Fig. 9.5 Trapping and activation of antigen-specific naive T cells in lymphoid tissue. naive T cells entering the lymph node from the blood encounter antigen-presenting dendritic cells in T-cell zones. T cells that recognize their specific antigen bind stably to the dendritic cells and are activated through their T-cell receptors, resulting in their retention within the lymph node as they develop into effector T cells. By 5 days after the arrival of antigen, activated effector T cells are leaving the lymph node in large numbers via the efferent lymphatics. Lymphocyte recirculation and recognition are so effective that all the naive T cells in the peripheral circulation specific for a particular antigen can be trapped by that antigen in one node within 2 days.
Fig. 9.6 Lymphocyte entry into a lymph node from the blood occurs in distinct stages involving the activity of adhesion molecules, chemokines, and chemokine receptors. naive T cells are induced to roll along the surface of a high endothelial venule (hev) by the interactions of selectins expressed by the T cells with vascular addressins on the endothelial cell membranes. Chemokines present at the hev surface activate receptors on the T cell, and chemokine receptor signaling leads to an increase in the affinity of integrins on the T cell for the adhesion molecules expressed on the hev. This induces strong adhesion. after adhesion, the T cells follow gradients of chemokines to pass through the hev wall into the paracortical region of the lymph node.
where it proliferates for several days, undergoing clonal expansion and differentiation to give rise to effector T cells and memory cells of identical antigen specificity. At the end of this period, most effector T cells exit the lymphoid organ and reenter the bloodstream, through which they migrate to the sites of infection (see Chapter 11). Some effector T cells that are fated to interact with B cells migrate instead to B-cell zones, where they participate in the germinal center response (see Chapter 10).
The efficiency with which T cells screen antigen-presenting cells in lymph nodes is very high, as can be seen by the rapid trapping of antigen-specific T cells in a single lymph node containing antigen; within 48 hours, all antigen-specific T cells in the body can be trapped in the lymph node draining a site of antigen injection (Fig. 9.5). Such efficiency is crucial for the initiation of an adaptive immune response, as only one naive T cell in 105–106 is likely to be specific for a particular antigen, and adaptive immunity depends on the activation and expansion of these rare cells.
9-5 Lymphocyte entry into lymphoid tissues depends on chemokines and adhesion molecules.
Migration of naive T cells into secondary lymphoid tissues depends on their binding to high endothelial venules (HEVs) through cell–cell interactions that are not antigen-specific but are governed by cell-adhesion molecules. The main classes of adhesion molecules involved in lymphocyte interactions are the selectins, the integrins, members of the immunoglobulin superfamily, and some mucin-like molecules (see Fig. 3.30). Entry of lymphocytes into lymph nodes occurs in distinct stages that include initial rolling of lymphocytes along the endothelial surface, activation of integrins, firm adhesion, and transmigration or diapedesis across the endothelial layer into the paracortical areas, the T-cell zones (Fig. 9.6). These stages are regulated by a coordinated interplay of adhesion molecules and chemokines that resembles the recruitment of leukocytes to sites of inflammation (see Chapter 3). Adhesion molecules have fairly broad roles in immune responses, being involved not only in lymphocyte migration but also in interactions between naive T cells and antigen-presenting cells (see Section 9-14).