工作细胞（三）：流感

原帖来自reddit论坛，作者brbEightball，是位医生

原帖地址：

https://www.reddit.com/r/anime/comments/913mov/hataraku_saibou_ep_3_doctors_notes/

Character Feature
角色介绍
CD8+ Lymphocyte
CD8+ 淋巴细胞，即杀手T细胞

Grr, am I ever going to get to talk about neutrophils? Whatever. This episode features a viral infection, so it really merits more discussion about lymphocytes generally, but particularly CD8+ ("cytotoxic) T-lymphocytes.
哎，我还有机会说到中性粒细胞吗？无所谓了。本集讲的是病毒性传染，所以得把淋巴细胞整体介绍下，但我会着重介绍CD8+(细胞毒性)T淋巴细胞。


The star of the episode, after all, is jojo new effector T-lymphocyte. Some (extremely brief) background on lymphocytes: These immune cells comprise the adaptive immune system. Your immune system can broadly be split into the innate and adaptive immune system. The innate immune system is always present and always active; neutrophil is a great example of this, along with NK cells and the complement system (later), but we can even extend this definition to include things like your skin and digestive acids, which also play a role in general defense.
本集的猪脚是Jojo，效应T淋巴细胞。简单介绍下淋巴细胞：这些免疫细胞组成了“获得性免疫系统（也叫‘后天免疫系统’）”。你的免疫系统可以大体分为“自发性（先天）”和“获得性（后天）”免疫系统。自发性免疫系统一直存在，一直工作。中性粒细胞就是其中一个例子，其他的例子还有NK细胞和补体系统。我们还可以把“自发性免疫系统”的概念扩展到你的皮肤、以及消化性的酸，因为它们也参与了一般性的防御。

On the other hand, the adaptive immune response is very specific to a microbial invader, takes some time to ramp up, and results in a robust response and long-term immunity through memory cells. The adaptive immune system can be further split into "T"-lymphocytes and "B"-lymphocytes. As a heuristic, think of T-cells as directly killing, and B-cells as producing helpful antibodies (the reality is more nuanced of course).
而“获得性免疫反应”只针对某种特定的微生物入侵者，它需要一些时间启动，会造成强烈的免疫反应，并通过记忆细胞产生长期性免疫。获得性免疫系统可以再分成T淋巴细胞和B淋巴细胞。类比下说，T细胞就是直接当杀手，B细胞则是产生有用的抗体，当然现实要比这个复杂的多。

So, CD8+ lymphocyte. Big burly scary/intimidating dude. Good choice, considering their role is to directly kill cells, usually through the effect of proteins (perforins & granzymes) which literally punch holes in the target cell's membrane, or through the Fas ligand system which induces apoptosis (tells the target cell to go kill itself). These CD8+ cells are targeted towards cells infected by viruses, which normally express the viral proteins on a specialized receptor on their surface, known as major histocompatibility complex (MHC), or human leukocyte antigen (HLA) class I receptors. The HLA system merits a separate discussion.
来说CD8+ 淋巴细胞。是个大块头的兄贵。画的好，因为他们就是直接杀死细胞，一般是通过蛋白质（穿孔蛋白和颗粒酶）给目标细胞的细胞膜上打个洞，或者通过‘Fas配体’引发‘细胞凋亡’（让细胞自己杀死自己）。CD8+ 细胞要干掉的是被病毒感染的细胞。感染的细胞的表面上，有专门的受体(receptor)表达病毒类蛋白质，它叫“主要组织相容性复合体”（MHC），或者叫“人类白细胞抗原(HLA)”I型受体。HLA以后再说吧。

T-cells are more generally stimulated by recognition of foreign antigens on various antigen-presenting cells (gee whiz), of which the dendritic cell is a great example, but macrophages and B-cells can present antigens too. Recognition of foreign antigens is a tricky matter; lymphocytes (which are normally "born" in the bone marrow and either mature there or in the thymus gland) have a pre-determined and semi-random "range" of foreign antigens that they can recognize, which is defined by an extremely complex mechanism called VDJ rearrangement. So, there's no guarantee that any one antigen will generate a response in any one lymphocyte. This is going too long, let's get to the episode.

T细胞通过‘抗原呈递细胞*（APC）’识别出抗原*时，就会启动。树状细胞就是‘抗原呈递细胞’的一员，巨噬细胞和B细胞也可以呈递抗原。要认出外界抗原挺不容易。淋巴细胞（一般出生于骨髓，成熟于骨髓或者胸腺）能识别出的抗原类型，有些是事先安排好的（具体见第9集‘胸腺细胞’），有些是随机的外界抗原。它们能识别的抗原类型，是由一个很复杂的过程“VDJ重排”来决定的。再说就太长了，还是来看本集剧情吧。

*抗原呈递细胞（Antigen-presenting cells）：一系列免疫细胞。它们可以分析抗原，并把抗原的信息传送给免疫性淋巴细胞。

*抗原(antigen)：可以诱发免疫反应的东西，比如病菌

Episode 3 - Influenza
第三集 - 流感

Hmm, dark and scary place. Wonder where this is. I'm guessing by the fact that it's where influenza is first sighted it's somewhere up in the nasopharynx. Or maybe Waldeyer's ring!
月黑风高的地方。这是哪里呢？我觉得既然这里是流感病毒被发现的地方，那应该是鼻咽那里吧。也许在瓦耳代尔氏扁桃体环那里。

Aw, a naive T-cell, how cute. These are T-lymphocytes that are "mature", but are not yet activated. They can be found in general circulation but are more often concentrated in lymphoid rich tissues (like the spleen, lymph nodes, but also peyer's patches and tonsils).
嗷嗷嗷，初始T细胞，好可爱的样子。它们是“成熟”的T淋巴细胞，但是还没有活化。它们可以在血液循环系统里出现，但更常在淋巴多的组织里出现，比如脾，淋巴结，和扁桃体。

Virus spotted! You may be wondering why virus infections are a zombie outbreak instead of a new character. Consider their size difference; influenza virion particles are maybe 100 microns in size, compared to a red blood cell which would be 75 times that. Not to mention viruses generally have to infect cells in order to reproduce, hijacking the cells normal protein-making machinery to make more virus particles (or alarmingly, integrating with the host cell's DNA).
发现病毒！你也许会想，为啥要把这个病毒弄成一群丧尸，而不是搞个新角色。这要考虑到它们的大小。流感病毒大概是100微米，红血球都比它大75倍。更何况，病毒一般通过感染细胞来繁殖，它抢来正常细胞里制造蛋白质的机器，用于搞出更多的病毒（或者，和宿主的DNA结合 Σ(っ °Д °;)っ）

Something very important to know about influenza is that it mutates a lot. It undergoes antigenic drift, resulting from minor changes over time, and causing the public health agencies to need to reformulate a new vaccine every year. But it can also infamously undergo antigenic shift, when it reassorts genomes with other flu viruses. This classically occurs in animals (hence "swine flu" and "avian flu"). Oh, and we mostly only have to care about influenza A & B.
关于流感病毒，有个特别重要的一点就是，它们非常会变异。它会“抗原转移”，会一点点发生变化，这让卫生部门每年都得换个疫苗配方。但更厉害的是，它会“抗原更换”，和其他的感冒病毒 重组 基因。这一般发生在动物身体里，所以会有“猪流感”，“禽流感”。哦，对了，我们主要对付的是“甲型流感(Influenza A)”和“乙型流感(influenza B)”

U-1146 to the rescue! Umm, what is he doing fighting virally infected cells? The role of the neutrophil in viral infections is unclear to me, but they are definitely not the main contributor. I'm not even sure how he would recognize the cells as foreign, since neutrophils do not have receptors for MHC class I receptors AFAIK (though they do express MHC I themselves). Oh, we discussed his wall-walking tricks (diapedesis) last discussion.
U-1146前来救援！呃……他为啥要和病毒细胞干架？我不太清楚中性粒细胞在病毒感染中的作用，但他肯定不算主角。我都不确定他是不是能认出坏掉了的细胞，因为中性粒细胞没有MHC I型的接收器AFAIK（尽管它们自己可以表达MHC I）。哦，我们上集也说过他特殊的穿墙技巧（血球渗出）

Okay, infocard for influenza time. Influenza is one of the most prevalent and significant viral infections. It's an RNA virus, and not a terribly complex one, with only 8 gene products (hemagglutinin, which helps it bind and fuse with cells, neuraminidase, which helps the virus be released from infected cells, and some membrane/capsular proteins). It normally causes infection in the upper respiratory tract, killing mucus-secreting and ciliated cells (in turn, disabling that part of the primary defense system). Importantly, this promotes secondary infections by bacteria (bacterial pneumonia can often follow influenza). Most of the symptoms result from immune-mediated responses, as we will see.
介绍下流感病毒。流行性感冒是最普遍、也是最重要的病毒性感染。流感病毒是RNA病毒。它结构不太复杂，只有8个基因产物（血球凝集素：帮它附着并渗入细胞；神经氨酸苷酶：帮它脱离被感染的细胞；以及一些膜/囊蛋白质）。它一般引发上呼吸道感染，杀死‘粘液分泌细胞’和‘纤毛细胞’（不让那个区域的一级防御系统发挥作用）。这，促进了由细菌引发的二级感染（流感后很有可能引发细菌性肺炎）。大部分的感冒症状都是由免疫反应产生的，我们马上就会看到。

Macrophage enters the scene! I have referred to them as the immune system's janitors, but they are also incredible multitaskers, killing microbes, ingesting them, presenting antigens, and coordinating local responses. They are also tied for my favorite immune cell (along with B-lymphocytes). Will defer further discussion to a future episode.
巨噬细胞登场！我管它们叫免疫系统的保安，但是它们也是身兼数职的小能手：杀微生物，消化它们，呈递抗原，协调局部反应。它和B-淋巴细胞，是我并列喜欢的免疫细胞。以后再细说他们。

Clever interaction! Helper CD4+ cells are called upon to coordinate an immune response. I'm not sure if it's fair for macrophage to just be able to phone it in though. I would have expected that she would carry the debris to a lymphoid center, or maybe passive flow of peptides would get picked up by the dendritic cell.
这个对话妙啊！辅助CD4+ 细胞被召唤出来，用来协调免疫反应。巨噬细胞能直接和他通话吗？我不太确定。我感觉她应该把抗原碎片送到淋巴中心，或者让树状细胞捡起流过的抗原体。

CD8+ cytotoxic lymphocytes are in-bound. Something to mention, is that during infection, there is passively increased flow of CD8+ lymphocytes to the site, but whether or not they stick around depends on if there is any antigen they can recognize. Perhaps these guys have seen influenza (or similar) before? Also them being dicks to newbie is not any specific behavior I'm aware of, lol. Neither is backup neutrophil needing a tug.
“CD8+ 细胞毒性淋巴细胞”入场。有点要说的是，感染期间，会有更多的 杀手细胞 自动流入感染处；但是，它们能不能留在那里，取决于它们是否能认出的那里的抗原。也许这些家伙之前见过这个（或者类似的）流感病毒？他们为啥对新人这么凶残，超出了我认知范围。白细胞的后援队也不需要帮助（注：动画里，白细胞帮助队友从墙里钻出来）。

Oh yeah, I guess there's a memory T-cell among them. Any adaptive immune response should normally generate some memory B/T cells that will generate a much, much faster reaction to a repeat infection than the first time around. Against infections that don't have much genetic/antigenic variability, this works great (you only get chickenpox once, right?), but against something like influenza which mutates constantly it is less helpful.
哦，它们之中还有个“记忆T细胞”。“获得性免疫反应”一般都会产生 记忆B或者记忆T细胞，它们会让免疫系统更快地对感染做出反应（比对第一次感染的反应速度快得多）。对于没有太多基因/抗原变化的感染，这个方法贼有效。比如，你只出一次水痘，对吧？但是对于不断变异的流感病毒，这就没那么大作用了。

I think the naive T-cell is retreating to a lymphoid center. This gets a little convoluted for the sake of making a better story. Remember that the activation of the CD8+ cell is done by antigen presenting cells, which this dendritic cell certainly is, but generally the APC would have encountered the antigen first. It's by display of the peptide that the lymphocyte is activated, though a motivational speech is nice too.
我估摸着“初始T细胞”退回到了淋巴中心。有点为了讲故事而讲故事。还记得吧，是“抗原呈递细胞（APC）”激活了CD8+ 淋巴细胞。当然了，树状细胞也是APC，但是APC需要先遇到抗原才成。看到了呈递的抗原，T淋巴细胞才能活化。不过呢，这里鸡汤对话也挺好。

“One feature unique to CD8+ T-cell activation is that its initiation often requires cytoplasmic antigen from one cell to be cross-presented by dendritic cells. Another characteristic...is that their differentiation...may require the concomitant activation of CD4+ helper T cells." 
激活CD8+ T细胞时，有一点很有意思。活化的开始，通常需要树状细胞呈递‘细胞质抗原’。另一个特点是……它们的分化……这个过程也许需要同时激活‘辅助T细胞’。

All right, let's not get too far into the weeds.

还是别偏题太远了。

Oh btw, I don't think the infected cells really try to fight back against the immune cells much, lol. Mostly they sit there churning out viral particles.
哦，我也不觉得被病毒感染的细胞会拼命反击免疫细胞。它们大部分就是呆坐在那里，量产病毒。

Activated T-lymphocyte! Now we have a subset of lymphocytes that is specifically targeted towards this particular flavor of influenza (via clonal expansion of this specific cell). In reality it would have taken him a few days to show up.
T细胞活化！现在有了专门对付这种流感病毒的淋巴小分队（通过克隆扩充的）。现实里他需要好几天才会出现。

B-cell shows up too. Okay, I must ask for your patience as I defer talking about him until later. We can't talk about ALL of adaptive immunity in one reddit post. Just know that he produces antibodies, though usually from a distance, and his antibody production is very specific and similarly programmed as the T-lymphocyte response is.
B细胞也出现了。我得以后才能聊到他。总不能一次把所有获得性免疫系统都说完啊。现在就知道他产生“抗体*”就好，不过通常在远处产生（所以动画里B细胞是拿枪的）。他产生的抗体很专一（只对特定的感染反应），就像T淋巴细胞那样。

抗体(antibody)：又称免疫球蛋白(immunoglobulin)，是免疫系统识别、中和外来病原体的工具。你也许在这次的新冠爆发中听过‘免疫球蛋白’。得了新冠的病人，需要在身体里注射已经康复了病人身上的“免疫球蛋白/抗体”，用来对抗新冠病毒。

Time for systemic response! Activation of immune cells (as well as responses from nearby stromal/epithelial cells) normally generates numerous cytokines (in this case probably things like interferon-gamma, interleukins 1 & 6, and so on); these generate a response in the hypothalamus that increases the "set point" of body temperature (fever), and a lot of the other general symptoms of malaise that we tend to refer to as a "viral syndrome". I am actually intrigued by the loss of appetite, I will read up on that for later.
系统性炎症反应！免疫细胞的活化（以及来自附近的基质/上皮细胞的反应），会产生许多“细胞因子*”（这里多半是干扰素γ，白细胞介素1和6等等）；它们引发“下丘脑*”的反应，让体温升高（发烧），还会产生一些其他的不舒服的病状，我们管这叫“似病毒症候群”。我觉得“没胃口”这点蛮有意思，会之后读读相关的东西。

细胞因子(cytokine)：又称细胞激素，细胞素等。它类似于细胞之间的‘传话员’，可以由多种细胞产生，比如免疫细胞、内皮细胞。它们协调、沟通免疫反应。

动画里，初始T细胞活化后，就会分泌细胞因子，从而引发炎症反应，比如发烧。

这次的新冠病毒里，你可能听说过一个词‘细胞因子风暴(cytokine storm)’，它是许多病人的死因。这是一种过度免疫反应：新冠病毒进入到肺部后，导致有些病人的免疫系统释放了过量的细胞因子，引起免疫细胞‘暴走’，从而引起过度发炎症状，危及生命。

下丘脑 (hypothalamus)：位于大脑腹面、丘脑的下方，是调节内脏活动和内分泌活动的高级神经中枢所在。

以下是免疫细胞活化后，产生的一系列炎症反应：

Oh shit, this virus is able to handle our CTL. This represents a virus that has undergone further genetic mutation and thus is not (yet) recognized by the immune system. Give it a few more days though.
Oh shit，这个病毒把我们的 杀手T细胞 打回了原型。这代表这个病毒经历过更多的基因变异，现在还不能被免疫系统识别。需要再给它们几天的时间。

Type A influenza is the form that is known to infect animals and thus is prone to antigenic shifts. Actually, I think we are forced to assume this is a new virus from outside the body.
甲型流感病毒，感染的是动物，所以更容易发生“抗原转移”。我们只能认为，这个新病毒来自于体外。

Platelets and dendritic cells don't have any real interactions that I'm aware of. Waiting for that primary research article to prove me wrong though, lol.
据我所知，血小板和树状细胞之间不会沟通。我就等着学术论文反驳我了，嘿嘿。

Summary
总结


A pretty substantial infection, influenza is no joke. While most people get through it just fine (though they will feel like absolute shit for the majority of it, with fever, upper respiratory symptoms, headache, and muscle aches), it can be very dangerous in vulnerable populations. You may have noticed that there has been no help from "outside" the body so far. The first two cases probably wouldn't have come to clinical attention, but I bet this would have. Alas, treatments for influenza are few (neuraminidase inhibitors, amantadine), with questionable efficacy and a very narrow timespan of effectiveness (eg first 48hrs of symptoms). Usual management would just be supportive (fluids, rest).
作为大规模感染，流感可不是小事。尽管大部分人都能挺过去（当然，他们大部分时间都感觉像shit，会发烧，上呼吸道感染，头疼，肌肉疼），但是对体弱的人群则非常危险。你也许注意到了，目前这几集里，都没有来自身体“外部”的帮助。前两集本就不需要医疗，但是这集会需要的。唉，不过呢，流感的治疗方法很少（神经氨酸酶抑制剂，金刚烷胺），效果也很难说，并且药效时间很短（比如症状发生后的48小时）。通常的治疗方法都是辅助性的（吃流质品，休息）


Next episode looks like it could be complex as well. Food poisoning is a broad category and can involve many different toxins and pathogens. Good thing I have the manga to read up on now...
下集看起来也比较复杂。食物中毒是个大头戏，和众多毒素和病原体有关。好在现在我可以读读漫画……

相关生物类单词：

Influenza  流感

lymphocyte  淋巴细胞

CD8+ cytotoxic T-lymphocytes  细胞毒性CD8+ T淋巴细胞，即杀手T细胞

innate immune system   自发性免疫系统，先天性免疫系统

adaptive immune system    获得性免疫系统，后天性免疫系统

memory cell  记忆细胞

antibody  抗体

antigen  抗原

antigen-presenting cell (APC)   抗原呈递细胞

perforin  穿孔蛋白

granzyme  颗粒酶

Fas ligand system  Fas配体

apoptosis  细胞凋亡

human leukocyte antigen(HLA)  人类白细胞抗原

nasopharynx  鼻咽

Waldeyer's ring   瓦耳代尔氏扁桃体环

naive T-cell  初始T细胞

spleen  脾

lymph node  淋巴结

tonsil  扁桃体

virus  病毒

infection  感染

mutate  变异

vaccine  疫苗

antigenic shift  抗原转移

genome  基因组

swine flu  猪流感

avian flu  禽流感

influenza A   甲型流感

influenza B   乙型流感

hemagglutinin   血球凝集素

neuraminidase   神经氨酸苷酶

upper respiratory tract  上呼吸道感染

ciliated cell   纤毛细胞

pneumonia   肺炎

chickenpox  水痘

clonal expansion  克隆繁殖

cytokine  细胞因子

hypothalamus  下丘脑

fever  发烧

loss of appetite  没胃口

neuraminidase inhibitor   神经氨酸酶抑制剂

amantadine  金刚烷胺

food poisoning  食物中毒