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主要角色

Deferred for now...probably will do a regulatory T-cell and helper T-cell combo next week.

現(xiàn)在就讓我推更下……下周我會做‘調(diào)節(jié)性T細胞’和‘輔助T細胞’的介紹。

譯者注：作者那周很忙，就沒有寫角色介紹。

另：胸腺細胞，就是還沒有完全成熟的各種T細胞。也是本集的主角們

Episode 9 - Thymocytes

第九集 - 胸腺細胞

3:35 - Killer T-lymphocyte refers to the adaptive immune response as the "last line of defense" for the body. This is pretty astute; we would expect that any infectious agent that is able to thwart adaptive immunity would be life-threatening.

殺手T細胞把‘適應(yīng)性免疫系統(tǒng)’叫做身體的‘最后一道防線’。高，實在是高。任何能夠突破適應(yīng)性免疫系統(tǒng)的感染源，都有可能危害生命。

3:45 - I wonder what this room is, filled with what are labeled as "antigens". Your immune system retains a memory of foreign antigens that it encounters, and it does so through, appropriately, the memory cells.

這房間是啥地方？還裝滿了標(biāo)著‘抗原’的書？免疫系統(tǒng)的確會記住自己曾碰到過的外界抗原，但它是通過‘記憶細胞’記住的。

4:20 - Who is regulatory T-cell, or T-reg? I will describe them in more detail next week, but they are a subset of lymphocytes whose primary role is to suppress immune responses, especially those that are inappropriately directed against "self" tissues. To illustrate how important they are, consider IPEX syndrome, in which a key transcription factor for T-regs is mutated. Without their function, these patients develop skin, gut, and endocrine disorders from inappropriate autoimmune responses.

那么，調(diào)節(jié)性T細胞（T-reg）是什么人呢？我下周會更詳細講它們；簡單來說，T-reg是淋巴細胞的一種，主要作用是抑制免疫反應(yīng)，特別是針對‘自身’細胞的免疫反應(yīng)。它們的重要性，可以從“IPEX癥候群”中看出來。這個病會讓T-reg的重要轉(zhuǎn)錄因子病變；沒有轉(zhuǎn)錄因子的正常運作，病人就會產(chǎn)生錯誤的自發(fā)免疫反應(yīng)*， 從而染上皮膚病、器官病、內(nèi)分泌失調(diào)。

注：免疫細胞攻擊正常細胞時，就會發(fā)生“自身免疫性疾病”，屬于人體異常的免疫反應(yīng)。這種疾病包括紅斑狼瘡（又叫蝴蝶斑），1型糖尿病等等。

這段話的大概意思是，如果調(diào)節(jié)性T細胞出了問題，它就不能讓異常的免疫細胞閉嘴。

5:49 - Oh and yeah, this dendritic cell has probably outlived several generations of lymphocytes. Seems fair for him to play the wizened elder role here.

哦，對了，樹狀細胞的確可以活過好幾代淋巴細胞。讓他演智慧的長者，挺合適。

7:10 - Maybe now would be a good time to explain what the thymus is. The thymus is a small gland that normally resides in your thorax, more or less just behind your sternum but anterior to the heart and lungs (in the mediastinum). The role of the thymus is simply to grow and mature lymphocytes. This organ normally involutes with age, becoming more fibrotic. The immature thymocytes are supported by a network of epithelial cells.

也該介紹下胸腺了。胸腺是胸部的一個小腺體，差不多在胸骨的后面，但是在心臟和肺之前（縱隔區(qū)）。胸腺的作用就是生產(chǎn)、養(yǎng)育淋巴細胞。胸腺一般會隨著年齡的增長而退化，變得更加纖維化。未成熟的胸腺細胞，由上皮細胞供養(yǎng)。

7:30 - As thymocytes mature, they go through two important processes that help guide their sensitivity. In the outer thymus (the cortex), they undergo a process known as positive selection, where they develop a receptor that can recognize foreign antigens. In the inner thymus (the medulla), they undergo negative selection, in which lymphocytes that overreact to self antigens are...selected against. This may mean destruction or development of a form of tolerance known as anergy.

胸腺細胞成熟時會經(jīng)歷兩個重要的過程，用來加強自身的敏感度。在外胸腺里（皮層上），它們會經(jīng)歷‘陽性選擇’，從而產(chǎn)生能辨別外來病原體的接收器。在內(nèi)胸腺里（髓質(zhì)），它們會經(jīng)歷‘陰性選擇’，對自身抗原反應(yīng)過度的淋巴細胞則……不會被選中。陰性選擇會破壞、或者促進免疫耐受性*。

*注：無反應(yīng)性(anergy)，指的是“各種原因?qū)е碌拿庖呒毎麑ο鄳?yīng)抗原失去特異性應(yīng)答能力”?！獊碜园俣劝倏?/p>

11:30 - No wonder killer T-cell has such an aggressive personality; everyone he interacts with in his formative years is a complete dickbag, lol.

怪不得殺手T細胞這么兇巴巴的。成年前他接觸的人都是什么爛玩意，哎呦我去。

12:45 - "Cytolysis" = Cyto (cell) + Lysis (rupturing or destruction), IE the primary means by which killer T-cells cause cell death. They have two primary means of doing this: enzymes such as perforins and granzyme B, which literally punch holes in plasma membranes, and Fas/FasL, a signal that induces apoptosis (literally tells cells to kill themselves).

細胞溶解(cytolysis)這個單詞，就是cyto（細胞）+lysis（分裂或毀掉）；它是殺手T細胞最主要的殺‘胞’手段。方法主要有兩個：1.用酶，比如用穿孔蛋白酶和‘粒酶B’，目的就是在細胞膜上打洞；2.用凋亡相關(guān)因子（Fas/FasL），發(fā)出誘發(fā)“細胞凋亡”的信號——就是讓細胞自己弄死自己。

14:30 - There we go. I'll let wikipedia summarize:

看吧。我直接放維基：

In order to be positively-selected, thymocytes will have to interact with several cell surface molecules, MHC/HLA, to ensure reactivity and specificity. Positive selection eliminates (by apoptosis) weakly-binding cells and only takes strongly- or medium-binding cells.

為了通過陽性選擇，也就是為了能夠辨別病原體，胸腺細胞必須要和一些細胞表層分子‘MHC/HLA’結(jié)合，用來確保自己的反應(yīng)性和針對性。陽性選擇(通過‘細胞凋亡’)會淘汰結(jié)合力弱的細胞，只保留結(jié)合力中等或者強的細胞。

I don't recall quite how many cells survive each individual phase of positive + negative selection, but overall only a few percent make it out of the whole process. Also as I'm watching this, it looks like they have integrated negative selection here as well. Wiki again...

我記不清究竟有多少細胞能各自通過“陽性+陰性”的選擇，但是整個過程完后，留下的應(yīng)該只有百分之幾。而且動畫貌似也弄了陰性選擇的過程。來，維基……

Negative selection is not 100% complete. Some autoreactive T cells escape thymic censorship, and are released into the circulation. Additional mechanisms of tolerance active in the periphery exist to silence these cells such as anergy, deletion, and regulatory T cells.

陰性選擇并非完美。有些"自身免疫性T細胞*"會逃過胸腺的篩選，跑到體液循環(huán)中。這些細胞，之后會被一些“外周耐受”的手段壓制住；這些手段包括無反應(yīng)性、消除、以及調(diào)節(jié)性T細胞。

注：自身免疫性T細胞(autoreactive T cell)，指的是這些T細胞在身體沒病的情況下，就發(fā)動了免疫反應(yīng)。這可能會造成“自體免疫性疾病”(見之前的標(biāo)注)，對身體產(chǎn)生危害。

20:40 - You may be wondering what the relationship between thymic training and the naive T-cell is. T-cells that have undergone positive and negative selection in the thymus are naive T-cells. So it's kind of weird to see the dendritic cell telling the newbies about stories long past...when they have probably just completed that process themselves, lol.

你可能在想，胸腺訓(xùn)練和‘初始T細胞’有什么關(guān)系。T細胞在胸腺中經(jīng)歷了“陽性”和“陰性”選擇之后，就變成初始T細胞。所以，樹狀細胞給這些新兵蛋子翻老黃歷，還是挺奇怪的……因為這些家伙自己，就剛剛經(jīng)歷了這個過程呀。

21:45 - Oh, the platelet piggybacking thing? Let me show you what that looks like in reality.

哦，血小板騎脖子上？現(xiàn)實里是這個樣子的

總結(jié)

A brief overview of the maturation of T-lymphocytes. To be clear, they are called thymocytes until they complete positive and negative selection. To avoid confusion: Although the final steps of maturation happen in the thymus (and later in circulation, especially in lymph nodes), the lymphocytes are "born" in the bone marrow, same as the erythrocyte and granulocytes, and have to migrate to the thymus to complete maturation.

本集簡單地介紹了T淋巴細胞的成長。我得說明一下，T細胞在完成了陽性和陰性選擇后，才可以叫胸腺細胞。還要說明下：盡管胸腺細胞最后成熟于胸腺中（之后還會在循環(huán)系統(tǒng)里成熟，特別是淋巴結(jié)），它們的“出生”地點在骨髓——和紅細胞、粒性白細胞一樣；它們必須要移動到胸腺才能完全成熟。

One thing not explicitly elaborated upon: By the time the T-lymphocyte is released from the thymus, it is committed to the CD4+ (helper) or CD8+ (killer) lineage. When they started, they expressed both markers. Perhaps their conversation at the river's edge was meant to convey that.

動畫里還有件事沒太細說：T淋巴細胞脫離胸腺時，它要么會進入CD4+（輔助性）路線，要么會進入CD8+(殺手性)路線。但最開始，這兩種標(biāo)記它們都會表達。也許殺手T細胞和輔助T細胞在河邊的談話，代表的就是這個路徑選擇。

Sorry again for brevity. Look forward to a bigger post next week.

不好意思，這期只有這么短。期待下周的長貼。

生物類單詞

EP9

regulatory T-cell? ?調(diào)節(jié)性T細胞

helper T-cell? ?輔助T細胞

thymocyte? ? 胸腺細胞

lymphocyte? 淋巴細胞

infectious? 感染性的

adaptive immunity? 適應(yīng)性免疫系統(tǒng)

antigen? 抗原

autoimmune responses? 自發(fā)免疫反應(yīng)

dendritic cell? 樹狀細胞

thymus? 胸腺

thorax? 胸部

sternum? 胸骨 （這三個單詞差的也太多了吧?。。?/p>

fibrotic? 纖維變性的

cortex? ?皮層

medulla? ?髓質(zhì)

anergy? 免疫失能

cytolysis 細胞溶解

perforin? ?穿孔蛋白

apoptosis? ?細胞凋亡

naive T-cell? ?初始T細胞