On recognizing its specific antigen on an activated antigen-presenting cell, a naive lymphocyte stops migrating, the volume of the nucleus and cytoplasm increases, and new mRNAs and new proteins are synthesized. Within a few hours, the cell looks completely different and is known as a lymphoblast. Dividing lymphoblasts are able to duplicate themselves two to four times every 24 hours for 3–5 days, so that a single naive lymphocyte can produce a clone of around 1000 daughter cells of identical specificity. These then differentiate into effector cells. In the case of B cells, the differentiated effector cells are the plasma cells, which secrete antibody. In the case of T cells, the effector cells are either cytotoxic T cells, which are able to destroy infected cells, or helper T cells, which activate other cells of the immune system (see Section 1-8).
Effector lymphocytes do not recirculate like naive lymphocytes. Some effector T cells detect sites of infection and migrate into them from the blood; others stay in the lymphoid tissues to activate B cells. Some antibody-secreting plasma cells remain in the peripheral lymphoid organs, but most plasma cells generated in the lymph nodes and spleen will migrate to the bone marrow and take up residence there, secreting large amounts of antibodies into the blood system. Effector cells generated in the mucosal immune system generally stay within the mucosal tissues. Most lymphocytes generated by clonal expansion in an immune response will eventually die. However, a significant number of activated antigen-specific B cells and T cells persist after antigen has been eliminated. These cells are known as memory cells and form the basis of immunological memory. They can be reactivated much more quickly than naive lymphocytes, which ensures a more rapid and effective response on a second encounter with a pathogen and thereby usually provides lasting protective immunity.
Fig. 1.25 The course of a typical antibody response. the first encounter with an antigen produces a primary response. Antigen A introduced at time zero encounters little specific antibody in the serum. After a lag phase (light blue), antibody against antigen A (dark blue) appears; its concentration rises to a plateau and then gradually declines, typical of a primary response. When the serum is tested for antibody against another antigen, B (yellow), there is little preset. When the animal is later challenged with a mixture of antigens A and B, a very rapid and intense antibody secondary response to A occurs, illustrating immunological memory. this is the main reason for giving booster injections after an initial vaccination. note that the response to B resembles the primary response to A, as this is the first encounter with antigen B.
The characteristics of immunological memory are readily observed by comparing an individual’s antibody response to a first or primary immunization with the response to a secondary or booster immunization with the same antigen. As shown in Fig. 1.25, the secondary antibody response occurs after a shorter lag phase and achieves a markedly higher level than in the primary response. During the secondary responses, antibodies can also acquire higher affinity, or strength of binding, for the antigen due to a process called affinity maturation, which takes place in the specialized germinal centers within B-cell follicles (see Section 1-16). Importantly, helper T cells are required for the process of affinity maturation, but T-cell receptors do not undergo affinity maturation. Compared with naive T cells, memory T cells show a lower threshold for activation, but as a result of changes in the responsiveness of the cell and not because of changes in the receptor. We describe the mechanisms of affinity maturation in Chapters 5 and 10.