Allergies Flashcards
What is the hygiene hypothesis?
Lack of early childhood exposure to infectious agents increases susceptibility to allergic diseases by suppressing the natural development of the immune system
Depends on environment; TH1 phenotype (immune system educated to differentiate pathogens and non-pathogens) associated with:
- variable intestinal microflora
- breastfed
- low antibiotic use
- poor sanitation (high orofaecal burden)
TH2 phenotype leads to production of IgE & IgA (increased sensitivity)
Define hypersensitvity. What are some of the different types?
Antigen-specific immune responses that are either inappropriate or excessive and result in harm to the host
Environmental non-infectious antigens (allergens): immediate IgE mediated response
Environmental infectious agents/self-antigens:
- Antibody mediated/immune complex mediated (IgM & IgG)
- Cell mediated (T cells & macrophages - no antigens involved)
Give some examples of some common allergens.
Dust mites/cockroaches (protein in droppings)
Domestic pets (dander)
Tree & grass pollens (seasonal variation)
Insect venom (wasp/bee stings)
Medicines e.g. penicillins
Chemicals e.g. latex
Foods e.g. milk, peanuts
Why does an allergy to one substance make allergy to other substances more likely?
Clinical cross-reactivity
Adaptive immune response to a particular antigen causes reactivity to other antigens that are structurally related to the inducer
What are some examples of mast cell mediators?
Activated by IgE which causes mast cell degranulation
Enzymes e.g. tryptase - remodels connective tissue matrix
Toxic mediators e.g. histamine - toxic to parasites, increases vascular permeability, smooth muscle contraction
Cytokines e.g. interleukins, TNF-alpha - regulates immune response
Chemokines - attract monocytes, macrophages, neutrophils (chronic inflammation)
Lipid mediators e.g. leukotrienes - smooth muscle contraction, increased vascular permeability, increased mucus secretion
What are the steps in developing an allergic reaction?
First exposure: sensitisation to antigen by producing antigen-specific IgE
Second exposure (effector phase): mast cells activated by IgE —> histamine produced —> anaphylactic shock
Explain how histamine causes the symptoms of an allergic reaction.
Histamine causes:
- urticaria (mast cells in epidermis cause itchy rash - raised pale lesions surrounded by flares)
- increased vascular permeability (angioedema -> swollen lips, eyes, tongue, upper resp. airways -> asphyxia)
- vasodilatation (hypotension -> shock -> cardiovascular collapse -> cardiac arrest)
- bronchial constriction (bronchospasm -> wheezing -> asphyxia)
What is the skin prick test?
Prick skin with allergens
A wheal/flare reaction which has a diameter >3mm indicates an allergic reaction
note: risk of anaphylaxis in highly sensitive subjects
What is the treatment for anaphylactic shock?
Immediate IM adrenaline (quickest entry) to reverse peripheral vasodilation (reduces oedema), reverse airway obstruction/bronchospasm, and increase the force of myocardial contraction
Adrenaline inhibits mast cell activation
note: multiple doses often required (30min after exposure)
How are allergies diagnosed?
Check for atopy (hereditary tendency to develop hypersensitivity reactions), ask about allergens (seasonality & route of exposure)
Blood:
- serum allergen-specific IgE
- serum mast cell tryptase & histamine (after suspected anaphylaxis)
Skin prick test
Challenge test: introduce suspected allergen to induce a reaction)
How are allergies managed?
- allergen avoidance/elimination if possible
- education (recognise symptoms & know how to use an EPIPEN)
- wear medic alert bracelet
- anti-histamines (alternate sedating & non-sedating forms)
- corticosteroids
- anti-IgE/IgG e.g. omalizumab
- adrenaline for anaphylaxis
- allergen desensitisation (introduce small amounts of allergen gradually)
What can the blood concentrations of histamine and tryptase indicate?
Systemic activation of mast cells i.e. Anaphylactic reaction
