T cell functions
TH cells orchestrate an acquired immune response by promoting intracellular killing by macrophages, antibody production by B lymphocytes, and clonal expansion of cytotoxic T lymphocytes. The TCRs of TH cells trigger cellular activation when they are bound by complexes between peptides and MHC class II membrane proteins on APCs.
TH Cells (CD4+ cells) secrete various growth factors called when they encounter an antigen-MHC complex and become activated. These are important in activating , TC cells, and . Differences in immune response also depend on the produced.
Of great importance in immunology, is the functional dichotomy between Th1-Th2. Th1 cells produce IFN-y, lymphotoxin, and IL-2, and mediate delayed-type hypersensitivity reactions, whereas Th2 cells produce IL-4, 5, 6, 9, 10 and 13 and stimulate antibody production. Reciprocal regulation occurs between these two subsets: IFN-y restricts the proliferation of Th2 clones and IL-4 and IL-10 interfere with IFN_y production by Th1 clones.
If an immune response is controlled by Th1 cells, it results in the production of IgG2a antibodies in mice or their equivalent in other animal species and humans. IgG2a antibodies bind serum complement proteins and are effective at neutralizing viral and bacterial pathogens. Th1 cells produce interferon (IFN)-y and interleukin (IL)-2 and IL-18. These cytokines are involved in macrophage activation, which is important in antimicrobial and antiviral defence and in the development of cytotoxic lymphocytes. Thus Th1 cells are said to promote the cell-mediated immune responses.
In contrast, Th2 cells help B cells mount a humoral immune response and help maintain T cytotxic cells by producing growth factors needed by the T cytotoxic cells. Th2 cells are involved in production of IgG1, IgE and IgA antibodies in mice or their equivalent in different animal species and humans. IgG1 antibodies are important in antimicrobial and antiviral humoral defenses. IgE antibodies play a role in allergic diseases and asthma. IgA antobides protect mucosal surfaces from infections. Th2 cells secrete IL-4 and IL-10. The Th2-type response is thought to play a critical role in the development of allergic diseases, and is recognized as a target for novel immunotherapies.
1. Helper T Cells Can Activate B cells, Proliferate and Change Isotopes (Humoral Response)
Whereas antigen presenting cells such as and macrophages ingest and present antigens nonspecifically, a generally presents only an antigen that it specifically recognizes. In a primary antibody response, naive helper T cells are activated in a peripheral lymphoid organ by binding to a foreign peptide bound to a class II MHC protein on the surface of a . Once activated, the effector helper T cell can then activate a B cell that specifically displays the same complex of foreign peptide and class II MHC protein on its surface. The T cell secretes a number of cytokines like IL-2, IL-4, IL-5, IL-6 and IFNy which serve to stimulate various stages of division and differentiation into both antibody secreting plasma and memory cells.
Secreted signals from helper T cells also help to proliferate and differentiate and, in some cases, to switch the class of antibody they produce. IL-4 is one such signal. Produced by TH2 cells, it works with CD40 ligand in stimulating proliferation and differentiation and it promotes switching to IgE antibody production.
In secondary antibody responses, memory B cells themselves can act as antigen presenting cells and activate helper T cells, as well as being the subsequent targets of the effector helper T cells.
2. T Helper Cells Activate , Macrophages, NK cells (Cell Mediated Response)
As with the humoral response, a clonally expanded population of antigen specific TH cells is also required for a . These TH cells serve to activate various T effector cells that generate cell mediated responses. For example, the Tc cell recognizes processed antigen associated with on the membrane of cells. In the presence of IL-2 secreted by the TH cell, the TC cell becomes a cytotoxic T lymphocyte (CTL).
The secreted by TH cells also regulate the proliferation and differentiation of a number of nonspecific effector cells that play various roles in cell mediated immune responses. For example, IL2 and interferon gamma have been shown to activate which show enhanced phagocytic activity and ability to kill ingested pathogens as well as the natural killer (NK) cell which has been shown to kill tumor cells.