Antigenicity of the infected-erythrocyte and merozoite surfaces in Falciparum malaria.

Abstract

Recent advances in techniques for the in vitro cultivation of Plasmodium falciparumhave now made it possible to obtain all stages of the asexual erythrocytic life cycle of the parasite (1). The protective properties of antisera from individuals immune to malaria and the antigenicity of parasite components can now be examined in vitro.During the erythrocytic cycle of Plasmodium falciparum two important foreign surfaces are exposed to the host immune system: the infected erythrocyte membrane and the plasma membrane of the parasite at the merozoite stage. This paper reports the results of our experiments on the immunocytochemical localization of antibodies from immune sera on these two surfaces.Infection with Plasmodium falciparum results in alterations of the host erythrocyte membrane, which develop as the parasite within matures. Most prominent of these are the knobs, electron-dense inverted cuplike protrusions from the erythrocyte surface. These knobs or excrescences arise in both in vivo and in vitro infections (2-6). They are believed to provide receptors by which erythrocytes, containing late-stage parasites, sequester in the capillaries (7,8). Although the knobs induced by P. falciparum may be antigenically distinct from the rest of the infected erythrocyte surface (8), their reactivity with the sera from animals which are immune to malaria has not been examined. P. knowlesi does not induce knobs but does induce antigenic variant-specific alterations in its host erythrocyte membrane. These alterations have been demonstrated by the agglutination of schizont-infected erythrocytes when treated with sera from monkeys immune to this malaria parasite (9).Several important questions have not yet been answered about the antigenicity of the P. falciparum-infected erythrocyte surface. Are the parasite-induced alterations which stimulate antibody in the immune host located on the knobs (7,8) or are other regions of the membrane also involved, such as with P. knowlesi (9)? Do different strains of P. falciparum from different geographic areas induce immunologically crossreactive alterations of the erythrocyte membrane, or are the alterations strain and/or variant specific? Are the knobs induced by a single strain of parasite antigenically similar in both human and monkey erythrocytes, or is their antigenicity influenced by the host cell?

Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falciparum.

“…The occurrence of parasite antigens on the surface of infected E in malaria is well established (16,17,(30)(31)(32)(36)(37)(38)(39). In most instances, these antigens appear to be synthesized during relatively late phases of parasite maturation and are assumed to be inserted into the E surface by the parasites from within the infected host cell (35).…”

Stage-specific proteins and glycoproteins of plasmodium falciparum: identification of antigens unique to schizonts and merozoites.

“…Despite the massive literature on immunology-of malaria, several aspects of acquired immunity remain unknown. Circulating antibodies have been shown to react with surfaces of merozoites and schizonts (13)(14)(15)(16)(17). After identification of schizont-and merozoite-associated proteins and glycoproteins, attempts were made to specify which of these constituents were possible candidates for functional antigens.…”

Homology between a histidine-rich protein from Plasmodium lophurae and a protein associated with the knob-like protrusions on membranes of erythrocytes infected with Plasmodium falciparum.

“…The knobs were found to be antigenically different from adjacent areas of erythrocyte membrane devoid of them (9). The presence of anti-knob antibody in serum of experimentally immunized monkeys was recently shown by immunoelectron microscopy (12). To date, all successful experimental vaccinations with a particular antigen in one species of malaria have been shown to be applicable to homologous antigens from other species.…”