Cell-Mediated Immunity
Unlike B cells, T lymphocytes are unable to recognize pathogens without assistance. Instead, dendritic cells and macrophages first engulf and digest pathogens into hundreds or thousands of antigens. Then, an antigen-presenting cell (APC) detects, engulfs, and informs the adaptive immune response about an infection. When a pathogen is detected, these APCs will engulf and break it down through phagocytosis. Antigen fragments will then be transported to the surface of the APC, where they will serve as an indicator to other immune cells. A dendritic cell is an immune cell that mops up antigenic materials in its surroundings and presents them on its surface. Dendritic cells are located in the skin, the linings of the nose, lungs, stomach, and intestines. These positions are ideal locations to encounter invading pathogens. Once they are activated by pathogens and mature to become APCs they migrate to the spleen or a lymph node. Macrophages also function as APCs. After phagocytosis by a macrophage, the phagocytic vesicle fuses with an intracellular lysosome. Within the resulting phagolysosome, the components are broken down into fragments; the fragments are then loaded onto MHC class II molecules and are transported to the cell surface for antigen presentation (Figure 12.15). Helper T cells cannot properly respond to an antigen unless it is processed and embedded in an MHC class II molecule. The APCs express MHC class II on their surfaces, and when combined with a foreign antigen, these complexes signal an invader.
Figure 12.15 An antigen-presenting cell (APC), such as a macrophage, engulfs a foreign antigen, partially digests it in a lysosome, and then embeds it in an MHC class II molecule for presentation at the cell surface. Lymphocytes of the adaptive immune response must interact with antigen-embedded MHC class II molecules to mature into functional immune cells.
T cells have many functions. Some respond to APCs of the innate immune system and indirectly induce immune responses by releasing cytokines. Others stimulate B cells to start the humoral response as described previously. Another type of T cell detects APC signals and directly kills the infected cells, while some are involved in suppressing inappropriate immune reactions to harmless or “self” antigens.
There are two main types of T cells: helper T lymphocytes (TH) and the cytotoxic T lymphocytes (TC). The TH lymphocytes function indirectly to tell other immune cells about potential pathogens. TH lymphocytes recognize specific antigens presented by the MHC class II complexes of APCs. There are two populations of TH cells: TH1 and TH2. TH1 cells secrete cytokines to enhance the activities of macrophages and other T cells. TH2 cells stimulate naïve B cells to secrete antibodies. Whether a TH1 or a TH2 immune response develops depends on the specific types of cytokines secreted by cells of the innate immune system, which in turn depends on the nature of the invading pathogen.
Cytotoxic T cells (TC) are the key component of the cell-mediated part of the adaptive immune system and attack and destroy infected cells. TC cells are particularly important in protecting against viral infections; this is because viruses replicate within cells where they are shielded from extracellular contact with circulating antibodies. Once activated, the TC creates a large clone of cells with one specific set of cell-surface receptors, as in the case with proliferation of activated B cells. As with B cells, the clone includes active TC cells and inactive memory TC cells. The resulting active TC cells then identify infected host cells. Because of the time required to generate a population of clonal T and B cells, there is a delay in the adaptive immune response compared to the innate immune response.
TC cells attempt to identify and destroy infected cells before the pathogen can replicate and escape, thereby halting the progression of intracellular infections. TC cells also support NK lymphocytes to destroy early cancers. Cytokines secreted by the TH1 response that stimulates macrophages also stimulate TC cells and enhance their ability to identify and destroy infected cells and tumors. A summary of how the humoral and cell-mediated immune responses are activated appears in Figure 12.16.
B plasma cells and TC cells are collectively called effector cells because they are involved in “effecting” (bringing about) the immune response of killing pathogens and infected host cells.
Figure 12.16. A helper T cell becomes activated by binding to an antigen presented by an APC via the MHCII receptor, causing it to release cytokines. Depending on the cytokines released, this activates either the humoral or the cell-mediated immune response.