allergy pathophysiology allsa 2010 (cơ chế 4 type dị ứng)

Allergy Pathophysiology Robin J Green PhD Department of Paediatrics, University Pretoria What I’m Going To Say!  Definitions are important  Describe the pathophysiology of IgE mediated allergy  Highlight the importance of inflammation  Describe some modifiers to this process The Hypersensitivity Reactions  Type I: Immediate  Type II: Cytotoxic  Type III: Immune complex  Type IV: Delayed Gell & Coombs Definition Allergy = Hypersensitivity reaction mediated by immunological mechanisms Atopy  ‘Inherited tendency to produce increased amounts of IgE in response to small quantities of allergen, and to produce a clinical syndrome (asthma, allergic rhinitis, atopic eczema)’  = Allergy + Clinical disease entity  Non-atopic conditions with elevated IgE: Bee venom hypersensitivity/Drug reactions JACI 2005 Hypersensitivity Non-Allergic Hypersensitivity Allergic Hypersensitivity IgE Mediated Atopic Non-IgE Mediated Non-Atopic Helminths, Insect reactions, drug reactions Primary Atopic Conditions  Allergic rhinitis (AR)  Intermittent allergic rhinitis (SAR)  Persistent allergic rhinitis (PAR)  Sinusitis  Atopic eczema (AE)  Allergic asthma (AA) Atopic Eczema Dermatitis (Inflammatory skin condition) Eczema Atopic Eczema (IgE mediated) Contact Dermatitis Non-Atopic Eczema (Non-IgE mediated) Pathophysiology of Allergy: Type I Hypersensitivity Reaction TH2 = Type helper T cell; IL = Interleukin; GM-CSF = Granulocyte-macrophage colony–stimulating factor; IgE = Immunoglobulin E Antigen Re-exposure TH2 = Type helper T cell; IL = Interleukin; GM-CSF = Granulocyte-macrophage colony– stimulating factor; IgE = Immunoglobulin E Broad Allergic Cascade - Mediators IL = Interleukin; TNF-a = Tumor necrosis factor-alpha; RANTES = Regulated on activation, normal T cell expressed and secreted; VCAM = Vascular cell adhesion molecule; ICAM-1 = Intercellular adhesion molecule-1 Antigen Antigen Nasal epithelium EPR Dendritic cell Antigen Sneeze/itch Antigen MHC II + T-cell receptor IL-4 IL-13 T H2 lymphocyte IL-4 IL-13 IL-5 Eotaxins RANTES + IL-5 CNS/peripheral nerves Histamine LTs PGs Tryptase + + IL-4 IL-13 Bone marrow Basophils + Rhinorrhea Mucosal edema Exudation Vasodilation Adhesion molecules (ICAM-1) + LPR Cellular infiltration Eosinophils: MBP, ECP Basophils: Cytokines Chemokines T lymphocytes Macrophages + B lymphocyte + + Plasma cell maturation IgE switching + Mast cell RANTES Eosinophils Endothelium + Chronic Nasal Obstruction Asthma Inflammation: Cells and Mediators Source: Peter J Barnes, MD Inflammation Asthma Inflammation: Cells and Mediators Source: Peter J Barnes, MD Role of CysLTs in the Airways Increased mucus secretion Decreased mucus transport Airway epithelium Cationic proteins (epithelial cell damage) Increased release of tachykinins Blood vessel CysLTs Oedema Inflammatory cells (e.g., mast cells, eosinophils) Sensory C fibres Smooth muscle Contraction and proliferation Adapted from Hay DW et al Trends Pharmacol Sci 1995;16:304-309 18 Mechanisms: Asthma Inflammation Source: Peter J Barnes, MD Inflammation Symptoms Signs Inflammation Complications Pathophysiology of Atopic Eczema THE IMMUNE SYSTEM: Factors Influencing the Immune system Malnourished are at a higher risk of diseases and infection Suppresses immune cells Mod Ex improves, Excess depresses Nerve and immune cells interact Viruses and Allergy/Asthma Influenza Genes Atopy Rhinovirus Asthma RSV Rhinovirus and asthma Rhinovirus Decrease in lamda interferon Increase in ICAM - Asthma exacerbations Remodeling Atopy Airway Inflammation and Pre-school Asthma Thank You  Prof Refiloe Masekela  Prof Max Klein  Dr Omolemo Kitchin  Dr Debbie White  Dr Carla Els  Dr Marian Kwofie-Mensah [...]... Intercellular adhesion molecule-1 Antigen Antigen Nasal epithelium EPR Dendritic cell Antigen Sneeze/itch Antigen MHC II + T-cell receptor IL -4 IL-13 T H2 lymphocyte IL -4 IL-13 IL-5 Eotaxins RANTES + IL-5 CNS/peripheral nerves Histamine LTs PGs Tryptase + + IL -4 IL-13 Bone marrow Basophils + Rhinorrhea Mucosal edema Exudation Vasodilation Adhesion molecules (ICAM-1) + LPR Cellular infiltration Eosinophils:... Sci 1995;16:3 04- 309 18 Mechanisms: Asthma Inflammation Source: Peter J Barnes, MD Inflammation Symptoms Signs Inflammation Complications Pathophysiology of Atopic Eczema THE IMMUNE SYSTEM: Factors Influencing the Immune system Malnourished are at a higher risk of diseases and infection Suppresses immune cells Mod Ex improves, Excess depresses Nerve and immune cells interact Viruses and Allergy/ Asthma... How does it function ? Antibody production (3rd line of defense) Stages in this process are:  Antigen detection  Activation of helper T cells  Antibody production by B cells Antigen Re-exposure TH2 = Type 2 helper T cell; IL = Interleukin; GM-CSF = Granulocyte-macrophage colony– stimulating factor; IgE = Immunoglobulin E Broad Allergic Cascade - Mediators IL = Interleukin; TNF-a = Tumor necrosis factor-alpha; ... some modifiers to this process The Hypersensitivity Reactions  Type I: Immediate  Type II: Cytotoxic  Type III: Immune complex  Type IV: Delayed Gell & Coombs Definition Allergy = Hypersensitivity... Antigen MHC II + T-cell receptor IL -4 IL-13 T H2 lymphocyte IL -4 IL-13 IL-5 Eotaxins RANTES + IL-5 CNS/peripheral nerves Histamine LTs PGs Tryptase + + IL -4 IL-13 Bone marrow Basophils + Rhinorrhea... Dermatitis Non-Atopic Eczema (Non-IgE mediated) Pathophysiology of Allergy: Type I Hypersensitivity Reaction TH2 = Type helper T cell; IL = Interleukin; GM-CSF = Granulocyte-macrophage colony–stimulating