Delayed Type (Type IV) Hypersensitivity

"Delayed" refers to the fact that induration slowly develops over 24-48 hr, and "hypersensitivity" refers to inappropriate damage of tissues by the immune system.

When some subpopulations of activated TH cells encounter certain types of antigens, they secrete cytokines that induce a localized inflammatory reaction which is characterized by large influxes of nonspecific inflammatory cells like macrophages. In contrast to a Type III reaction then, there is recruitment of macrophages as opposed to neutrophils and also there is a delay in time required for the reaction to develop.

The DTH skin test is used to test if prior exposure to an antigen has occurred. When small quantities of antigen are injected dermally, a hallmark response is elicited which includes induration, swelling and monocytic infiltration into the site of the lesion within 24 to 72 hours. The reaxon has been shwon to be dependent on the presence of memory T cells (both CD4+ and CD8+).

The histology of DTH can be different for different species, but the general characteristics are an influx of immune cells at the site of injection, either macrophages and basophils in humans and mice or neutorophils in guinea pigs, and induration which becomes apparent within 24-72 hours.

A model for DTH is that upon injection of the antigen, Langerhan's cells process antigen and present it to local memory T cells. These T cells in concert with activated Langerhan's cells secrete numerous cytokines that cause inflammation. Within 2 hours neutrophils begin to infiltrate the injection site.