into wild-type mice. In addition, CD8 effector cells transferred into mice lacking MHC class II had a relative impairment of CD8 effector functions. These experiments imply that CD4 T cells activated by MHC class II-expressing antigen-presenting cells during an immune response have a significant impact on the quantity and quality of the CD8 T-cell response, even when they are not needed for the initial CD8 T-cell activation. CD4 T cells help to program naive CD8 T cells to be able to generate memory T cells, help to promote efficient effector activity, and help to maintain memory T-cell numbers.
11-24 In immune individuals, secondary and subsequent responses are mainly attributable to memory lymphocytes.
In the normal course of an infection, a pathogen proliferates to a level sufficient to elicit an adaptive immune response and then stimulates the production of antibodies and effector T cells that eliminate the pathogen from the body. Most of the effector T cells then die, and antibody levels gradually decline, because the antigens that elicited the response are no longer present at the level needed to sustain it. We can think of this as feedback inhibition of the response. Memory T and B cells remain, however, and maintain a heightened ability to mount a response to a recurrence of infection with the same pathogen.
Antibody and memory lymphocytes remaining in an immunized individual can have the effect of reducing the activation of naive B and T cells on a subsequent encounter with the same antigen. In fact, passively transferring antibody to a naive recipient can be used to inhibit naive B-cell responses to that same antigen. This phenomenon has been put to practical use to prevent Rh– mothers from making an immune response to an Rh+ fetus, which can result in hemolytic disease of the newborn (see Appendix I, Section A-6). If anti-Rh antibody is given to the mother before she is first exposed to her child’s Rh+ red blood cells, her response will be inhibited. The mechanism of this suppression is likely to involve the antibody-mediated clearance and destruction of fetal red blood cells that have entered the mother, thus preventing naive B cells and T cells from mounting an immune response. Presumably, the anti-Rh antibody is in excess over antigen, so that not only is antigen eliminated, but immune complexes are not formed to stimulate naive B cells through Fc receptors. Memory B-cell responses are, however, not inhibited by antibody, so the Rh– mothers at risk must be identified and treated before a primary response has occurred. Because of their high affinity for antigen and alterations in their B-cell receptor signaling requirements, memory B cells are much more sensitive to the small amounts of antigen that cannot be efficiently cleared by the passive anti-Rh antibody. The ability of memory B cells to be activated to produce antibody, even when exposed to preexisting antibody, also allows secondary antibody responses to occur in individuals who are already immune.
These suppressive mechanisms might also explain a phenomenon called original antigenic sin. This term was coined to describe the tendency of people to make antibodies only against the epitopes expressed on the first influenza virus variant to which they are exposed, even in subsequent infections with viral variants that have additional, highly immunogenic epitopes (Fig. 11.34). Antibodies against the original virus will tend to suppress responses of naive B cells specific for the new epitopes. This might benefit the host by using only those B cells that can respond most rapidly and effectively to the virus. This pattern is broken only if the person is exposed to an influenza virus that lacks all epitopes seen in the original infection, because now no preexisting antibodies bind the virus, and naive B cells are able to respond.