Figure 24–15 Clonal selection. An antigen activates only those lymphocytes that are already committed to respond to it. The committed cell expresses cell-surface receptors that specifically recognize the antigen. The human adaptive immune system consists of many millions of different T and B lymphocyte clones, with cells within a clone expressing the same unique antigen receptor. Before its first encounter with antigen, a clone would usually contain only one or a small number of cells. A particular antigen may activate hundreds of different clones, each expressing a different antigen receptor that binds either a different part of the antigen or the same part with a different binding affinity. Although only B cells are shown here, T cells are selected in a similar way. Note that the antigen receptors on the  B cells labeled β in this diagram have the same antigen-binding site as the antibodies secreted by the effector Bβ cells. As we discuss later, B cells require co-stimulatory signals from T cells to become activated by antigen to proliferate and differentiate into antibody-secreting cells (not shown).
antibodies in blood(arbitrary units, Iog scale) frst immunization second immunization with antigen A with antigen A frst immunization with antigen B
Thus, during the primary response, clonal expansion and differentiation of antigen-stimulated naïve cells creates many memory cells, which are able to respond to the same antigen more sensitively, rapidly, and effectively. And, unlike most effector cells, which die within days or weeks, memory cells can persist for the lifetime of the animal, even in the absence of their specific antigen, thereby providing lifelong immunological memory. Although most effector B and T cells die after an immune response is over, some survive as effector cells and help provide long-term protection against the pathogen. A small proportion of the plasma cells produced in a primary B cell response, for example, can survive for many months or years in the bone marrow, where they continue to secrete their specific antibodies into the bloodstream.
Pathogens generally enter the body through an epithelial surface, usually through the skin, gut, or respiratory tract. To induce an adaptive immune response, microbes or their products must travel from these entry points to a peripheral lymphoid organ, such as a lymph node or the spleen, which are the sites where lymphocytes are activated (see Figure 24–11). The route and destination depend on the site of entry. Lymphatic vessels carry antigens that enter through the skin or respiratory tract to local lymph nodes; antigens that enter through the gut end up in gut-associated peripheral lymphoid organs such as Peyer’s patches; and the spleen filters out antigens that enter the blood (see Figure 24–12). As discussed earlier (see Figure 24–11), in many cases, activated dendritic cells will carry the antigen from the site of infection to the peripheral lymphoid organ, where they play a crucial part in activating T cells, as we discuss later.
But only a tiny fraction of naïve B and T cells can recognize a particular microbial antigen in a peripheral lymphoid organ, a reasonable estimate being between 1/10,000 and 1/1,000,000 of each class of lymphocyte, depending on the antigen. How do these rare cells find an antigen-presenting cell displaying their specific antigen? The answer is that the lymphocytes continuously recirculate between one peripheral lymphoid organ and another via the lymph and blood. In a lymph node, for example, lymphocytes continually leave the bloodstream by squeezing out between specialized endothelial cells lining small veins called postcapillary
Figure 24–17 A model for the cellular basis of immunological memory.