting complexes, release lysosomes causing damage Type III : Type III Immune complex quantity varies over time Symptomatic periods alternate with periods of remission Type III: Serum Sickness : Type III: Serum Sickness Repeated intravenous antigen injections Immune complexes deposited in tissues Fever, rash, pain, lymphadenopathy Type III: Raynaud’s Phenomenon : Type III: Raynaud’s Phenomenon Temperature governs immune complex deposition in peripheral circulation Exposure to cold causes redness, pain of fingers, toes followed by numbness, cyanosis, gangrene Type III: Arthus Reaction : Type III: Arthus Reaction Occurs after repeated LOCAL exposure to exogenous antigen Immune complexes in vessel walls Examples Celiac disease from wheat protein Hemorrhagic alveolitis from moldy hay inhalation Type IV : Type IV Delayed Mediated by Td (lymphokine-producing) or Tc (cytotoxic) cells No antibody involved Type IV : Type IV Examples Graft rejection Contact allergic reactions (poison ivy) Hypersensitivity Targets : Hypersensitivity Targets Allergins Pollen (hay fever) Drug reactions Foods Hypersensitivity Targets : Hypersensitivity Targets Neoantigens Hapten binds to protein molecule Changes its antigenicity Causes it to become an allergen Hypersensitivity Targets : Hypersensitivity Targets Autoantigens Sequestered cells (cornea, testes) Foreign antigen triggered (infection) Suppressor T-cell malfunction Genetic causes Hypersensitivity Targets : Hypersensitivity Targets Isoantigens Tissue grafts, transplants Rh negative sensitivity Autoimmune Disease : Autoimmune Disease Clinical disorder produced by immune response to normal tissue component of patient’s body Graves’ Disease : Graves’ Disease Antibody stimulates thyroid hormone over production Produces hyperthyroidism Antibody, disease can be passed through placenta Rheumatoid Arthritis : Rheumatoid Arthritis Antibody reaction to collagen in joints Causes inflammation, destruction of joints Myasthenia Gravis : Myasthenia Gravis Antibodies destroy acetylcholine receptors on skeletal muscle Produce episodes of severe weakness Antibodies can cross placenta, affect newborn Immune Thrombocytopenic Purpura : Immune Thrombocytopenic Purpura Antibodies destroy platelets Produces clotting disorders, hemorrhaging Antibodies can cross placenta, affect newborn Isoimmune Neutropenia : Isoimmune Neutropenia Antibodies attack, destroy neutrophils Can cross placenta, affect newborn Other Autoimmune Diseases : Other Autoimmune Diseases Type I diabetes mellitus Primary myxedema Rheumatic fever Crohn’s disease Ulcerative colitis Systemic Lupus Erythematosis (SLE) SLE : SLE Chronic, multi-system auto-immune disease Highest incidence Women, 20-40 years of age Black, Hispanic women Mortality after diagnosis averages 5% per year SLE : SLE Antibody against nucleic acid components (ANA, anti-nuclear antibody) Immune complex precipitates in tissues, causes widespread destruction Especially affected are renal system, blood vessels, heart SLE : SLE Signs/Symptoms Facial rash/skin rash triggered by sunlight exposure Oral/nasopharyngeal ulcers Fever Arthritis SLE : SLE Signs/Symptoms Serositis (pleurisy, pericarditis) Renal injury/failure CNS involvement with seizures/psychosis Peripheral vasculitis/gangrene Hemolytic anemia SLE : SLE Chronic management Anti-inflammatory drugs Aspirin Ibuprofen Corticosteroids Avoidance of emotional stress, physical fatigue, excessive sun exposure Disorders of Immunity : Disorders of Immunity Immunodeficiency Diseases Immunodeficiency Disease : Immunodeficiency Disease Patient unable to fight off infection Hallmarks Repeated infections Opportunistic infections Immunodeficiency Disease : Immunodeficiency Disease Most are defects in T cells or B cells T cells, macrophage defects = fungal, viral infections B cells, complement defects = bacterial infections Immunodeficiency Disease : Immunodeficiency Disease Congenital Acquired Congenital : Congenital B-cell Deficiency IgA Deficiency DiGeorge’s Syndrome Severe Combined Immunodeficiency B Cell Deficiency : B Cell Deficiency Agammaglobulinemia Hypogammaglobulinemia IgA Deficiency : IgA Deficiency Most common immune deficiency disorder Genetic condition Failure of IgA synthesis Patient has repeated, recurrent sinus, lung, GI infections DiGeorge’s Syndrome : DiGeorge’s Syndrome Thymic hypoplasia Severe decrease in T-cell production, function Defects of face, ears, heart Severe Combined Immunodeficiency : Severe Combined Immunodeficiency Thymus development arrested at ~6-8 weeks gestation. Deficiency, defective maturation of stem cells that produce B and T cells Little to no antibody production SCID : SCID Two types Autosomal recessive X-linked disease recessive SCID : SCID Recurrent, frequently overwhelming infections Particularly respiratory, gastrointestinal Most die in first few years of life, usually by one year of age Death usually due to opportunistic infection Acquired : Acquired Nutritional deficiency Iatrogenic (drugs, radiation) Trauma (prolonged hypoperfusion) Stress Infection (HIV) Immune Deficiency Therapies : Immune Deficiency Therapies B-cell deficiency: Gamma globulin SCID: Bone marrow transplants, enzyme replacement DiGeorge’s Syndrome: Fetal thymus transplants Gene therapy

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