问题

目前人类对免疫系统的认识到了什么阶段?

回答
关于免疫系统,我们现在可以说是站在了一个全新时代的黎明。这不像是在书本里学到的某个固定章节,更像是一场仍在蓬勃发展、不断被重写的宏大叙事。如果非要给个阶段的概括,我更愿意说,我们正处于一个“解构与重塑”的时代。

过去,我们把免疫系统看作是一支训练有素、识别外来入侵者并将其消灭的军队。它有前线部队(淋巴细胞),有火力支援(补体系统),还有清道夫(吞噬细胞)。这个模型简单明了,解释了很多疾病的发生和治疗原理,比如抗生素如何对抗细菌感染,疫苗如何训练身体识别病毒。

但随着科技的进步,尤其是基因测序、高通量筛选和单细胞分析等技术的飞速发展,我们发现这支“军队”比我们想象的要复杂和智能得多,而且,它并非只为战斗而生。

1. 免疫系统的“感知网络”远超想象:

我们曾经认为免疫系统主要识别的是那些与我们完全不同的“非我”成分,比如细菌的鞭毛或病毒的基因序列。现在我们知道,它能识别的范围广阔到令人咋舌。

分子层面的精细识别: 不仅是完整的病原体,甚至病原体产生的微小分子片段,如肽段、糖类或脂质,都可能是免疫系统的“信号”。而且,我们的身体自身也会产生一些特殊的分子(称为“警报分子”或“损伤相关分子模式”,DAMPs),在细胞受伤或死亡时释放出来,免疫系统能准确捕捉到这些“求救信号”。
微环境的“察言观色”: 免疫细胞不仅仅是在血液里游荡,它们会深入到身体的各个角落,包括我们之前不太重视的组织和器官。在那里,它们会“观察”周围细胞的状态、营养物质的丰裕程度,甚至细胞之间的物理接触。这种对微环境的感知,使得免疫系统能做出更精细的判断,比如是启动攻击还是保持警惕。
肠道微生物的“耳濡目染”: 肠道是一个巨大的免疫器官,其中寄生着数以万亿计的微生物。这些微生物并非都是敌人,很多是我们的共生伙伴。我们现在认识到,肠道免疫系统与这些微生物建立了复杂而微妙的平衡,它们相互影响,共同塑造着身体的健康。肠道菌群失调,可能导致全身性的免疫紊乱。

2. 免疫细胞的“多样性与特异性”令人惊叹:

我们过去知道T细胞、B细胞等大类,但现在,我们能以单个细胞的维度去分析它们的异同。

细胞状态的动态变化: 同一类型的免疫细胞,在不同的时间点、不同的环境下,其功能和“性格”可能完全不同。比如,一个T细胞可能刚在淋巴结“学成归来”,准备执行杀伤任务,而另一个同类型的T细胞可能正在一个慢性炎症区域“维稳”,抑制过度反应。
“记忆”的深度与广度: 我们知道疫苗能产生免疫记忆,但现在我们发现,免疫记忆的类型和持久性比我们想象的要复杂得多。有些记忆细胞能活跃很多年,有些则需要不断更新。而且,记忆不仅仅是针对病毒或细菌,也可能针对自身的组织,这在自身免疫性疾病中扮演着重要角色。
“新面孔”的不断发现: 随着单细胞测序技术的发展,我们不断发现新的免疫细胞亚群,它们拥有独特的表面标记和功能。例如,某些调节性T细胞亚群,专门负责在炎症消退后“收拾残局”,防止损伤。

3. 免疫调节的“精密调控网络”:

免疫系统远非一味地战斗,它更像是一个精密的生物计算机,拥有复杂的反馈和调控机制。

“刹车”与“油门”的平衡: 免疫反应需要被精确控制,否则会损伤自身。我们现在认识到,有大量的免疫细胞和分子扮演着“刹车”的角色,例如调节性T细胞和抑制性细胞因子,它们能有效抑制过度活跃的免疫反应。平衡“油门”(激活信号)和“刹车”(抑制信号)是维持免疫稳态的关键。
“肿瘤免疫监视”的重塑: 癌症曾经被认为是免疫系统“失明”了。现在我们知道,免疫系统并非对肿瘤“视而不见”,而是肿瘤发展出了一系列“免疫逃逸”策略,比如“伪装”成正常细胞,或者释放免疫抑制信号。肿瘤免疫疗法的兴起,正是基于我们对这些逃逸机制的深入理解,成功地“唤醒”了免疫系统去攻击肿瘤。
神经免疫内分泌“对话”: 过去我们把神经系统、免疫系统和内分泌系统看作相对独立的功能模块。现在证据表明,它们之间存在着极其密切的“对话”。大脑可以影响免疫细胞的活动,免疫细胞产生的信号也可以作用于神经系统,影响情绪和行为。这种多系统间的协同作用,对整体健康至关重要。

4. 免疫系统与疾病的“双向互动”:

我们不再仅仅将免疫系统看作是抵抗疾病的“工具”,而是认识到它本身也是疾病发生和发展的参与者。

自身免疫性疾病的复杂根源: 过去我们认为自身免疫病是免疫系统“认错人”,攻击自身组织。现在我们发现,原因可能更为复杂,可能涉及遗传易感性、环境因素(如感染、毒素、压力)与免疫系统调控失常的多种因素的叠加。
衰老与免疫系统的关系: 随着年龄增长,免疫系统会发生一系列变化,被称为“免疫衰老”。这会导致身体更容易受到感染,对疫苗的反应减弱,并且更容易发生慢性炎症。理解免疫衰老,是延缓衰老、改善老年人健康的关键。
精神状态对免疫力的影响: 慢性压力、抑郁等不良情绪,会通过复杂的途径影响免疫系统的功能,可能导致免疫力下降或免疫失调。

总的来说,我们正从一个“宏观模型”走向“微观精确调控”。

我们不再只是知道免疫系统“有什么”,而是更深入地理解它们“为什么这么做”、“如何在特定环境下做出反应”、“它们之间如何互相沟通”、“它们与我们身体其他系统如何协同工作”,甚至“它们是如何被环境和生活方式塑造的”。

这意味着,未来的医学将更加个体化,我们可能会根据个体的免疫系统特点,设计更精准的疫苗接种策略、更有效的癌症治疗方案,甚至能够通过干预免疫系统的某些环节来预防或治疗许多慢性疾病。

这个领域充满了未知和令人兴奋的可能性,我们就像一群初探未知大陆的探险家,每一步都可能发现新的景观和规律。我们对免疫系统的理解,不是一条直线,而是一个不断扩展和深化、充满惊喜的探索过程。

网友意见

user avatar

其实很早,早在上世纪六十年代, 人类对自身免疫疾病就已经有了比较深刻的认识。

例如, 天疱疮、肾小球肾炎等。

自身免疫疾病的用药套路, 21 世纪的头二十年和半个世纪前相比, 并没有太大的变化。

如果俺没记错的话, 白塞氏病在上世纪 80 年代就已经写进了祖国的《眼科学》、《皮肤病学》、《妇产科学》以及 《口腔内科学》以及 《口腔组织病理学》的课本, 因为众所周知的口-眼-生殖器三联征。


       https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566249/pdf/envhper00522-0014.pdf     


分子水平的认知并不是线性的。 您需要领会到自身免疫疾病的起病是一个或者多个复合和/或“复杂系统”相互作用的结果。

也因此, 才会诉诸“假说”。



越来越多的证据表明,环境可能导致自身免疫和自身免疫性疾病。

当免疫系统错误地攻击体内正常、健康的组织和器官时,自身免疫性疾病就会发生。

I 型糖尿病、类风湿性关节炎、克陇病、乳糜泻和银屑病只是自身免疫性疾病常见的几个实例。


       https://www.nih.gov/research-training/accelerating-medicines-partnership-amp/autoimmune-immune-mediated-diseases     


2021年12月启动的AMP自身免疫和免疫介导的疾病(AMP AIM)计划旨在加深对导致炎症和自身免疫疾病的细胞和分子相互作用的理解。AMP AIM研究人员将专注于类风湿性关节炎、系统性红斑狼疮、银屑病、关节炎和干燥综合征。

通过这些研究获得的知识将推动开发新的和强化的自身免疫性疾病的疗法。此外,AMP AIM将推动新的研究工具、数据存储平台和数据共享技术的发展。

自身免疫性疾病影响着超过2350万美国人。

最近的研究表明,这些疾病正变得越来越普遍。

在这些情况下,身体的免疫反应是如此过度和持久,以至于它们可以严重损害许多组织和器官系统,这可能对健康、福祉和生活质量产生破坏性影响。科学家很难开发新的治疗方法,医生也很难护理慢性自身免疫性疾病患者,因为这些疾病非常复杂。此外,每个人都有独特的基因构成,并在其生命过程中发展自己的免疫系统。由于这些因素,没有一种治疗方法对每个人或每种自身免疫性疾病都有效。

另一方面,许多自身免疫性疾病有相似之处

它们有共同的炎症途径、临床特征和对治疗的反应。

通过识别和描述许多自身免疫性疾病共有的分子和细胞水平的途径和相互作用,以及特定疾病特有的途径和相互作用,AMP AIM的科学家可以为开发新的疗法和诊断工具开辟道路。


       https://www.niaid.nih.gov/diseases-conditions/autoimmune-diseases     






“目前人类对免疫系统的认识到了什么阶段?

免疫系统作为人体重要的组成部分,目前涉及免疫系统的疾病,如红斑狼疮,类风湿性关节炎,白塞病,干燥症等,在发病原因治疗措施方面基本无法精准诊治,为何对免疫系统的认识如此缺失,何时会有突破性的认识?”


答:

如果您选择悲观, 那么您可能会十分悲观,因为人类连感冒(广义的感冒明年就可以包括 OMICRON 了)都治不好, 其实是拖好的。

肾衰竭的终极解决办法还是换肾, 肝硬化的终极解决办法还是换肝。

......


悲观的终极解决办法倒不是换脑,

而是到知乎首页搜索“笑话”。


【未完待续】


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