When stimulated by their specific antigen and co-stimulatory signals, naïve lymphocytes proliferate and differentiate. Most become effector cells, which function and then usually die, while others become memory cells. During a subsequent exposure to the same antigen, the memory cells respond more readily, rapidly, and efficiently than did the naïve cells: they proliferate and give rise to effector cells and to more memory cells. Some memory T cells also develop from a minority of effector T cells (not shown). It is not known how the decision to become an effector cell versus a memory cell is made.
Figure 24–16 Immunological memory: primary and secondary antibody responses. The secondary response induced by a second exposure to antigen A is faster and greater than the primary response and is specific for A, indicating that the adaptive immune system has specifically remembered its previous encounter with antigen A. The same type of immunological memory is observed in T-cell-mediated responses (not shown). As we discuss later, the types of antibodies produced in the secondary response are different from those produced in the primary response, and these antibodies bind the antigen more tightly.
frst exposure to antigen venules. After percolating through the node, they accumulate in small lymphatic vessels that leave the node and connect with other lymphatic vessels that pass through other lymph nodes downstream (see Figure 24–12). Passing into larger and larger vessels, the lymphocytes eventually enter the main lymphatic vessel (the thoracic duct), which carries them back into the blood (Figure 24–18).
The continuous recirculation of a lymphocyte between the blood and lymph ends only if its specific antigen activates it in a peripheral lymphoid organ. In that case, the lymphocyte remains in the peripheral lymphoid organ, where it proliferates and differentiates into either effector cells or memory cells. Many of the effector T cells leave the lymphoid organ via the lymph and migrate through the blood to the site of infection (see Figure 24–11), whereas others stay in the lymphoid organ and help activate (or suppress) other immune cells there. Some effector B cells (plasma cells) remain in the peripheral lymphoid organ and secrete antibodies into the blood for days until they die; others migrate to the bone marrow, where they secrete antibodies into the blood for months or years. The memory T and B cells produced join the recirculating pool of lymphocytes.
Lymphocyte recirculation depends on specific interactions between the lymphocyte cell surface and the surface of the endothelial cells lining the blood vessels in the peripheral lymphoid organs. Lymphocytes that enter a lymph node via the blood, for example, adhere weakly to specialized endothelial cells lining the postcapillary venules via homing receptors that belong to the selectin family of cell-surface lectins that bind to specific sugar groups on the endothelial cell surface (see Figure 19–28). The lymphocytes roll slowly along the surface of the endothelial cells until another, much stronger adhesion system, dependent on an integrin protein, is called into play by chemokines secreted by the endothelial cells. Now, the lymphocytes stop rolling, and they crawl out of the blood vessel into the lymph node by using yet another cell adhesion protein called CD31 (Figure 24–19). Although B and T cells initially enter the same region of a lymph node, different chemokines guide them to separate regions of the node—B cells to lymphoid follicles and T cells to the paracortex (Figure 24–20).
specialized endothelial cell of postcapillary venule
Figure 24–19 Migration of a lymphocyte out of the bloodstream into a lymph node.