Cell-mediated immunity is most dramatically expressed as a response to obligate or facultative intracellular pathogens. These include certain slow-growing bacteria, such as the mycobacteria, against which antibody responses are ineffective. In experimental infections, cell-mediated immunity can be passively transferred from one animal to another by T lymphocytes but not by serum. (In contrast, short-term, antibody-mediated [B-cell] immunity can be passively transferred with serum.) The mechanisms of cell-mediated immunity are complex and involve a number of cytokines with amplifying feedback mechanisms for their production. The initial processing of antigen is accompanied by sufficient IL-1 production by the macrophages to stimulate activation of the antigen-recognizing CD4+ (helper) cell. Lymphokine feedback from the CD4+ T cells to macrophages further increases IL-1 production. IL-2 produced by the CD4+ T cells facilitates their clonal expansion and activates CD8+ (cytotoxic) T lymphocytes. Other lymphokines from CD4+ T cells chemotactically attract macrophages to the site of infection, hold them there, and activate them to greatly enhance microbicidal activity. The sum of the individual and collaborative activities of T cells, macrophages, and their products is a progressive mobilization of a range of nonspecific host defenses to the site of infection and greatly enhanced macrophage activity. In the case of viruses, IFN- γ inhibits replication, and CD8+ cytotoxic lymphocytes destroy their cellular habitat, leaving already assembled virions accessible to circulating antibody. The interplay among cells of the innate immune system, including monocytes, macrophages, and dendritic cells; the essential elements of specific immune system, T cells (particularly TH1 and TH2 cells), B cells, and antibodies; and the regulatory roles of proinflammatory (eg, IL-2, IFN-γ) and anti-inflammatory (eg, IL-4, IL-6) cytokines in adaptive resistance to particular types of pathogenic organisms will be considered below.
With certain infections in which reaction to protein antigens is particularly strong (eg, in the response to Mycobacterium tuberculosis), the cell-mediated responses are of such mag-nitude that they become major deleterious factors in the disease process itself. This is called delayed-type hypersensitivity, because reexposure of the host to the antigen that elicited the immune response produces a maximum hypersensitive reaction only after a day or two, when mobilization of immune lymphocytes and of phagocytic macrophages is at its peak.