Allergy overview. Mike Levin Division of Asthma and Allergy Department of Paediatrics University of Cape Town Red Cross Hospital
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1 Allergy overview Mike Levin Division of Asthma and Allergy Department of Paediatrics University of Cape Town Red Cross Hospital
2 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
3 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
4 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
5 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
6 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)
7 Allergen Antigen causing allergic disease Proteins Carbohydrate side chains LMW chemicals: Haptens (e.g. isocyanates, anhydrides)
8 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.
9 Asthma Drug reactions ALLERGY Eczema Urticaria Angioedema Food intolerance Rhinitis
10 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
11 Mast cell Histamine Acute symptoms of allergy Allergen (e.g. pollen) IgE antibody Mast cell degranulation
12 Allergen (e.g. pollen) APC CD4+ Th2 cell Th2 cytokines and chemokines Chronic symptoms of allergy
13 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
14 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
15 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
16
17 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.
18 Regulatory T-cells
19 Progression of allergy Allergy can progress from one form to another the march Not all children progress
20 Progression of allergy
21 Family history Low risk Neither parent has allergies One parent has allergies High risk Both parents have allergies Chance of child with allergies % % %
22 Family history Low risk Neither parent has allergies One parent has allergies High risk Both parents have allergies Chance of child with allergies % % %
23 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
24 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
25 Allergic Diseases
26 Allergic Diseases Food Hypersensitivity Urticaria Anaphylaxis Eczema Rhinitis Asthma Conjunctivititis Drug Hypersensitivity Insect sting or bite hypersensitivity
27 Allergic Diseases Food Hypersensitivity Urticaria Anaphylaxis Eczema Rhinitis Asthma Treatment in general Prevention
28 The Treatment of Allergy Education Allergen avoidance Anti-allergic medicines Immunotherapy
29 The Treatment of Allergy Education Allergen avoidance Anti-allergic medicines Immunotherapy
30 House Dust Mite Avoidance
31 The Treatment of Allergy Education Allergen avoidance Anti-allergic medicines Immunotherapy
32 Anti-allergic Medicines
33 The Treatment of Allergy Education Allergen avoidance Anti-allergic medicines Immunotherapy
34
35
36 Pollen Counts Symptoms Drug usage Varney, Kay, Durham et al BMJ. 1991
37 Anti-IgE (omalizumab,xolair )
38 Anti-IgE (omalizumab,xolair ) for the treatment of allergy IgE R Circulating IgE Secretory granule Allergen cross-bridging Histamine Anchored IgE Anti-IgE IgE
39
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