人体可以精确记录回忆很久以前遇到的病毒及细菌,使我们不会经历二次麻疹和水痘,这也是疫苗发挥功效的原因。
但研究人员对于记忆系统的机制仍不是很清楚。一个国际合作小组发现一条重要线索,可解释免疫系统如何记忆曾经遇到过的敌人,并且快速地作出反应。研究结果刊载于10月23日的PNAS中。
Wisconsin-Madison大学的研究人员Marulasiddappa Suresh带领的研究小组鉴定出一种与刺激免疫细胞活化过程有关的蛋白质。
免疫系统T细胞能够攻击病毒感染的细胞、外源细胞和癌细胞,并且在细胞表面传感器抗原受体的刺激下产生记忆。这种被研究人员称为Lck的蛋白,在T细胞对病原体特征进行记忆的过程中发挥至关重要的作用。Lck可以帮助未曾暴露于特异抗原的原始T细胞(naïve T cells)捕获、收藏入侵抗原以备后患。感染或者接种疫苗后,Lck启动一条生化途径,扩大了发挥抵抗作用的T细胞数量。
等到感染被镇压后,抵抗此抗原的T细胞大军数量急剧下降。但有一小部分保留下来,即所谓的记忆细胞,保留了侵略者的印记,在若干年后相同的病原体卷土重来时,记忆细胞能够迅速作出反应。
Suresh等人发现,与原始T细胞不同,记忆T细胞的活动范围不止于淋巴系统,它周游身体各处,辅助身体感觉、更加迅速消灭先前遇到过的抗原。这项新发现不也可以辅助抗AIDS等病毒的疫苗开发,为自体免疫疾病患者和器官排斥反应的患者带来福音。
英文原文:
Scientists find key to immune system’s ability to remember
Its ability to accurately catalog and recall long-past encounters with viruses, bacteria and other pathogens is why we get the measles or chicken pox only once, and is why exposure to deactivated virus particles in vaccines confers protection from disease.
But how that memory system works — how it acts at the finest level of detail to thwart the pathogens that invade our bodies — is not well understood. Now, however, an international team of scientists has ferreted out an important clue to how the key cells of the immune system are able to remember old foes and quickly mount a response to hold them at bay.
Writing this week (Oct. 23) in the Proceedings of the National Academy of Sciences (PNAS), a team of researchers led by University of Wisconsin-Madison researcher Marulasiddappa Suresh identify the role of a protein that is important in stimulating the cells of the immune system, whose role is to take quick and effective action when agents of disease reinvade the body.
"We have found at least a part of how the immune system remembers its encounters," says Suresh, a professor of pathobiological sciences in the UW-Madison School of Veterinary Medicine. "We now know one of the reasons why we get such a quick (immune) response" when we are exposed to pathogens we've experienced before.
The new insight is important not only because it sheds light on the biochemical intricacies of immune system memory, but also because it may one day aid in the development of vaccines against infections such as AIDS, and help victims of autoimmune diseases and transplant patients whose immune systems reject donor organs.
The protein, which scientists call Lck, is essential for immune system T cells — white blood cells that attack virus-infected cells, foreign cells and cancer cells — to cement the memory induced by cell surface sensors known as antigen receptors that act to identify the signatures of pathogens like measles virus and HIV, agents that hide inside cells.
Lck is important in helping "naïve" T cells — those cells that have never been exposed to a particular pathogen — capture the receptor template of the invading agent and store it for future reference. Among the millions of naïve T cells, there are a few that are primed for active duty against an individual infectious agent. Following infection or vaccination, Lck initiates a biochemical chain of events that vastly increases the number of T cells that march off to combat the invader.
After the infection subsides, the number of T cells marshaled to fight that agent decreases dramatically. But a smaller subset, known as "memory" cells, retains the imprint of its previous encounter should the pathogen make a return appearance.
According to the study, while Lck primes naïve cells to fight a pathogen, it is not required by memory cells, which initiate the fast and furious response when that same pathogen comes calling again years later. Unlike naïve T cells, which are confined to the lymphatic system, memory T cells are found everywhere in the body, enabling them to sense and react more quickly when an infectious agent is reencountered.
"Now we know one of the reasons we get such a quick response and clearance (of the pathogen) with re-infection," Suresh explains. "If you increase the size of your army, you can clear your enemies faster. The memory T cells are greater in number and they are more potent."
The new insight could help refine therapeutic targets to treat autoimmune diseases and may inform new strategies for suppressing T cell response after transplantation. Now, transplant patients require lifelong regimens of drugs to suppress immune response to the foreign cells in the donated organ.
In addition to Suresh, authors of the new PNAS report include Kavita Tewari, Jane Walent and John Svaren, all of UW-Madison, and Rose Zamoyska of the United Kingdom's Medical Research Council National Institute for Medical Research. The research was funded by the U.S. Public Health Service.