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Role of Complement in Immunity Against Malaria

  • José A. Stoute
Chapter

Abstract

The role of complement in the immunity against malaria has been severely understudied. As a result, we know very little about this subject. Antibodies play an important role in suppressing parasitemia and could work by any or a combination of several mechanisms: inhibition of sporozoite invasion of hepatocytes, by blocking merozoite invasion of red blood cells (RBCs), by inducing phagocytosis of merozoites, or by inducing the phagocytosis of infected RBCs (IRBCs). Although there are some data that sporozoites are susceptible to complement activation, this seems to require high antibody levels. Complement can enhance the phagocytosis of IRBCs in the presence of nonimmune serum. In this system, natural antibodies that recognize altered native membrane antigens may play a role in activating complement, but there is also evidence of antibody-independent complement activation on the surface of IRBCs. The contribution of complement to anti-merozoite immunity was recently studied using filter-purified merozoites. C1q appeared to have a critical role in the inhibitory activity of anti-merozoite antibodies, but further studies are needed to confirm this and other contradictory observations reporting that antibody and complement can also enhance RBC invasion by merozoites. In vivo, cobra venom factor (CVF) has been used commonly in animal models to deplete complement. However, this approach is confounded by the fact that CVF is a complement activator that can promote indiscriminate deposition of C3b. Thus, CVF has produced contradictory results. Although there is now wide availability of genetically modified mice that are deficient in specific complement factors, relatively little work has been done with these animals. C1q−/− mice have been shown to have increased P. chabaudi parasitemia upon reinfection. On the other hand, C3−/− mice showed decreased P. berghei parasitemia. Much more work is needed before we have a clear picture of the role of complement in anti-malarial immunity. A better understanding of the role of complement in malaria immunity is needed if we are ever to develop a highly effective vaccine against malaria.

Keywords

Antibody Complement Red blood cell Merozoite Malaria Sporozoite Immunity ADCI Phagocytosis C1q C3b 

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Authors and Affiliations

  1. 1.Department of Medicine, and Microbiology and ImmunologyPenn State University College of MedicineHersheyUSA

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