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Allergy and Hypersensitivity (Anaphylaxis (Most common triggers are stings…
Allergy and Hypersensitivity
ALLERGY DEFINITION: An abnormal response to harmless foreign material
ATOPY DEFINITION: Hereditary tendency to overproduce IgE antibodies to common environmental antigens.
Symptoms of Allergy
Airways: Excessive mucus production, bronchoconstriction
GI: Abdominal bloating, vomiting, diarrhoea
Skin: Eczema, itching, reddening
Pathogenesis of Allergy
High affinity IgE cells: Eosinophils, mast cells, basophils
Mast Cell
Produces prostaglandin D2: induces smooth muscle contraction
Produces platelet activating factor (PAF): Increases platelet aggregation and degranulation, increases vascular permeability and activates neutrophil secretion
Produces leukotrienes which induce capillary endothelial contraction with vascular leakage
Produces histamine which causes: arteriolar dilation, capillary leakage, bronchospasm (constriction), eosinophil activation
Low affinity IgE cells: B cells, T cells, monocytes, platelets, neutrophils
Indirect mast cell activators:
allergens e.g. latex, wasp
bacterial + viral antigens
IgE is key in allergy. Serum concentration: 0.3-100 ug/ml
Direct mast cell activators:
aspirin
complement
asthma
Allergens
Presence of weak PAMPs - results in weak innate immunity activation but not adaptive immunity
Nasal/skin delivery
Particulate delivery of antigens
Anaphylaxis
Most common triggers are stings, nuts, food, drugs
Elevated serum tryptase and histamine
Occurs rapidly
Symptoms: vasodilation, increased vascular permeability, lowered BP, bronchial smooth muscle contraction, mucus production, rash, swelling
= An acute allergic reaction to an antigen to which the body has become hypersensitive
Immediate treatment: 0.15-0.3 mg of IM adrenaline
Can also give IV histamine receptor antagonists, prostaglandin antagonists, tryptase inhibitors, high flow oxygen and IV glucocorticoids
Adrenaline dilates bronchi, contracts heart, inhibits mast cell activation, allows peripheral vasoconstriction and reduces oedema
Give immunotherapy by increasing doses of allergen antigen to desensitise
Hypersensitivity
Type 2
IgG antibodies bind to antigens, leading to tissue injury
Example:
haemolytic disease of the foetus
. Mother has rhesus negative blood, baby has rhesus positive. Mother produces antibodies against baby, destroying the baby's RBC
IgG mediated cytotoxicity
Type 3
IgG binds to soluble antigen forming a circulating immune complex
Complexes are deposited in organs, causing inflammation and tissue damage
Immune complex deposition
Granulomas form
Example: Farmers lung. Inhale mould hay, causes local inflammatory response in lungs
Type 1
Need prior exposure to drug, IgE antibodies are formed after exposure and attach to mast cells. Re-exposure causes mast cell degranulation
Hay fever, eczema, asthma
Acute anaphylaxis
IgE mediated
= An extreme sensitivity to a substance
Type 4
Independent of antibodies
Caused by a pronounced secretion of cytokines by T helper cells
T cell mediated
Example: contact dermatitis from poison ivy