The basal cell membrane of an M cell is extensively folded, forming a pocket that encloses lymphocytes and which makes close contacts with local myeloid cells, including dendritic cells (see Fig. 12.7). Macrophages and dendritic cells take up the transported material released from the M cells and process it for presentation to T lymphocytes. Local dendritic cells are in a favorable position to acquire gut antigens, and they are recruited toward, or even into, the follicle-associated epithelium in response to chemokines that are released constitutively by the epithelial cells. The chemokines include CCL20 (MIP-3α) and CCL9 (MIP-1γ), which bind to the receptors CCR6 and CCR1, respectively, on dendritic cells (see Appendix IV for a listing of chemokines and their receptors). The antigen-loaded dendritic cells then migrate from the dome region to the T-cell areas of the Peyer’s patch, where they meet naive, antigen-specific T cells. Together, the dendritic cells and primed T cells then activate B cells and initiate class switching to IgA. All these processes— the uptake of antigen by M cells, the migration of dendritic cells into the epithelial layer, the production of chemokines, and the subsequent migration of dendritic cells into T-cell areas—are markedly increased in the presence of pathogenic organisms and their products due to the ligation of pattern recognition receptors on epithelial cells and immune cells (see Section 3-5). Similar processes also underlie the induction of immune responses in isolated lymphoid follicles of the gut and in the MALT of other mucosal surfaces.
12-4 The mucosal immune system contains large numbers of effector lymphocytes even in the absence of disease.
In addition to the organized lymphoid organs, mucosal surfaces such as the gut and lung contain enormous numbers of lymphocytes and other leukocytes scattered throughout the tissue. Most of the scattered lymphocytes have the appearance of cells that have been activated by antigen, and they comprise the effector T cells and plasma cells of the mucosal immune system. In the intestine, effector cells are found in two main compartments: the epithelium and the lamina propria (see Fig. 12.5).
These tissues are quite distinct in immunological terms, despite being separated by only a thin layer of basement membrane. The lymphoid component of the epithelium consists mainly of lymphocytes, which in the small intestine are virtually all CD8 T cells. The lamina propria contains many types of immune cells, including IgA-producing plasma cells, conventional CD4 and CD8 T cells with effector and memory phenotypes, innate lymphoid cells, dendritic cells, macrophages, and mast cells. T cells in the lamina propria of the small intestine express the integrin α4:β7 and the chemokine receptor CCR9 (Fig. 12.8), which attracts them into the tissue from the bloodstream. Intraepithelial lymphocytes (IELs) are mostly CD8 T cells and express either the conventional