字幕表 動画を再生する 字幕スクリプトをプリント 翻訳字幕をプリント 英語字幕をプリント Every living being needs to fight off other living beings that want to feast on them. どんな生物でも 天敵と戦わなければならない Every living being needs to fight off other living beings that want to feast on them. 多細胞生物は何十億年もの進化を経て 防衛手段を身に付けた Every living being needs to fight off other living beings that want to feast on them. 今では 人間は高度な防御機構を持つ So as multicellular life evolved over billions of years, it came up with ways to defend itself. 物理的な障壁・防御細胞・武器工場などだ So as multicellular life evolved over billions of years, it came up with ways to defend itself. しかし かなり重要な防御機構なのに あまり知られていないものが一つある So as multicellular life evolved over billions of years, it came up with ways to defend itself. それが「補体系」だ Today humans have a sophisticated defense network, 7億年以上前の進化で獲得した能力で Today humans have a sophisticated defense network, 30種以上のタンパク質の大群が Today humans have a sophisticated defense network, 複雑・華麗な動きで 協調して侵入者を食い止める like physical barriers, defense cells, and weapons factories. およそ1500垓(京の1万倍)個の大群が 今もあなたの体液を満たしている like physical barriers, defense cells, and weapons factories. 化学物質で誘導されると like physical barriers, defense cells, and weapons factories. このタンパク質は 侵入者への超強力な対抗手段となる But one of the most important defenses of our body is largely unknown: 他の免疫システムは 補体系を活性化させるツールに過ぎない But one of the most important defenses of our body is largely unknown: だが同時に危険もはらむ But one of the most important defenses of our body is largely unknown: 今にも爆発する小型爆弾が 血液中に何兆個とあるようなものだ The Complement System そのため我々の細胞は 様々な方法で 補体がうっかり自己を攻撃するのを防いでいる The Complement System では 補体は何をしているのか? なぜそんなに危険なのだろうか? The Complement System 簡単に言うと 補体系の役割は3つある It evolved over 700 million years ago and is an army of over 30 different proteins 敵の無力化、免疫システムの活性化 そして敵に穴を開けて殺すことだ It evolved over 700 million years ago and is an army of over 30 different proteins 「でもどうやって?」 It evolved over 700 million years ago and is an army of over 30 different proteins 「意志や目的地もなく ランダムに漂うただのタンパク質じゃないか」 that work together in a complex and elegant dance to stop intruders. まあ 実はこれも戦略の一部だ that work together in a complex and elegant dance to stop intruders. 補体タンパク質はある種の迎撃態勢で浮遊する that work together in a complex and elegant dance to stop intruders. 活性化して変形するまでは何もしない All in all, about 15 quintillion of them are saturating every fluid in your body right now. タンパク質の世界では 何ができて何ができないかは形が決める All in all, about 15 quintillion of them are saturating every fluid in your body right now. なぜなら 誰に・どのように働きかけるかは 形で決まるからだ All in all, about 15 quintillion of them are saturating every fluid in your body right now. 例えば 不活性状態では特に何も起こらないが Guided by nothing but chemistry, 変形して活性化すると 他のタンパク質に働きかけるようになり Guided by nothing but chemistry, そのタンパク質も形を変えて 以下同様な反応が続く Guided by nothing but chemistry, このような仕組みで 一度始まった反応は急速に広がっていく these proteins are one of the most effective weapons we have against invaders. 補体タンパク質は 密集した何百万本ものマッチのようなものだ these proteins are one of the most effective weapons we have against invaders. 一本に火が付くと 周りのマッチにも火が移り these proteins are one of the most effective weapons we have against invaders. どんどん燃え広がって 一気に大きな炎になる Many other parts of the immune system are just tools to activate the Complement System. 補体系を全て説明するのは やや複雑で気が滅入るので Many other parts of the immune system are just tools to activate the Complement System. かみ砕いて説明する Many other parts of the immune system are just tools to activate the Complement System. 例えば切り傷を負ったとする But it's also really dangerous. 大量の細菌が傷口から入って 周囲の組織に広がっていくだろう But it's also really dangerous. 補体の攻撃は「C3」から始まる But it's also really dangerous. C3は一本目のマッチで 炎の元となる最初の火花だ Imagine having trillions of little bombs inside your blood that could go off at any moment. 火花を発生させるには C3を活性化させる必要がある Imagine having trillions of little bombs inside your blood that could go off at any moment. 仕組みは複雑なのだが Imagine having trillions of little bombs inside your blood that could go off at any moment. ランダムに起こる反応だと言っておこう So our cells use numerous mechanisms to prevent complement from accidentally attacking them. 反応は敵にくっついた別の補体タンパク質や 抗体を通じて起こる So our cells use numerous mechanisms to prevent complement from accidentally attacking them. 重要なのは C3が2つのタンパク質に分離し So our cells use numerous mechanisms to prevent complement from accidentally attacking them. C3aとC3bが活性化することだ Okay, what exactly does it do and what makes it so dangerous? C3から分かれたC3bタンパク質は Okay, what exactly does it do and what makes it so dangerous? ホーミング弾のようなもので Okay, what exactly does it do and what makes it so dangerous? 細菌・菌類・ウイルスに特化している In a nutshell, The Complement System does three things: 標的を探すのに与えられた時間は一瞬で In a nutshell, The Complement System does three things: それを過ぎると水分子で不活性化される In a nutshell, The Complement System does three things: C3bが標的を見つけると it cripples enemies, it activates the immune system, and it rips holes in things until they die. 標的の表面上で強力に固定され 離れないようになる it cripples enemies, it activates the immune system, and it rips holes in things until they die. そうすると タンパク質は再び変形する it cripples enemies, it activates the immune system, and it rips holes in things until they die. 新しい形になると 他のタンパク質と結合し But, how? 小規模の反応が始まる But, how? 形は次々に変わっていき 他の補体タンパク質と一体化していく But, how? 最終的には 「C3コンバターゼ」で知られる再生産工場に変形する After all, these are mindless proteins randomly drifting around without will or direction. この工場は C3の一連の反応を促進させるのに特化している After all, these are mindless proteins randomly drifting around without will or direction. こうして増幅ループが始まり After all, these are mindless proteins randomly drifting around without will or direction. 間もなく何千ものタンパク質が細菌を覆う Well, this is actually part of the strategy. 細菌にとっては大変よろしくない事態だ Well, this is actually part of the strategy. 体にまとわりつかれて 無力化ないし消耗させられるからだ Well, this is actually part of the strategy. 何千匹ものハエに覆われていると想像すればいい Complement proteins float around in a sort-of passive mode. だが、思い出してほしい Complement proteins float around in a sort-of passive mode. C3の分身はまだ他にもあった Complement proteins float around in a sort-of passive mode. そう、「C3aタンパク質」だ They do nothing, until they get activated and change their shape. C3aは救難信号のようなものだ They do nothing, until they get activated and change their shape. 何千ものC3aが流れていき 戦場から離れた場所に危険を知らせる They do nothing, until they get activated and change their shape. 免疫細胞がC3aタンパク質を感知すると In the world of proteins, your shape determines what you can and cannot do. 眠りから覚め C3bタンパク質を辿って 感染部位まで移動する In the world of proteins, your shape determines what you can and cannot do. 細胞が出会うC3bが多いほど 細胞はより活性化する In the world of proteins, your shape determines what you can and cannot do. こうして 補体が援軍を適材適所へと導く Because shape determines what you can interact with and in what way. ここまでは 補体は侵入者の動きを鈍くさせるか 助けを呼んでくるだけだったが Because shape determines what you can interact with and in what way. ここからは 補体も積極的に敵の処分を支援し始める Because shape determines what you can interact with and in what way. 戦場に真っ先に到着する免疫細胞は「食細胞」だ For example, in your passive shape you might do nothing. この細胞は敵を丸々飲み込むと For example, in your passive shape you might do nothing. 小さな檻に閉じ込めたまま 酸で溶かして殺す For example, in your passive shape you might do nothing. しかし 飲み込むには敵を掴む必要がある In your active shape, however, you might, for example, change the shape of other proteins 細菌はツルツルで掴みにくいので そう簡単ではない In your active shape, however, you might, for example, change the shape of other proteins だが細菌に固定された補体が一種の接着剤として働き In your active shape, however, you might, for example, change the shape of other proteins 免疫細胞が標的を捕まえるのを容易にする activating them so they can activate others. しかしこれだけでは終わらない activating them so they can activate others. ハエの例えを思い出そう activating them so they can activate others. ハエがハチになったらどうなるだろう Mechanisms like this one can start cascades that spread very quickly. 反応経路は他にもある Mechanisms like this one can start cascades that spread very quickly. 細胞表面のC3コンバターゼがその形を再び変えて Mechanisms like this one can start cascades that spread very quickly. 新しいタンパク質を呼び込み始める Imagine the complement proteins as being like millions of matches very close together. それらはより大きな構造体を構築する Imagine the complement proteins as being like millions of matches very close together. それが「膜侵襲複合体」だ Imagine the complement proteins as being like millions of matches very close together. 長槍のような形をした別のタンパク質が 一本ずつやってきて Once one catches fire, it ignites the ones around it. 絶対に塞げない程の穴が開くまで Once one catches fire, it ignites the ones around it. 細菌の細胞膜深くに打ち込まれていく Once one catches fire, it ignites the ones around it. 液体が外から内に流れ込み 細菌の中身が外に漏れ出てくる They ignite more and suddenly you have a big fire. 細菌の出血死だ They ignite more and suddenly you have a big fire. 残りの細菌も攻撃してくる補体に気を取られ They ignite more and suddenly you have a big fire. 到着した免疫細胞に素早く処理される To show the actual mechanisms of The Complement System is a tad complicated and overwhelming. 大事に至る前に 侵入者を早い段階で潰すことができた To show the actual mechanisms of The Complement System is a tad complicated and overwhelming. まあ本人は知る由もない To show the actual mechanisms of The Complement System is a tad complicated and overwhelming. 細菌は補体のことを快く思わないが So, we'll simplify here. 補体はウイルスにこそ最も効果的に働く So, we'll simplify here. ウイルスには弱点が一つある 細胞から細胞へと移動しなければならないことだ So, we'll simplify here. 細胞外ではランダムに細胞にぶつかっていくので 感染するかどうかは運次第だ Now, let's imagine you cut yourself and a bunch of bacteria enter the wound 細胞外では全く無防備なので Now, let's imagine you cut yourself and a bunch of bacteria enter the wound ウイルスは補体に迎撃・無力化され Now, let's imagine you cut yourself and a bunch of bacteria enter the wound 無害化されたのちに 免疫システムに導かれ貪食される and make it into the surrounding tissue. 補体が無ければ ウイルス感染はもっと致命的だったであろう and make it into the surrounding tissue. しかし 補体がそれほど強力なら どうして病気に罹るのか and make it into the surrounding tissue. 理由は 敵も補体に対抗してくるからだ Our complement attack begins with C3. 例えば ワクシニアウイルスは細胞に感染すると Our complement attack begins with C3. 補体を不活化させるタンパク質を細胞に産生させる Our complement attack begins with C3. こうして 感染細胞の周りに ウイルスの安全地帯が出来上がる C3 is the first match, the initial spark that will start our fire. 細胞は死滅し感染は広がるので 症状が出る可能性は高くなる C3 is the first match, the initial spark that will start our fire. 補体系を鎮静化させる物質を血中から横取りし 透明になってやり過ごす細菌もいる C3 is the first match, the initial spark that will start our fire. 要するに 補体系はとても重要だが And to do that, C3 needs to switch from passive to active. 複雑で美しい免疫システムを組織する 一構成員に過ぎない And to do that, C3 needs to switch from passive to active. 「個々では弱くとも協力すれば知性を発揮できる」 And to do that, C3 needs to switch from passive to active. 免疫システムは我々にそう教えてくれる How this happens is complex, but let's just say it can happen randomly この動画はあなたの支援で制作できています How this happens is complex, but let's just say it can happen randomly あなたの直接の支援が無ければ このチャンネルは立ち行かなかったでしょう How this happens is complex, but let's just say it can happen randomly そのことには本当に感謝してもしきれません through other complement proteins that bind to enemies or through antibodies. 2019年は kurzgesagtの動画を一本制作するのに 最低でも1200時間はかかりました through other complement proteins that bind to enemies or through antibodies. 私たちは数ヶ月かけて 調査・草稿の作成・専門家との協議 through other complement proteins that bind to enemies or through antibodies. 全イラスト・アニメーションの作成 オリジナル音声の作成をこなします All you really need to know is that C3 breaks into two smaller proteins, これもひとえにスポンサーの方々や All you really need to know is that C3 breaks into two smaller proteins, Patreonで寄付して下さる視聴者の方 All you really need to know is that C3 breaks into two smaller proteins, 補体系をテーマにしたポスターやポストカードなどを 購入して下さる方々のおかげです C3a and C3b, that are now activated. もし支援して下さるのなら C3a and C3b, that are now activated. 動画を見たり Patreonで寄付したり できればパーソナルバードをゲットしたりして下さい C3a and C3b, that are now activated. カレンダーやポスターを購入して下さるだけでも 励みになります One of these parts, the C3b protein, is like a seeker missile specialized in bacteria, fungi, and viruses. Kurzgesagtの意義は 精一杯制作した最高の動画を通して One of these parts, the C3b protein, is like a seeker missile specialized in bacteria, fungi, and viruses. 科学にもっと親しみを持ってもらうことです One of these parts, the C3b protein, is like a seeker missile specialized in bacteria, fungi, and viruses. いつも応援してくださりありがとうございます 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.