1. T1HS Flashcards
Explain the pathogenesis of T1HS
i. 1st exposure to trigger/allergen… abnormal TH2 activation… plasma cell production of antigen-specific IgE (sensitisation)
ii. 2nd exposure to antigen… IgE crosslinking on mast cells… mast cell activation and degranulation… release of histamine and chemokines
iii. increased vascular permeability, vasodilation and bronchial constriction
name 3 examples of allergens
- tree and glass pollens
- house dust mite
- animal dander (cats and dogs)
- fungal spores
- insect venom (wasp and bee stings)
- medicines, e.g. penicllin
- chemicals, e.g. latex
- foods, e.g. milk, peanuts, etc.
suggest 3 reasons why allergies are more prevalent in westernised countries than developing countries
- hygiene hypo. - children exposed to animals, pets and microbes in the early post-natal period appear to be protected against allergic diseases
- biodiversity hypo. - western lifestyle induces alteration of the symbiotic relationships with parasites and bacteria leading to DYSBIOSIS of the microbiome at mucosal surfaces (gut)
- some influence by genetics
describe the location of mast cells
- most mucosal and epithelial tissues (GI tract, skin, resp. tract)
- in connective tissue surrounding blood cells
what does mast cell activation in the epidermis cause? which mediators are involved?
- URTICARIA
- if prolonged/chronic exposure: ATOPIC DERMATITIS and ECZEMA
mediators = histamine and leukotrienes/cytokines
what does mast cell activation in the deep dermis cause? which mediators are involved?
ANGIOEDEMA (lips, eyes, tongue and upper resp. airways)
mediators = histamine and bradykinin
what does systemic activation of mast cells cause
anaphylactic shock:
- increased vascular permeability and vasodilation… hypotension and cardiovascular collapse, generalised urticaria and angioedema
- bronchial constriction… breathing probs.
name 3 signs and symptoms of anaphylaxis
- CNS
- lightheadedness and confusion
- loss of consciousness
- headache
- anxiety - Respiratory
- dyspnoea
- wheezes or stridor
- hoarseness
- pain with swallowing
- cough - Heart and vasculature
- brady- or tachycardia
- low BP - Skin
- hives
- itching
- flushing - GI
- crampy abdo pain
- diarrhoea and vomiting - pelvic pain, loss of bladder control, runny nose, conjunctival swelling
what is allergen desensitisation/immunotherapy
administration of increasing doses of allergen extracts over a period of yrs, given to Ps by injection or sublingual
potential mechanisms:
- CD4+ CD25 Treg cells
- shift from TH2 to TH1
- inhibitory anti-inflammatory cytokines
- allergen specific blocking IgG (instead of IgE)
name 4 possible treatments for T1HS
1. anti-IgE mAb prevention of mast cell activation: 2. anti-histamines 3. leukotriene R antagonists 4. corticosteroids