Vanham G, Bisalinkumi E
Laboratoire d'Immunologie, Institut de Médecine Tropicale, Antwerpen, Belgique.
Ann Soc Belg Med Trop. 1995 Sep;75(3):159-78.
The various stages of Plasmodium falciparum (sporozoites and liver stages, asexual blood stages and gametocytes) each interact in a particular way with the human immune system. Specific immunity against the liver stages is achieved through a coordinated action of CD8 T cells and specific antibodies, the latter in collaboration with NK cells and macrophages. In this reaction, interferon-gamma plays an essential role. A non-specific "concomitant" immunity against sporozoites is based on a cytokine reaction, elicited by the blood stages. In practice, the high variability in the immunogenic structures of the sporozoite precludes completely protection against recurrent infections. The spleen macrophages have a pivotal role in the immune defense against the asexual blood stages. The elimination of merozoites and parasitized red blood cells (RBC) is facilitated by specific antibodies, produced under the control of CD4 T cells. There are, however, multiple mechanisms of immune deviation, suppression and evolutionary adaptation, which inhibit a sterilizing immunity against the blood stages. Nevertheless, symptoms may be absent in exposed adults, even when parasitemia persists. This clinical resistance, however, is relatively short-lived, once exposition is interrupted. The observation that HIV infection has no adverse effect on malaria also is a remarkable but consistent finding. All these data indicate that a strong T cell-mediated immune memory is absent in human P. falciparum infections. Cerebral malaria and some other serious complications are the consequence of insufficient elimination of parasitized erythrocytes by the spleen, presumably in combination with parasite factors (particular variant surface structures) and with human host genetics (HLA type, blood group etc.). Parasitized RBC massively stick to the endothelium of the micro-vessels and non-parasitized RBC roset around the parasitized ones. Eventually, serious problems in the micro-perfusion and in the local metabolism occur and organ failure may finally ensue. The immune reaction against the surface-antigens of the sexual stage is limited and insufficient, most probably for similar reasons as in the asexual stages. Internal structures of the gametocytes, however, are highly immunogenic, but, unfortunately. Normally cannot be reached by the immune system. Based on these fundamental data, some of the perspectives of vaccination and new therapeutic tools are critically discussed.
恶性疟原虫的各个阶段（子孢子和肝脏阶段、无性血液阶段和配子体）均以特定方式与人体免疫系统相互作用。针对肝脏阶段的特异性免疫是通过CD8 T细胞和特异性抗体的协同作用实现的，后者与自然杀伤细胞和巨噬细胞协作。在这种反应中，γ干扰素起着至关重要的作用。针对子孢子的非特异性“伴随”免疫基于血液阶段引发的细胞因子反应。实际上，子孢子免疫原性结构的高度变异性使得无法完全预防复发性感染。脾脏巨噬细胞在针对无性血液阶段的免疫防御中起关键作用。在CD4 T细胞的控制下产生的特异性抗体促进了裂殖子和被寄生红细胞（RBC）的清除。然而，存在多种免疫偏离、抑制和进化适应机制，这些机制抑制了针对血液阶段的无菌免疫。尽管如此，即使寄生虫血症持续存在，暴露的成年人也可能没有症状。然而，一旦接触中断，这种临床抵抗力相对短暂。HIV感染对疟疾没有不利影响这一观察结果也是一个显著但一致的发现。所有这些数据表明，人类恶性疟原虫感染中缺乏强大的T细胞介导的免疫记忆。脑型疟疾和其他一些严重并发症是脾脏对被寄生红细胞清除不足的结果，可能与寄生虫因素（特定的变异表面结构）和人类宿主遗传学（HLA类型、血型等）有关。被寄生的红细胞大量黏附在微血管内皮上，未被寄生的红细胞围绕被寄生的红细胞形成玫瑰花结。最终，微灌注和局部代谢出现严重问题，最终可能导致器官衰竭。针对性成熟阶段表面抗原的免疫反应有限且不足，很可能与无性阶段的原因类似。然而，配子体的内部结构具有高度免疫原性，但不幸的是，免疫系统通常无法触及。基于这些基础数据，对疫苗接种和新治疗工具的一些前景进行了批判性讨论。
