EFFECTS OF CHEMICALS ON ALLERGIC DISEASE in Visual Studio .NET

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EFFECTS OF CHEMICALS ON ALLERGIC DISEASE
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Xenobiotics can affect allergic disease in one of two ways. They can themselves act as antigens and elicit hypersensitivity responses, or they can enhance the development or expression of allergic responses to commonly encountered allergens, such as dust mite. Chemicals that act as allergens include certain proteins that can by themselves induce an immune response and low molecular weight chemicals (known as haptens) that are too small to induce a speci c immune response but may react with a protein to induce an immune response that is then hapten speci c. Haptens have been associated with both allergic contact dermatitis (ACD), sometimes called contact hypersensitivity
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EFFECTS OF CHEMICALS ON ALLERGIC DISEASE
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(CHS), and respiratory hypersensitivity. Proteins have been associated with respiratory hypersensitivity and food allergies. When a chemical is an allergen or a hapten, there are two doses of concern, the sensitizing dose and the elicitation dose. In general, the dose required for sensitization is greater than that required to elicit a response in a sensitized individual. Chemicals that enhance the development of allergic sensitization are referred to as adjuvants. Air pollutants have been associated both with enhanced sensitization and exacerbation of allergic respiratory symptoms.
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19.5.1 Allergic Contact Dermatitis
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Allergic contact dermatitis (ACD) or contact hypersensitivity (CHS) is one of the most common occupational health problems and hence is one of the most common problems associated with immunotoxicity. It is a type IV response that occurs as a result of dermal exposure to chemicals that are haptens. Following dermal exposure, the chemical reacts with host cell protein at the surface of the skin and is picked up by epidermal dendritic cells, known as Langerhans cells. Cytokines released from the epidermal keratinocytes and from Langerhans cells cause maturation and mobilization of the Langerhans cells, which travel to the draining local lymph node and present antigen to lymphocytes. Clonal expansion occurs, enlarging the number of T lymphocytes speci c for that allergen and generating memory cells that, in addition to speci city for the allergen, have the propensity to home to the skin. On re-exposure to the chemical, these speci c T cells are activated, proliferate, home rapidly to the site of exposure, and produce erythema and edema typical of a type IV response. The reaction to poison ivy is the classic example. Methods to assess chemicals (drugs, pesticides, dyes, cosmetics, and household products, etc.) for potential to induce CHS are well established, and several protocols using guinea pigs have been in use since the 1950s. These protocols assess the actual disease end point, skin erythema, and edema, following sensitization and challenge with the test agent. Two commonly used tests are the guinea pig maximization test and the Buehler occluded patch test. The sensitization procedure for the maximization tests includes intradermal injection of the test chemical with an adjuvant (intended to enhance the sensitization process) as well as topical application. The Buehler test relies on topical sensitization alone. In both cases, after approximately 2 weeks, animals are challenged at a different site on the skin and erythema and edema are assessed 24 to 48 hours later. This assessment is somewhat subjective and these tests are fairly expensive. A chemical is considered to be a sensitizer if 30% (maximization) or 15% (Buehler) of the animals respond. Recently a more economical, less subjective, test for CHS has been developed using mice. This test, the local lymph node assay (LLNA), assesses the proliferative response of lymphocytes in the draining lymph node following application of the agent to the ear and is based on our understanding of the immunologic mechanisms underlying CHS; that is, clonal expansion has to occur in the draining lymph node if there is to be allergic sensitization (Figure 19.5). The LLNA is gaining acceptance as a stand-alone alternative to the guinea pig tests and is likely to become the assay of choice. Finally structure activity approaches have recently been developed to identify contact sensitizers. This approach is based on the concept that the biologic mechanisms that determine a chemical s effect are related to its structure and hence chemicals with similar structures will have similar effects. Computer models have been developed to compare the structure of an unknown chemical to structures in a database for known
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