A circulating lymphocyte adheres weakly to the surface of the specialized endothelial cells lining a postcapillary venule in a lymph node. This initial adhesion is mediated by L-selectin (discussed in chapter 19) on the lymphocyte surface. The adhesion is sufficiently weak to enable the lymphocyte, pushed by the flow of blood, to roll along the surface of the endothelial cells. Stimulated by chemokines secreted by specialized endothelial cells in the node (curved red arrow), the lymphocyte rapidly activates a stronger adhesion system, mediated by an integrin. This strong adhesion enables the cell to stop rolling. The lymphocyte then uses an immunoglobulin-like cell adhesion protein (cD31) to bind to the junctions between adjacent endothelial cells and migrate out of the venule. The subsequent migration of the lymphocyte in the lymph node depends on chemokines produced within the node (straight red arrow). The migration of other types of leukocytes out of the bloodstream into sites of infection occurs in a similar way (see Figure 19–28 and Movie 19.2).
Figure 24–18 The path followed by lymphocytes as they continuously recirculate between the lymph and blood. The circulation through a lymph node (yellow) is shown here. Microbial antigens are usually carried into the lymph node by activated dendritic cells (not shown), which enter the node via afferent lymphatic vessels draining an infected tissue (green). B and T cells, by contrast, enter via the blood, migrating out of the bloodstream into the lymph node through postcapillary venules. Unless they encounter their antigen, the B and T cells leave the lymph node via efferent lymphatic vessels, which eventually join the thoracic duct. The thoracic duct empties into a large vein carrying blood to the heart, completing the circulation cycle for T and B cells. A typical circulation cycle for these lymphocytes takes about 12–24 hours.
Unless they encounter their antigen, both B and T cells soon leave the lymph node via efferent lymphatic vessels. If they encounter their antigen, however, they are stimulated to display adhesion receptors that trap the cells in the node; the cells accumulate at the junction between the B cell and T cell areas, where the rare antigen-specific B and T cells can interact, leading to their proliferation and differentiation into either effector cells or memory cells. Many of the effector cells leave the node, expressing different chemokine receptors that help guide them to their new destinations—effector plasma B cells to the bone marrow and effector T cells to sites of infection.
As discussed earlier, cells of the innate immune system use PRRs to distinguish microbial molecules from self molecules made by the host. The adaptive immune system has the far more difficult recognition task of responding specifically to an almost unlimited number of foreign molecules while not responding to the large number of self molecules. How does it accomplish this feat? It helps that self molecules normally do not induce the innate immune reactions required to activate adaptive immune responses. But even when an infection or tissue injury triggers innate reactions, the vast majority of self molecules normally still fail to induce an adaptive immune response. Why?