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Immune Responses: Adverse Versus Non-Adverse Effects

Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfi eld, Cheshire SK10 4TJ, ian.kimber{at}syngenta.com .

Rebecca J. Dearman

Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfi eld, Cheshire SK10 4TJ

The adaptive immune system in vertebrates has evolved to provide host resistance to infectious microorganisms and malignant disease. Normal immune function and the induction of specific immune responses require the orchestrated interaction between cells and molecules both within and outside the lymphoid system. Immunotoxicology can be defined as the study of adverse health effects that may result from the interaction of xenobiotics with the immune system. In general terms such effects can take one of two forms. The first of these is immunotoxicity (or immunosuppression) where there is a perturbation of, or damage to, one or more components of the immune system resulting in impaired immune function and reduced host resistance. The design and interpretation of experimental immunotoxicity studies and the investigation of clinical immunosuppression require consideration of the relationship between changes in the structure and/or function of discrete components of the immune system and holistic changes in the susceptibility to infectious and malignant disease. The other main way in which chemicals may cause adverse health effects secondary to interaction with the immune system is through stimulation of specific immune responses that result in allergic disease. Allergy to chemicals and proteins can take many forms, including allergic contact dermatitis, allergic sensitization of the respiratory tract (associated with rhinitis and/or asthma), systemic allergic reactions (associated frequently with drug treatment), and gastrointestinal disease. Here there is a need to distinguish between immunogenic responses per se and those immune responses that are of sufficient vigor and of the quality necessary to provoke allergic sensitization. The purpose of this article is to explore the extent to which distinctions can be drawn between adverse and nonadverse effects in the context of immunotoxicity and allergy.

Key Words: Immunotoxicology • allergy • immunotoxicity testing • skin sensitization • respiratory sensitization • adverse effects • nonadverse effects.

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