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Immunological Diseases
Spectrums and Mechanisms Assistant Professor Kiat Ruxrungtham, M.D. Division of Allergy and Clinical Immunology Department of Medicine, Faculty of Medicine Chulalongkorn University
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Principles of Immunology
Key roles of immune responses Terminology Primary and Secondary Immune Responses Cells and Molecules involved Immunological Disorders Mechanisms and Clinical Implications
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Key Roles of Immune System
Prevent and control infection Prevent and control autoimmune diseases Prevent and control malignancy Prevent and control allergic diseases Prevent and control graft-versus-host (GVH)
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Terminology Antigen, allergen, immunogen and epitope
Innate and Acquired Immunity Allergy Autoimmunity, autoimmune diseases
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Innate and Acquired Immunity
Innate Acquired Ag specificity no yes Magnitude (10, 20) same higher (20 > 10) Memory no yes Key components PMN, NK T, B lymphocytes Cā, barriers APCs
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Primary and Secondary Immune Responses
Primary IR 7-10 relatively low Mostly IgM relatively high Secondary IR 2-5 days relatively high Other class (IgG, IgA, etc) relatively low Lag period Peak response Ig class Antigen [ ]
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Cells and Molecules Involved in Immunology
Innate Immunity Cells: epithelium, phagocytes (neutrophils, monocyte-macrophages) NK cells, mast cells Molecules: complement, inflammatory mediators, cytokines, chemokines, adhesion molecules
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Cells and Molecules Involved in Immunology
Acquired Immunity Cells: APCs (macrophages), T (CD4+, CD8+) and B lymphoctyes (plasma cells), monocytes Molecules: HLA, cytokines, immunoglobulins, adhesion molecules
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Immunological disorders
Hypersensitivity mediated disorders Immunodeficiency : 10 and 20 ID
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Classification of Hypersensitivity
Gell and Coombās Classification: 4 Types Type 1 : IgE-mediated Type 2 : Cytotoxic antibodies Type 3 : Ag-Ab Immune complexes Type 4 : Delayed-type, cell-mediated hypersensitivity
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Type I Hypersensitivity
Allergen exposure, sensitization and re-exposure IgE antibody, mast cells/ basophils and itsā mediators Target organ immediate reactions Clinical allergy: atopic diseases, drug allergy, insect allergy and anaphylaxis
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Pathogenesis of Allergic Disease
Genetic Susceptibility Adjuvant factors: Tobacco smoke Air pollutants Lack of protective factors: Infection ? Immunization ? Nutrition ? Allergic Sensitzation Allergen Exposure Upper/lower airway or Skin hyperresponsiveness Pollutants Infection Excercise Vary in spectrum and severity Allergic Diseases Modified from Ulrich Wahn 1998
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Principle Pathogenesis of Allergic Diseases
Durham and Till 1998, Lu 1998, Drazen 1996 Allergen APC CD4+ T-cell IL-12 Allergen Th-1 Th-2 IL-4 IgE IFN-g IL-5 IL-3 GM-CSF B-cell B-cell CD8+ cell IgG Mast cell IL-5 Other cells _ + Eosonophil MBP ECP, LTs Late Phase Reaction Tryptase, LTs AllergyChula
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Pathogenesis of Allergic Diseases Cells & Molecules Involved in Allergic Inflammation Modified from Robert Davies
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Mediators of Mast Cells and Basophils
Secondary Mediators Primary Mediators Prostaglandins Leukotrienes PAF Histamine RFs IL-3, 4, 5, 6, 7, 8 GM-CSF, TNFa Chemokines -MCP1, MIP1 Oxygen radicals Histamine Tryptase Chymotryptase Heparin/Chondroitin Kininogenase Chemotactic Factors AllergyChula Sim TC, Grant JA 1996
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Mediators of Mast Cells and Allergy
Blood Vessels Urticaria, Angioedema Laryngeal edema, Shock H, PGD2, LTs, PAF Kinin Bronchospasm Abd. pain, Vomiting Smooth Muscles H, PGD2, LTs, PAF Diarrhea, Rhinorhea Bronchial secretion Mucus Glands H Mast Cell Basophil Sensory Nerves Itching LTB4 PAF IL3, IL5 Chemokines Leukocytes Inflammation - LPAR AllergyChula
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Epidemiology of Allergic Diseases in Thai Children
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Skin Prick Test
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Factors Affecting Clinical Outcomes of Allergic Diseases
Treatment Anti-inflammatory Anti-allergic Relievers Enivronmental Allergens Irritants Westernization Genetic Degree of atopy Compliance Avoidance Medication uses Infection Viral Bacterial Allergen Immunotherapy Allergic Diseases Future Therapy ? Remission Mild Moderate Severe AllergyChula
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Clinical Uses of H1 Antagonists
Generation of Antihistamines Clinical First Second and Third Allergic Rhinitis (better compliance) Urticaria (better compliance) Atopic dermatitis ++/ (better compliance) Asthma /++ (Meta-analysis= NS)URI/NAR Itching dermatosis ++/ Anti-motion sickness Antiemetic Appetite stimulation (+ for astemizole) Insomnia AllergyChula
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Treatment of Allergic Rhinitis in Adults
Allergy 1994; suppl. 19
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Treatment of Allergic Asthma
Allergy 1994; suppl. 19
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Type II Hypersensitivity
Cytotoxic antibodies: IgG, IgM Mechanisms of cytolysis: Fix complement and/or ADCC Clinical spectrums: Autoimmune Hemolytic anemia (AIHA) ABO Miss-matched ITP Stimulatory antibody: Graveās disease Inhibitory antibody: Myasthenia gravis (anti-Ach Rc)
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Principle treatments in Type II
ABO matching For AIHA, ITP: Steroid, immunosuppressive agents, +/- splenectomy
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Type III Hypersensitivity
Mechanisms: Ag (protein, drugs) + Ab (IgG, IgM) --> Immune complex --> deposit at subendothelial basement membrane --> fix complement --> chemotaxis ---> PMNs --> vasculitis Immune complex diseases: Serum sickness Autoimmune diseases: prototype-SLE Vasculitis
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Principle treatments in Type III
Serum sickness: Avoidance of heterogeneous protein injection: ERIG antirabies Autoimmune diseases: SLE Avoidance sun exposure Steroid Immunosupressive agents
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Type IV Hypersensitivity
Delayed-type cell-mediated reaction Mechanism: Antigen (contactants) --> sensitized T-lymphoctyes --> re-exposure --> T cells activation --> cytokines ---> mononuclear cell recruitment --> DTH Clinical disorder: Atopic contact dermatitis
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Principle treatments in Type IV
Avoidance Topical steroid Systemic steroid, if severe
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