How do lymphocyte proliferation and survival contribute to immunological memory in health, ageing and HIV infection?

淋巴细胞增殖和存活如何影响健康、衰老和艾滋病毒感染中的免疫记忆？

• 批准号: G1001052/1
• 负责人: Derek Macallan
• 金额: $ 77.22万
• 依托单位: St George's, University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1001052%2F1
• 关键词: How; do; lymphocyte; proliferation; survival

The immune system protects us from infections by ?remembering? the infections we have encountered in the past to stop them causing harm again. How does the immune system do this? It sets aside families of cells called lymphocytes, each specific for a particular infection. Paradoxically, these cells appear to be short-lived (weeks-months), whereas we know that immune memory lasts years-decades. The immune system must preserve these families of ?memory cells? somehow, but at the same time it must accommodate new families of memory lymphocytes, as new infections are encountered, and also retain sufficient numbers of cells to combat new microbes.Problems occur when this system of protection fails. Two common situations leading to problems in the immune system are ageing and HIV infection; both affect an increasing proportion of our population. As we age, the immune system becomes less able to combat infections. This results from an imbalance between different families of memory cells. HIV infection damages some immune cells directly, but it also affects all memory cells indirectly, making immune problems worse. We still do not understand how exactly this happens.This project investigates how long-term immune memory is maintained by measuring the division rate and survival of different families of lymphocytes within the human body. We will assess how many are short-lived, long-lived and very long-lived by applying four different kinds of measurement, three depending on harmless tracers given to track how fast cells divide, and one measuring changing amounts of radioactive carbon naturally found in the body. The project represents a collaboration five different centres: London, Oxford Cardiff, Stockholm and the National Institutes for Health in the USA.Understanding why the immune system is weaker in the elderly will help us devise ways to prevent this decline and design better vaccination schemes for elderly people. Understanding immune memory in HIV infection will help us think of new ways to help the immune system fight the virus and improve the use of vaccination in people with HIV/AIDS. Our results will be made widely available to the general public, through the press, and to those specifically interested, eg. those who wish to ensure they stay healthy as they age and those affected by HIV/AIDS, through specialist interest groups and lay publications.

免疫系统通过“记忆”来保护我们免受感染。我们过去遇到过的感染，以阻止它们再次造成伤害。免疫系统是如何做到这一点的？它保留了称为淋巴细胞的细胞家族，每个细胞都针对特定的感染。矛盾的是，这些细胞的寿命似乎很短（数周至数月），而我们知道免疫记忆可持续数年至数十年。免疫系统必须保存这些“记忆细胞”家族。但同时，当遇到新的感染时，它必须容纳新的记忆淋巴细胞家族，并保留足够数量的细胞来对抗新的微生物。当这种保护系统失效时，就会出现问题。导致免疫系统出现问题的两种常见情况是衰老和艾滋病毒感染；两者都影响着我们人口中越来越多的比例。随着年龄的增长，免疫系统抵抗感染的能力变得越来越差。这是由于不同存储单元家族之间的不平衡造成的。 HIV感染会直接损害一些免疫细胞，但也会间接影响所有记忆细胞，使免疫问题变得更糟。我们仍然不明白这是如何发生的。该项目通过测量人体内不同淋巴细胞家族的分裂率和存活率来研究长期免疫记忆是如何维持的。我们将通过应用四种不同的测量方法来评估有多少是短命的、长命的和非常长命的，其中三种取决于用于追踪细胞分裂速度的无害示踪剂，另一种测量体内天然存在的放射性碳的变化量。该项目代表了五个不同中心的合作：伦敦、牛津卡迪夫、斯德哥尔摩和美国国立卫生研究院。了解老年人免疫系统较弱的原因将有助于我们设计防止这种下降的方法，并为老年人设计更好的疫苗接种计划。了解艾滋病毒感染中的免疫记忆将有助于我们想出新的方法来帮助免疫系统对抗病毒并改善艾滋病毒/艾滋病患者的疫苗接种使用情况。我们的研究结果将通过媒体和那些特别感兴趣的人广泛提供给公众，例如。通过专家兴趣小组和非专业出版物，那些希望确保自己在老年时保持健康的人和受艾滋病毒/艾滋病影响的人。