T Cells and Cell-Mediated Immunity
T cells are the type of lymphocyte associated with the component of an immune response known as cell-mediated immunity. Whereas the humoral response involves antibodies that can have their effect at sites distant from their site of production, the cell-mediated immune response requires that the responding T cells be in contact with the cells bearing the foreign antigen.
As with B cells, T cells have various subtypes, each with its specific functions. The subtypes include cytotoxic T cells, helper T cells, memory T cells (Fig. 16-1), and NK T cells. NK T cells and helper T cells are introduced earlier in this chapter.
As with the humoral response, antigen recognition initiates the cell-mediated response. However, antigen recognition by T cells requires that the antigenic material be presented as part of a complex on the cell membrane of other immune cells. This complex consists of the antigenic material and intrinsic cell membrane proteins known as major histocompatibility complex (MHC) proteins.
The genes that code for MHC proteins are found on a single chromosome, and MHC proteins are continuously synthesized in all cells of an animal’s body except for erythrocytes, which do not have nuclei and are not capable of protein synthesis. After synthesis, MHC proteins enter the outer cell membrane so that a portion is exposed to the exterior. As MHC proteins prepare for insertion in the cell membrane, they form complexes with antigenic materials found within the cell. When the complex enters the membrane, the antigen is exposed to the exterior. The exposed antigen is then in a position to be recognized by T cells.
Cell membranes hold two major classes of MHC proteins, class I and class II (Fig. 16-1). Class i MHC proteins are found in all cells except for erythrocytes.
Class I MHC proteins continuously present potential antigenic materials on the surface of all cells. These materials include peptides and other antigenic materials normally produced in cells, as well as antigenic materials produced as a result of an abnormality in cell function. If a foreign cell (i.e., not self) is introduced into an animal’s body, the antigenic material presented by its class I MHC proteins is unique for that foreign cell and differs from endogenous self cells. When viruses infect normal cells and alter their synthetic pathways, they change the antigenic materials presented by the class I proteins of the infected cell. By recognizing these new antigens, T cells recognize foreign or infected cells, allowing initiation of a cellular immune response directed at cells bearing the foreign antigen.only selected cell types have class II MHC proteins. These include lymphocytes, free and fixed macrophages, microglia in the central nervous system, and a population of cells in the spleen and lymph nodes known as dendritic cells. Cells that contain class II MHC proteins are termed antigen-presenting cells (APCs), for they process and present antigens derived from foreign material or microbes (Fig. 16-1). These antigens are derived from microbes or material that the APCs take up by phagocytosis or pino- cytosis. APCs process materials in phagocytic or pinocytic vesicles to produce antigens that are complexed to class II MHC proteins and inserted into the APC cell membrane.
As with B cells, clones of T cells exist that are specific for a given antigen, and the process of antigen recognition permits a specific clone to be selected. However, the selection and activation of T cells also requires interaction between the MHC proteins holding the antigenic material and other proteins in the cell membranes of the various T cells known as cluster of differentiation markers (CD markers). These marker proteins determine the interactions that are possible for the different types of T cells.
Helper T cells have CD4 markers (Fig. 16-1), which interact with class II MHC proteins, and cytotoxic T cells have CD8 markers, which interact with class I MHC proteins. Thus, helper T cells can recognize antigenic material presented by APCs, and cytotoxic T cells can detect foreign antigenic material presented by almost any type of cell (Fig. 16-1).After recognizing antigens presented by APCs, the selected helper T cells are activated by interactions between other of their membrane proteins and membrane proteins found in the APCs. This interaction (costimulation) leads to full helper T cells activation. The activated helper T cells multiply and produce a subset to serve as memory cells (memory Th cells). A major function of the other activated helper T cells is to secrete cytokines to promote and amplify all aspects of the innate and specific immune responses. This includes attraction and stimulation of additional macrophages and NK cells, promoting the action of cytotoxic T cells, and promoting the development of selected B cells. A key cytokine produced by helper T cells to stimulate macrophages, NK cells, cytotoxic cells, and B cells is interleukin-2.
Costimulation by cells presenting the specific antigen to selected cytotoxic T cells is also required for full activation of those cytotoxic T cells. The activated cytotoxic T cells also undergo a series of cell divisions to provide increased numbers of the selected clone and also produce a subset to serve as memory cells (memory Tc cells). Activated cytotoxic cells (killer cells) destroy cells bearing the antigen for which they were selected. Physical contact and binding between the cells bearing the antigen and the cytotoxic T cells are required for the destruction of antigen-bearing cells (Fig. 16-1), and secretions from the cytotoxic T cells, including perforin to disrupt the cell membrane of the antigen-bearing cells, accomplish it.