Delayed-type hypersensitivity (DTH) is an injurious cytokine-mediated inflammatory reaction resulting from the activation of T cells, particularly CD4+ T cells. The reaction is called hypersensitivity because it reflects excessive (i.e., injurious) immune responses (which are reflections of sensitivity to an antigen) and delayed because it typically develops during 24 to 48 hours after antigen challenge.
In the classic animal model of DTH, a guinea pig is first immunized by the administration of a protein antigen in adjuvant; this step is called sensitization. About 2 weeks later, the animal is challenged subcutaneously with the same antigen, and the subsequent reaction is analyzed; this step is called the elicitation phase. Humans may be sensitized for DTH reactions by microbial infection, by contact sensitization with chemicals and environmental antigens, or by intradermal or subcutaneous injection of protein antigens (Fig. 18-6). Subsequent exposure to the same antigen (called challenge) elicits the reaction. For example, purified protein derivative (PPD), a protein antigen of Mycobacterium tuberculosis, elicits a DTH reaction, called the tuberculin reaction, when it is injected into individuals who have been exposed to M. tuberculosis. A positive tuberculin skin test response is a widely used clinical indicator for evidence of previous or active tuberculosis infection.
The characteristic response of DTH evolves during 24 to 48 hours. About 4 hours after the injection of antigen, neutrophils accumulate around the postcapillary venules at the injection site. By about 12 hours, the injection site becomes infiltrated by T cells and blood monocytes, also organized in a perivenular distribution (Fig. 18-7). The
primary infection or immunization
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