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Large molecules such as vaccines, insulin and dextrans can provoke immune reactions themselves but most drugs are too small to be antigenic on their own. In some patients, something that cannot be predicted is that a drug or drug metabolite can combine with tissue proteins to form an antigenic conjugate. In this situation, the patient shows a response, which can be described under one of the classical definitions of allergic response (that is, type see below). Such reactions require initial exposure to the drug to cause sensitization, after which, subsequent exposure to the same drug triggers an immunological reaction.

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