The antibody binding assays described above do not identify a potential functional role for antibody binding to antigens exposed at the infected-erythrocyte surface

The antibody binding assays described above do not identify a potential functional role for antibody binding to antigens exposed at the infected-erythrocyte surface. of intact sp. parasites demonstrate inter- and intraspecies behavioral, biochemical, genetic, and antigenic differences (17, 19). Host populations are thus infected with a range of genetically variant parasites. Furthermore, during an infection with in a single host, a repertoire of parasite variants (32, 37), which are antigenically distinct at the infected-erythrocyte surface, may be produced. In spite of this diversity, it is well established that people living in areas where malaria is endemic gradually develop naturally acquired immunity to the disease, a fact that has encouraged research on the development of a vaccine. However, semi-immune individuals remain susceptible to reinfection, and it may take many infections over several years before Glecaprevir a level of immunity capable of preventing clinical disease is reached. Immunity involves both cell-mediated and humoral responses (10). The latter may develop partly through the acquisition of a repertoire of specific protective antibodies directed against polymorphic antigens sequentially expressed by antigenically distinct parasite variants. The finding that protective immunity can be passively transferred to children by immunoglobulin G (IgG) antibodies from immune adults is consistent with this suggestion (6, 26, 35). PfEMP1 (erythrocyte membrane protein 1) is one such polymorphic antigen exposed on the surfaces of infected erythrocytes. Antibody responses to this antigen in adults remain predominantly variant specific (32) and may be linked to protective immunity (4). However, defining the true importance of such antigens and the specific antibody responses directed to them in a natural infection is problematic. It is difficult to fully characterize either the parasite population(s) infecting individuals and populations or the immune status of those affected (29). Inbred naive CBA/Ca mice infected with a cloned population Glecaprevir of AS experience a pattern of infection similar to that seen with in nonimmune humans. Initially the parasitemia is high and acute, but then partial resolution of the infection FGF6 occurs and the infection goes chronic. This generally low-level, chronic phase is interspersed with recrudescences of parasitemia consisting of antigenically variant parasites (28). For these and other reasons discussed elsewhere (9, 17, 30, 31) this host-parasite combination is a useful model for certain aspects of infection in humans. In AS infections the antibody-mediated part of this response is directed at parasite line-specific epitopes predominantly exposed on the surfaces of trophozoite- or schizont-infected erythrocytes (18, 30, 36). These antibodies enhance the phagocytosis and destruction of infected erythrocytes in vitro (30). Opsonizing antibodies with a similar specificity have been associated with protection in infections (11, 12). Full resolution Glecaprevir of a primary AS infection renders mice relatively resistant to reinfection with the same parasite line, but they remain susceptible to reinfection with heterologous parasites (17). After six or seven further injections with large numbers of AS-parasitized erythrocytes, the resulting hyperimmune mice are refractory to further challenge with homologous parasites but remain susceptible to heterologous challenge (19; W. Jarra and K. N. Brown, unpublished results). This situation is similar to that seen in protective (hyper-) immunity in humans. In order to further investigate the specificity of immune responses operating in such situations, we examined the specificity of antibody binding to AS-infected erythrocytes in the sera of mice hyperimmune to either the AS or CB lines of or KSP-11. The highest levels of antibody binding were seen with AS hyperimmune serum although cross-reactive antibodies were evident in the other sera. Antibody binding to the surface of intact AS-infected erythrocyte was predominantly.

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