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你身体的免疫力就是这样来的

This Is How Your Body Builds Immunity

Vaccines are possibly the greatest thing that humans ever created.
疫苗 不仅在医学而且大概在整个人类创造领域中
Not just in the realm of medicine, but like all of human creation.
都可能是人类有史以来创造的最伟大的发明
Space travel is awesome.
太空旅行很了不起
Agricultural revolution? For the most part, pretty sweet.
农业革命? 蛮不错的
The entirety of YouTube? Up there
整个YouTube的创立?也不错
but maybe not as lifesaving as vaccination.
但也许不像疫苗那样可以救人性命
Vaccinations has its root in variolation,
疫苗起源于人痘接种
a technique developed by Asian physicians prior to the 1700s.
它是亚洲医生在18世纪之前发明的一种技术
They would take dust from someone’s smallpox scab
医生从他人身上取天花痂粉末
and blow it into their patient’s nose
将其吹入病人的鼻子里
the patient would experience a weaker version of smallpox,
病人会产生较轻微的天花症状
but then they’d be immune to it for life.
但之后他们将会对天花病毒终身免疫
Variolation was far from perfect, and just sounds gross,
人痘接种一点都不完美 听起来还很恶心
but when the alternative is contracting a potentially fatal version of smallpox,
但是 既然另一种选择是感染上可能致命的天花病毒
it was a good first step.
那么 人痘接种算是很好的第一步了
In the hundreds of years since,
在那之后的几百年里
doctors have made huge advances in vaccination technology,
医生们在疫苗技术上取得了巨大的进步
like Edward Jenner’s famous smallpox vaccine made from cowpox virus,
比如爱德华·詹纳著名的用牛痘病毒制成的天花疫苗
or Louis Pasteur’s vaccines against rabies and anthrax.
或路易斯·巴斯德的狂犬病疫苗和炭疽疫苗
But here’s the thing,
但事情是这样的
all of these revolutionary concepts in science came before we knew
在我们了解免疫系统在细胞层面是如何工作之前
how our immune system worked on a cellular level.
所有这些革命性的科学概念就都已经出现了
So today, we’re going to go through the story of early immunology
今天 我们将要回顾早期免疫学的故事
to learn how they figured out the cells of the immune system.
来了解他们是如何找出免疫系统细胞的
Around the same time as Pasteur,
和巴斯德在差不多同一时间
a Russian researcher named Elie Metchnikoff was studying starfish larvae
俄罗斯研究员伊・梅契尼柯夫在研究海星幼虫的过程中
and noticed that certain cells would engulf foreign objects.
注意到某些细胞会吞噬异物
He called these cells phagocytes, which meant devouring cells.
他称这些细胞为巨噬细胞 意思是吞噬细胞
This seemed like a viable explanation for how immunity worked.
这似乎可以解释免疫是如何起作用的
Our cellular defenses gobbled up potential threats.
我们的细胞防御机制吞噬了潜在的威胁
But during the development of the diphtheria vaccine,
但在白喉疫苗研制过程中
another idea was put forward.
人们提出了另外一种观点
German scientist Paul Ehrlich hypothesized that there was
德国科学家保罗·埃尔利希猜想
some kind of anti-toxin floating in the blood that would confer immunity.
血液中漂浮着某种会产生免疫力的抗毒素
These would later become known as antibodies.
这些抗毒素就是后来所说的抗体
So by the end of the 19th century,
所以到了19世纪末
scientists knew that germs caused disease,
科学家们知道了细菌会导致疾病
that substances in the blood could confer immunity,
血液中有物质可以产生免疫力
and that cells could swallow up pathogens.
细胞可以吞噬病原体
But we still had some big questions to answer.
但我们还有一些重大问题需要回答
Specifically, there were two schools of thought regarding how immunity works.
具体来说 关于免疫是如何起作用的有两个学派
On one team were the “cellularists”,
其中一派是“细胞主义者”
who thought that free floating phagocytes were more important to immunity than antibodies.
他们认为自由漂浮的吞噬细胞比抗体对免疫更重要
This became known as cellular immunity.
这被称为细胞免疫
On the other team were the “humoralists”
另一派是“体液主义者”
who believed in humoral immunity. To them,
他们相信体液免疫 对他们来说
clearly something dissolved in the blood had to mediate immunity.
显然 血液中溶解有某种会影响免疫力的物质
So to start with,
首先
your body has an immune system that keeps you safe from pathogens,
你体内有一个使你免受病原体侵害的免疫系统
anything that causes disease like a bacteria, parasite, or virus.
病原体指任何会引起疾病的东西 如细菌 寄生虫或病毒
Those researchers at the end of the nineteenth and start of the twentieth century
从19世纪末到20世纪初
were debating two types of immunity
研究人员在讨论两种免疫机制
that we now know are both present in our bodies
而这两种免疫机制 我们现在知道是共同存在于人体中的
From 1900 to the 1940s,
从1900年到1940年
it seemed like the humoralists had a better case.
似乎体液主义者的论据 更有说服力
Experiment after experiment showed that antibodies conferred immunity.
一个接一个的实验表明 抗体会给予人体免疫力
Plus, scientists were zeroing in on
此外 科学家们重点研究了
how antigens hook up to antibodies and antibodies’ structure.
抗原与抗体的结合方式 以及抗体的结构
But the importance of the humoral theory was challenged
但是在1942年的一次重要实验中
during a major experiment in 1942,
体液学说的重要性受到了质疑
by our old friend Karl Landsteiner,
表示质疑的是 我们的老朋友卡尔·兰德斯坦纳
that dude discovered ABO blood types,
他是ABO血型的发现者
and his colleague Merrill Chase.
还有 他的同事Merrill Chase
They took one set of guinea pigs and gave them the tuberculosis bacteria,
他们找来一组豚鼠 让它们感染肺结核细菌
which meant they would build antibodies and thus immunity to TB.
这意味着豚鼠会产生抗体从而对结核病产生免疫力
Then they injected the blood serum with TB antibodies
然后 他们将含有结核抗体的血清注射到
into naive guinea pigs, or non-immunized guinea pigs,
没有抗体 或者说无免疫力的豚鼠体内
and later exposed them to the TB antigen.
然后将这些豚鼠暴露在结核抗原中
But the immunity transfer didn’t work.
但是免疫力转移并没有起作用
So maybe antibodies weren’t the only thing conferring immunity?
所以也许抗体不是唯一能给予人体免疫力的东西
Chase next tried to immunize his guinea pigs with a new solution,
接下来Chase尝试用一种新溶液让豚鼠产生免疫
which accidentally contained lymphocytes,
而这种溶液意外含有淋巴细胞
white blood cells that play a huge role in our immunity.
一种在人体免疫中发挥巨大作用的白细胞
When the research team looked under the microscope,
当研究小组在显微镜下观察时
they saw these immune cells at work,
他们看到这些免疫细胞在起作用
which strengthened the cellular immunity theory.
这一发现巩固了细胞免疫理论
We had way more questions though.
但是我们还有更多问题
Like, if there are millions and millions of types of pathogens out there
比如 如果外面有数百万种病原体
how does our immune system make antibodies for all of them?
我们的免疫系统如何产生应对所有病原体的抗体
There was no way millions of species of cells
我们体内不可能为数百万种抗原
were built into our bodies for millions of antigens.
生成数百万种免疫细胞
so we must have to manufacture antibodies after being exposed to the pathogen.
所以我们肯定是在接触病原体后才产生抗体
This gave rise to something in the late 50s called clonal selection theory,
由此在50年代后期出现了克隆选择学说
which, as the name suggests, implies clones, or copies of cells.
顾名思义 指的是克隆或细胞复制
First, humans along with other animals have immune cells called lymphocytes.
首先 人类和其他动物都有名为淋巴细胞的免疫细胞
They’re a thing that exist and have a name by this point.
淋巴细胞 在那个时代已经被发现 并进行了命名
Lymphocytes respond to antigens according to receptors on the lymphocyte’s surface.
淋巴细胞根据自身表面的受体对抗原作出反应
When that lymphocyte gets in contact with its appropriate antigen,
当淋巴细胞接触到特异性抗原时
it will proliferate, or clone itself.
淋巴细胞会增殖或自我复制
From there, the clones will either secrete antibodies
随后 克隆体要么分泌抗体
or recruit more cells to respond to the pathogen.
要么动员更多的细胞对病原体做出反应
But that still didn’t show us how lymphocytes recognize antigens themselves.
但这还是没有告诉我们 淋巴细胞是如何自行识别抗原的
Then, in the early 1960s,
然后 在20世纪60年代初
scientists started paying more attention to an organ called the thymus,
科学家们开始更多地关注胸腺这个器官
an organ in the lymphatic system
胸腺是淋巴系统的组成部分
which until then, wasn’t completely understood.
直到那时 人们尚未完全了解胸腺
So a scientist named Jacques Miller removed the thymus from infant mice
所以科学家雅克·米勒移除了幼鼠的胸腺
and noticed that the mice developed more severe infections
发现老鼠的感染加重了
and mounted weaker antibody responses.
并且抗体应答减弱了
So that seemed like some easy math
这看起来像是简单的数学题
Take out the thymus and the immune system weakens.
去掉胸腺后免疫系统就会减弱
But how exactly the thymus supported immunity was still a mystery.
但是 胸腺究竟是如何对免疫力有帮助的 仍然是一个谜
By this point,
到了这个时期
scientists knew that cells in the bone marrow could make hematopoietic stem cells,
科学家们知道了骨髓中的细胞能够产生造血干细胞
those types of cells that can become any type of blood cell.
而造血干细胞又能够分化成任何类型的血细胞
So maybe lymphocytes started in bone marrow and mature in the thymus.
所以 或许淋巴细胞 只是在胸腺中成熟 而来源处却是骨髓
Enter James Gowans,
詹姆斯·高恩斯
who traced lymphocytes all around the body
追踪了人体各处的淋巴细胞
and found that they went from the blood into lymphatic circulation,
发现了 淋巴细胞从血液进入淋巴循环
then into lymph nodes, and back into the bloodstream.
然后进入淋巴结 最后又回了血液中
This gave us the idea that the thymus manufactured lymphocytes
这让我们明白 胸腺会产生淋巴细胞
which then traveled through circulation,
而淋巴细胞之后会通过循环
eventually coming to secondary lymphoid organs like lymph nodes.
最终来到 比如淋巴结 这类二级淋巴器官中
Now that we knew where lymphocytes came from,
既然我们知道了淋巴细胞从哪来
we could tie that back to the old clonal selection theory.
我们可以将其与古老的克隆选择学说联系起来
They got the idea that naive lymphocytes,
他们认为没有抗体的淋巴细胞
or lymphocytes that hadn’t been activated by an antigen yet,
或者说 尚未被抗原激活的淋巴细胞
grew up in the thymus.
是在胸腺里成熟的
Then when they were excreted and made it to the lymph nodes,
然后 它们被分泌出来 成功抵达淋巴结后
they would differentiate into fully functioning, antibody-producing plasma cells
会分化成功能齐全能产生抗体的浆细胞
depending on which antigen they encountered.
这种分化取决于他们遇到了哪种抗原
So they were born in the bone marrow but grew up in the thymus.
所以他们在骨髓中生成但是在胸腺中成熟
These thymus derived cells became known as T cells.
这些胸腺衍生细胞被称为T细胞
Around the same time, separate scientists saw that
大约与此同时 不同的科学家们发现
lab chickens developed an impaired antibody responsiveness
实验室的鸡在被摘除法氏囊后
when they removed their bursa of Fabricius,
抗体反应开始受损
a bird-specific lymphatic organ found near their little chicken butts.
法氏囊是鸡屁股附近发现的鸟类特有的淋巴器官
That complicated our nice, tidy definition a bit
这让我们美好简洁的定义变得复杂了一些
because that meant that there might be two types of lymphocytes.
因为这意味着可能有两种淋巴细胞
Through a series of experiments on chicken embryos,
通过对鸡胚胎做的一系列实验
scientists found that different lineages of lymphocytes developed in the thymus
对照鸡法氏囊 科学家们发现了新的淋巴细胞
compared to the chicken’s bursa.
它们与在胸腺成熟的淋巴细胞 属于不同的谱系
These became known as bursa derived cells, or B-cells,
这些淋巴细胞 被称为囊源细胞或b细胞
which mediated humoral immunity.
它们可以调节体液免疫能力
Thus, the two superstar cells of the adaptive
从而 适应性免疫系统中的两个
immune system got their names.
巨星细胞 就都有了名字
Fun fact, humans do have structures called synovial bursa
有趣的是 人类确实有滑膜囊结构
but they’re more cushioning for our joints.
但它更多的是对我们的关节起缓冲作用
So they’re different from the bird version.
所以与鸟类的囊并不相同
That raises another question though.
但这又引出了另一个问题
Humans aren’t birds. Like not even a little bit.
人类不是鸟 一点也不像鸟
So we don’t have the organ that produces B cells that birds do.
所以我们没有像鸟类那样能产生B细胞的器官
So where do humans make B cells,
那么 人类是在哪里制造B细胞
and how does the whole immune response work with all these moving pieces?
以及 B细胞介导的整个免疫反应是如何工作的
As it turns out,
正如人们所发现的
B cells both form and mature in the bone marrow itself.
B细胞自己在骨髓中形成并发育成熟
They only start to differentiate
只有当抗原与它表面的
once an antigen hooks up to any of the receptors on its surface.
任一受体结合时 它们才开始分化
By now we’re in the 1970s,
我们现在来到20世纪70年代
and we still had a few things to figure out,
我们还有一些事情需要弄清楚
like how the T cells don’t just self destruct and kill our own cells.
比如T细胞如何不自我毁灭 如何不杀死我们自己的细胞
See, bacteria infect our bodies differently than viruses.
看 细菌和病毒感染人体的方式不同
Bacteria will invade our bodies somehow,
细菌会以某种方式入侵人体
then reproduce by splitting apart into two cells
然后 繁殖分裂成两个细胞
But viruses get directly into the host’s living cells,
但病毒则是直接进入宿主活细胞
and use their host’s cellular machinery to reproduce,
并且利用宿主的细胞机制进行繁殖
and eventually burst out of those cells to infect more cells
最终从宿主细胞中破体而出 感染更多的细胞
and keep the process going.
并不断重复这个过程
So to keep that virus from hijacking more of your cells,
所以为了防止病毒强行控制你的更多细胞
sometimes your immune system needs to kill off your own cells.
有时你的免疫系统需要大量杀死自身的细胞
During an experiment published in 1974,
在1974年发表的一项实验中
researchers saw how our immune systems could differentiate
研究人员发现了我们的免疫系统
our infected cells from other cells.
是如何把受感染的细胞和其他细胞区别开来的
In it, they gave a virus to a bunch of lab mice,
实验中 他们将一种病毒注入一群实验室小鼠体内
and swapped T cells from one mouse to another.
并将T细胞从一只小鼠转移到另一只体内
The T cells did their normal job as expected.
T细胞像预料的那样正常工作
They’d destroy cells infected with viruses
它们会破坏被病毒感染的细胞
but, unexpectedly, only if the infected cell
但出乎意料 只有与提供T细胞小鼠相同种类的
came from the same strain of mice as the T cell.
小鼠的感染细胞 才会被破坏
If a T cell detected that a random cell was infected with a virus,
如果T细胞发现了一个被病毒感染的细胞
but it was from some other mouse,
只要 这个感染细胞是其他种类小鼠的细胞
it wouldn’t destroy it.
那么 它就不会被T细胞摧毁
Basically, T cells showed that
说穿了 T细胞表明
they would only help cells from their same family.
它们只会帮助来自同一家族的细胞
This would become known as self-nonself discrimination.
这被称为自我-非我辨别
This was a big development because it showed that
这是一个重大的进展 因为它表明
T cells only destroyed foreign cells
T细胞摧毁外来细胞 唯一的条件是
if they presented an antigen
外来细胞要呈递一个抗原 以及
and presented a molecule that identified it as a “self” cell.
呈递一个表明其是“自身细胞”的分子
That identifying molecule was major histocompatibility complex,
这种表明身份的分子是主要的组织相容性复合体
or MHC for short,
简称MHC
a molecule that presents the antigen-of-interest to different T cells.
它将特异性抗原呈递给不同的T细胞
Then in 1978, scientists identified the dendritic cell,
然后在1978年 科学家发现了树突状细胞
a phagocytic cell that eats up pathogens
这种噬菌细胞吞噬病原体
and presents its antigen to the other cells,
把自己的抗原呈递给其他细胞
helping to eventually grant immunity to that pathogen.
帮助其最终获得对病原体的免疫力
That made it an APC, or antigen-presenting cell.
因此被称为APC 或者说 抗原呈递细胞
I have slayed this E coli for you! Behold!
我已经帮你杀死了大肠杆菌 看呐
Feast thine eyes upon its carcass!
尽情欣赏它们的尸体吧
One of the most recent discoveries in the story of B and T cells
一个关于B细胞和T细胞故事的最新发现
shed some light on how these two types of immune cells work together.
让我们更加明白了 这两种免疫细胞是如何协同工作的
In order for our cells to remember that pathogen,
为了让我们的细胞记住那个病原体
the APC will present an antigen to one type of T cell
APC会向一种T细胞呈递抗原
so it can destroy the pathogen,
以便 它能够摧毁病原体
while another type of T cell will share that antigen with B cells,
而另一种T细胞会与B细胞共享抗原
which then make antibodies for it.
然后B细胞会制造出针对抗原的抗体
That development would let us understand
这一进展让我们了解了
how those early vaccines at the start of the twentieth century worked.
20世纪初的那些早期疫苗发挥作用的原理
The vaccine itself is a weakened or imitation pathogen
疫苗本身是一种被削弱或仿制的病原体
that we administer to people without immunity to that pathogen.
我们用来给那些对病原体没有免疫力的人接种
Their bodies respond first by attacking the pathogen,
人体第一个反应是攻击病原体
but then build up a reservoir of memory T cells and antibodies from B cells
然后形成记忆T细胞库和增加B细胞抗体
to attack that pathogen in the future.
以便 在未来攻击那种病原体
After all those years of not knowing how vaccines were saving lives,
多年来我们一直不了解疫苗发挥作用的原理
we finally learned how.
但如今我们终于知道了
Next time, we’ll learn about a major source of those
下次 我们将学习淋巴系统
B and T cells, the lymphatic system.
它是B细胞和T细胞的重要来源
I hoped you liked this episode of Seeker Human,
希望你们喜欢本期的《探索人类》
I always love these history based episodes. They’re so fun to write.
我一直很喜欢以历史为主的这几期节目 写起来很有趣
I’m Patrick Kelly and thanks for watching.
我是Patrick Kelly 感谢收看

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视频概述

人体是如何产生免疫的?细胞免疫?还是体液免疫?又或是二者兼有?通过本视频,将为您揭秘

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https://www.youtube.com/watch?v=ZTz4qA1gX3k

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