Atopy and allergy 1 Flashcards
Early phase allergic reaction
Exposure to allergens in sensitised individuals leads to rapid development of symptoms.
Mechanism
- Allergens specific to IgE bind to IgE on mast cells
- IgE are bound to FceR1 on mast cells.
- Binding of allergen triggers degranulation of mast cells to release histamines and other inflammatory mediators.
Leukotrienes
Delayed mediator that triggers inflammation
Can be released as a result of mast cell activation
- Through the release of phospholipase A2 (to arachidonic acid)
Pharmacological effects of mast cell mediators and leukotrienes
- skin
- nose
- eyes
- lungs
Skin= wheal and flare
Nose
- Increased mucus production
- Sneezing
Eyes
- Conjunctivitis
Lung
- Wheeze
Effects of mast cell activation of
- GI
- Airway
- Blood vessels
GI
- Increased fluid secretion and peristalsis= vomiting and diarrhoea.
Airway
- Bronchoconstriction and increased mucus= wheeze, cough, swelling.
Blood vessels
- Increases blood flow and permeability= oedema, lymph enlargement, increase of effector response in tissues.
Common allergen sources
Pollen [hayfever]
House dust mite faeces
Stinging insect venom
Characteristics of allergens
Mainly proteins
- Because that is what T cells recognise
Can cross mucus membranes [soluble, LMW]
- Allows it to activate immunity
Biologically active
Moderate homology with self-antigens
- Enough to bind to MHC without getting deleted during negative selection
Anaphylasxis
Generalised allergic reaction
- Release of histamine causes generated vasodilator and fluid entry into tissue.
Causes:
- Food allergens
- Drugs
- Insect venom
Presents:
- Hives
- Angioedema
- Laryngeal oedema
- Bronchoconstriction
Oral allergy syndrome
Food allergy
- IgE against pollen [mainly birch] cross reacts with homologous proteins in plant foods [rosaceae fruits].
Secondary exposure to food after allergen exposure= oral itching with raw fruits, nuts, vegetables.
Airway disease
Exposure to allergen causes lower airway obstruction/ rhinitis
Can be:
- Seasonal [hayfever]
- Episodic [occupational, animal]
Allergic march
Progression of disease from infancy that typically leads to asthma.
- Eczema
- Food allergy
- Rhinitis
- Asthma
- Eczema and food allergies usually outgrown
Chronic allergic inflammation in asthma
Airway undergoes remodelling due to constant exposure of airborne allergens
- Inflammatory infiltrates
- Thickened basement membrane and smooth muscle
- due to late phase allergic reaction
Late phase allergic reaction
Follows early phase
- Less rapid response
- Involves infiltration of inflammatory cells: CD4, eosinophils, mast cells
Th1
Releases IFN-gamma, IL-2
- Stimulates inflammation
Th2 cells
Releases IL-4, 5, 9, 13.
- Acts eosinophils, basophils, and mast cells, B cells.
- Important in the production of IgE and activation of mast cells
Overactivation against autoantigen will cause Type1 IgE-mediated allergy and hypersensitivity
Th17 cells
Produces IL-17= proinflammatory
Th2 and allergy
Important in allergic inflammation, by releasing IL 4, 5, 9, 13.
IL-4
- B cell class switching to IgE
- [w/ IL-3] Mucus hyper secretion
IL-5
- Required for eosinophil survival
IL-9
- Recruits mast cells
IL-13
- Bronchial hyper-responsivemenss
Hygiene hypothesis
States that lack of early childhood exposure to infectious agents, leads to the increased susceptibility into developing allergies.
Environments less likely to develop allergic diseases (but more likely to develop infectious disease) - low hygiene levels - High pathogen load - High helminth infection load = skews immunity from th2 to Th1 - induces Treg cells
