第五集：杉树花粉过敏
Character Highlight 角色介绍
B-lymphocyte B淋巴细胞
The B-cell is perhaps my favorite immune cell, along with the macrophage. It is a member of the adaptive immune system, and as such responds to specific stimuli including but not limited to bacteria, viruses, and parasites. They are the effectors of the humoral component of adaptive immunity, which is to say that they are the cells chiefly responsible for producing antibodies.
B细胞，加上巨噬细胞，可能是我最喜欢的免疫细胞。B细胞属于适应性免疫系统（即“后天免疫系统”），会对外界刺激作做出反应，比如对细菌，病毒，还有寄生虫作出反应。它们是体液免疫系统的适应器。这是啥意思？就是说，B细胞主要负责生产抗体。
What are antibodies (AKA immunoglobulins)? They are small, Y-shaped proteins that can recognize specific peptide and other structures (known as antigens). When antibodies bind such antigens, they can help remove them by "flagging" them to the other cells of the immune system, and through a few other mechanisms. First, by coating a foreign microbe, antibodies can reduce their ability to interact with their surroundings and target tissues. Second, coating of a microbe, known as "opsonization", marks it for consumption by macrophages and other cells. Third, antibodies can activate complement, a sort of biochemical kill-switch assembly that floats in your plasma, only activated under specific circumstances.
什么是抗体（也叫“免疫球蛋白”）？它是小小的，Y形状的蛋白质，可以识别特定的蛋白质结构（后者也叫“抗原antigen”）。抗体和抗原结合时，会想办法消灭抗原；它就会给抗原贴个flag（标签），让免疫系统的其他细胞识别出它们。首先，抗体会附着在微生物的表面，用于减少病菌对周围环境和组织的影响。附在微生物表面的这个动作，又叫“调理素作用”，就是给微生物立个flag，表示病菌可以被巨噬细胞或者其他细胞吃掉。最后，抗体可以激活“补体”，就是浮在你血浆里的某种生化的‘杀手开关’，只能在特定的条件下激活。
再次强调：抗体(antibody)，就是免疫球蛋白(immunoglobulins)
There are other interactions too, as we will see. There are many types (specifically, isotypes) of immunoglobulins, which are defined by changes in the "Fc" region of the protein (basically, the base of the Y), which confers different functionality. IgA is responsible for mucosal immunity. IgG is sort of a general effector with many subclasses (1-4). IgM is a short-term effector and usually precedes IgG. IgE plays a role in parasite defense and is involved in allergic reactions.
抗体还有些其他的作用，一会儿就会看到。免疫球蛋白有很多种，它根据其底部的“Fc”区域的（即Y的底部）的不同，从而分出不同种类，也会因此有不同的功能。IgA（免疫球蛋白A）负责黏膜免疫；IgG（免疫球蛋白G）是普遍型效应器，包含许多亚种（subclass 1-4）。IgM是短期效应器，通常是出现在IgG之前。IgE负责抵抗寄生虫，以及参与到过敏反应。
IgA can form \"dimers\", made of two antibodies back-to-back, while IgM can form \"pentamers\", made of five.
IgA可以形成“二聚体”，就是两个抗体背靠背连在一起，而IgM可以形成五巨头，啊不，“五聚体”。
up注：这次的新冠病毒期间，你一定听说过‘核酸检测’，它用来判断病人是否感染了病毒。除了核酸检测，还有一种办法用于帮助确诊，就是‘抗体检测’，检查的就是IgM和IgG这两种抗体。
新冠病毒进入身体后，免疫系统就会针对这种病原体发生作用，产生相应抗体。
病毒入侵约一周后（即14天内），产生的是IgM抗体，但是它存活时间比较短。在入侵后的2-4星期里（即14天以后），存活时期更长的抗体，IgG会产生。
但是，这种检测方法不是特别靠谱，因为有些病人可能已经感染病毒，但身体没产生抗体（假阴性），反之亦然（假阳性）。只能作为辅助参考。
The discovery of immunoglobulins is incredibly important to the field of not just medicine but biology and chemistry as a whole, as we have learned to engineer immunoglobulins in a way that allows us to specifically target certain antigens. This is useful everywhere from laboratory techniques (I may use immunohistochemistry to determine if a tumor expresses a certain growth factor receptor) to therapeutics (the new paradigm in cancer treatment revolves around immunotherapy using engineered monoclonal antibodies against cancer antigens).
免疫球蛋白的发现，不仅对医学很重要，对生物和化学也很重要。我们可以控制免疫球蛋白，让它去攻击特定的抗原。从实验技术（我可以用‘免疫组织化学’，去看肿瘤是否表达了某种成长因子受体）到现实的治疗学（癌症治疗的新方法就是免疫疗法，它利用创造的单克隆抗体去攻击癌症抗原），它的用处都很广。
So, what else to say about the B-cell? In a nutshell, they form in the bone marrow from the same precursor as T-cells and can either mature there or in various other tissues. Their maturation largely revolves around their ability to not only recognize foreign antigens, but also not overreact to normal "self" antigens. This is an extremely complex process that we do not need to go into, but note that one B-lymphocyte expresses one type of B-cell receptor (BCR, which is essentially an antibody that is bound to its membrane), and upon the right stimulation/activation it clonally expands, dividing to produce more B-cells. The mature form of the B-cell is the plasma cell, which has a distinctive cytomorphology and is tasked with just churning out high volumes of antibody.
那关于B细胞还能说些什么呢？简单来说，它们出生在骨髓，它的前身和T细胞的前身一样。它们可以在骨髓里成熟，也可以在其他组织里成熟。B细胞的成熟，很大程度上不仅取决于辨认外来抗原的能力，也要看它会不会对正常的“自身”抗原产生过激反应。这个过程蛮复杂的，我就不细讲了，但是注意，一个B淋巴细胞表只达一种B细胞的受体(B-cell receptor, BCR, 就是结合在B细胞膜上的抗体)，在适当的刺激/激活下，它会无性繁殖，分裂成更多的B细胞。成熟的B细胞是“浆细胞”。浆细胞的形状独特，任务就是量产抗体。
In addition, a small subset of matured B-cells become memory cells, to help expedite the adaptive response the next time its specific antigen is encountered. Okay, let's get to the episode.
另外，少量成熟的B细胞会变成‘记忆细胞’，以便下次遇到同样的抗体时，做出更快的反应。好了，开讲剧情。
(to be discussed: Neutrophil, macrophage, mast cell, basophil, dendritic cell, CD4+ helper T-cell, T-regulatory cell, NK cell)
（以后还要讲的人物：嗜中性粒细胞，巨噬细胞，肥大细胞，嗜碱性粒细胞，树状细胞，CD4+ 辅助T细胞，调节性T细胞，NK细胞）
Episode 5 - Cedar Pollen Allergy
第五集：杉树花粉过敏
Foreword: I'm happy to see an episode that doesn't revolve around a true infectious etiology. Looking up bug virulence factors was getting old...
前言：终于有一集不说感染病了，看病毒已经看烦了。。。
It's very interesting how the immune cells are all excited about a foreign body that hasn't actually contacted the body yet. Your body doesn't have a way of "knowing" until actual contact is made.
免疫细胞对即将到来的外来物这么兴奋是闹哪样。外来物和身体接触之前，你身体是不会知道的。
CD4+ cells do not play a major role in immunity. As testament to that, plenty of severely HIV-affected patients can still experience allergic reactions--supposedly, they experience even more.
CD4+细胞对免疫系统没有太大的作用。证据就是，患严重艾滋病的病人，还会有过敏反应 - 而且还会反应得更剧烈。
Woof, okay. This is another regional malady the likes of which we don't often specifically see in the west. Like with Anisakis though, our principles still apply. Seems that this cedar pollen is due to Cryptomeria Japonicum, which like many other plants releases pollen in a characteristic seasonal fashion.
哇，又是一个在西方不太常见的区域性疾病。这个雪松花粉貌似来自日本柳杉，和许多其他的植物一样，会在特定的季节传播花粉。
Touchdown! I suppose the ocean there represents the tear film, a surprisingly complex fluid layer that overlies your eyes that is normally replenished by glands when you blink. The tear film is actually important to your vision, as it does have refractive effect. The head & neck is often the first point of ingress for environmental allergens.
触地！我觉得海洋代表了‘泪液膜’。它是蛮复杂的液体层，覆盖在你的眼睛上。你眨眼时，膜里的液体就会得到补充。泪液膜对视觉很重要，因为它有折射作用。头部和颈部通常是外界过敏源最先进入的地方。
I'm trying to work out what this "drain" is that the allergens are escaping through. Perhaps it represents the lacrimal duct, which drains tears into the nasal cavity, or perhaps it is referring to lymphatic channels...I honestly do not know if lymphatic channels are present on the surface of the eye; it's a highly specialized site that I should probably review a bit.
我在想这些过敏原出来的“下水道”是什么。也许它代表“泪小管”，它会把眼泪排到鼻腔，也许它代表淋巴管。。。。我还真不知道淋巴管会不会在眼睛表面出现。这个问题太专业了，我得查查。
Why is the neutrophil attacking a pollen granule? As far as I am aware they do not express the sorts of antigens that a neutrophil's pattern recognition receptors would be excited by. But this guy also fought viruses in past episodes, so I guess he's really special.
这个白细胞攻击花粉干嘛？据我所知，花粉不会释放抗原，让嗜中性粒细胞检测出它们。但是这家伙以前还打过病毒，所以只能说他很特别吧。
5m25s: Phagocytosis is indeed carried out by neutrophils, but that is generally not for recognition like it is in antigen-presenting cells like macrophages. Neutrophils eat to kill, not eat to learn.
‘嗜中性粒细胞’的确会有‘吞噬作用’，但是通常不是为了识别病原——那是‘抗原呈递’型细胞的工作，比如巨噬细胞。嗜中性粒细胞吃是为了杀人，而不是学习。
A memory B-cell! He recognizes the antigen, so this guy probably was part of a prior immune response to the same allergy. Funny how he acts all worked up when in reality he's been churning out the very antibodies which will precipitate the doomsday he foretells. Wait, is this guy a memory B cell or a memory T cell?
记忆B细胞！他认识这个抗原，所以这家伙八成之前参与过同一种过敏反应。他可真能演啊，因为现实里，他正大量生产抗体 —— 就是他说的会带来末日的那种抗体。等等，这家伙是记忆B细胞还是记忆T细胞？
Oh, a legend that has been passed down. As far as I'm aware memory cells do not "share" memory. One memory cell recognizes one antigen.
哦，代代流传的传说。据我所知，记忆细胞不会“共享”记忆。一个记忆细胞只识别一种抗原。
Why is the pollen destroying stuff? Pretty sure it just floats around accomplishing nothing.
哎我去，为啥这个花粉会搞破坏？很确定它就是到处飘，啥都不干。
B-cell is here! Or a plasma cell? Whatever, some B-lymphocyte. As you probably guessed, his Y-shaped rifle is a nod to the structure of the immunoglobulins he secretes. Here he is producing lots of IgE to respond to the offending invaders, but in reality the IgE is always produced (once the patient has been properly sensitized) and is present at a low level, often already bound to the surfaces of mast cells & basophils, awaiting the right antigen to bind. IgE also has no direct cytotoxic effect. Actually this scene is very far off from how the allergic response begins, but the true process is more confusing.
B细胞登场！还是浆细胞？管他呢，反正是某种B淋巴细胞。也许你已经看出来了，他手上Y型的枪致敬了他产生的免疫球蛋白的结构。这里，他搞出了一大堆IgE去对抗入侵者。但是现实中，IgE会一直被生产出来，只是含量比较低，通常都是吸附在‘肥大细胞’和‘嗜碱性粒细胞’的表面上，等着和适合的抗原结合。IgE没有直接的细胞毒素作用。现实中，过敏反应的初始阶段，和动画里挺不一样的，实际过程更混乱。
Mast cells are tissue-resident granuocytes (of sorts) that are similar to basophils but should be considered as distinct/different. See this discussion from last week for more details on them.
肥大细胞是住在组织里的粒细胞（大概），和嗜碱粒细胞类似，但是还不太一样。具体详见上一集的帖子。
What you should know now is that the mast cell is responsible for Type 1 hypersensitivity reactions, which is exactly what is going on here. IgE bound to their surfaces, when cross-linked by the right stimulatory antigen, results in rapid release of their granules, which contain things like histamine and various leukotrienes, which promote inflammation by acting as chemoattractants and by promoting vascular leakage.
肥大细胞参与到1型过敏反应的过程，和这里描述的基本一致。IgE跑到肥大细胞的表面，当它适当的抗原交联在一起时，就会让肥大细胞快速“脱粒”。这些颗粒中包含了‘组织胺’，各种‘白三烯’；这些物质会通过‘化学引诱’和‘血管渗漏’ 引起炎症。
up注：‘肥大细胞’脱粒的过程挺猎奇的，类似于自杀性爆炸行为，具体请见第12集的解释。
Histamine is actually a relatively small, simple molecule, but it has extremely variable effects and is involved in multiple processes in the body, from driving edema like this to promoting acid secretion in the stomach and also has a role in neural signaling.
组织胺是相对比较小的、简单的分子，但是它产生的作用非常多；它还参与了身体里多种反应，比如这里的‘水肿’，比如刺激胃酸的产生。它在神经信号里也起作用。
People are getting washed away by the "histamine", but to be clear: The fluid in edema and vascular leakage is basically the same fluid that composes your serum and your interstitial fluids. It is just allowed to leak forth from vessels under histamine's influence--this is what causes runny noses.
大家看到“组织胺”就害怕，但其实，水肿和“血管渗漏”里的液体，和你的“血清”、“间质液”里的液体是一样的。只是在‘组织胺’的影响下，液体从血管里流出来了而已 —— 导致你流鼻子。
Hmm, who are these orange guys?
这些橘红色的家伙是谁？
Actually, I am very unclear on what this "emergency response" is, or what the "secretory center" is meant to represent. We saw B-cell coming out of there...does that make it a lymphoid aggregate? It is not plainly obvious. Once the mast cells degranulate, I am not familiar with any additional "killswitch" that is activated that further heightens the hypersensitivity reaction.
这“紧急反应”到底是个啥？“分泌中心”又是个啥？B细胞倒是从那里走出来。。。难道那里是‘淋巴结’？不太像。在肥大细胞脱粒后，还有别的开关引更加刺激过敏反应吗？我不清楚。
The increased presence of neutrophils makes sense. They will be attracted to any inflamed tissue even in the absence of bacterial signals due to the cytokines secreted there. Wonder why we don't see any eosinophils though.
更多的中性粒细胞出现，挺对的。即便没有细菌的信号，他们也会冲向发炎的组织，因为那里分泌了细胞因子。不知道为啥没看到嗜酸性粒细胞。
Oh, lemme explain the symptoms in allergic rhinitis. Drippiness is from the histamines promoting vascular leak and edema. Coughing is often from irritation of the vocal cords from post-nasal dripping. Sneezing is from irritation of nerves in the nasal mucosa. Redness is a direct effect of the inflammation (more blood cells!). I don't know how tears are stimulated here, I'll trust the anime on this one. So far all of these narrations are correct.
我来解释下过敏性鼻炎。流鼻子是因为‘组织胺’引发了‘血管渗漏’和‘水肿’，咳嗽通常是因为声道受到了刺激。喷嚏是因为鼻黏膜上的神经受到刺激。红肿是因为发炎（更多红细胞！）。我不清楚眼泪是如何产生的，但是我相信动画里讲的。目前这些讲解都是对的。
（过敏性的症状包括：流鼻水，流泪，喷嚏，眼睛红肿）
Let me share what is going on histologically...
Nasal mucosa in allergic rhinitis. The stromal tissue below looks cleared out, a result of waterlogging in edema. It is infiltrated by numerous inflammatory cells, prominently eosinophils. It is hard for us to see here but we expect to see increased numbers of mast cells and basophils as well.
从组织学上来讲讲这些过程……
过敏性鼻炎的鼻黏膜。因为水肿，下面的基质组织貌似已经被冲没了。大量炎症细胞，特别是嗜酸性细胞，会渗透到这里。虽然我们看不太出来，但是应该也会有更多的肥大细胞和嗜碱性细胞到这里。
Okay, this will require some discussion. It looks like a steroid has been sent in from outside the body to help limit this inflammatory response. First of all, we can't tell how it is being administered. Red blood cell delivered it, which suggests it is in systemic circulation, further implying that it was an orally (or parenterally) administered steroid. This is not a standard practice in western medicine, and I would be surprised to hear if it was standard in Japan, frankly. A topical steroid (say, given as a nasal spray) would be completely appropriate, but steroids have pleiotropic effects and shouldn't be given systemically for local symptoms. In the short term, it is probably safe, but should be limited. An antihistamine would be a more common oral drug for allergic rhinitis.
这里需要多讨论下。身体外部注入了类固醇，用于减缓炎症反应。首先，我们不能判断它是如何摄入的。它由红细胞运输，所以应该是来自血液循环，暗示它是口服激素。在西方，这种方法不是很常见，其实个人觉得在日本也不常见。用局部类固醇（比如‘鼻用喷雾’）就可以了。动画里这种全身性类固醇会造成太多副反应，不能用于局部病状。短期服用，它可能还算安全，但是应当限制使用。对于过敏性鼻炎，抗组织胺剂应该是更常用的口服药。
Soo...what do steroids do? Quite a bit, but in the context of the immune response, they act on white blood cells at the level of their DNA to reduce production of inflammatory cytokines (plus other stuff). They do not directly kill white cells, or frankly any other cells. Again going pretty wild with creative license here. In fact, there is even a transient reaction with steroids in which there is a huge surge of neutrophils in circulation (the marginated pool), it would have been cool to see that.
所以，类固醇是干啥的呢？能干很多事哇，但在免疫反应里，它们会对白细胞的DNA起作用，让他们减少‘炎症细胞因子’的产量。它们不会直接消灭掉白细胞，也不会消灭别的细胞。所以这里编剧放飞自我了。其实嘛，类固醇会产生一种瞬间反应，造成大量中性粒细胞在血液里涌出。如果能画出这点就好了。
Jesus Christ, it's annihilating EVERYTHING. Steroids have a lot of effects, but they would not cause your mucosa to be torn asunder like this. Remember that these drugs are taken to reduce symptoms... I guess they are depicting this to put the fear of chronic steroid use in you. Seems like this is indeed an orally taken steroid and not a topical. If you want to know what actually happens with chronic steroid overexposure, check out Cushing's syndrome.
天哪噜，这家伙要灭掉所有人啊。类固醇有许多作用，但他们不会把你的黏膜搞得翻天覆地。还记得吧，这药是用来减缓症状的。。。我估摸着这是吓唬你，让你别用慢性激素。看来这还真是口服激素，而不是局部激素。如果你想了解过量服用慢性激素会怎样的话，请自行查阅‘库兴氏综合征’。
Summary
总结
A mild allergic reaction caused by a seasonal pollen. The role of IgE's interplay with mast cells and histamine are nicely characterized, but a lot of creative liberties were taken here to make a complex, multiplayer process more relatable. We finally have some outside intervention being depicted, but I take issue with it.
本集说的是季节性花粉导致的轻微过敏，很好地体现了‘IgE’和肥大细胞、组织胺之间的相互作用。但是编剧加入了太多的自由发挥，估计是想更生动地体现这个复杂的过程。我们终于看到了外界的干扰因素，但是我觉得表现的并不好。
I'm not a prescribing provider (this month I actually work in the blood bank), but I would not personally prescribe an oral steroid as its effects would be too slow to be helpful in the acute phase and systemic effects too many. A topical nasal steroid spray and/or an antihistamine (diphenhydramine, chlorpheniramine, or the less stupor-inducing second generations like cetirizine, loratadine, and fexofenadine) would be a preferable choice.
我不能开药方，但是我本身不会开口服的激素，因为它的药效太慢，对急性病作用不大，而且系统性影响也太多。开局部喷雾剂，或者抗组胺素（苯海拉明，扑尔敏，或者不那么致晕的药，比如西替利嗪， 氯雷他定，或者盐酸非索非那定片）应该会更好。
Although we are seeing an allergic reaction to this japanese cedar pollen, the same reactions would play out in eg a Ragweed allergy, just with a different IgE targeting a different antigen. The same Type I hypersensitivity is also involved in more serious allergic reactions like anaphylaxis. Those cases would be worth treating not only with steroids but also epinephrine and aggressive airway management.
尽管我们看到的是日本杉树花粉过敏，但是‘豚草’过敏等也会有类似的反应，只不过是不同的IgE攻击不同的抗原罢了。I型过敏反应也会出现在更严重的过敏症状中，比如‘全身性过敏反应’。这时，不仅需要激素治疗，还得用药物肾上腺素，以及处理呼吸道。
生物类单词
B-lymphocyte B淋巴细胞
immune cells 免疫细胞
macrophage 巨噬细胞
adaptive immune system 适应性免疫系统
stimuli 刺激
antibody 抗体，也叫immunoglobulin 免疫球蛋白，是Y形状的
antigens 抗原
plasma 血浆
IgA 免疫球蛋白A
mucosal 黏膜的
bone marrow 骨髓
plasma cell 浆细胞
pollen 花粉
allergy 过敏
CD4+ cells CD4+细胞，也就是辅助T细胞
allergen 过敏原
lacrimal duct 泪小管
lymphatic channels 淋巴管
phagocytosis 吞噬作用（把入侵物吃掉）
mast cells 肥大细胞
basophils 嗜碱性细胞
allergic response 过敏反应
histamine 组织胺
inflammation 发炎
vascular leakage 血管渗漏
edema 水肿
serum 血清
interstitial fluids 间质液
running noses 流鼻子
cytokine 细胞因子
allergic rhinitis 过敏性鼻炎
vocal cord 声道
irritation of nerves 神经受刺激
steroid 类固醇，激素
orally administered steroid 口服激素
annihilate 消灭
chronic 慢性的
acute 急性的
