Scientists Are Starting to Unlock the Nanoscale Secrets of the Immune System
Scientists Are Starting to Unlock the Nanoscale Secrets of the Immune System
科学家们正开始揭开免疫系统的纳米级秘密
The immune system operates at a scale scientists are only just beginning to be able to see. That new view could change how diseases like cancer are tackled. 免疫系统的运作尺度，科学家们才刚刚开始能够观测到。这种全新的视角可能会改变我们应对癌症等疾病的方式。
Speaking at WIRED Health on April 16, Daniel Davis, an immunologist at Imperial College London, detailed how researchers are using advanced microscopes to uncover previously invisible dynamics in the human immune system, showing that there are multiple processes happening on a “nanoscale” that was previously out of reach. 4月16日，在 WIRED Health 大会上，伦敦帝国理工学院的免疫学家丹尼尔·戴维斯（Daniel Davis）详细介绍了研究人员如何利用先进的显微镜揭示人体免疫系统中此前不可见的动态过程，并指出有多种“纳米级”的生理过程正在发生，而这些过程在过去是无法触及的。
That new view is already reshaping how immunity is understood. “We have discovered something that’s known as the immunological synapse, which is that lots of different protein molecules are known to trigger the immune system,” Davis said. 这种全新的视角正在重塑人们对免疫的理解。戴维斯说：“我们发现了一种被称为‘免疫突触’的结构，即许多不同的蛋白质分子被证实能够触发免疫系统。”
Today’s microscopes reveal worlds that “we just had no idea that existed,” he explained. “There wasn’t really a hypothesis that led us to that,” he said. “It was watching things happen under a microscope.” 他解释道，今天的显微镜揭示了那些“我们根本不知道其存在”的世界。“这并非源于某种假设的引导，”他说，“而是通过在显微镜下观察事物发生的真实过程。”
At this scale, even the first moments of contact between cells look different. “When an immune cell sticks to another cell, it’s got to decide if that other cell is healthy or diseased. Small, nanoscale protrusions come out from the immune cell to make that initial contact,” he said. 在这一尺度下，细胞接触的最初瞬间看起来也与众不同。他说：“当一个免疫细胞附着在另一个细胞上时，它必须判断对方是健康的还是患病的。免疫细胞会伸出微小的纳米级突起，以建立最初的接触。”
In collaboration with pharmaceutical company Bristol Myers Squibb, his lab is exploring how this level of detail can be used not just to observe immune responses, but influence them. After killing a diseased cell, for instance, an immune cell has to detach and move on to attack another, a process scientists have only recently been able to observe in detail. 通过与制药公司百时美施贵宝（Bristol Myers Squibb）合作，他的实验室正在探索如何利用这种精细度，不仅用于观察免疫反应，还能对其施加影响。例如，在杀死一个病变细胞后，免疫细胞必须脱离并继续攻击下一个目标，这一过程科学家直到最近才得以详细观察。
Davis’s team is experimenting with reengineered antibodies—Y-shaped molecules that act as a bridge between immune cells and cancer cells—to strengthen the signals that activate those immune cells. By binding to the immune cell in this way and bringing key proteins closer together, these molecules can “send a really strong potent signal for the immune cell to switch on and kill the cancer.” 戴维斯的团队正在试验重新设计的抗体——这些 Y 型分子充当了免疫细胞和癌细胞之间的桥梁——以增强激活免疫细胞的信号。通过这种方式与免疫细胞结合并将关键蛋白质拉近，这些分子能够“发送一个非常强效的信号，促使免疫细胞启动并杀死癌细胞。”
Conceptually, this suggests that arranging molecules on immune cells could make them more effective at killing target cells, potentially improving how the immune system attacks cancer or, in autoimmune disease, eliminates harmful cells. While the work is currently early stage, Davis says that “it might produce something in the end that could be tried in patients.” 从概念上讲，这意味着排列免疫细胞上的分子可以使它们在杀伤目标细胞时更有效，从而可能改善免疫系统攻击癌症的方式，或者在自身免疫性疾病中更有效地清除有害细胞。虽然这项工作目前处于早期阶段，但戴维斯表示，“它最终可能会产生一些可以用于患者临床试验的成果。”
There are many different kinds of molecules you could tweak the positioning of on the immune cell surface, he explains. “I don’t have any real idea about which ones would be good to target or not target. At the moment, the strategies place lots of bets.” 他解释说，免疫细胞表面有许多不同种类的分子，你可以调整它们的位置。“我并不真正清楚哪些分子适合作为靶点，哪些不适合。目前，这些策略更像是在进行多方押注。”
“Lots of different small startup companies are trying lots of different versions of that type of therapy” as they try to find out what would enable that powerful response, he said. 他说，许多不同的小型初创公司正在尝试各种版本的此类疗法，试图找出究竟是什么因素能够激发那种强大的免疫反应。
Alongside these advances, Davis emphasized that immune health is inherently individual. Of all a human’s genes, the ones that vary most between people are—perhaps surprisingly—not those that determine appearance, but those linked to the immune system, he explained. 在这些进展之外，戴维斯强调，免疫健康本质上是个体化的。他解释说，在人类所有的基因中，人与人之间差异最大的——或许令人惊讶的是——并非决定外貌的基因，而是与免疫系统相关的基因。
“There’s a fundamental biological reason why humans are so diverse and that is because it’s how our species has evolved to survive all different kinds of diseases,” he said. “人类之所以如此多样化，有着根本的生物学原因，这是我们物种为了在各种疾病中生存而进化出的结果，”他说。
That means people respond differently to the same infection. “I might think I haven’t exercised enough, I haven’t eaten the right stuff, I’m too stressed,” he said. In reality, “you might have inherited a particular set of immune system genes that make you better at fighting off that kind of illness.” 这意味着人们对同一种感染的反应各不相同。他说：“我可能会认为自己运动不足、饮食不当或压力太大。但实际上，你可能只是遗传了一套特定的免疫系统基因，使你更擅长抵御那种疾病。”
“There’s no hierarchy in the system,” he added. “这个系统中没有高低优劣之分，”他补充道。
Right now, immune health practice is not at the point where it can tailor treatments to those differences. Davis added that though some companies are working toward personalized approaches, the ability to truly harness individual immune health remains a future goal. 目前，免疫健康实践尚未达到能够根据这些差异量身定制治疗方案的程度。戴维斯补充说，尽管一些公司正在致力于个性化治疗方法，但真正利用个体免疫健康的能力仍然是一个未来的目标。
In the meantime, Davis warned against blindly following simplistic health advice. “Any time you hear a sound bite” about improving immune health, he said, it is important to look more closely at the evidence behind it. 与此同时，戴维斯警告人们不要盲目听从简单的健康建议。他说，每当你听到关于改善免疫健康的“只言片语”时，仔细审视其背后的证据至关重要。
He pointed to the enduring belief that vitamin C can prevent or shorten colds, an idea popularized by chemist Linus Pauling, who won Nobel Prizes in 1954 and 1962. Despite the persistence of that advice, Davis said the effect is minimal: “[Pauling] cherry-picked the evidence.” 他指出了一个长期存在的信念，即维生素 C 可以预防或缩短感冒时间，这一观点由曾于 1954 年和 1962 年获得诺贝尔奖的化学家莱纳斯·鲍林（Linus Pauling）推广。尽管这一建议流传甚广，但戴维斯表示其效果微乎其微：“（鲍林）挑选了对自己有利的证据。”
Similarly, there was Hans Selye, often described as the “father of stress research,” whose work showed that stress can produce physical effects in the body. While that insight remains important, Davis noted that eventually it was revealed that Selye had received funding from the tobacco industry, which sought to position smoking as a way to reduce stress. 同样，还有常被称为“压力研究之父”的汉斯·塞利（Hans Selye），他的研究表明压力会对身体产生生理影响。虽然这一见解依然重要，但戴维斯指出，后来人们发现塞利曾接受过烟草行业的资助，而烟草行业试图将吸烟包装成一种减轻压力的方式。
The broader lesson, Davis said, is to be cautious of confident claims about immune health, regardless of their source. 戴维斯说，更广泛的教训是，无论来源如何，对有关免疫健康的自信言论都要保持谨慎。
“Please be wary of any one person’s view, even if they’ve won two Nobel Prizes,” he said. “请对任何人的观点保持警惕，即使他们曾获得过两次诺贝尔奖，”他说。