On Immunological Memory

Abstract

Immunological memory is a hallmark of the immune system. Evolution can teach us which effector arms of immunological memory are biologically relevant against which virus. Antibodies appear to be the critical protective mechanism against cytopathic viruses. Since these viruses cause cell damage and disease directly, particularly in the absence of an immune response, mothers protect their offspring during a critical immunoincompetent period (a consequence of MHC- restricted T cell recognition) by passive transfer of neutralizing antibodies. In contrast, CTL appear to be the crucial effector mechanism against noncytopathic viruses. Since MHC polymorphism has made vertical transmission of T cell memory impossible, immunoincompetent offspring are not, and need not be, protected against such noncytopathic viruses. During the primary response and again during secondary infection, the most important function of CTL is to eliminate noncytopathic viruses, which may otherwise cause lethal immunopathology. Increased precursor frequencies of B and T cells appear to remain in the host independent of antigen persistence. However, in order to protect against cytopathic viruses, memory B cells have to produce antibody to maintain protective elevated levels of antibody; B cell differentiation into plasma cells is driven by persisting antigen. Similarly, to protect against infection with a noncytopathic virus, CTL have to recirculate through peripheral organs. Activation and capacity to emigrate into solid tissues as well as cytolytic effector function are also dependent upon, and driven by, persisting antigen. Because no convincing evidence is available yet of the existence of identifiable B or T cells with specialized memory characteristics, the phenotype of immunological memory correlates best with antigen-driven activation of low frequency effector T cells and plasma cells.

TLR2 is expressed on activated T cells as a costimulatory receptor

“…Our findings reported here suggest that there may be a parallel between T and B cells in that TLR signaling helps to maintain long-term memory of these cells. This observation may also help to resolve a current central controversy on the requirement for the continuous presence of specific pathogen for the maintenance of long-term specific T cell memory (40)(41)(42).…”

Postexposure vaccination massively increases the prevalence of γ-herpesvirus-specific CD8+T cells but confers minimal survival advantage on CD4-deficient mice

“…Much has been written about the possible role of persisting antigen in the long-term maintenance of virus-specific CD8 ϩ T cells (33)(34)(35). Previous comparison of ␥HV-68-infected I-A bϩ/ϩ and I-A bϪ/Ϫ mice established that the higher virus load in the I-A bϪ/Ϫ group was indeed associated with the continued presence of more CD8 ϩ p56D b -specific T cells in the lymphoid tissue, with this population still constituting 3-4% of the total CD8 ϩ pool (8).…”

Antigen Localization and Migration in Immunity and Tolerance

“…Leakage of small quantities of hidden antigen to lymphoid organs may maintain enough activated T cells to control the infection efficiently but not enough to clear the peripheral foci of organisms. 2,24,61,62 Between the two extremes shown in Figures 2A and 2B, an unrelenting immune response to the persisting microorganism expressed in many host cells can result in serious immunopathologic conditions (e.g., chronic active hepatitis) (Fig. 2C).…”