Chapter 13 : Immunological Memory and Infection

The natures of effector T- and B-cell responses are different. Most microbial infections induce prolonged serum antibody responses that can persist for months or years after resolution of the infection. In contrast, effector T-cell responses (i.e., active killer cells and cytokine producers) are short-lived and are seen only during the acute phase of infection.

Model of memory B-cell differentiation. Following antigenic stimulation, naïve B cells differentiate along separate pathways into memory B cells and plasma cells (PC). In this model, low-affinity B cells differentiate into short-lived plasma cells whereas high-affinity B cells give rise to long-lived plasma cells. Memory B cells, in general, are extremely long-lived and, on reencountering antigen (Ag), can rapidly differentiate into plasma cells and also proliferate to generate more memory B cells. Plasma cells are terminally differentiated effector cells that can neither divide in response to antigen nor revert to memory B cells.

Kinetics and anatomic site of antibody production after infection. Initial antibody production is by plasma cells within GCs in the spleen and lymph nodes, but after the infection is resolved, the bone marrow becomes the site of long-term antibody production. On secondary infection, the spleen and lymph nodes mount a rapid but transient antibody response, and after a return to homeostasis, the bone marrow is again the predominant source of antigen-specific plasma cells.

Antiviral CD8 and CD4 T-cell responses. The three phases of the immune response are indicated at the top. The increase in cell number during the expansion phase is due to clones of T cells undergoing cell division. Soon after the virus is cleared, there is a death phase, characterized by decreasing numbers of virus-specific T cells due to apoptosis. Following the death phase, the number of virus-specific T cells stabilizes and can be maintained for extended periods (the memory phase). The CD4 T-cell response is similar to the CD8 T-cell response, except that the magnitude of the CD4 response is lower and the death phase can be more protracted than the CD8 response.

The size of the memory T-cell pool is determined by the clonal burst size during the expansion phase. In this figure, lines 1, 2, and 3 represent the T-cell responses induced by three different vaccines. Vaccine 1 induces the largest expansion of T cells and hence generates the largest pool of memory T cells; vaccine 2 is next; and vaccine 3 is the weakest. The asterisk denotes the minimum number of antigen-specific T cells required for protective immunity. In this scenario, vaccines 1 and 2 will confer long-term immunity whereas protective immunity induced by vaccine 3 will be of short duration. The main reason for the failure of vaccine 3 is a smaller burst size during the expansion phase. Note that the maintenance of the memory T cell pool is similar for all three vaccines.

Models of memory T-cell differentiation. Model 1 represents the B-cell paradigm of dichotomy in memory and effector pathways. Model 2 is the more traditional view of memory T-cell differentiation representing a linear-differentiation pathway. Model 3 is a variation of model 2 and takes into account the finding that only 5 to 10% of the effector cells survive to become memory T cells. In this model, progress toward terminal differentiation (driven by antigen [Ag]) is accompanied by increased susceptibility to apoptosis and a decreased potential for memory cell development. In all of these models the effector cells represent a transient population whereas the memory cells survive for long periods. On reexposure to antigen, the memory T cells can develop into effector cells and can also generate more memory cells.

Model of memory T-cell differentiation incorporating the development of central and effector memory T cells. In this model, a short duration of antigenic (Ag) stimulation favors the development of central memory cells whereas a longer duration favors differentiation to effector memory T cells.