Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum
Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum
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DOI：
10.1080/00034989859366
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发表时间：
1998-06-01
影响因子：
--
通讯作者：
Baird, JK
中科院分区：
文献类型：
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作者：
Baird, JK
对恶性疟原虫的自然获得性免疫力可能与免疫系统的关键特征有关，这些特征在正常发育和衰老过程中会发生变化。在居住在流行病肆虐的印度尼西亚爪哇伊里安的非免疫爪哇移民中就可以看到这一点的证据。居住1-2年后，成年移民的寄生虫血症发生频率和强度均低于其子女。脾肿大和疟疾样症状在成人中也较少见。这些对恶性疟原虫相对抵抗力的年龄依赖性模式反映了终身居民的情况。与儿童相比，爪哇成年人相对较快地获得了针对长期感染的保护性免疫力。然而，在初次接触感染期间，成人因临床诊断为疟疾而紧急医疗后送至医院的发生率是儿童的 7 倍。据报道，其他人群在初次接触感染时，成年人对严重发病和死亡的易感性过高。因此，虽然成年人比儿童更快地获得针对长期接触的保护，但他们最初更容易患上严重疾病。对这些发现的一种可能的解释是衰老过程中通常发生的免疫系统的变化。这些变化可能会在儿童和成人之间建立差异，从而深刻影响恶性疟原虫的感染过程。由于在正常生命过程中接触到的无数抗原的累积效应，幼稚 T 细胞与记忆 T 细胞的比例在衰老过程中逐渐减少。此外，胸腺的逐渐退化逐渐限制了幼稚 T 细胞的产生。用交叉反应抗原刺激记忆T细胞的可能性可能会随着年龄的增长而增加，这可能会使免疫反应偏向于在长期暴露下对宿主相对有利，或者在急性暴露下对宿主不利。随年龄变化的免疫系统的内在特征可能决定对恶性疟原虫感染的免疫反应的关键特征，并且该反应是相对有害还是有益可能取决于暴露条件（即急性或慢性）。
Naturally acquired immunity to Plasmodium falciparum may be linked to key features of the immune system that change during normal development and ageing, Evidence of this was seen in non-immune Javanese transmigrants taking up residence in hyperendemic Irian Java, Indonesia. After 1-2 years of residence, the adult migrants had less frequent and less intense parasitaemias than their children. Splenomegaly and malaria-like symptoms were also less common in the adults. These age-dependent patterns of relative resistance to P. falciparum mirrored those in lifelong residents. The Javanese adults acquired protective immunity against chronic exposure to infection relatively quickly compared with their children. However, during tl;e initial exposure to infection, the incidence of emergency medical evacuation to hospital with a clinical diagnosis of malaria was 7-fold higher among the adults than in their children. The exaggerated susceptibility of adults to severe morbidity and mortality has been reported in other populations during initial exposure to infection. Thus, whereas adults acquired protection against chronic exposure more rapidly than the children, they were initially more susceptible to severe disease. One possible explanation for these findings is the changes in the immune system that normally occur during ageing. Such changes may establish differences between children and adults that profoundly affect the course of infection by P. falciparum. The ratio of naive to memory T cells gradually diminishes during ageing, as a result of the cumulative effect of exposure to the myriad antigens encountered throughout the normal course of life. Moreover, the gradual involution of the thymus progressively limits the production of naive T cells. The likelihood of stimulating memory T cells with cross-reactive antigens may increase with age and this may bias the immune response to the relative benefit of the host under chronic exposure, or to the detriment of the host under acute exposure. Intrinsic features of the immune system that change with age may determine key characteristics of the immune response to infection by P. falciparum, and whether that response is relatively harmful or beneficial may depend upon the conditions of exposure (i.e. acute or chronic).