字幕列表 影片播放 列印所有字幕 列印翻譯字幕 列印英文字幕 Every living being needs to fight off other living beings that want to feast on them. 每個生物都需要與那些以他們為食的生物對抗 Every living being needs to fight off other living beings that want to feast on them. 所以在多細胞生物經過了數億年的演化後, 也衍生出了保護自己的方法 Every living being needs to fight off other living beings that want to feast on them. 現今,人類擁有複雜的防禦系統 So as multicellular life evolved over billions of years, it came up with ways to defend itself. 像是物理屏障(皮膚)、防禦細胞(巨噬細胞), 以及武器生產工廠(B細胞) So as multicellular life evolved over billions of years, it came up with ways to defend itself. 其中一個我們身體裡 但大多都還不太瞭解的防禦系統: So as multicellular life evolved over billions of years, it came up with ways to defend itself. 補體系統 Today humans have a sophisticated defense network, 它已經演化超過7億年, 也是超過30種不同蛋白質的武裝軍隊 Today humans have a sophisticated defense network, 他們合作跳起一支複雜而優雅的舞步, 來阻止外來入侵者 Today humans have a sophisticated defense network, 總而言之,現在大約有1千5百萬兆的補體蛋白 充斥在你全身上下的液體當中 like physical barriers, defense cells, and weapons factories. 指引他們的沒有別的,全是化學 like physical barriers, defense cells, and weapons factories. 這些蛋白質是我們用來對抗入侵者的武器中 最有效的其中一種 like physical barriers, defense cells, and weapons factories. 免疫系統中的許多部份, 都只是用來活化補體系統的工具 But one of the most important defenses of our body is largely unknown: 但他同時也充滿危險性 But one of the most important defenses of our body is largely unknown: 想像一下,在你的血液中,有數兆個小炸彈 而他們隨時都有可能會爆炸 But one of the most important defenses of our body is largely unknown: 因此,我們的細胞用多種機制來防止補體意外的攻擊 The Complement System 好,那他們又有什麼功用?又是為什麼讓他們看起來這麼危險呢? The Complement System 簡而言之,補體系統有3樣工作。 The Complement System 它會癱瘓敵人, 它會啟動免疫系統 它會在菌體上鑿洞直到它們死亡 It evolved over 700 million years ago and is an army of over 30 different proteins 但是,要怎麼做? It evolved over 700 million years ago and is an army of over 30 different proteins 畢竟,這些無意識的蛋白質們會隨意飄動 沒有任何目的或方向 It evolved over 700 million years ago and is an army of over 30 different proteins 實際上這算是一種戰略 that work together in a complex and elegant dance to stop intruders. 隨意飄動的補體蛋白處於一種被動狀態 that work together in a complex and elegant dance to stop intruders. 他們沒有任何影響力,直到他們被啟動 並且改變他們的形狀 that work together in a complex and elegant dance to stop intruders. 在蛋白質的世界裡,你的形狀決定了什麼事情你可以做 什麼事情你不能做 All in all, about 15 quintillion of them are saturating every fluid in your body right now. 因為形狀決定了可以互動的對象和方式 All in all, about 15 quintillion of them are saturating every fluid in your body right now. 舉例來說,處於被動狀態的形狀下 你可能不會有任何的功能 All in all, about 15 quintillion of them are saturating every fluid in your body right now. 然而,在你啟動的狀態下 你可能可以啟動其他蛋白質的形體 Guided by nothing but chemistry, 藉此啟動他們,讓他們也可以啟動其他蛋白 Guided by nothing but chemistry, 像這樣的串聯反應的機制可以快速地擴散出去 Guided by nothing but chemistry, 想像一下這些補體蛋白就像一組互相放的很近的火柴 these proteins are one of the most effective weapons we have against invaders. 一但其中一根火柴起火了 它會立即點燃其他根靠近它的火柴 these proteins are one of the most effective weapons we have against invaders. 當它點燃的越多,突然間你就有可以有一團大火 these proteins are one of the most effective weapons we have against invaders. 要列舉出補體系統的實際機制和樣貌會很複雜 Many other parts of the immune system are just tools to activate the Complement System. 所以我們在此會簡化它們 Many other parts of the immune system are just tools to activate the Complement System. 現在,想像一下你不小心劃傷了自己 有一群細菌從傷口的位置 Many other parts of the immune system are just tools to activate the Complement System. 進入了周圍組織 But it's also really dangerous. 補體系統C3 就會開始進行攻擊 But it's also really dangerous. C3就會是最開始的火花,可以點燃我們的火團 But it's also really dangerous. 要點燃他,C3必須得要從被動狀態切換成啟動狀態 Imagine having trillions of little bombs inside your blood that could go off at any moment. 要解釋它如何啟動是有點複雜 在這邊當成它是隨機的 Imagine having trillions of little bombs inside your blood that could go off at any moment. 通過其他被細菌啟動的補體蛋白,或從抗體啟動的 Imagine having trillions of little bombs inside your blood that could go off at any moment. 現在你要知道C3已經分裂成2個比較小的蛋白質 So our cells use numerous mechanisms to prevent complement from accidentally attacking them. 已經被啟動的C3a和C3b So our cells use numerous mechanisms to prevent complement from accidentally attacking them. 其中一個部分,蛋白質C3b會像一個追蹤導彈一樣 尋找特定的細菌、真菌和病毒 So our cells use numerous mechanisms to prevent complement from accidentally attacking them. 它只有不到一秒鐘的時間來找到它的敵人 不然它就會被水分子中和掉 Okay, what exactly does it do and what makes it so dangerous? 假設C3b找到一個目標 它會將自己緊緊的固定在敵人的表面且不會鬆開 Okay, what exactly does it do and what makes it so dangerous? 通過這樣做以後,蛋白質會再次變換形狀 Okay, what exactly does it do and what makes it so dangerous? 藉由這個新的形狀,它現在可以與其它蛋白質做連結 並且在啟動比較小的串聯反應 In a nutshell, The Complement System does three things: 經過多次變換它的形狀,來增加其他蛋白質在它身上 In a nutshell, The Complement System does three things: 最後,它會將它自己轉變成一個名為C3 Convertase 的招收平台 In a nutshell, The Complement System does three things: 這個專門的平台,可以將更多C3蛋白質轉換 並且重新開始整個循環 it cripples enemies, it activates the immune system, and it rips holes in things until they die. 一個增幅循環開始了 it cripples enemies, it activates the immune system, and it rips holes in things until they die. 不用多久,成千的蛋白質就包覆著細菌了 it cripples enemies, it activates the immune system, and it rips holes in things until they die. 對菌體來說,這對它非常的不利 But, how? 它們會削弱這個菌體,讓他們無法求助或是緩慢它們 But, how? 想像被好幾千隻的蒼蠅包覆著的感覺 But, how? 還不只這些呢! After all, these are mindless proteins randomly drifting around without will or direction. 你還記得C3的另一部分嗎? C3a蛋白質 After all, these are mindless proteins randomly drifting around without will or direction. C3a就像是一個求救信標 After all, these are mindless proteins randomly drifting around without will or direction. 成千上萬的湧出戰場,引起大量的注意 Well, this is actually part of the strategy. 被動的免疫細胞注意到這些C3a以後 Well, this is actually part of the strategy. 會從休眠狀態甦醒過來 並且跟著蛋白質的軌跡到達感染的部位 Well, this is actually part of the strategy. 當接觸到越多的求救信標蛋白,它們就會越具有侵略性 Complement proteins float around in a sort-of passive mode. 用這種方式 補體蛋白可以正確的引導他們到最需要增援的地方 Complement proteins float around in a sort-of passive mode. 到現在,補體蛋白已經成功求救並拖住入侵者了 Complement proteins float around in a sort-of passive mode. 現在開始,它們要開始積極地幫助到殺死敵人 They do nothing, until they get activated and change their shape. 第一批到達戰場的免疫細胞是吞噬細胞 They do nothing, until they get activated and change their shape. 這代表著,吞噬細胞會把你整個吞掉 把你關在一個小監牢裡,再用酸殺掉你 They do nothing, until they get activated and change their shape. 但是要吞掉一個敵人,它們必須要先抓到敵人才行 In the world of proteins, your shape determines what you can and cannot do. 這不太簡單,因為細菌不喜歡被抓住,而且它們滑滑的 In the world of proteins, your shape determines what you can and cannot do. 但是現在,補體蛋白已經將自己固定在細菌身上 In the world of proteins, your shape determines what you can and cannot do. 當作一個像是膠水一樣 讓免疫細胞可以輕易抓住它們的敵人 Because shape determines what you can interact with and in what way. 更好的是 Because shape determines what you can interact with and in what way. 想像一下! 你又一次被一堆蒼蠅給包覆著 Because shape determines what you can interact with and in what way. 現在,這些蒼蠅變成了黃蜂 For example, in your passive shape you might do nothing. 另一個串聯反應要開始了 For example, in your passive shape you might do nothing. 另一個串聯反應要開始了 For example, in your passive shape you might do nothing. 在這個菌體的表面,C3 Convertase 再次地變換它的形狀 In your active shape, however, you might, for example, change the shape of other proteins 並且開始招募新的蛋白質 In your active shape, however, you might, for example, change the shape of other proteins 他們會變成一個比較大的結構: 膜攻擊複合物 In your active shape, however, you might, for example, change the shape of other proteins 一片一片的,新的蛋白質(C9)將長得像矛的自己扎進細菌膜裡 activating them so they can activate others. 直到他們撐開出無法修復的大洞 activating them so they can activate others. 流體衝入菌體以後,他們的內部也就隨之溢出 activating them so they can activate others. 如同流血致死 Mechanisms like this one can start cascades that spread very quickly. 剩下的菌體也因為被補體騷擾而分心,甚至重傷 Mechanisms like this one can start cascades that spread very quickly. 馬上就被到場的免疫細胞給解決掉了 Mechanisms like this one can start cascades that spread very quickly. 在入侵變得更危險之前,這次的攻擊行動就已經被剷除了 Imagine the complement proteins as being like millions of matches very close together. 你可能都還沒有注意到 Imagine the complement proteins as being like millions of matches very close together. 細菌也只是很不喜歡補體而已 Imagine the complement proteins as being like millions of matches very close together. 實際上補體對抗病毒更為有效 Once one catches fire, it ignites the ones around it. 病毒有一個大問題,它們必須得要在細胞之間移動 Once one catches fire, it ignites the ones around it. 病毒在細胞外基本上以只能祈禱希望以極小的機率撞到且感染細胞 Once one catches fire, it ignites the ones around it. 在這裡,他們是完全沒有防禦的 They ignite more and suddenly you have a big fire. 在此,補體就可以直接攔截並削弱他們 They ignite more and suddenly you have a big fire. 讓它們變得無害並引導免疫系統來吞噬它們 They ignite more and suddenly you have a big fire. 如果沒有補體,病毒感染會變得非常致命 To show the actual mechanisms of The Complement System is a tad complicated and overwhelming. 等等,如果我們有這麼有效的武器 為什麼我們還會生病? To show the actual mechanisms of The Complement System is a tad complicated and overwhelming. 問題是在戰爭之中,雙方都會互相適應 To show the actual mechanisms of The Complement System is a tad complicated and overwhelming. 舉例來說,當牛痘病毒感染了一個細胞時 So, we'll simplify here. 它會強迫細胞制造出一種蛋白質來關閉補體蛋白 So, we'll simplify here. 用這種方式,病毒能夠在被感染的細胞周圍 形成一個安全區 So, we'll simplify here. 當病毒殺死這個細胞以後 可以有更高的機率感染附近其他的健康細胞 Now, let's imagine you cut yourself and a bunch of bacteria enter the wound 或是像其他的細菌,舉例來說,它可以從血液裡抓取一些特定的分子,不觸發補體系統 Now, let's imagine you cut yourself and a bunch of bacteria enter the wound 進而達成隱形的效果 Now, let's imagine you cut yourself and a bunch of bacteria enter the wound 所以補體系統,是非常非常重要的 and make it into the surrounding tissue. 但是它在我們美麗並且複雜的免疫系統組織之中 只是其中一員 and make it into the surrounding tissue. 這是一個無意識的小東東 卻可以一起做一些聰明合作的漂亮例子 and make it into the surrounding tissue. 這個影片是由 你 來贊助的 Our complement attack begins with C3. 沒有你的直接支持,這個頻道就不會存在 Our complement attack begins with C3. 而且非常難形容我們對此的感激之情 Our complement attack begins with C3. 在2019年 每一部kurzgesagt的影片至少要花1200小時來製造 C3 is the first match, the initial spark that will start our fire. 我們要花上好幾個月來做研究及 寫腳本並向專家們確認 C3 is the first match, the initial spark that will start our fire. 並且製做一張一張的插圖、製成動畫 再加入原創的音樂 C3 is the first match, the initial spark that will start our fire. 依靠著贊助商 And to do that, C3 needs to switch from passive to active. 你們在Patreon上的支持還有販賣一些周邊 才有可以達成 And to do that, C3 needs to switch from passive to active. 像是我們製作了補體系統的張海報和明信片 And to do that, C3 needs to switch from passive to active. 如果你有興趣,想要支持我們 How this happens is complex, but let's just say it can happen randomly 你可以觀看我們的影片 訂閱Patreon並且製作一隻專屬於你的小鳥鳥 How this happens is complex, but let's just say it can happen randomly 或是購買我們的日曆或海報 How this happens is complex, but let's just say it can happen randomly 製作最好的影片 through other complement proteins that bind to enemies or through antibodies. 和讓科學更靠近我們的生活 是kurzgesagt的宗旨 through other complement proteins that bind to enemies or through antibodies. 謝謝你讓這一切變得可能 through other complement proteins that bind to enemies or through antibodies. All you really need to know is that C3 breaks into two smaller proteins, All you really need to know is that C3 breaks into two smaller proteins, All you really need to know is that C3 breaks into two smaller proteins, C3a and C3b, that are now activated. C3a and C3b, that are now activated. C3a and C3b, that are now activated. One of these parts, the C3b protein, is like a seeker missile specialized in bacteria, fungi, and viruses. One of these parts, the C3b protein, is like a seeker missile specialized in bacteria, fungi, and viruses. One of these parts, the C3b protein, is like a seeker missile specialized in bacteria, fungi, and viruses. It has a fraction of a second to find a victim or it will be neutralized by water molecules. It has a fraction of a second to find a victim or it will be neutralized by water molecules. It has a fraction of a second to find a victim or it will be neutralized by water molecules. If C3b does find a target, it anchors itself very tightly to its surface and doesn't let go. If C3b does find a target, it anchors itself very tightly to its surface and doesn't let go. If C3b does find a target, it anchors itself very tightly to its surface and doesn't let go. By doing so, the protein changes its shape again. By doing so, the protein changes its shape again. By doing so, the protein changes its shape again. In its new shape, it's now able to grab other proteins and start a small cascade, In its new shape, it's now able to grab other proteins and start a small cascade, In its new shape, it's now able to grab other proteins and start a small cascade, changing its shape multiple times, adding other complement proteins to itself. changing its shape multiple times, adding other complement proteins to itself. changing its shape multiple times, adding other complement proteins to itself. Finally, it transforms itself into a recruiting platform known as C3 Convertase. Finally, it transforms itself into a recruiting platform known as C3 Convertase. Finally, it transforms itself into a recruiting platform known as C3 Convertase. This platform is an expert at activating more C3 proteins that start the whole cycle anew. This platform is an expert at activating more C3 proteins that start the whole cycle anew. This platform is an expert at activating more C3 proteins that start the whole cycle anew. An amplification loop begins. An amplification loop begins. An amplification loop begins. Soon, thousands of proteins cover the bacteria. Soon, thousands of proteins cover the bacteria. Soon, thousands of proteins cover the bacteria. For the bacteria, this is very bad. For the bacteria, this is very bad. For the bacteria, this is very bad. It can cripple the bacteria and make them helpless, or slow them down. It can cripple the bacteria and make them helpless, or slow them down. It can cripple the bacteria and make them helpless, or slow them down. Imagine being covered by thousands of flies. Imagine being covered by thousands of flies. Imagine being covered by thousands of flies. But, there's more. But, there's more. But, there's more. Do you remember the other part of C3—the C3a protein? Do you remember the other part of C3—the C3a protein? Do you remember the other part of C3—the C3a protein? C3a is like a distress beacon. C3a is like a distress beacon. C3a is like a distress beacon. Thousands of them flood away from the site of battle screaming for attention. Thousands of them flood away from the site of battle screaming for attention. Thousands of them flood away from the site of battle screaming for attention. Passive immune cells notice the C3a proteins, Passive immune cells notice the C3a proteins, Passive immune cells notice the C3a proteins, and awaken from their slumber to follow the protein tracks to the site of infection. and awaken from their slumber to follow the protein tracks to the site of infection. and awaken from their slumber to follow the protein tracks to the site of infection. The more alarm proteins they encounter, the more aggressive they get. The more alarm proteins they encounter, the more aggressive they get. The more alarm proteins they encounter, the more aggressive they get. This way, complement guides reinforcements exactly to the place where they're needed the most. This way, complement guides reinforcements exactly to the place where they're needed the most. This way, complement guides reinforcements exactly to the place where they're needed the most. So far, the complement has slowed down the invaders and called for help. So far, the complement has slowed down the invaders and called for help. So far, the complement has slowed down the invaders and called for help. Now, it's beginning to actively help to kill the enemy. Now, it's beginning to actively help to kill the enemy. Now, it's beginning to actively help to kill the enemy. The first immune cells to arrive at the battlefield are phagocytes. The first immune cells to arrive at the battlefield are phagocytes. The first immune cells to arrive at the battlefield are phagocytes. Which means, cells that swallow you whole, trap you in a tiny prison, and then kill you with acid. Which means, cells that swallow you whole, trap you in a tiny prison, and then kill you with acid. Which means, cells that swallow you whole, trap you in a tiny prison, and then kill you with acid. But, to swallow an enemy, they need to grab it first. But, to swallow an enemy, they need to grab it first. But, to swallow an enemy, they need to grab it first. Which is not easy because bacteria prefer not to be grabbed and are sort-of slippery. Which is not easy because bacteria prefer not to be grabbed and are sort-of slippery. Which is not easy because bacteria prefer not to be grabbed and are sort-of slippery. But now, the complement that has anchored itself to the bacteria But now, the complement that has anchored itself to the bacteria But now, the complement that has anchored itself to the bacteria acts as a sort-of glue that makes it easy for the immune cells to catch their victims. acts as a sort-of glue that makes it easy for the immune cells to catch their victims. acts as a sort-of glue that makes it easy for the immune cells to catch their victims. But it gets even better. But it gets even better. But it gets even better. Imagine being covered in flies again. Imagine being covered in flies again. Imagine being covered in flies again. Now, imagine them turning into wasps. Now, imagine them turning into wasps. Now, imagine them turning into wasps. Another cascade is about to begin. Another cascade is about to begin. Another cascade is about to begin. On the surface of a bacteria, the C3 recruitment platform changes its shape again On the surface of a bacteria, the C3 recruitment platform changes its shape again On the surface of a bacteria, the C3 recruitment platform changes its shape again and begins to recruit new proteins. and begins to recruit new proteins. and begins to recruit new proteins. Together, they begin the construction of a bigger structure: a Membrane Attack Complex. Together, they begin the construction of a bigger structure: a Membrane Attack Complex. Together, they begin the construction of a bigger structure: a Membrane Attack Complex. Piece-by-piece, new proteins shaped like long spears anchor themselves deep into the bacteria's membranes, Piece-by-piece, new proteins shaped like long spears anchor themselves deep into the bacteria's membranes, Piece-by-piece, new proteins shaped like long spears anchor themselves deep into the bacteria's membranes, until they rip a hole into them that can't be closed again. until they rip a hole into them that can't be closed again. until they rip a hole into them that can't be closed again. Fluids rush into the bacteria and their insides spill out. Fluids rush into the bacteria and their insides spill out. Fluids rush into the bacteria and their insides spill out. They bleed to death. They bleed to death. They bleed to death. The remaining bacteria are maimed and distracted by the complement, The remaining bacteria are maimed and distracted by the complement, The remaining bacteria are maimed and distracted by the complement, and quickly taken care of by the arriving immune cells. and quickly taken care of by the arriving immune cells. and quickly taken care of by the arriving immune cells. The invasion has been nipped in the bud before it had the opportunity to become dangerous. The invasion has been nipped in the bud before it had the opportunity to become dangerous. The invasion has been nipped in the bud before it had the opportunity to become dangerous. You probably didn't even notice it. You probably didn't even notice it. You probably didn't even notice it. But while bacteria are not happy about complement, But while bacteria are not happy about complement, But while bacteria are not happy about complement, the enemies it might be the most useful against are actually viruses. the enemies it might be the most useful against are actually viruses. the enemies it might be the most useful against are actually viruses. Viruses have one problem: they need to travel from cell to cell. Viruses have one problem: they need to travel from cell to cell. Viruses have one problem: they need to travel from cell to cell. Outside of cells, they're basically hoping to randomly bump against a cell to infect by pure chance. Outside of cells, they're basically hoping to randomly bump against a cell to infect by pure chance. Outside of cells, they're basically hoping to randomly bump against a cell to infect by pure chance. Here, they're completely defenseless. Here, they're completely defenseless. Here, they're completely defenseless. And here, complement is able to intercept and cripple them, And here, complement is able to intercept and cripple them, And here, complement is able to intercept and cripple them, so they become harmless and guide the immune system to devour them. so they become harmless and guide the immune system to devour them. so they become harmless and guide the immune system to devour them. Without complement, virus infections would be a lot more deadly. Without complement, virus infections would be a lot more deadly. Without complement, virus infections would be a lot more deadly. But wait, if we have such an effective weapon, why do we ever get sick? But wait, if we have such an effective weapon, why do we ever get sick? But wait, if we have such an effective weapon, why do we ever get sick? The problem is that in a war, both sides adapt. The problem is that in a war, both sides adapt. The problem is that in a war, both sides adapt. For example, when the vaccinia virus infects a cell, For example, when the vaccinia virus infects a cell, For example, when the vaccinia virus infects a cell, it forces it to produce a protein that shuts complement activation down. it forces it to produce a protein that shuts complement activation down. it forces it to produce a protein that shuts complement activation down. This way, the virus creates safe zones around the cells it infects. This way, the virus creates safe zones around the cells it infects. This way, the virus creates safe zones around the cells it infects. When it kills them, and tries to infect more, it has a higher chance of being successful. When it kills them, and tries to infect more, it has a higher chance of being successful. When it kills them, and tries to infect more, it has a higher chance of being successful. Or some bacteria, for example, can grab certain molecules from the blood that keep the complement system calm Or some bacteria, for example, can grab certain molecules from the blood that keep the complement system calm Or some bacteria, for example, can grab certain molecules from the blood that keep the complement system calm and make themselves invisible. and make themselves invisible. and make themselves invisible. So the complement system, while being extremely important, So the complement system, while being extremely important, So the complement system, while being extremely important, is only one player in the complex and beautiful organization that is our immune system. is only one player in the complex and beautiful organization that is our immune system. is only one player in the complex and beautiful organization that is our immune system. A beautiful example of how many mindless things can do smart things together. 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B1 中級 中文 美國腔 蛋白質 細胞 啟動 免疫 細菌 病毒 血液中的小炸彈--------補充系統 (Tiny Bombs in your Blood - The Complement System) 51 6 ally.chang 發佈於 2021 年 01 月 14 日 更多分享 分享 收藏 回報 影片單字