Hypersensitivity reactions underlie a number of autoimmune and allergic conditions. The classification of these reactions . Type I reaction (reaginic/anaphylactic/immediate hypersensitivity reaction) This is an allergic reaction produced within 30 min of exposure to a specific allergen. Allergens, e.g. house dust, pollens, animal danders or moulds, only elicit reactions in certain genetically predisposed individuals, who are said to be atopic. Atopy is diagnosed on skin-prick testing when a reaction is elicited by sensitizing allergens. Type I reactions can be passively transferred by injection of serum containing IgE antibody into the skin (passive cutaneous anaphylaxis). The antibody will remain fixed to the mast cells in the skin for up to 4-S days and an injection of the antigen will produce a wheal and flare reaction (Prausnitz-Kustner reaction).
Type I reactions are mediated via allergen-specific antibodies of the IgE class and occur as follows.
ALLERGEN INHALATION OR INGESTION results in local generation of specific IgE via the interaction of macrophages and receptive Band T-helper cells.
LOCALLY PRODUCED ALLERGEN-SPECIFIC IGE then binds to the Fc receptors of mast cells and, to a lesser extent, eosinophils and macrophages sensitizing them. IgE also enters the circulation, where it sensitizes basophils.
SUBSEQUENT EXPOSURE TO ALLERGEN results in the cross-linking of the IgE antibodies on the cells and to mediator release.
Binding of allergen to sensitized cells results in the de novo synthesis and/or release of several inflammatory mediators:
HISTAMINE. Present as a preformed mediator in sensitized mast cells and basophils, histamine produces vasodilation and bronchial smooth-muscle constriction.
ARACHIDONIC ACID METABOLITES. Arachidonic acid is generated in sensitized cells from membrane lipids following the binding of specific allergen. It is subsequently metabolized to produce prostaglandins (cyclooxygenase pathway), leukotrienes (lipoxygenase pathway) or platelet-activating factor (p AF acetylation), depending on which cell type is being activated.
Leukotrienes and prostaglandins are together termed eicosanoids. The arachidonic acid metabolites involved in Type 1 hypersensitivity reactions are PAF, leukotrienes (LT) B., C., D. and E. and prostaglandins (PG) D2, E2 and F2£<. They have four main actions:
1 Inflammatory cell mucosal infiltration. This is mediated by LTB. and PAF, which attract and activate neutrophils, eosinophils and monocytes/macrophages. LTB. is released by actated mast cells and macrophages and PAF is released by mast cells, neutrophils and eosinophils.
2 Bronchoconstriction. This is mediated by several metabolites including PAF, LTC., LTD. and LTE. and PGD2 and PG F2a• LTC4 and PGD2 are the major arachidonic acid metabolites released by mast cells. The remaining eicosanoids are generated by human lung tissue and/or alveolar macro phages.
3 Bronchial mucosal oedema is mediated by LTC4 and LTD4 and PGE2• PGE2 is released from alveolar macrophages and human lung tissue.
4 Mucus hypersecretion is mediated by LTC4 and LTD4