Table 5.3 ). The route of antigen exposure often determines the nature of the reaction. Systemic exposure to protein antigens (e.g., in bee venom) or drugs (e.g., penicillin) may result in systemic anaphylaxis. Within minutes of the exposure in a sensitized host, itching, urticaria (hives), and skin erythema appear, followed in short order by profound respiratory difficulty caused by pulmonary bronchoconstriction and accentuated by hypersecretion of mucus. Laryngeal edema may exacerbate matters by causing upper airway obstruction. In addition, the musculature of the entire gastrointestinal tract may be affected, with resultant vomiting, abdominal cramps, and diarrhea. Without immediate intervention, there may be systemic vasodilation with a fall
Table 5.3 Examples of Disorders Caused by Immediate Hypersensitivity
Allergicrhinitis,Increasedmucussecretion;inflammationofsinusitis(hayfever)upperairwaysandsinuses
FoodallergiesIncreasedperistalsisduetocontractionofintestinalmuscles,resultinginvomitinganddiarrhea http://ebooksmedicine.net in blood pressure (anaphylactic shock), and the patient may progress to circulatory collapse and death within minutes.
Local reactions generally occur when the antigen is confined to a particular site, such as the skin (following contact), the gastrointestinal tract (following ingestion), or the lung (following inhalation). Atopic dermatitis, food allergies, hay fever, and certain forms of asthma are examples of localized allergic reactions. However, ingestion or inhalation of allergens also can trigger systemic reactions.
Immediate(typeI)sensitivityisalsocalledanallergic reaction, orallergy.
TypeIhypersensitivityisinducedbyenvironmentalantigens(allergens)thatstimulatestrongTH2responsesandIgEproductioningeneticallysusceptibleindividuals.
IgEcoatsmastcellsbybindingtotheFcεRIreceptor;reexposuretotheallergenleadstocross-linkingoftheIgEandFcεRI,activationofmastcells,andreleaseofmediators.
Principalmediatorsarehistamine,proteases,andothergranulecontents;prostaglandinsandleukotrienes;andcytokines.
Mediatorsareresponsiblefortheimmediatevascularandsmoothmusclereactionsandthelate-phasereaction(inflammation).
Theclinicalmanifestationsmaybelocalorsystemic,andrangefrommildlyannoyingrhinitistofatalanaphylaxis.
Antibody-mediated (type II) hypersensitivity disorders are caused by antibodies directed against target antigens on the surface of cells or other tissue components. The antigens may be normal molecules intrinsic to cell membranes or in the extracellular matrix, or they may be adsorbed exogenous antigens (e.g., a drug metabolite). These reactions are the cause of several important diseases (
Table 5.4
Mechanisms of Antibody-Mediated Diseases
Antibodies cause disease by targeting cells for phagocytosis, activating the complement system, or interfering with normal cellular functions (
Fig. 5.14 ). The antibodies that are responsible typically are high-affinity antibodies capable of activating complement and binding to the Fc receptors of phagocytes.
• Opsonization and phagocytosis. When circulating cells, such as red blood cells or platelets, are coated (opsonized) with autoantibodies, with or without complement proteins, the cells become targets for phagocytosis by neutrophils and macrophages (