Immediate hypersensitivity reactions have diverse clinical and pathologic features, all of which are attributable to mediators produced by mast cells in different amounts and in different tissues (Fig. 1).

Fig1. Clinical manifestations of immediate hypersensitivity reactions. Immediate hypersensitivity may be manifested in many other ways, as in development of skin lesions (e.g., urticaria, eczema).

 • Some mild manifestations, such as allergic rhinitis and sinusitis, which are common in hay fever, are reactions to inhaled allergens, such as a protein of ragweed pollen. Mast cells in the nasal mucosa produce histamine, and Th2 cells produce IL-13, and these two mediators cause increased production of mucus. Late-phase reactions may lead to more pro longed inflammation.

• In food allergies, ingested allergens trigger mast cell degranulation, and the released histamine and other mediators causes increased peristalsis, resulting in vomiting and diarrhea.

• Asthma is a clinical syndrome characterized by difficulty in breathing, cough, and wheezing, related to intermittent obstruction of expiratory airflow. The most common cause of asthma is respiratory allergy in which inhaled allergens stimulate bronchial mast cells to release mediators, including leukotrienes, which cause repeated bouts of bronchial constriction and airway obstruction. In chronic asthma, large numbers of eosinophils accumulate in the bronchial mucosa, excessive secretion of mucus occurs in the airways, and the bronchial smooth muscle becomes hypertrophied and hyperreactive to various stimuli. Some cases of asthma are not associated with IgE production and may be triggered by cold or exercise; how either of these causes bronchial hyperreactivity is unknown.

 • The most severe form of immediate hypersensitivity is anaphylaxis, a systemic reaction characterized by edema in many tissues, including the larynx, accompanied by a fall in blood pressure (anaphylactic shock) and bronchoconstriction. Some of the most frequent inducers of anaphylaxis include bee stings, injected or ingested penicillin-family antibiotics, and ingested nuts or shellfish. The reaction is caused by widespread mast cell degranulation in response to the systemic distribution of the antigen, and it is life threatening because of the sudden fall in blood pressure and airway obstruction.

The therapy for immediate hypersensitivity diseases is aimed at inhibiting mast cell degranulation, antagonizing the effects of mast cell mediators, and reducing inflammation (Fig. 2). Common drugs include antihistamines for hay fever, inhaled beta- adrenergic agonists and corticosteroids that relax bronchial smooth muscles and reduce airway inflammation in asthma, and epinephrine in anaphylaxis. Many patients benefit from repeated administration of small doses of allergens, called desensitization or allergen-specific immunotherapy. This treatment may work by changing the T cell response away from Th2 dominance or the antibody response away from IgE, by inducing tolerance in allergen-specific T cells, or by stimulating regulatory T cells (Tregs). Antibodies that block various cytokines or their receptors, including IL-4 and IL-5, are now approved for the treatment of some forms of asthma and atopic dermatitis, and other cytokine antagonists are being tested in patients.

Before concluding the discussion of immediate hypersensitivity, it is important to address the question of why evolution has preserved an IgE antibody– and mast cell–mediated immune response whose major effects are pathologic. There is no definitive answer to this puzzle, but immediate hypersensitivity reactions likely evolved to protect against pathogens or toxins. It is known that IgE antibody and eosinophils are important mechanisms of defense against helminthic infections, and mast cells play a role in innate immunity against some bacteria and in destroying venomous toxins produced by arachnids and snakes. 

Fig2. Treatment of immediate hypersensitivity reactions. The figure summarizes the principal mechanisms of action of the various drugs used to treat allergic disorders. Ig, Immunoglobulin.

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