Fig. 9.1 Secondary lymphoid tissues serve as anatomical crossroads for interactions of antigens and lymphocytes. secondary lymphoid tissues are specialized to serve as sites that facilitate interactions between lymphocytes and antigens. In lymph nodes (upper panel), antigen (denoted by red dots) is delivered in lymph either free or as cargo of dendritic cells that have taken up the antigen in the tissues drained by the lymph node. The antigen is conducted via afferent lymphatics to the subcapsular sinus, from which it is delivered to T-cell zones, where T cells can recognize it on the surface of dendritic cells; or, in the case of B cells, it is detected as a free antigen at the border of the T-cell zone and B-cell follicles. T and B cells enter the lymph node via high endothelial venules (hevs) in T-cell zones, and then diverge into T-cell and B-cell zones. In the spleen (middle panel), antigen is delivered via arterioles that branch from the central arteriole to the marginal sinus, which is the boundary between the white pulp and red pulp, with which the marginal sinus communicates. In the marginal sinus, antigen can be taken up by marginal zone B cells, macrophages, or dendritic cells, which can transport antigen into either T-cell zones (periarteriolar lymphoid sheath, or paLs) or B-cell follicles. T and B cells enter the spleen via the same route as antigen, and leave the marginal sinus to travel to either the paLs or the B-cell follicles. In the intestines (lower panel), antigens are transported from the lumen via the microfold or M cells—specialized epithelium that overlays peyer’s patches—to dendritic cells that reside in the subepithelial dome. antigen-loaded dendritic cells are then surveyed by T cells in T-cell zones, and if the antigens they bear are not recognized by T cells locally, the dendritic cells can migrate to mesenteric lymph nodes to be further surveyed. as for lymph nodes, T and B cells enter the peyer’s patches via hevs in the T-cell zones.
Each area of white pulp is demarcated from the red pulp by a marginal sinus, a vascular network that is formed from branches of the central arteriole. Circulating T and B cells are initially delivered to the marginal sinus, which is a highly organized region of cells that is specialized for the capture of blood-borne antigens or intact microbes, such as viruses and bacteria. It is rich in macrophages and contains a unique population of B cells, the marginal zone B cells, which do not recirculate. Pathogens reaching the bloodstream are efficiently trapped in the marginal zone by macrophages, and it could be that marginal zone B cells are adapted to provide the first responses to such pathogens.
From the marginal sinus, T and B cells migrate centrally toward the central arteriole, where they bifurcate into T-cell zones that are clustered around the central arteriole—the so-called periarteriolar lymphoid sheath (PALS)— and B-cell zones, or follicles, that are located more peripherally. Some follicles may contain germinal centers, in which B cells involved in an adaptive immune response are proliferating and undergoing somatic hypermutation (see Section 1-16). The antigen-driven production of germinal centers will be described in detail when we consider B-cell responses in Chapter 10.