Baird J K
Malaria Program, Naval Medical Research Institute, Rockville, MD 20852, USA.
Ann Trop Med Parasitol. 1998 Jun;92(4):367-90. doi: 10.1080/00034989859366.
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 Jaya, 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 the 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 benefits 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).
对恶性疟原虫的自然获得性免疫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。在印度尼西亚伊里安查亚高疟区定居的非免疫爪哇移民中就可见到这方面的证据。居住1 - 2年后，成年移民的疟原虫血症频率和强度低于他们的孩子。脾肿大和疟疾样症状在成年人中也较少见。这些对恶性疟原虫相对抵抗力的年龄依赖性模式与长期居民中的模式相似。与他们的孩子相比，爪哇成年人相对较快地获得了针对慢性感染的保护性免疫。然而，在初次接触感染期间，临床诊断为疟疾而紧急医疗后送入院的发生率在成年人中比在他们的孩子中高7倍。在其他人群初次接触感染期间，也报道了成年人对严重发病和死亡的易感性过高。因此，虽然成年人比孩子更快地获得了针对慢性接触的保护，但他们最初更容易患严重疾病。这些发现的一个可能解释是衰老过程中免疫系统的变化。这种变化可能导致儿童和成年人之间的差异，从而深刻影响恶性疟原虫感染的病程。随着年龄增长，由于在正常生命过程中接触无数抗原的累积效应，初始T细胞与记忆T细胞的比例逐渐降低。此外，胸腺的逐渐退化逐渐限制了初始T细胞的产生。用交叉反应抗原刺激记忆T细胞的可能性可能随年龄增加，这可能使免疫反应偏向于慢性接触下宿主的相对益处，或在急性接触下对宿主不利。免疫系统随年龄变化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，而这种反应是相对有害还是有益可能取决于接触条件（即急性或慢性）。
