Allergy overview Mike Levin Division of Asthma and Allergy Department of Paediatrics University of Cape Town Red Cross Hospital
Adaptive Immune Responses Adaptive immune responses allow responses against specific antigens and are essential for normal health However, adaptive immune responses can sometimes cause serious disease when elicited to antigens not associated with infectious pathogens Adaptive immune response Pathogens Protection Harmless, environmental antigens Hypersensitivity, Allergy Self-antigens Autoimmunity
Hypersensitivity Objectively reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal persons No reference to pathological mechanism
Hypersensitivity Objectively reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal persons No reference to pathological mechanism
Allergy Exaggerated immune reaction to trigger molecules, usually benign proteins, called allergens. Hypersensitivity reaction - initiated by an immunological mechanism Antibody mediated IgE antibodies IgE-mediated allergy Cell mediated Non-IgE mediated allergy Allergic inflammation
Atopy Personal or familial tendency to produce IgE antibodies in response to low doses of allergens, and is accompanied by typical symptoms of asthma, rhinoconjunctivitis or eczema/dermatitis Genetic predisposition to become IgE sensitised to allergens IgE sensitisation (IgE in serum or +ve SPT)
Allergen Antigen causing allergic disease Proteins Carbohydrate side chains LMW chemicals: Haptens (e.g. isocyanates, anhydrides)
Allergy Allergy is not a disease! It is a mechanism that is important in some diseases all the time, and in others for some of the time.
Asthma Drug reactions ALLERGY Eczema Urticaria Angioedema Food intolerance Rhinitis
Sensitisation Phase Allergen IL-4 Other cytokines? Antigen presenting cells APC Type I IL-4R MHC II T cell receptor Allergen specific IgE B cell Allergen specific B cells IL-4 Th2 Allergen specific Th2 cells Allergen specific T- and B-cell memory response
Mast cell Histamine Acute symptoms of allergy Allergen (e.g. pollen) IgE antibody Mast cell degranulation
Allergen (e.g. pollen) APC CD4+ Th2 cell Th2 cytokines and chemokines Chronic symptoms of allergy
Mast cell Histamine Type I IgE mediated allergy Allergen (e.g. pollen) IgE antibody Mast cell degranulation APC CD4+ Th2 cell Th2 cytokines and chemokines Type IV Th2 hypersensitivity
IgE Sensitisation and elicitation -switch B lymphocyte Allergic mediators Allergic Inflammation: eosinophils and lymphocytes Plasma cell Release of IgE Allergens Allergic Exacerbation Mast cells Basophils
Early & Late phase IgE reaction IgE Allergens Fc RI Immediate Release Granule contents: Histamine, PAF, TNF-, Proteases, Heparin Sneezing Nasal congestion Itchy, runny nose Watery eyes Over Minutes Lipid mediators: Prostaglandins Leukotrienes Wheezing Bronchoconstriction Over Hours Cytokine production: Specifically IL-4, IL-13 Mucus production Eosinophil recruitment
Intracellular Pathogens Interleukin 12 T H 1 Interferon Interleukin 2 Cell-mediated immunity Intracellular pathogens Autoimmunity T H 0 Parasites Allergens Interleukin 4 T H 2 Interleukin 4 Interleukin 5 Interleukin 13 Humoral Immunity Parasite defense Allergic Disease JAMA. 1997;278:1845.
Regulatory T-cells
Progression of allergy Allergy can progress from one form to another the march Not all children progress
Progression of allergy
Family history Low risk Neither parent has allergies One parent has allergies High risk Both parents have allergies Chance of child with allergies 10 15 % 30 40 % 70 80 %
Family history Low risk Neither parent has allergies One parent has allergies High risk Both parents have allergies Chance of child with allergies 10 15 % 30 40 % 70 80 %
Prevention of allergy Recommendations No dietary restriction in pregnancy Oily fish +- omega 3 supplementation. Fruit and vegetables Breast feed (No diet restriction) for 4-6 months If high risk and cannot BF hydrolysed formulae (not CM, AAF or soy) Introduce solids from 4-6 months. No data on later or earlier. Avoid exposure to cigarette smoke Mixed data on probiotics and prebiotics Mixed data on pets &HDM so no environmental interventions
Prevention of allergy Secondary prevention Rhinitis : Better treatment helps asthma Immunotherapy for rhinitis reduces sensitisations and may prevent asthma Asthma : Better treatment helps rhinitis Food allergy : Treats eczema Eczema May prevent food allergy and onset of asthma Drugs ETAC and EPAAC
Allergic Diseases
Allergic Diseases Food Hypersensitivity Urticaria Anaphylaxis Eczema Rhinitis Asthma Conjunctivititis Drug Hypersensitivity Insect sting or bite hypersensitivity
Allergic Diseases Food Hypersensitivity Urticaria Anaphylaxis Eczema Rhinitis Asthma Treatment in general Prevention
The Treatment of Allergy Education Allergen avoidance Anti-allergic medicines Immunotherapy
The Treatment of Allergy Education Allergen avoidance Anti-allergic medicines Immunotherapy
House Dust Mite Avoidance
The Treatment of Allergy Education Allergen avoidance Anti-allergic medicines Immunotherapy
Anti-allergic Medicines
The Treatment of Allergy Education Allergen avoidance Anti-allergic medicines Immunotherapy
Pollen Counts Symptoms Drug usage Varney, Kay, Durham et al BMJ. 1991
Anti-IgE (omalizumab,xolair )
Anti-IgE (omalizumab,xolair ) for the treatment of allergy IgE R Circulating IgE Secretory granule Allergen cross-bridging Histamine Anchored IgE Anti-IgE IgE