The relative contributions of the Bimand Fas-mediated apoptotic pathways to effector T-cell loss depend on the infectious agent, but they appear to be complementary mechanisms, as mice with specific deficiencies of Bim or Fas have milder defects in T-cell clearance than mice with deficiencies of both. Thus, the two pathways appear to be nonredundant; what aspects of infection contribute to the dominance of one mechanism over the other in response to different pathogens is unclear. Irrespective of whether their death is induced by the intrinsic or extrinsic pathway, dying T cells are rapidly cleared by phagocytes that recognize on their surface the membrane lipid phosphatidylserine. This lipid is normally found only on the inner surface of the plasma membrane, but in apoptotic cells it rapidly redistributes to the outer surface, where it can be recognized by specific receptors on many cells. Thus, not only is the pathogen removed at the end of infection, but most of the pathogen-specific effector cells are also removed. Some of the pathogen-specific effector cells survive, however, and provide the basis for memory T-cell and B-cell responses, as will be discussed in the next section.
Summary.
CD4 T cells develop in response to, and subsequently amplify and sustain, innate immune responses that are induced by pathogens. Pathogen antigens are transported to local lymphoid organs by migrating dendritic cells and are presented to antigen-specific naive T cells that continuously recirculate through the lymphoid organs. T-cell priming and the differentiation of effector T cells occurs here, and the effector T cells either leave the lymphoid organ to provide cell-mediated immunity at sites of infection in the tissues or remain in the lymphoid organ to participate in humoral immunity by activating antigen-binding B cells. Distinct types of CD4 T cells develop in response to infection by different types of pathogens, and their development is influenced largely by the cytokines produced by innate sensor cells and ILCs that are activated early in the response.
Effector CD4 T cells serve to amplify and enhance early innate responses orchestrated by ILCs, while TFH cells that develop in concert with each subset of effector T cells direct the production of high-affinity antibodies that arm innate effector cells for heightened pathogen elimination. TH1 responses promote the development and activation of classical, M1 macrophages to protect against intracellular pathogens. TH2 responses are directed against infections by parasites such as helminths, and promote the development and activation of alternative, M2 macrophages and the recruitment of eosinophils and basophils to sites of infection. TH17 cells are integral to the clearance of extracellular bacteria and fungi, by orchestrating sustained neutrophil recruitment and production of antimicrobial peptides by epithelial cells of barrier tissues such as the intestines, lungs, and skin. CD8 T cells have an important role in protective immunity, especially in protecting the host against infection by viruses and intracellular infections by Listeria and other microbial pathogens that have special means for entering the host cell’s cytoplasm. Primary CD8 T-cell responses to pathogens usually require CD4 T-cell help, but can occur in response to some pathogens without such help. The patterns of anti-pathogenic response are not fixed, and effector T cells retain plasticity for adapting their response as pathogens alter their survival strategy in response to pressure from the immune system. Ideally, the adaptive immune response eliminates the infectious agent, at which time the expanded clonal populations of effector T cells contract, retaining only small populations of long-lived memory cells that provide the host with a state of protective immunity against reinfection with the same pathogen.
Immunological memory.