Type I Hypersensitivity - Allergy Flashcards
What immunoglobulin is involved in Type I hypersensitivity?
IgE
Describe type I hypersensitivity reactions
- immediate reaction <30 mins
- local reaction: ingested or inhaled allergen
- systemic reaction: insect sting or IV administration
- mediated by IgE
What helper T cell elicits IgE production?
TH2
Mechanisms of Type I hypersensitivity
- abnormal adaptive immune response against allergens: TH2 response (IL-4,5,13) > IgE response
- mast cell activation
Define type I hypersensitivity
Immediate excessive adaptive immune response to allergens mediated by IgE
What is the hygiene hypothesis?
Children exposed to animals, pets + microbes in early postnatal period appears to be protected against certain allergic diseases
What is the ‘old friend hypothesis?
Western lifestyle induces alteration of symbiotic relationships with parasites + bacteria leading to dysbiosis of micro biome at mucosal surfaces
What is dysbiosis?
Compositional + functional alteration of micro biome
Outline the mechanism of allergic reaction
- allergen breaches mucosal barrier
- phagocytosis by dendritic cells
- antigens presented to naive T cells by MHC class II
- plasma cells produce IgE
- IgE binds to mast cells
- mast cell degranulation > histamines, chemokines, leukotrienes + prostaglandins release
- vasodilation, bronchial constriction + increased vascular permeability
Location of mast cells
- Most mucosal + epithelial tissues e.g. skin + GI tract
- Connective tissue surround blood cells
What is urticaria?
What is it caused by?
What mediators are involved?
- Itchy raised rash
- Caused by mast cell activation within epidermis
- histamine + leukotrienes
What is angioedema?
What is it caused by?
What mediators are involved?
- swelling
- caused by mast cell activation in deep dermis or subcutaneous or submucosal tissue
- histamine + bradykinin
Signs + symptoms of anaphylaxis
- dyspnoea
- urticaria
- angioedema
- hypotension
- dysphagia
- confusion
- loss of consciousnesses
Treatment of type I hypersensitivity reactions due to abnormal adaptation immune response against allergens
- allergen desensitisation (oral immunotherapy)
- omalizumab: anti IgE monoclonal antibody
- mepolizumab: anti-IL5 monoclonal antibody
Treatment of Type I hypersensitivity due to mast cell activation
Antihistamines
Corticosteroids
Leukotriene receptor antagonists
Define allergen desensitisation
Involves the administration of increasing doses of allergen extracts over period of years, given to patient by infection or tablets sublingual
Treatment of anaphylactic shock
How does it work including the receptors involved?
IM adrenaline
- *a1**: reverses peripheral vasodilation > reduces oedema + alleviates hypotension
- B2: reverses bronchoconstriction
- B1: increases force of myocardial contraction
- inhibits mast cell activation
What represents the main trigger of clinical manifestation of allergic disorders?
Cross linking of antigen specific IgE
Examples of mast cell mediators
Tryptase
Histamine
Leukotrienes
Platelet activating factor
