Type IV reactions are cell-mediated rather than antibody-mediated, differentiating them from type I, II, and III hypersensitivities. There are two forms of type IV hypersensitivity. One form is T cell–mediated cytotoxicity, in which cytotoxic T (Tc) cells recognize the antigen that has bound to the surface of a cell and either destroy the cell directly (Tc recognition) or recruit phagocytic macrophages by releasing cytokines (Th recognition). Tc cells directly destroy the antigen-presenting cells by releasing toxins. Macrophages recruited by T helper (Th) cells release cell-lysing enzymes and reactive oxygen species that destroy the cells.
Another form of T cell–mediated cytotoxicity is delayed-type hypersensitivity, which is mediated predominantly by Th cells. The Th cells recognize a particular antigen and recruit phagocytic macrophages by releasing cytokines (Th recognition). Cytokines also further propagate the immune response and induce inflammation. Whereas type I, II, and III hypersensitivities will often manifest in minutes to hours, type IV reactions require many hours to several days between exposure to the allergen and immune response.Common skin contact allergies act through type IV hypersensitivity—for example, the contact dermatitis reactions in response to skin contact with poison ivy or jewelry made of nickel. In a person exposed to a poison ivy leaf or nickel jewelry for the first time, Th cells respond and form memory cells. With repeat exposure, the memory T cells rush to the exposure site in greater numbers and activate macrophages, thereby inducing inflammation. These reactions result in rashes and inflammation on the skin at the point of contact and may advance to cause blisters and necrosis of the skin.