Immunology and immunity studied with viruses.

Abstract

Immunity to viruses is used to define important biological parameters of immunology. Specificity, tolerance and T and B cell memory were analysed with murine model infections. The key parameters of antigen kinetics, localization and patterns of T and B cell response induction in maintaining memory and in causing deletion of reactive lymphocytes were compared for self and for viral foreign antigens. Evidence is reviewed that suggests that B cells essentially recognize antigen patterns, whereas T cells react against antigens newly brought into lymphoid tissues; antigens outside lymphoid tissues are ignored, and antigens always present in, or spreading too fast throughout, lymphoid tissues exhaust and delete T cell responses. Finally, effector mechanisms of antiviral immunity are summarized, as they vary with different viruses. On this basis immunological T and B cell memory against viruses is reviewed. Memory studies suggest that 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 non-cytopathic virus, cytotoxic T cells 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 yet available of the existence of identifiable B or T cells with specialized memory characteristics, the phenotype of protective immunological memory correlates best with antigen-driven activation of low frequency effector T cells and plasma cells.