Type 1 hypersensitivity Flashcards
How long after exposure does a type 1 reaction occur?
Immediately <30 mins
Which T cell response is triggered in allergy?
TH2
TH1 triggered in non-allergic (immunotolerance)
What events occur following TH2 activation?
B- cells produce IgE.
IgE binds to mast cells and cause activation.
Why might there by more allergies in westernised countries?
Reduced Infection burden - “hygiene hypothesis”
Microbial dysbiosis - alterations in biome
Other- small families, good sanitation, high antibiotic use = more TH2 responses
Where are mast cells produced and where do they mature and differentiate?
Produced in bone marrow.
Mature and differentiate once in tissues.
Where are mast cells located?
Mucosal and epithelial tissues - GI tract, skin, resp epithelium
Give examples of mediators released by mast cells.
Tryptase Histamine Cytokines + chemokines - IL-4 Leukotrienes C4, D4 and E4 Platelet-activating factor
What effect does histamine have?
Increased vascular permeability
SM contraction
Toxic to parasites
What does tryptase do?
Remodels connective tissue matrix
What do leukotrienes do?
SM constriction - Bronchoconstriction
Vascular permeability- hypotension and CV collapse
Mucus secretion
What does platelet-activating factor do?
Attracts leukocytes
Activates neutrophils, eosinophils + platelets
What happens upon 1st exposure to an allergen?
TH2 response and sensitisation produces IgE.
Antigen-specific IgE binds to mast cells and waits. No response.
What happens upon 2nd exposure to allergen?
Antigen binding causes IgE cross-linking of mast cells and degranulation. Allergic response.
What are the 3 main effects triggered by mast cell degranulation?
- Increased vascular permeability
- Vasodilation
- Bronchial constriction
What is urticaria?
Mast cell activation within the epidermis.
What is angioedema?
Mast cell activation in the deep dermis.
Lips, eyes, tongue and upper RT affected - emergency.
What are the main mediators in angioedema?
Histamine + bradykinin
What causes anaphylaxis?
Systemic activation of mast cells
What are the signs/symptoms of anaphylaxis?
Hypotension CV collapse Angioedema Generalised urticaria Breathing problems
What causes the signs/symptoms associated with anaphylaxis?
Vasodilation
Increased permeability
Bronchial constriction
What treatment targeting the abnormal TH2 response can be used for allergies ?
Allergen desensitisation
Anti-IgE monoclonal antibody
What treatment targeting mast cell degranulation can be used?
Anti-histamines
Leukotriene receptor antagonists
Corticosteroids
What is sensitisation?
Activation of APCs and memory effector cells upon first exposure to an antigen.
Antigen specific IgE made.
What if the effect of IL-4 secretion from mast cells?
Stimulate and activate TH2 response.
What treatments are there aimed at symptoms of allergic reaction?
Anti-histamines
Leukotriene receptor antagonists
Corticosteroids
What treatments are there aimed at desensitisation?
Allergen desensitisation
Anti-IgE mAb
What 4 lifestyle advice could you give to somebody with an allergy?
Avoid the allergen
Carry epipen
Carry allergy card
Check labels
What does prolonged epidermal exposure to antigens cause?
Eczema
Atopic dermatitis
What type of reaction is anaphylaxis?
Systemic manifestation of type 1
What are 5 signs/symptoms of anaphylaxis?
Hypotension CV collapse Generalised urticaria Angioedema Breathing problems
