TUMOR NECROSIS FACTOR-DEPENDENT PARASITE-KILLING EFFECTS DURING PAROXYSMS IN NONIMMUNE PLASMODIUM-VIVAX MALARIA PATIENTS
TUMOR NECROSIS FACTOR-DEPENDENT PARASITE-KILLING EFFECTS DURING PAROXYSMS IN NONIMMUNE PLASMODIUM-VIVAX MALARIA PATIENTS
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DOI：
10.1111/j.1365-2249.1992.tb06478.x
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发表时间：
1992-06-01
影响因子：
4.6
通讯作者：
MENDIS, KN
中科院分区：
文献类型：
--
作者：
KARUNAWEERA, ND;CARTER, R;MENDIS, KN
无免疫个体的间日疟原虫疟疾感染表现为周期性临床发热、发冷和僵硬，称为阵发性发热。我们已经证明，在非免疫患者中，发作期与血浆因子的短暂存在有关，这些因子杀死配子体，疟原虫的红细胞内性阶段将感染从人类传播给蚊子，使它们对蚊子没有传染性。突发性血浆中的配子体杀伤是由肿瘤坏死因子（TNF）与其他必需血清因子联合作用介导的。发作时血浆TNF水平升高。在间日疟原虫流行地区的半免疫个体中，疟疾的临床症状是轻微的，并且在发作期间不会诱导寄生虫杀伤因子。地方性患者发作时血清TNF水平相应较低。间日疟原虫血期寄生虫提取物可以在体外刺激人外周血单个核细胞（PBMC）产生TNF和相关的寄生虫杀伤因子，从而在体外模拟发作期间发生的事件，即分裂体破裂释放寄生虫外抗原，随后诱导PBMC产生TNF和其他寄生虫杀伤因子。我们能够证明间日疟原虫半免疫个体的恢复期血清在体外阻断疟疾抗原对TNF和寄生虫杀伤因子的诱导，可能是通过中和寄生虫外抗原的抗体。因此，生活在疟疾流行地区的个人似乎通过在感染期间避免诱导而获得对疟疾的临床免疫；我们已经证明，其中一种机制是寄生虫外抗原的中和，诱导寄生虫杀伤因子的产生。
Plasmodium vivax malaria infections in non-immune individuals manifest as periodic clinical episodes of fever with chills and rigors known as paroxysms. We have demonstrated that in non-immune patients the period of paroxysm is associated with the transient presence of plasma factors which kill gametocytes, the intra-erythrocytic sexual stages of the malaria parasite which transmit the infection from humans to mosquito, rendering them non-infectious to mosquitoes. Gametocyte killing in paroxysm plasma is mediated by tumour necrosis factor (TNF) acting in conjunction with other essential serum factor(s). Plasma TNF levels were elevated during a paroxysm. In semi-immune individuals from a P. vivax-endemic area clinical symptoms of malaria are mild and the parasite killing factors are not induced during paroxysm. Serum TNF levels were correspondingly lower in endemic patients during a paroxysm. Human peripheral blood mononuclear cells (PBMC) can be stimulated in vitro by extracts of P. vivax blood stage parasites to produce TNF and associated parasite killing factor(s), thus simulating in vitro the events that occur during a paroxysm, this being the release of parasite exo-antigens by rupturing schizonts and the subsequent induction of PBMC to produce TNF and other parasite-killing factors. We were able to show that convalescent serum from P. vivax semi-immune individuals block the induction of TNF and parasite-killing factors by malaria antigens in vitro, presumably through antibodies that neutralize parasite exo-antigens. Thus, individuals living in malaria-endemic areas appear to acquire clinical immunity to malaria by avoiding their induction during infection; we have shown that one such mechanism is the neutralization of parasite exo-antigens that induce the production of parasite killing factors.