The Peyer’s patches of the small intestine, the lymphoid tissue of the appendix, and the isolated lymphoid follicles are located within the intestinal wall. Peyer’s patches are important sites for the initiation of immune responses in the gut. Visible to the naked eye, they have a distinctive appearance, forming dome-like aggregates of lymphoid cells that project into the intestinal lumen (see Fig. 1.24). There are 100–200 Peyer’s patches in the human small intestine. They are much richer in B cells than the systemic peripheral lymphoid organs, each Peyer’s patch consisting of a large number of B-cell follicles with germinal centers, with small T-cell areas between and immediately below the follicles (see Fig. 12.5). The subepithelial dome area lies immediately beneath the epithelium and is rich in dendritic cells, T cells, and B cells. Separating the lymphoid tissues from the gut lumen is a layer of follicle-associated epithelium. This contains conventional intestinal epithelial cells known as enterocytes and a smaller number of specialized epithelial cells called microfold cells (M cells), as shown in Fig. 1.24. M-cell development is controlled by local B cells and RANK ligand (RANKL), which is a member of the tumor necrosis factor (TNF) superfamily like CD40L (see Section 7-23). Unlike the enterocytes that make up most of the intestinal epithelium, M cells have a folded luminal surface instead of microvilli and do not secrete digestive enzymes or mucins, and so lack the thick layer of surface mucus (the glycocalyx) found covering conventional epithelial cells (see Fig. 1.24). They are therefore directly exposed to microorganisms and particles within the gut lumen and are the preferred route by which antigens such as microbes enter the Peyer’s patch from the lumen (Fig. 12.7). The follicle-associated epithelium also contains lymphocytes and dendritic cells.
Several thousand isolated lymphoid follicles can be identified microscopically throughout the small and large intestines, but they are more frequent in the large intestine, correlating with the load of local microorganisms. Like Peyer’s patches, these follicles have an epithelium containing M cells that lies over the organized lymphoid tissue. However, they contain mainly B cells and develop only after birth in response to antigen stimulation due to colonization of the gut by commensal microorganisms. Peyer’s patches, in contrast, are already present in the fetal gut, although their full development is not completed until after birth. In the mouse gut, isolated lymphoid follicles seem to arise from small aggregates in the intestinal wall called cryptopatches, which contain dendritic cells and lymphoid tissue inducer (LTi) cells (see Section 9-2). Cryptopatches have not yet been identified in the human gut. Peyer’s patches and isolated lymphoid follicles are connected by lymphatics to the draining lymph nodes.
The tissues of the small intestine drain to the mesenteric lymph nodes, which are located in the connective tissue that tethers the intestine to the rear wall of the abdomen. These are the largest lymph nodes in the body and play a crucial role in initiating and shaping immune responses to intestinal antigens. The mucosal surface and lymphoid aggregates of the large intestine drain to part of the mesenteric lymph node and to a separate node known as the caudal lymph node, found close to the bifurcation of the aorta.