Centre for Immunology, Infection and Evolution, Institute of Immunology & Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
PLoS Comput Biol. 2011 Oct;7(10):e1002237. doi: 10.1371/journal.pcbi.1002237. Epub 2011 Oct 20.
Urogenital schistosomiasis is a tropical disease infecting more than 100 million people in sub-Saharan Africa. Individuals in endemic areas endure repeated infections with long-lived schistosome worms, and also encounter larval and egg stages of the life cycle. Protective immunity against infection develops slowly with age. Distinctive age-related patterns of infection and specific antibody responses are seen in endemic areas, including an infection 'peak shift' and a switch in the antibody types produced. Deterministic models describing changing levels of infection and antibody with age in homogeneously exposed populations were developed to identify the key mechanisms underlying the antibody switch, and to test two theories for the slow development of protective immunity: that (i) exposure to dying (long-lived) worms, or (ii) experience of a threshold level of antigen, is necessary to stimulate protective antibody. Different model structures were explored, including alternative stages of the life cycle as the main antigenic source and the principal target of protective antibody, different worm survival distributions, antigen thresholds and immune cross-regulation. Models were identified which could reproduce patterns of infection and antibody consistent with field data. Models with dying worms as the main source of protective antigen could reproduce all of these patterns, but so could some models with other continually-encountered life stages acting as the principal antigen source. An antigen threshold enhanced the ability of the model to replicate these patterns, but was not essential for it to do so. Models including either non-exponential worm survival or cross-regulation were more likely to be able to reproduce field patterns, but neither of these was absolutely required. The combination of life cycle stage stimulating, and targeted by, antibody was found to be critical in determining whether models could successfully reproduce patterns in the data, and a number of combinations were excluded as being inconsistent with field data.
泌尿生殖系统血吸虫病是一种热带疾病，影响撒哈拉以南非洲地区的 1 亿多人。在流行地区，人们反复感染寿命长的血吸虫，并遇到幼虫和卵期的生命周期。针对感染的保护性免疫会随着年龄的增长而缓慢发展。在流行地区，会出现与年龄相关的独特感染模式和特异性抗体反应，包括感染“峰值转移”和产生的抗体类型转换。描述在同质暴露人群中随年龄变化的感染和抗体水平的确定性模型被开发出来，以确定抗体转换的关键机制，并检验保护性免疫缓慢发展的两个理论：(i) 接触死亡（长寿）的蠕虫，或 (ii) 经历抗原的阈值水平，是刺激保护性抗体所必需的。探索了不同的模型结构，包括作为主要抗原来源和保护性抗体主要靶标的生命周期的替代阶段，不同的蠕虫生存分布、抗原阈值和免疫交叉调节。确定了可以复制与现场数据一致的感染和抗体模式的模型。以死亡蠕虫为保护性抗原主要来源的模型可以复制所有这些模式，但一些以其他持续存在的生命阶段为主要抗原来源的模型也可以复制所有这些模式。抗原阈值增强了模型复制这些模式的能力，但不是必需的。包括非指数型蠕虫生存或交叉调节的模型更有可能复制现场模式，但这两者都不是绝对必需的。发现刺激和针对抗体的生命周期阶段的组合对于确定模型是否能够成功复制数据中的模式至关重要，并且有几个组合被排除，因为它们与现场数据不一致。
