第9集 - 胸腺细胞

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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.

现在就让我推更下……下周我会做‘调节性T细胞’和‘辅助T细胞’的介绍。

译者注：作者那周很忙，就没有写角色介绍。

另：胸腺细胞，就是还没有完全成熟的各种T细胞。也是本集的主角们

Episode 9 - Thymocytes

第九集 - 胸腺细胞

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.

杀手T细胞把‘适应性免疫系统’叫做身体的‘最后一道防线’。高，实在是高。任何能够突破适应性免疫系统的感染源，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.

这房间是啥地方？还装满了标着‘抗原’的书？免疫系统的确会记住自己曾碰到过的外界抗原，但它是通过‘记忆细胞’记住的。

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，调节性T细胞（T-reg）是什么人呢？我下周会更详细讲它们；简单来说，T-reg是淋巴细胞的一种，主要作用是抑制免疫反应，特别是针对‘自身’细胞的免疫反应。它们的重要性，可以从“IPEX症候群”中看出来。这个病会让T-reg的重要转录因子病变；没有转录因子的正常运作，病人就会产生错误的自发免疫反应*， 从而染上皮肤病、器官病、内分泌失调。

注：免疫细胞攻击正常细胞时，就会发生“自身免疫性疾病”，属于人体异常的免疫反应。这种疾病包括红斑狼疮（又叫蝴蝶斑），1型糖尿病等等。

这段话的大概意思是，如果调节性T细胞出了问题，它就不能让异常的免疫细胞闭嘴。

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，对了，树状细胞的确可以活过好几代淋巴细胞。让他演智慧的长者，挺合适。

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.

也该介绍下胸腺了。胸腺是胸部的一个小腺体，差不多在胸骨的后面，但是在心脏和肺之前（纵隔区）。胸腺的作用就是生产、养育淋巴细胞。胸腺一般会随着年龄的增长而退化，变得更加纤维化。未成熟的胸腺细胞，由上皮细胞供养。

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.

胸腺细胞成熟时会经历两个重要的过程，用来加强自身的敏感度。在外胸腺里（皮层上），它们会经历‘阳性选择’，从而产生能辨别外来病原体的接收器。在内胸腺里（髓质），它们会经历‘阴性选择’，对自身抗原反应过度的淋巴细胞则……不会被选中。阴性选择会破坏、或者促进免疫耐受性*。

*注：无反应性(anergy)，指的是“各种原因导致的免疫细胞对相应抗原失去特异性应答能力”。——来自百度百科

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.

怪不得杀手T细胞这么凶巴巴的。成年前他接触的人都是什么烂玩意，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).

细胞溶解(cytolysis)这个单词，就是cyto（细胞）+lysis（分裂或毁掉）；它是杀手T细胞最主要的杀‘胞’手段。方法主要有两个：1.用酶，比如用穿孔蛋白酶和‘粒酶B’，目的就是在细胞膜上打洞；2.用凋亡相关因子（Fas/FasL），发出诱发“细胞凋亡”的信号——就是让细胞自己弄死自己。

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

看吧。我直接放维基：

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.

为了通过阳性选择，也就是为了能够辨别病原体，胸腺细胞必须要和一些细胞表层分子‘MHC/HLA’结合，用来确保自己的反应性和针对性。阳性选择(通过‘细胞凋亡’)会淘汰结合力弱的细胞，只保留结合力中等或者强的细胞。

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...

我记不清究竟有多少细胞能各自通过“阳性+阴性”的选择，但是整个过程完后，留下的应该只有百分之几。而且动画貌似也弄了阴性选择的过程。来，维基……

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.

阴性选择并非完美。有些"自身免疫性T细胞*"会逃过胸腺的筛选，跑到体液循环中。这些细胞，之后会被一些“外周耐受”的手段压制住；这些手段包括无反应性、消除、以及调节性T细胞。

注：自身免疫性T细胞(autoreactive T cell)，指的是这些T细胞在身体没病的情况下，就发动了免疫反应。这可能会造成“自体免疫性疾病”(见之前的标注)，对身体产生危害。

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，胸腺训练和‘初始T细胞’有什么关系。T细胞在胸腺中经历了“阳性”和“阴性”选择之后，就变成初始T细胞。所以，树状细胞给这些新兵蛋子翻老黄历，还是挺奇怪的……因为这些家伙自己，就刚刚经历了这个过程呀。

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

哦，血小板骑脖子上？现实里是这个样子的

总结

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.

本集简单地介绍了T淋巴细胞的成长。我得说明一下，T细胞在完成了阳性和阴性选择后，才可以叫胸腺细胞。还要说明下：尽管胸腺细胞最后成熟于胸腺中（之后还会在循环系统里成熟，特别是淋巴结），它们的“出生”地点在骨髓——和红细胞、粒性白细胞一样；它们必须要移动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.

动画里还有件事没太细说：T淋巴细胞脱离胸腺时，它要么会进入CD4+（辅助性）路线，要么会进入CD8+(杀手性)路线。但最开始，这两种标记它们都会表达。也许杀手T细胞和辅助T细胞在河边的谈话，代表的就是这个路径选择。

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

不好意思，这期只有这么短。期待下周的长贴。

生物类单词

EP9

regulatory T-cell   调节性T细胞

helper T-cell   辅助T细胞

thymocyte    胸腺细胞

lymphocyte  淋巴细胞

infectious  感染性的

adaptive immunity  适应性免疫系统

antigen  抗原

autoimmune responses  自发免疫反应

dendritic cell  树状细胞

thymus  胸腺

thorax  胸部

sternum  胸骨 （这三个单词差的也太多了吧！！）

fibrotic  纤维变性的

cortex   皮层

medulla   髓质

anergy  免疫失能

cytolysis 细胞溶解

perforin   穿孔蛋白

apoptosis   细胞凋亡

naive T-cell   初始T细胞