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Immunological Diseases Spectrums and Mechanisms Assistant Professor Kiat Ruxrungtham, M.D. Division of Allergy and Clinical Immunology Department of Medicine,

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Presentation on theme: "Immunological Diseases Spectrums and Mechanisms Assistant Professor Kiat Ruxrungtham, M.D. Division of Allergy and Clinical Immunology Department of Medicine,"— Presentation transcript:

1 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

2 Principles of Immunology Key roles of immune responsesKey roles of immune responses TerminologyTerminology Primary and Secondary Immune ResponsesPrimary and Secondary Immune Responses Cells and Molecules involvedCells and Molecules involved Immunological DisordersImmunological Disorders Mechanisms and Clinical ImplicationsMechanisms and Clinical Implications

3 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)

4 Terminology Antigen, allergen, immunogen and epitope Innate and Acquired Immunity Allergy Autoimmunity, autoimmune diseases

5 Innate and Acquired Immunity InnateAcquired Ag specificity noyes Magnitude (1 0, 2 0 )samehigher (2 0 > 1 0 ) Memorynoyes Key componentsPMN, NKT, B lymphocytes C, barriers APCs

6 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 [ ]

7 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

8 Cells and Molecules Involved in Immunology Acquired Immunity Cells: APCs (macrophages), T (CD4+, CD8+) and B lymphoctyes (plasma cells), monocytesCells: APCs (macrophages), T (CD4+, CD8+) and B lymphoctyes (plasma cells), monocytes Molecules: HLA, cytokines, immunoglobulins, adhesion moleculesMolecules: HLA, cytokines, immunoglobulins, adhesion molecules

9 Immunological disorders Hypersensitivity mediated disorders Immunodeficiency : 1 0 and 2 0 ID

10 Classification of Hypersensitivity Gell and Coombs Classification: 4 Types Type 1 : IgE-mediated Type 2 : Cytotoxic antibodies Type 3 : Ag-Ab Immune complexes Type 4 : Delayed-type, cell-mediated hypersensitivity

11 Type I Hypersensitivity Allergen exposure, sensitization and re- exposure IgE antibody, mast cells/ basophils and its mediators Target organ immediate reactions Clinical allergy: atopic diseases, drug allergy, insect allergy and anaphylaxis

12 Pathogenesis of Allergic Disease Genetic Susceptibility Allergic Sensitzation Upper/lower airway or Skin hyperresponsiveness Allergic Diseases Allergen Exposure Adjuvant factors: Tobacco smoke Air pollutants Lack of protective factors: Infection ? Immunization ? Nutrition ? Pollutants Infection Excercise Modified from Ulrich Wahn 1998 Vary in spectrum and severity

13 Principle Pathogenesis of Allergic Diseases Th-2Th-1 IL-12 IFN-g IL-5 IL-3 GM-CSF Eosonophil Mast cell IL-4 IgE B-cell APC Allergen CD4+ T-cell Late Phase Reaction _ + IgG Durham and Till 1998, Lu 1998, Drazen 1996 CD8+ cell AllergyChula IL-5 B-cell Allergen Tryptase, LTs MBP ECP, LTs Other cells

14 Pathogenesis of Allergic Diseases Cells & Molecules Involved in AllergicInflammation Modified from Robert Davies

15 Mediators of Mast Cells and Basophils Histamine Tryptase Chymotryptase Heparin/Chondroitin Kininogenase Chemotactic Factors Prostaglandins Leukotrienes PAF Histamine RFs IL-3, 4, 5, 6, 7, 8 GM-CSF, TNF Chemokines - MCP1, MIP1 Oxygen radicals Primary Mediators Secondary Mediators Sim TC, Grant JA 1996 AllergyChula

16 Mediators of Mast Cells and Allergy Mast Cell Basophil Blood Vessels Smooth Muscles Mucus Glands Sensory Nerves LeukocytesLeukocytes H, PGD 2, LTs, PAF Kinin H H, PGD 2, LTs, PAF LTB4PAF IL3, IL5 Chemokines Urticaria, Angioedema Laryngeal edema, Shock Bronchospasm Abd. pain, Vomiting Diarrhea, Rhinorhea Bronchial secretion Itching Inflammation - LPAR AllergyChula

17 Allergic Rhinitis Allergic Rhinitis Allergic Asthma Allergic Asthma Atopic Dermatitis Atopic Dermatitis Urticaria Urticaria Food Allergy Food Allergy Drug Allergy Drug Allergy Allergy Chula 1999

18 Epidemiology of Allergic Diseases in Thai Children 2533; 2541

19 Skin Prick Test



22 Factors Affecting Clinical Outcomes of Allergic Diseases AllergyChula Enivronmental Allergens Irritants Westernization Infection Viral Bacterial Treatment Anti-inflammatory Anti-allergic Relievers Compliance Avoidance Medication uses Allergic Diseases Remission Moderate Mild Severe Allergen Immunotherapy Genetic Degree of atopy Future Therapy ?

23 Clinical Uses of H 1 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

24 Treatment of Allergic Rhinitis in Adults Allergy 1994; suppl. 19

25 Treatment of Allergic Asthma Allergy 1994; suppl. 19

26 Type II Hypersensitivity Cytotoxic antibodies: IgG, IgMCytotoxic antibodies: IgG, IgM Mechanisms of cytolysis: Fix complement and/or ADCCMechanisms of cytolysis: Fix complement and/or ADCC Clinical spectrums:Clinical spectrums: –Autoimmune Hemolytic anemia (AIHA) –ABO Miss-matched –ITP Stimulatory antibody: Graves diseaseStimulatory antibody: Graves disease Inhibitory antibody: Myasthenia gravis (anti-Ach Rc)Inhibitory antibody: Myasthenia gravis (anti-Ach Rc)

27 Principle treatments in Type II ABO matching For AIHA, ITP: Steroid, immunosuppressive agents, +/- splenectomy

28 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

29 Principle treatments in Type III Serum sickness: Avoidance of heterogeneous protein injection: ERIG antirabies Autoimmune diseases: SLE –Avoidance sun exposure –Steroid –Immunosupressive agents

30 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

31 Principle treatments in Type IV Avoidance Topical steroid Systemic steroid, if severe

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