第四集 - 食物中毒
Character Highlight 角色介绍
Eosinophil 嗜酸性粒细胞
Eosinophils are white blood cells that are closely related to neutrophils. Those two, together with basophils, constitutes the granulocytes, so named for their appearance, composed of numerous secretory granules which contain various antimicrobial weaponry.
嗜酸性粒细胞是白细胞，和中性粒细胞关系很近。它俩，再加上 嗜碱粒细胞，组成了“颗粒性白血球”。这个名字是根据它们的外观来的：它们带有许多分泌颗粒，内部装有各种武器，用来对抗微生物。
Let me break down their name. In typical histological slides (IE, human tissue prepared to examine under the microscope), dyes are required to stain the tissue for study. Otherwise, human tissue would all look colorless except for the few pigments we express (hemoglobin, melanin, bile...). These chemical stains are meant to target different properties of tissue to stain it distinctively. The most common of these is called the hematoxylin & eosin stain which stains acidic (basophilic) tissues with hematoxylin (blue), and basic (acidophilic) tissues with eosin (red). An eosinophil is so named because it takes up a lot of this eosin dye--hence the character's pink garb, and the basophil's blue garb. Actually, blood smears are usually stained with the "Romanowsky method"...but that doesn't matter right now.
说说它们的名字。我们在显微镜下观察人类的组织时，通常需要染料。否则，组织看起来都是无色的，当然，少数几个自带颜料的（比如血红蛋白，黑色素，胆汁...）的除外。这些化学染料会根据细胞的特性，染上不同的颜色。最常见的染色法是“苏木精- 曙红染色”，它们给酸性的组织染上苏木精（蓝色），给碱性的组织染上曙红（红色），所以自古红蓝出cp嘛（划掉）。嗜酸性粒细胞（英文叫“嗜曙红细胞”）叫这个名字，就是因为它可以吸收许多曙红染料。正因如此，嗜酸性穿的是粉衣服，嗜碱性穿的是蓝衣服。
The Eosinophil's twin tails? It's actually a visual representation of the cell's two lobules!
嗜酸性粒细胞的双马尾？那就是它细胞上的叶片。
The role that eosinophils play is multifaceted, but the most historically significant would be in defense against parasitic infection. Usually, these are large helminths--worms of various types that are too big to be phagocytosed by macrophages. Eosinophils migrate towards them, attracted to antibodies bound on their surface, and degranulate, releasing their antimicrobial payload.
嗜酸性粒细胞的工作多种多样，但是最重要的是它能防御寄生虫感染。它们通常对抗的是蠕虫 - 就是各种的虫子，因为体型太大，无法被巨噬细胞吃掉。嗜酸性粒细胞向它们移动，吸附到它们表面的抗体上，然后“脱粒”，释放抗微生物武器。
The most significant of this payload would be major basic protein, which is...somehow toxic to helminths, though 2 textbooks and a wikipedia article aren't telling me how exactly. Let's call her spear MBP? You may think that antiparasitic defense is quite insignificant nowadays, and it is, thanks to public sanitation and pest control. But spend an hour reading about neglected tropical diseases and you'll understand how serious they were in our evolutionary history.
在这些武器中，最重要的一个是“主要碱性蛋白（MBP）”，它对蠕虫有毒性。但我查遍了2本教科书和维基都没搞明白，这毒性怎么来的。要不就把她的戟看成MBP好了。
你也许觉得，现在这个社会，抗寄生虫已经不重要了。的确，这要感谢公共卫生部和害虫管理部。但如果你花点时间，读读那些‘不起眼’的热带病，你就知道寄生虫在我们历史上，曾经有多严重。
Eosinophils also play a role in mediating allergic reaction, and their concentration in tissues not actively infected by parasites is a hallmark for disease there (examples: eosinophilic esophagitis, lupus, various dermatitides...). They are also implicated in a number of cancers, but so are all of the immune cells, really (except mature platelets and erythrocytes).
嗜酸性粒细胞也会参与调节“过敏反应”。在未被寄生虫感染的组织里，嗜酸性粒细胞的浓度，是判断疾病的重要标志（例子：嗜酸性食道炎，狼疮，各种皮炎等……）。它们还会参与对抗一些癌症，不过所有的免疫细胞都会参与的（除了成熟的血小板和红细胞）
第四集 - 食物中毒
Oh, we start in the stomach. You remember how I talked about the innate immune system last time? Well, the gastrointestinal system has many elements that contribute to innate (or really, passive) immunity. The GI tract is, arguably, exposed to the outside world! The most obvious defense is stomach acid, yes, but we also express lots of antibodies on the mucosae, and secrete many other antimicrobial peptides. It's a harsh environment. From a non-immunologic perspective, the stomach's main role is in digestion, but specifically digestion of protein, as the chief cells of the stomach produce an enzyme called pepsin, which degrades protein, while the parietal cells secrete hydrochloric acid.
片头就是胃。还记得上回我们说过“自发性免疫系统”不？肠胃系统有许多东西都属于自发性免疫。消化道，那是直接通向外部世界的！这里最明显的防御系统是胃酸，但是胃黏膜上也有许多抗体，胃还会分泌许多抗微生物的蛋白质。那里环境险恶。不看免疫作用的话，胃的主要作用是消化，特别是消化蛋白质。胃的主细胞会产生“胃蛋白酶”，用来降解蛋白质，而壁细胞则分泌盐酸。
Digestion of carbohydrates and fats, however, are the job of the pancreas. The stomach also plays an important role in regulating the release of food for absorption in the small intestine. See how rocky and rough the walls are? Those are a nod to gastric rugae, folds of gastric mucosa that can flatten out when the stomach is distended.
但是，消化糖类和脂肪，就是胰的工作了。胃也控制着食物的释放，以便小肠的吸收。看到这些墙有多糙了不？它们象征着“胃皱褶”，它们是“胃粘膜”的皱纹，一旦胃撑开，它们就摊平了。
You don't have THAT much acid in your stomach relative to food! Remember that acid is harmful to all tissues, and the gastric lining is constantly A) replenishing itself and B) secreting mucin to offset these effects. The regulation of acid secretion is controlled by a complex interaction of hormones, which are sensitive to things like the presence of caloric content in the food you eat, as well as the physical distension of the stomach, and even the brain in anticipation of eating food.
你身体里的酸可没这么多（相对于食物的量来说）！！还记得吧，酸危害所有组织；为此，胃黏膜会不断地 1）自我更新 2）分泌粘液素抵消伤害。荷尔蒙控制胃酸的分泌，过程很复杂，并且会受很多因素的影响；比如你吃的东西的卡路里含量，胃本身的扩张，甚至当你脑子觉得马上会有吃的时，也会影响它。
Lol, neutrophil, are you really surprised at the presence of bacteria here? Hope you don't go anywhere near the colon.
哎呦我的天白血球，这里出现细菌，你真心觉得吃惊？那你可千万别去大肠。
Not sure who this blue & gray aquatic looking guy is. Maybe Vibrio (cholera)? Pure conjecture.
不太清楚这个蓝灰色的水生物是谁。也许是“霍乱弧菌”？瞎猜的
Eosinophils are always present in the gastric submucosa. As are lymphocytes and macrophages, despite this asshat's commentary. Actually, neutrophils are the ones you wouldn't expect to see in healthy gastric tissue. If we are looking at a stomach biopsy and we see neutrophils (known as active inflammation), we start searching for H. Pylori infection. Hey, maybe this guy is H. Pylori? He should be chilling out just within the edge of the tank then.
胃黏膜下层总会有嗜酸性细胞，淋巴球和巨噬细胞也会在那里。其实嘛，健康的胃里，中性粒细胞是最不应该出现的。如果我们做胃的活体切片检查，并且看到了中性粒细胞的话(叫“活动性炎症”)，我们会去找“幽门螺杆菌感染”。哎，也许这家伙是“幽门螺杆菌”？他应该会在水箱*的边上活动才是。
*注：指胃部的水族馆
I do not know what to make of the commentary that eosinophils are "weak". They do not play a significant role in general antibacterial defense, but bacteria wouldn't really enjoy bathing in major basic protein, either. I bet the nearby stromal or epithelial cell talking smack wouldn't appreciate being hit by it too.
不明白为啥说“嗜酸性细胞”很弱。的确，它们在一般的抗菌过程中作用不大，但是细菌也不喜欢泡在碱性的蛋白质（嗜酸性细胞是碱性的）里。我估计在旁边喷她的“基质细胞”或者是“上皮细胞”也不喜欢撞上她。
Oh, and I wonder what these "chef" cells are. They seem to be packaging/preparing food for supply, which we could argue is the job of the liver (hepatocytes). Or maybe they represent the absorptive enterocytes that take up the nutrients.
我也在想这些“厨子”细胞是什么。他们好像在准备食物，貌似肝脏（肝细胞）的工作。或者，它们代表了吸收养分的“吸收性肠上皮细胞"。
A new character again! Mast cells are related to basophils, but are tissue-resident instead of circulating (EDIT: This is a common misconception that is still perpetuated in the medical pedagogy. Please see these articles for a more comprehensive review of the relationship between basophils and mast cells). They play a major role in mediating allergic hypersensitivity through the release of histamine, which has many effects including but not limited to vasodilation and gastric acid release. For a professional analysis, please see this dissertation. Also, I have never heard of them called "fat cells", I think that's translational. (confirmed)
又一个新角色登场！肥大细胞和嗜碱粒细胞有关，但是它们住在组织里，而不是循环系统里（注：这其实是医学教育领域里常见的误解。想要了解肥大细胞和嗜碱粒细胞的关系，请参考更全面的文章）。它们通过释放“组胺”（histamine），调节过敏反应。这会引发一系列反应，包括“血管舒张”和“胃酸释放”。另外，我从没听过它们叫“肥大”细胞，应该是翻译的问题。*
*up注：实际上“肥大细胞”的英语“mast cell”，来自于德文的mast，意思就是胖）
They just keep coming. Basophils are the third granulocytes, and they are the least common and least well-understood of the three, but they too probably play a role in hypersensitivity/allergic reactions. They are not phagocytic like neutrophils and eosinophils, but do degranulate. This guy is dressed like he's from S.T.A.L.K.E.R., wonder if that's an allusion to how he's always wandering. As a pathologist (in training) I rarely give a shit about their presence, they make up less than 1% of white cells in circulation. Basophilia, or abundance of basophils, hearkens a particular leukemia (CML). See this actual article for a review of basophil functions.
新角色层出不穷。嗜碱粒细胞是第三种粒细胞（颗粒性白血球），它也是三种细胞中，最不常见、人们了解最少的那个。它很可能也协调了过敏反应。它不会像中性粒细胞和嗜酸细胞那样吃掉细菌，但是它会“脱粒”（释放杀掉细菌的东西）。这家伙穿的像“尾行”的人一样，可能是因为它总是漫无目的地走来走去吧。作为一个在陪的病理学家，我都不想鸟它，因为这家伙在循环系统里，占的白血球比例还不到1%。嗜碱粒细胞，或者说一大堆嗜碱细胞，标志了某种白血病（CML，慢性髓细胞性白血病）。想大概了解它的作用吗？那就读文章吧。（但up懒得放链接了）
Someone posed a question in the other thread if the platelets use a "buddy system"...not that I'm aware of.
有人问血小板是不是有“哥们儿”系统，据我所知，没有。
Okay, my guess on the first guy is wrong, lol. Vibrio is a genus of gram-negative bacilli with a distinctive flagellum which are known to inhabit aquatic environments and cause GI illness, especially with contaminated seafood. The most famous of these is Vibrio cholerae, which causes cholera, a disease characterized by profuse watery diarrhea (mediated by the cholera toxin) that can be fatal if fluid balance is not maintained. There have been several major epidemics of vibrio in human history, and even now there are 3-5 million cases per year, with maybe 100,000 deaths per year (most of them children in underdeveloped nations). I am unaware of what species this guy is, but note that there are many subspecies that each have unique geographic distributions. Maybe it's Vibrio vulnificus? Parahaemolyticus?
第一个家伙我猜错了哪。弧菌是杆菌属的，革兰氏阴性。它有独特的鞭毛，它住在有水的地方，会引起肠胃性疾病，尤其当它出现在坏掉的海鲜，就更容易引发病情。最有名的家伙就是“霍乱孤菌”，它会引起霍乱；这种疾病的特点是严重腹泻（由霍乱毒素传达），如果流失液体过多的话，就会致死。人类历史上有过好几次大型孤菌感染，即便是现在，每年也有300-500万个病例，每年死亡人数可能是10万（大部分都是不发达国家的儿童）。我不知道这个家伙的种类是什么，但是注意，每一个亚种都分布在独特的地理位置。也许是创伤孤菌？副溶血弧菌？
Neutrophils are NOT phagocytosed by any vibrio species. Neutrophils are generally larger than vibrio; we just need to be sure that big fuzzy doesn't represent something else. This makes for a cool display, however.
中性粒细胞不能被任何孤菌吃掉。中性粒细胞一般比孤菌要大。我们得确定下这个毛茸茸的家伙不代表别的东西。不过真是一场好戏啊。
Next bug! Anisakis! Wait, wtf is Anisakis? It's not even in my medical microbio textbook. It must not be common in the west. Thankfully, review articles are available...Anisakis is a marine nematode (worm), and like most parasites it has a complex life cycle, infecting many marine animals. Humans are an incidental host, that is, we do not normally play a role in their life cycle, and ending up in a human usually represents a reproductive "dead-end" for the bug. At any rate, if it ends up in a human, it causes gastrointestinal pain from the resulting inflammation. It doesn't really do much else in the GI tract besides leech nutrients and shit out eggs. It seems more common in Japan and Portugal than in the west, though it is not a disease that is reportable to the CDC, so its incidence here may be underestimated.
下个虫子！海兽胃线虫！等下，这他喵的是啥？我教科书里都没有。在西方应该不常见。不过，好在有文献……海兽胃线虫是海洋类线虫，和其他寄生虫一样，它有复杂的生命周期，可以感染许多海洋动物。人类是它的意外宿主，也就是，我们一般不掺和进它的生活。对于这虫子来说，进入到人体就意味着没后代了。不管怎样，如果它最终到达人体，会导致发炎引起的肠胃痛。除了榨取营养、排卵之外，它在消化道也没什么大的作用。比起西方，它在日本和葡萄牙更常见。尽管这病不需要上报给疾控中心，但是它在美国的发生概率可能比预想的多。
Gross. That's a whale stomach, btw, an intended host for the worm.
呃，这是鲸鱼的胃。哦，这也是虫子的原始宿主。
Aw shit, the host is ralphing. Emesis is a physiologic process by which we uhh...you know what? You know damn well what it does and why it happens.
宿主在呕吐。呕吐是一种生理现象，会让我们……不说了，你们都他喵的知道这代表啥
Breaking through the gastric wall? Whoa whoa whoa. Generally, GI parasites are not capable of breaking through the GI wall, which has several layers of muscle. That would constitute a perforation, which is life-threatening as the GI contents can then spill into the normally sterile peritoneal space. Some parasites can cause erosion and bleeding, but perf'ing your host is probably not a smart idea for the parasite, which would prefer to lay low. Looking now, there are a few case reports, but they result from extreme bulk effect (so many parasites that the tube erupts). (per /u/Rathurue: The parasite worm does not invade through gastric wall. However, they do show at the computer screen (14:11) that the worm invades through the mucosal layer of the stomach, to be specific at the bottom of gastric pit.)
穿透胃壁？哇哇哇。一般来说，消化道的寄生虫不能穿透消化壁，因为它有好几层肌肉组成。除非发生了胃穿孔，那可是致命的，因为食道里的东西可以飞溅到毫无保护的腹膜上。有些寄生虫的确可以引起腐蚀和流血，但是它们给宿主打洞可不够机智，因为寄生虫喜欢低调。出现了一些事故报告，但是问题主要来自于“膨胀效应(bulk effect)”（寄生虫太多导致管道破裂）。（更正：寄生虫没有打破胃壁，计算机屏幕上表明，它们打穿了胃的一层黏膜，具体说，是‘胃小凹’的底部）
Yay, eosinophil took out the parasite! In reality it would take a lot more than one, all of which would mob the everloving shit out of any parasite, gradually taking it out (or at least slowing it down) via toxic effect of their granules. See below.
耶，嗜酸性细胞干掉寄生虫！现实里，需要的嗜酸性细胞可不止一个，它们得一起才能把寄生虫踢走，通过它们颗粒上的毒性慢慢把寄生虫赶出去（或者减缓寄生虫的速度）。见下图。
Lol, that view of the stomach. Evidently this anisakis organism is huge. That hole at the top is the cardiac sphincter, or the gastroesophageal junction, where food is dropped in from the esophagus.
噗，胃的风景独好。能看出这只海兽胃线虫够大的。顶上的那个洞是“贲门括约肌”，又叫“胃食管连接部”，就是食物从食道里掉下去的地方。
Summary
总结
A myriad of gastrointestinal insults from contaminated seafood. How would the average person fare? Well, vibrio is no joke, as we have discussed, but how severe an infection results depends in part on the inoculum, or really how many of the organisms you ingest. For some bugs, it takes a large inoculum. For some, it only takes a few (famously, Shigella only takes 10 or so organisms to cause symptomatic infection). I could totally believe your immune system could fight off a small Vibrio party unassisted. Anisakis, however, I can only make conjecture about. It is generally unclear to modern medicine whether or not GI parasitic infections can usually self-resolve. Many come to clinical attention, due to weight loss or prolonged GI symptoms that do not resolve, resulting in some tests (either endoscopic examination of the GI tract, or microscopic examination of the stool for the eggs & segments of the parasite) and usually resulting in a one or two-time dose of an antiparasitic agent (eg Albendazole).
坏掉的海鲜引发的一系列肠胃问题。普通人如何应对呢？我们说过，孤菌不是小事，但是感染的严重性部分取绝于（疫苗）接种，就是你吃进去多少病菌。对于有些寄生虫，需要大量疫苗。而另外一些只需要少量（痢疾杆菌只需要10几个细菌就可以引发“症状性感染”）。我完全相信你的免疫系统可以自我抵抗一小撮孤菌。但海兽胃线虫就不一定了。现在医学还不能确定食道寄生虫感染，是否能完全交给身体自行解决。许多病情都需要护理，因为有体重下降和长期性的肠胃症状。医生会让你去做一些检测（要么是食道的内镜检查，要么是通过显微镜检查shit里的寄生虫卵/碎片），通常会吃一次，或者两次的抗寄生虫药（比如阿苯达唑）
Antimicrobial resistance is generally not a concern in parasites, which are much larger and more complex than bacteria or viruses and take much longer to evolve significant resistance. Truly, most parasites belong to kingdom Animalia, and have more in common with us than they do with bacteria. It would be impressive (impossible?) for a single eosinophil to take down an entire worm, that's for sure.
寄生虫一般没有抗药性，因为它们比细菌或者病毒要大得多，复杂得多，需要更长的时间来进化出抗药性。许多寄生虫都是动物界的成员，比起细菌来说，和我们人类更类似。可以肯定的是，一个嗜酸性细胞，基本不可能独自干掉整个虫子的。
生物类单词：
food poisoning 食物中毒
eosinophil 嗜酸性粒细胞
basophil 嗜碱粒细胞
granulocyte 粒细胞，有粒白细胞
histology 组织学(研究细胞的学科)
stain 染色
hematoxylin & eosin stain 苏木精- 曙红染色
melanin 黑色素
parasite 寄生虫
helminth 肠虫，蠕虫
phagocytose 巨噬
degranulate 脱粒
infection
public sanitation 公共卫生部
allergy 过敏
lupus 狼疮
gastrointestinal system 肠胃系统
GI tract 消化道
mucosae 胃黏膜
pepsin 胃蛋白酶
carbohydrate 碳水化合物
pancrea 胰
intestine 小肠
colon 结肠
gastric 胃的
submucosa 粘膜下层
biopsy 活组织检查
stromal cell 基质细胞
epithelial cell 上皮细胞
hepatocyte 肝细胞
mast cell 肥大细胞
histamine 组胺
leukemia 白血病
toxin 毒素
gastroenteritis 胃肠炎
Vibrio cholerae 霍乱孤菌
epidemic 流行病
Anisakis 海兽胃线虫
host 宿主
emesis 呕吐
perforation 穿孔
inoculum 疫苗接种
