Post on 19-Jul-2018
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 Self-antigens Harmless,
environmental antigens
Protection
Hypersensitivity, Allergy
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.
Th2 B cell
Allergen
specific
IgE
Allergen
Antigen
presenting
cells
APC
IL-4
Allergen
specific
Th2 cells
Allergen
specific
B cells
Allergen specific T-
and B-cell memory
response
Type I IL-4R
MHC II
T cell receptor
IL-4
Sensitisation Phase
Other
cytokines?
Allergen
(e.g. pollen)
IgE antibody Mast cell
degranulation
Acute
symptoms
of allergy
Histamine
Mast cell
Th2 cytokines
and chemokines
Allergen
(e.g. pollen)
Th2
cell
IgE antibody Mast cell
degranulation
Histamine
APC
Type I
IgE mediated
allergy
CD4+
Mast cell
Type IV
Th2
hypersensitivity
Release of IgE
Plasma cell
B lymphocyte
-switch
Allergic Exacerbation
Allergic Inflammation:
eosinophils and lymphocytes
Allergens
Mast cells Basophils
Allergic mediators
IgE Sensitisation and elicitation
IgE
Allergens
FcRI
Over Minutes Lipid mediators: Prostaglandins Leukotrienes
Wheezing Bronchoconstriction
Over Hours Cytokine production: Specifically IL-4, IL-13
Mucus production Eosinophil recruitment
Immediate Release Granule contents: Histamine, PAF, TNF-, Proteases, Heparin
Sneezing Nasal congestion Itchy, runny nose Watery eyes
Early & Late phase IgE reaction
TH0
TH1
TH2
Interferon
Interleukin 2
Cell-mediated immunity
Intracellular pathogens
Autoimmunity
Interleukin 4
Interleukin 5
Interleukin 13
Humoral Immunity
Parasite defense
Allergic Disease
Intracellular
Pathogens
Interleukin 12
Parasites
Allergens
Interleukin 4
JAMA. 1997;278:1845.
Progression of allergy
• Allergy can progress from one form to another – the march…
• Not all children progress
Low risk High risk
Family
history
Neither parent
has allergies
One parent has
allergies
Both parents
have allergies
Chance of
child with
allergies
10 – 15 %
30 – 40 %
70 – 80 %
Low risk High risk
Family
history
Neither parent
has allergies
One parent has
allergies
Both parents
have allergies
Chance of
child with
allergies
10 – 15 %
30 – 40 %
70 – 80 %
• 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
Prevention of allergy
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
Histamine
Secretory
granule
IgER
Allergen
cross-bridging
Anchored IgE
Circulating IgE
IgE
Anti-IgE
Anti-IgE (omalizumab,Xolair®) for the
treatment of allergy