Porth's Essentials of Pathophysiology, 4e

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Disorders of the Immune Response

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Delayed-Type Hypersensitivity Disorders Delayed-type hypersensitivity (DTH) reactions (see Fig. 16-4B) occur in response to soluble protein antigens and primarily involve antigen-presenting cells such as macro- phages and CD4 + helper T cells of the T H 1 type. During the reaction T H 1 cells are activated and secrete an array of cytokines that recruit and activate macrophages, lym- phocytes, fibroblasts, and other inflammatory cells. 7 These T-cell–mediated responses require the synthesis of effector molecules and take 24 to 72 hours to develop, which is why they are called “delayed-type” hypersensitivity disorders. The best-known DTH response is the reaction to the tuberculin test, in which inactivated tuberculin or puri- fied protein derivative is injected under the skin. In a person who has been sensitized by previous infection, a local area of redness and induration develops within 8 to 12 hours, reaching a peak in 24 to 72 hours. The tubercu- lin reaction is characterized by perivascular accumulation of T H 1 cells and, to a lesser extent, macrophages. Local secretion of cytokines by these mononuclear inflamma- tory cells leads to increased microvascular permeability with local redness and swelling. The sequence of events in DTH, as demonstrated by the tuberculin reaction, begins with the first exposure to the tubercle bacilli (see Chapter 22). The T H 1 cells recognize the peptide antigens of the tubercle bacilli in association with class II MHC antigens on the surface of monocytes and antigen-pre- senting cells that have processed the mycobacterial anti- gens. This process leads to formation of sensitized T H 1 memory cells that remain in the circulation for years. Subsequent injection of tuberculin into such an individ- ual results in the secretion of T H 1 cell cytokines that are ultimately responsible for the DTH response. In addition to its beneficial protective role, DTH can also be the cause of disease, including allergic contact der- matitis and hypersensitivity pneumonitis. It also can be involved in transplant rejection and autoimmune disorders. Allergic Contact Dermatitis. Allergic contact dermati- tis denotes an inflammatory response confined to the skin that is initiated by re-exposure to an allergen to which a person had previously become sensitized (e.g., cosmet- ics, hair dyes, metals, topical drugs). 14,15 The most com- mon form of this condition is the dermatitis that follows an encounter with poison ivy or poison oak antigens, although many other substances can trigger a reaction. Contact dermatitis is characterized by erythematous, papular, and vesicular lesions associated with intense pruritus and weeping. The affected area often becomes swollen and warm, with exudation, crusting, and poten- tially the development of a secondary infection. The location of the lesions often provides a clue about the antigen causing the disorder. The severity of the reac- tion associated with contact dermatitis ranges from mild to intense, depending on the person and the allergen. Because this condition follows the mechanism of a DTH response, the reaction does not become apparent for at least 12 hours and usually more than 24 hours after exposure. Depending on the antigen and the duration of exposure, the reaction may last from days to weeks.

Diagnosis of contact dermatitis is made by observing the distribution of lesions on the skin surface and associ- ating a particular pattern with exposure to possible aller- gens. If a particular allergen is suspected, a skin patch test can be used to confirm the suspicion. Treatment usually is limited to removal of the irritant and appli- cation of topical preparations (e.g., ointments, cortico- steroid creams) to relieve symptomatic skin lesions and prevent secondary bacterial infections. Severe reactions may require systemic corticosteroid therapy. Hypersensitivity Pneumonitis. Hypersensitivity pneu- monitis, which is associated with exposure to inhaled organic dusts or related occupational antigens, is another example of a DTH reaction. 16 The disorder is thought to involve a susceptible host and activation of pulmonary T cells, followed by the release of cytokine mediators of inflammation. The inflammatory response that ensues (usually several hours after exposure) produces labored breathing, dry cough, chills, fever, headache, and mal- aise. The symptoms usually subside within hours after the sensitizing antigens are removed. A primary exam- ple of hypersensitivity pneumonitis is “farmer’s lung,” a condition resulting from exposure to moldy hay. Other sensitizing antigens include tree bark, sawdust, animal dander, and Mycobacteria that are occasionally found in humidifiers, hot tubs, and swimming pools. Exposure to small amounts of antigen for a long period may lead to chronic lung disease with minimal reversibility. This can occur in persons exposed to avian or animal antigens or a contaminated home air humidifier. The most important element in the diagnosis of hyper- sensitivity pneumonitis is to obtain a good history (occu- pational and otherwise) of exposure to possible antigens. Treatment consists of first identifying and then avoiding the offending antigens. Severe forms of the disorder may be treated with systemic corticosteroid therapy. ■■ Hypersensitivity disorders are immune responses to environmental, food, or drug antigens that would not affect most of the population. ■■ Type I hypersensitivity responses are mediated by IgE and include anaphylactic shock, hay fever, and bronchial asthma; ■■ Type II hypersensitivity responses include antibody-mediated cell destruction (e.g., transfusion reactions, hemolytic disease of the newborn, and certain drug reactions), complement- and antibody-mediated inflammation (e.g., some forms of glomerulonephritis), and antibody-mediated cell dysfunction (e.g., Graves disease and myasthenia gravis). ■■ Type III hypersensitivity reactions involve the formation and deposition of insoluble antigen– SUMMARY CONCEPTS

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