Episode 6 - Erythroblasts and Myelocytes
第六集?- 有核紅血球 和 中幼粒細胞（也叫‘髓細胞’）


Character Highlight? ?角色介紹

Macrophage? ?巨噬細胞


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.
巨噬細胞，還有B淋巴細胞，是我最喜歡的免疫細胞。巨噬細胞非常復雜，是骨髓細胞后代中的多面手。它們會積極參與到吞噬作用中（巨噬細胞的英文‘macrophage’就來自于：macro = 大，phage = 吃貨）。它們產(chǎn)生于骨髓，可以存在于體循環(huán)系統(tǒng)，但也可以根據(jù)所在的組織，細分為不同形式（胚胎形成時，就會產(chǎn)生這種劃分）。在這些組織里，巨噬細胞會有不同的名字。比如肝里的‘庫普弗細胞’，中樞神經(jīng)系統(tǒng)的‘小神經(jīng)膠質(zhì)細胞’，骨頭里的‘破骨細胞’等等。它們在這些地方的作用，通常都是做免疫反應(yīng)、或者是清理不要的東西。巨噬細胞會吃掉 殘渣，細菌，骨基質(zhì)（在‘骨重建’的過程中）等。吃了以后，這些殘渣就會和巨噬細胞里的溶酶體（里面有各種消化性的酶）結(jié)合，最終被消化掉。

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.
但也不能光把巨噬細胞當作吃貨和看門的。在免疫系統(tǒng)這首管弦樂中，巨噬細胞是重要樂手。一部分原因是，它們可以通過自身的HLA（人類白細胞抗原），呈現(xiàn)細菌或者病毒的蛋白質(zhì)，從而激發(fā)“適應(yīng)性免疫反應(yīng)”——還記得吧，第一次見到她時，她就撿起、并檢查了流感病毒的尸塊，并上報給總部。

巨噬細胞還能分泌‘細胞因子’，告訴其他炎癥細胞這里有值得注意的東西。有意思的是，巨噬細胞還可以阻止炎癥；這種類型的巨噬細胞是M2（而不是促進發(fā)炎的M1）。

盡管聽上去簡單，但是巨噬細胞在許多細胞進程中都非常重要，包括傷口愈合，血管形成。典型的急性感染，始于中性粒細胞的大量集結(jié)，終于巨噬細胞對炎癥的冷卻（一般來說）。

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.
巨噬細胞也有不好的一面。她們會在腫瘤所在地，幫助生成新的血管，從而促進腫瘤的增長。實際上，它們的滲漏作用（通常是M2型（抑制炎癥的那種））會導致許多腫瘤的誤診。

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.
關(guān)于她的人設(shè)？她蒼白的面孔，很可能表示她和‘中性粒細胞’有類似的形態(tài)。人們想到白細胞時，通常都會想到它倆（但是注意，目前出現(xiàn)的角色，除了血小板和紅血球，基本都是白細胞）。至于女仆裝？可能是致敬她會清理殘渣。她的武器大砍刀？如果不是“溶酶體”的話（因為我們還沒看到她真正吃掉入侵者），也許就是一氧化氮、或者是活性氧原子，和中性粒細胞用的武器類似。還有一點要說明的是：巨噬細胞很大大大大。她比任何免疫細胞都大，除了巨核細胞之外（也許還有樹狀細胞，我不清楚）。我在想以后能否碰到不同組織里的不同類型的巨噬細胞，比如上面提到的那幾種。*

*up注：工作細胞black里，的確出現(xiàn)了“庫普弗細胞”，就是肝里的巨噬細胞

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.
“單核細胞”和“巨噬細胞”的關(guān)系也值得一說，但是還是等以后吧 （注：這點在第10集里有講）

Episode 6 - Erythroblasts and Myelocytes
第六集 - 有核紅血球 和 骨髓細胞


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.
這里是紅骨髓！紅骨髓就是血細胞生成的地方，它和黃骨髓很不一樣，后者充滿了脂肪。隨著年齡的增長，骨髓被脂肪替代。有種快速判斷骨髓細胞的方法，就是骨髓細胞量（造血細胞和脂肪的體積比），應(yīng)該等于（100-你的年齡）%。 疾病會導致骨髓里造血細胞太多，或者是脂肪/纖維太多。

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.
這個圖是骨髓的組織切片。上面粉色的部分是‘骨小梁’。純白色部分是脂肪。其他的就是生長期的骨髓（以及淋巴）細胞的混合物。黑箭頭指的是巨核細胞，青箭頭指的是紅細胞群…就是動畫里的教室咯？我估計這個骨髓的細胞量是80%（即擁有80%的造血細胞，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“網(wǎng)織紅細胞（不成熟的紅細胞）”脫掉細胞核的過程。這個過程對細胞的成長很重要，因為它能給細胞編碼，讓細胞執(zhí)行自己的工作。我們不清楚為什么紅細胞會‘去核’，但是所有哺乳動物的血液里 都有這個過程。

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.
紅細胞從何而來呢？骨髓（而不是淋巴）干細胞（CD34+ 干細胞）會產(chǎn)生一種前體，叫‘原紅細胞’，它接下來會經(jīng)歷一系列變化：從'早幼紅細胞'，到‘中幼紅細胞’，再到‘晚幼紅細胞’。動畫里，描繪產(chǎn)生‘有核紅細胞’的過程 挺有意思?，F(xiàn)實里，它們從‘CD34+干細胞’的前體上脫落（大致如此）。我不太清楚每種脊髓細胞的命運…等我輪值做血液病理時，就會學到這里。還有一點，血液循環(huán)里，有時也會看到帶細胞核的‘網(wǎng)織紅細胞’。如果它們在外周血里很多的話，通常代表了‘貧血’反應(yīng)，因為身體想把新形成的紅血球盡快推出去。

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.
不用太看這個地圖。地圖上個心形的東西（心臟），按理說應(yīng)該是所有“道路”（血管）通向或者產(chǎn)生的地方。應(yīng)該有比這更好的地圖

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。不知道這在身體里代表什么。據(jù)我所知，造血細胞時，沒有任何‘篩選’過程，這和淋巴細胞不一樣。很多疾病會產(chǎn)生有缺陷的紅細胞，令它們不能正常工作（血紅蛋白病，比如‘鐮狀細胞’和‘地中海貧血癥’；結(jié)構(gòu)缺陷，比如‘遺傳性球形紅細胞癥’；還有酶缺陷，比如‘ G6PD缺乏癥’）

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.
紅細胞一般不能識別病原體 或者對它做出反應(yīng)。這里主要是賣萌。中性粒細胞會參與血細胞生成嗎？我并不覺得。

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‘假單胞菌’出現(xiàn)在骨髓里？骨髓里出現(xiàn)細菌感染叫‘骨髓炎’。這種感染非常難治療，通常需要長期使用IV抗生素，以及積極的清創(chuàng)手術(shù)（清理不健康的組織）。我們只能假設(shè)這家伙不聽話，但是要知道，他可以產(chǎn)生beta溶血現(xiàn)象（可以完全分解紅細胞），他對所有的‘有核紅細胞’都有強力威脅。

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.
不讓出門這件事也有問題。網(wǎng)織紅細胞可以離開骨髓，但是，大量‘有核紅細胞’在血管里出現(xiàn)的話，就代表一系列的疾病了，比如‘巨成紅細胞性貧血’、或者某種惡性疾病。

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前來救援的套路。這里他是未完全成熟的‘中幼粒細胞’。雖然他、嗜酸性粒細胞、嗜堿性粒細胞共享同一種‘前體’，但是在‘中幼粒細胞’階段，他已經(jīng)按自己的軌道發(fā)展，所以他的人設(shè)就是這種黑白色。我不太清楚‘中幼粒細胞’是否能有效對抗細菌，但是他應(yīng)該沒有成熟的‘中性粒細胞’的攻擊力強。

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.
這孩子承諾道，‘中性粒細胞會犧牲自己、擋住病原’，說的賊對。中性粒細胞活不長，它們雖然對感染的反應(yīng)強烈、但卻很短暫。如果他不是主角的話，我會把他搞得更傻、更暴力些，讓他爬過他戰(zhàn)友的尸體，迎擊入侵者。

Summary
總結(jié)
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“紅細胞生成”和“骨髓細胞生成”的簡介。我沒想到會時不時地蹦出一些敵人，但是它們八成不重要。還記得第一集的肺炎球菌吧，它也是這種亂闖亂晃、但卻不重要的角色。這里的‘假單胞菌’也應(yīng)該是這樣。這周我的分析比較短，但是我保證會深入討論本集的后半部分，還有第7集。

EP6單詞
macrophage 巨噬細胞
myeloid cell 骨髓細胞
bone marrow 骨髓
liver 肝臟
HLA = human leukocyte antigen 人類白細胞抗原
angiogenesis 血管形成
megakaryocyte 巨核細胞
dendritic cells 樹狀突細胞
monocyte 單核細胞
erythrocyte 紅細胞
hematopoiesis 血細胞生成
histopathology 組織病理學
myeloid 脊髓的
lymphoid 淋巴的
enucleation 去核
reticulocyte 網(wǎng)織紅細胞
stem cell 干細胞
proerythroblast 原紅細胞
erythroblast 成紅細胞，有核紅細胞
lymphocyte 淋巴細胞
pseudomonad 假單胞菌
osteomyelitis 骨髓炎
anemia 貧血
malignancy 惡性
myelocyte 中幼粒細胞
myelopoiesis 骨髓細胞生成
pneumococcus 肺炎球菌