Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.
Front Immunol. 2021 Jun 8;12:683404. doi: 10.3389/fimmu.2021.683404. eCollection 2021.
Antibody immunity against malaria is effective but non-sterile. In addition to antibody-mediated inhibition, neutralisation or opsonisation of malaria parasites, antibody-mediated complement activation is also important in defense against infection. Antibodies form immune complexes with parasite-derived antigens that can activate the classical complement pathway. The complement system provides efficient surveillance for infection, and its activation leads to parasite lysis or parasite opsonisation for phagocytosis. The induction of complement-fixing antibodies contributes significantly to the development of protective immunity against clinical malaria. These complement-fixing antibodies can form immune complexes that are recognised by complement receptors on innate cells of the immune system. The efficient clearance of immune complexes is accompanied by complement receptor internalisation, abrogating the detrimental consequences of excess complement activation. Here, we review the mechanisms of activation of complement by alternative, classical, and lectin pathways in human malaria at different stages of the life cycle with special emphasis on how complement-fixing antibodies contribute to protective immunity. We briefly touch upon the action of anaphylatoxins, the assembly of membrane attack complex, and the possible reasons underlying the resistance of infected erythrocytes towards antibody-mediated complement lysis, relevant to their prolonged survival in the blood of the human host. We make suggestions for further research on effector functions of antibody-mediated complement activation that would guide future researchers in deploying complement-fixing antibodies in preventive or therapeutic strategies against malaria.
抗疟疾抗体具有免疫效果，但无法实现完全免疫。除了抗体介导的对疟原虫的抑制、中和或调理作用外，抗体介导的补体激活在抗感染防御中也很重要。抗体与寄生虫来源的抗原形成免疫复合物，从而可以激活经典补体途径。补体系统为感染提供了有效的监测，其激活可导致寄生虫裂解或寄生虫调理作用，从而被吞噬细胞吞噬。补体结合抗体的诱导对临床疟疾的保护性免疫的发展有重要贡献。这些补体结合抗体可以形成免疫复合物，被免疫系统的先天细胞上的补体受体识别。有效的免疫复合物清除伴随着补体受体内化，从而消除了补体过度激活的有害后果。在这里，我们综述了补体在人类疟疾生命周期的不同阶段通过替代途径、经典途径和凝集素途径的激活机制，特别强调了补体结合抗体如何有助于保护性免疫。我们简要介绍了过敏毒素的作用、膜攻击复合物的组装，以及感染的红细胞对抗体介导的补体裂解具有抗性的可能原因，这与它们在人类宿主血液中的延长生存有关。我们对抗体介导的补体激活的效应功能提出了进一步研究的建议，这将为未来的研究人员在预防或治疗疟疾的策略中部署补体结合抗体提供指导。
