第六集 - 有核红血球 和 中幼粒细胞

Episode 6 - Erythroblasts and Myelocytes
第六集 - 有核红血球 和 中幼粒细胞（也叫‘髓细胞’）


Character Highlight   角色介绍

Macrophage   巨噬细胞


My favorite immune cell, along with the B-lymphocyte. Macrophages are extremely complex and versatile members of the myeloid cell lineage. They are characterized by their avidity towards phagocytosis ("macro" + "phage" = "big eater"). They develop in the bone marrow and can be found in circulation, but notably also differentiate into many different forms of tissue-resident cells (which occurs during embryogenesis). In these tissues, the macrophages may be known by different names; Kupffer cells in the liver, microglia in the CNS, osteoclasts in bone... they have specialized function in these sites that often pertains to respond to and cleaning up unwanted things. Debris, bacteria, bony matrix (during the normal process of remodeling)...all of these things are eaten by macrophages. Once phagocytosed, this unwanted crud is fused with a lysosome, which contains all sorts of nasty digestive enzymes.
巨噬细胞，还有B淋巴细胞，是我最喜欢的免疫细胞。巨噬细胞非常复杂，是骨髓细胞后代中的多面手。它们会积极参与到吞噬作用中（巨噬细胞的英文‘macrophage’就来自于：macro = 大，phage = 吃货）。它们产生于骨髓，可以存在于体循环系统，但也可以根据所在的组织，细分为不同形式（胚胎形成时，就会产生这种划分）。在这些组织里，巨噬细胞会有不同的名字。比如肝里的‘库普弗细胞’，中枢神经系统的‘小神经胶质细胞’，骨头里的‘破骨细胞’等等。它们在这些地方的作用，通常都是做免疫反应、或者是清理不要的东西。巨噬细胞会吃掉 残渣，细菌，骨基质（在‘骨重建’的过程中）等。吃了以后，这些残渣就会和巨噬细胞里的溶酶体（里面有各种消化性的酶）结合，最终被消化掉。

But it's not fair to just call macrophages eaters and janitors. Macrophages a major orchestrators of the immune response, partly through their ability to invoke the adaptive immune response through presentation of bacterial and viral peptides on their HLA molecules (remember how when we first met her, she picked up a hunk of dead influenza and examined it, reporting it to HQ?), and also by their secretion of cytokines that signal to many other inflammatory cells the presence of something concerning. What is more interesting is that macrophages can also signal to stop inflammation; a subset known as M2 (as opposed to pro-inflammatory M1). Though this sounds simple, this role makes macrophages central to a huge number of cellular processes, including wound healing and angiogenesis. A typical nidus of acute inflammation begins with neutrophils swarming en masse, and usually ends with a macrophage calming the inflammation.
但也不能光把巨噬细胞当作吃货和看门的。在免疫系统这首管弦乐中，巨噬细胞是重要乐手。一部分原因是，它们可以通过自身的HLA（人类白细胞抗原），呈现细菌或者病毒的蛋白质，从而激发“适应性免疫反应”——还记得吧，第一次见到她时，她就捡起、并检查了流感病毒的尸块，并上报给总部。

巨噬细胞还能分泌‘细胞因子’，告诉其他炎症细胞这里有值得注意的东西。有意思的是，巨噬细胞还可以阻止炎症；这种类型的巨噬细胞是M2（而不是促进发炎的M1）。

尽管听上去简单，但是巨噬细胞在许多细胞进程中都非常重要，包括伤口愈合，血管形成。典型的急性感染，始于中性粒细胞的大量集结，终于巨噬细胞对炎症的冷却（一般来说）。

Macrophages have an unwanted behavior too. They are known to contribute to the growth of tumors by promoting things like angiogenesis at the site of tumor formation. In fact, their infiltration (usually of the M2 type) is correlated with poor prognosis in many tumors.
巨噬细胞也有不好的一面。她们会在肿瘤所在地，帮助生成新的血管，从而促进肿瘤的增长。实际上，它们的渗漏作用（通常是M2型（抑制炎症的那种））会导致许多肿瘤的误诊。

What about her design? Her pale appearance is probably a nod towards her and neutrophil's similar morphology. Both are sort of the prototypical "white blood cells" that people tend to envision (but please note, that just about everyone except for the platelet and erythrocyte so far introduced are white blood cells). The maid outfit is likely a nod to her role in clearing debris. Her weapon? If not a lysosome (since we have yet to see her actually eating bacterial invaders), perhaps we can call it nitric oxide or a reactive oxygen species, similar to the weapons that the neutrophil wields. And to be clear: Macrophages are big. Bigger than any immune cell except megakaryocytes (and maybe dendritic cells, I'm not sure). I wonder if we will meet different tissue-resident forms of macrophages, as discussed above.
关于她的人设？她苍白的面孔，很可能表示她和‘中性粒细胞’有类似的形态。人们想到白细胞时，通常都会想到它俩（但是注意，目前出现的角色，除了血小板和红血球，基本都是白细胞）。至于女仆装？可能是致敬她会清理残渣。她的武器大砍刀？如果不是“溶酶体”的话（因为我们还没看到她真正吃掉入侵者），也许就是一氧化氮、或者是活性氧原子，和中性粒细胞用的武器类似。还有一点要说明的是：巨噬细胞很大大大大。她比任何免疫细胞都大，除了巨核细胞之外（也许还有树状细胞，我不清楚）。我在想以后能否碰到不同组织里的不同类型的巨噬细胞，比如上面提到的那几种。*

*up注：工作细胞black里，的确出现了“库普弗细胞”，就是肝里的巨噬细胞

The relationship between "monocytes" and macrophages is worth discussing, but we will save that for when we talk about the monocyte in a future episode.
“单核细胞”和“巨噬细胞”的关系也值得一说，但是还是等以后吧 （注：这点在第10集里有讲）

Episode 6 - Erythroblasts and Myelocytes
第六集 - 有核红血球 和 骨髓细胞


2:14 - It's the red bone marrow! Red bone marrow is where hematopoiesis occurs, and is distinct from yellow marrow which is mostly just fat-infiltrated. As you age, marrow is replaced by fat. A quick heuristic we use in bone marrow histopathology is that your bone marrow cellularity should be equal to (100 - your age)%. Many diseases can cause the bone marrow to become too cellular or too fatty/fibrotic.
这里是红骨髓！红骨髓就是血细胞生成的地方，它和黄骨髓很不一样，后者充满了脂肪。随着年龄的增长，骨髓被脂肪替代。有种快速判断骨髓细胞的方法，就是骨髓细胞量（造血细胞和脂肪的体积比），应该等于（100-你的年龄）%。 疾病会导致骨髓里造血细胞太多，或者是脂肪/纤维太多。

Histopathologic section of normal bone marrow. The pink stuff at the top is a bony trabeculum. The cleared out white spaces are fat. Everything else is a soup of developing myeloid (and some lymphoid) cells. Black arrows indicate megakaryocytes, while the cyan arrow indicates an erythroid colony...our classroom? I estimate this marrow to be of 80% cellularity.
这个图是骨髓的组织切片。上面粉色的部分是‘骨小梁’。纯白色部分是脂肪。其他的就是生长期的骨髓（以及淋巴）细胞的混合物。黑箭头指的是巨核细胞，青箭头指的是红细胞群…就是动画里的教室咯？我估计这个骨髓的细胞量是80%（即拥有80%的造血细胞，20%的脂肪）

2:42 - Enucleation is the process by which a reticulocyte (immature red blood cell) sheds its nucleus, which was important to its development as it is needed to encode the cellular machinery that lets the cell perform its function, but is not necessary later. It is unclear why this happens, but enucleation occurs in the blood of all mammals.
去核就是“网织红细胞（不成熟的红细胞）”脱掉细胞核的过程。这个过程对细胞的成长很重要，因为它能给细胞编码，让细胞执行自己的工作。我们不清楚为什么红细胞会‘去核’，但是所有哺乳动物的血液里 都有这个过程。

3:18 - How do red blood cells form? A myeloid (as opposed to lymphoid) stem cell lineage ("CD34+ stem cells") gives rise to a precursor known as a pro-erythroblast, which advance through characteristic stages of development (basophilic erythroblast, polychromatophilic erythroblast, orthochromatic erythroblast). It's very interesting how mechanical the birth of the erythroblasts are being depicted. In reality they just sort of bud off of the CD34+ stem cell precursor. How exactly each member of the myeloid lineage is committed to its cellular fate is not clear to me...I will likely learn this in the next couple of months when I do a hematopathology rotation. One thing I will mention is that you can occasionally see circulating reticulocytes that are still nucleated. An abundance of them in the peripheral blood indicates a physiologic response to usually anemia, as the body tries to push out new RBCs quickly.
红细胞从何而来呢？骨髓（而不是淋巴）干细胞（CD34+ 干细胞）会产生一种前体，叫‘原红细胞’，它接下来会经历一系列变化：从'早幼红细胞'，到‘中幼红细胞’，再到‘晚幼红细胞’。动画里，描绘产生‘有核红细胞’的过程 挺有意思。现实里，它们从‘CD34+干细胞’的前体上脱落（大致如此）。我不太清楚每种脊髓细胞的命运…等我轮值做血液病理时，就会学到这里。还有一点，血液循环里，有时也会看到带细胞核的‘网织红细胞’。如果它们在外周血里很多的话，通常代表了‘贫血’反应，因为身体想把新形成的红血球尽快推出去。

4:26 - Wouldn't try to read too much into this map. There's a heart shaped thing...which logically all of the "roads" (vessels) should lead to or from. This would have been a better example.
不用太看这个地图。地图上个心形的东西（心脏），按理说应该是所有“道路”（血管）通向或者产生的地方。应该有比这更好的地图

4:35 - Cute. No idea what this refers to in vivo. I am unaware of any sort of "selection" process in erythrogenesis, like there is with lymphocytes. And there are plenty of diseases that result in formation of defective erythrocytes that are ineffectual at their job (hemoglobinopathies like sickle cell & thalassemias, structural disorders like hereditary spherocytosis, and enzymatic disorders like G6PD deficiency).
卡哇伊。不知道这在身体里代表什么。据我所知，造血细胞时，没有任何‘筛选’过程，这和淋巴细胞不一样。很多疾病会产生有缺陷的红细胞，令它们不能正常工作（血红蛋白病，比如‘镰状细胞’和‘地中海贫血症’；结构缺陷，比如‘遗传性球形红细胞症’；还有酶缺陷，比如‘ G6PD缺乏症’）

5:35 - Red cells generally do not have any mechanism by which to recognize or respond to pathogens. This is mostly just more cute stuff. Do neutrophils play any role in erythropoiesis? I don't believe so.
红细胞一般不能识别病原体 或者对它做出反应。这里主要是卖萌。中性粒细胞会参与血细胞生成吗？我并不觉得。

8:15 - What in the name of god is a pseudomonal organism doing in the bone marrow? A true bacterial infection in the bone marrow is called osteomyelitis. These infections are notoriously difficult to treat and often require long courses of IV antibiotics and aggressive surgical debridement. We are forced to assume this is some wayward organism, but recall that as it is capable of "beta-hemolysis" (can completely lyse red blood cells), it is a true danger for any erythrocytes (or blasts, frankly) that it encounters.
他喵的‘假单胞菌’出现在骨髓里？骨髓里出现细菌感染叫‘骨髓炎’。这种感染非常难治疗，通常需要长期使用IV抗生素，以及积极的清创手术（清理不健康的组织）。我们只能假设这家伙不听话，但是要知道，他可以产生beta溶血现象（可以完全分解红细胞），他对所有的‘有核红细胞’都有强力威胁。

9:05 - The door-hat-lock thing is again questionable. Reticulocytes can and do leave the bone marrow, though the presence of an abundance of erythroblasts (megaloblasts?) can indicate a variety of diseases such as the megaloblastic anemias or certain malignancies.
不让出门这件事也有问题。网织红细胞可以离开骨髓，但是，大量‘有核红细胞’在血管里出现的话，就代表一系列的疾病了，比如‘巨成红细胞性贫血’、或者某种恶性疾病。

10:45 - The start of a long trend of U-1146 coming to the rescue. Here is an incompletely matured myelocyte, a precursor to the neutrophil. Though he, the eosinophil, and the basophil all share a common precursor, by the myelocyte stage they are committed to their lineage, hence his white and black appearance. I am unaware of the efficacy of a myelocyte in fighting off a bacterial pathogen, but it seems reasonable that it would be less effective than a mature neutrophil.
又是U-1146前来救援的套路。这里他是未完全成熟的‘中幼粒细胞’。虽然他、嗜酸性粒细胞、嗜碱性粒细胞共享同一种‘前体’，但是在‘中幼粒细胞’阶段，他已经按自己的轨道发展，所以他的人设就是这种黑白色。我不太清楚‘中幼粒细胞’是否能有效对抗细菌，但是他应该没有成熟的‘中性粒细胞’的攻击力强。

12:15 - Kiddo's assertion that neutrophils will sacrifice themselves in stopping pathogens is very accurate. They tend to be short-lived and their response to infection is intense but also short. If he weren't such a major character, I'd have made him a lot dumber and more aggressive, climbing over the cadavers of his dead colleagues to get a foreign invader.
这孩子承诺道，‘中性粒细胞会牺牲自己、挡住病原’，说的贼对。中性粒细胞活不长，它们虽然对感染的反应强烈、但却很短暂。如果他不是主角的话，我会把他搞得更傻、更暴力些，让他爬过他战友的尸体，迎击入侵者。

Summary
总结
A short vignette on normal erythro- and myelopoiesis. A transient organism here or there is not expected, but probably not significant, depending on what organism it is exactly. Recall that our pneumococcus in episode 1 was quite wayward and insignificant, well so probably was this pseudomonad. I leave you with a shorter analysis this week, but promise to have a lot more depth covering the second half of this episode and all of episode 7.
本集是“红细胞生成”和“骨髓细胞生成”的简介。我没想到会时不时地蹦出一些敌人，但是它们八成不重要。还记得第一集的肺炎球菌吧，它也是这种乱闯乱晃、但却不重要的角色。这里的‘假单胞菌’也应该是这样。这周我的分析比较短，但是我保证会深入讨论本集的后半部分，还有第7集。

EP6单词
macrophage 巨噬细胞
myeloid cell 骨髓细胞
bone marrow 骨髓
liver 肝脏
HLA = human leukocyte antigen 人类白细胞抗原
angiogenesis 血管形成
megakaryocyte 巨核细胞
dendritic cells 树状突细胞
monocyte 单核细胞
erythrocyte 红细胞
hematopoiesis 血细胞生成
histopathology 组织病理学
myeloid 脊髓的
lymphoid 淋巴的
enucleation 去核
reticulocyte 网织红细胞
stem cell 干细胞
proerythroblast 原红细胞
erythroblast 成红细胞，有核红细胞
lymphocyte 淋巴细胞
pseudomonad 假单胞菌
osteomyelitis 骨髓炎
anemia 贫血
malignancy 恶性
myelocyte 中幼粒细胞
myelopoiesis 骨髓细胞生成
pneumococcus 肺炎球菌