which is critical for the activation of macrophages to destroy pathogens that either invaded the macrophage or were ingested by it; the IFNγ can also induce B cells to switch the class of Ig they are making. Naïve TH cells activated in the presence of IL4 develop into TH2 cells. These effector cells are important for the control of extracellular pathogens, including parasites. They stimulate B cells to undergo somatic hypermutation and to switch the class of Ig they produce: for example, the TH2 cells themselves produce IL4, which can induce B cells to switch from making IgM and IgD to making IgE antibodies, which can bind to mast cells, as discussed earlier. Naïve TH cells activated in the presence of IL6 and IL21 develop into follicular helper T cells (TFH), which are located in lymphoid follicles and secrete a variety of cytokines, including IL4 and IL21; these cells are especially important for stimulating B cells to undergo Ig class switching and somatic hyper-mutation. Naïve TH cells activated in the presence of IL6 and TGFβ develop into TH17 cells. These effector cells secrete IL17, which recruits neutrophils and stimulates epithelial cells and fibroblasts in the skin and gut to produce pro-inflammatory cytokines. TH17 cells are important in controlling extracellular bacterial and fungal infections and in wound healing, but they can also have a major role in autoimmune diseases and allergy.
In some cases, naïve TH cells that encounter their antigen in a peripheral lymphoid organ in the presence of TGFβ and the absence of IL6 develop into induced regulatory T cells (Treg cells), which suppress rather than help immune cells; as mentioned earlier, natural Treg cells develop in the thymus during thymocyte development (see Figure 24–41). In either case, the Treg cells suppress the development, activation, or function of most other types of immune cells, by means of both secreted suppressive cytokines such as IL10 and TGFβ and inhibitory proteins on the Treg cell surface. Induced Treg cells seem mainly to suppress immune responses to foreign antigens—preventing responses to harmless ingested or inhaled antigens and limiting responses against pathogens to avoid excessive responses that cause unwanted pathology; natural Treg cells are needed to prevent immune responses to self molecules (see Figure 24–21). Treg cells express the transcription regulator FoxP3, which serves as both a marker of these cells and a master controller of their development: if the gene encoding this protein is inactivated in mice or humans, the individuals fail to produce Treg cells and develop a fatal autoimmune disease involving multiple organs—findings that establish the crucial importance of Treg cells in self-tolerance.
Foreign antigen binding to BCRs or TCRs initiates the process whereby the T and B cells are stimulated to proliferate and differentiate into effector or memory cells. As mentioned earlier, these antigen receptors do not act on their own: they are stably associated with invariant transmembrane polypeptide chains that are required to relay the signal into the cell. In B cells, these are called Igα and Igβ (Figure 24–45A), while in T cells they exist in a complex called CD3, composed of four types of polypeptide chains (Figure 24–45B). In both cases, the associated proteins help convert extracellular antigen binding to the TCR or BCR into intracellular signals, and they do so in similar ways.