(A) This resting lymphocyte could be either a B cell or a T cell, as these cells are difficult to distinguish morphologically until antigen activates them to become effector cells. (B) An effector B cell (a plasma cell). It is filled with an extensive rough endoplasmic reticulum (er), which is distended with antibody molecules that are secreted in large amounts. (c) An effector T cell, which has relatively little rough er but is filled with free ribosomes; it secretes cytokines, but in relatively small amounts. The three cells are shown at the same magnification. (A, courtesy of Dorothy Zucker-Franklin; B, courtesy of carlo Grossi; A and B, from D. Zucker-Franklin et al., Atlas of Blood cells: Function and pathology, 2nd ed. Milan, Italy: edi. ermes, 1988; c, courtesy of Stefanello de petris.) activates the lymphocyte; this causes the lymphocyte to proliferate, thereby producing many more cells with the same receptor—a process called clonal expansion. The encounter with antigen also causes some of the cells to differentiate into effector cells. An antigen therefore selectively stimulates those cells that express complementary antigen-specific receptors and are thus already committed to respond to it (Figure 24–15). This arrangement, called clonal selection, provides an explanation for immunological memory, whereby we develop lifelong immunity to many common infectious diseases after our initial exposure to the pathogen—either through natural infection or vaccination.
It is easy to demonstrate such immunological memory in experimental animals. If an animal is immunized once with antigen A, an immune response (antibody, T-cell-mediated, or both) can be detected after several days; the response rises rapidly and exponentially, and then, more gradually, declines. This is the characteristic course of a primary immune response, occurring on an animal’s first exposure to an antigen. If, after some weeks, months, or even years have elapsed, the animal is immunized again with antigen A, it will usually produce a secondary immune response that differs from the primary response: the lag period is shorter, because there are now many more preexisting B or T cells (or both) with specificity for antigen A, and the response is greater and more efficient. These differences indicate that the animal has “remembered” its first exposure to antigen A. If the animal is given a different antigen (for example, antigen B) instead of a second immunization with antigen A, the response is typical of a primary, and not a secondary, immune response. The secondary response therefore reflects antigen-specific immunological memory for antigen A (Figure 24–16).
Immunological memory depends on both lymphocyte proliferation and differentiation. In an adult animal, the peripheral lymphoid organs contain a mixture of lymphocytes in at least three stages of maturation: naïve cells, effector cells, and memory cells. When naïve cells encounter their specific foreign antigen for the first time, the antigen stimulates some of them to proliferate and differentiate into effector cells, which then carry out an immune response (effector B cells secrete antibody, whereas effector T cells either kill infected cells or influence the response of other immune cells—by secreting cytokines, for example). Some of the antigen-stimulated naïve cells multiply and differentiate into memory cells, which are more easily and more quickly induced to become effector cells by a later encounter with the same antigen: like naïve cells, when memory cells encounter their antigen, they give rise to either effector cells or more memory cells (Figure 24–17).