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  • Every living being needs to fight off other living beings that want to feast on them.​

  • Every living being needs to fight off other living beings that want to feast on them.​

  • Every living being needs to fight off other living beings that want to feast on them.​

  • So as multicellular life evolved over billions of years, it came up with ways to defend itself.​

  • So as multicellular life evolved over billions of years, it came up with ways to defend itself.​

  • So as multicellular life evolved over billions of years, it came up with ways to defend itself.​

  • Today humans have a sophisticated defense network,​

  • Today humans have a sophisticated defense network,​

  • Today humans have a sophisticated defense network,​

  • like physical barriers, defense cells, and weapons factories.​

  • like physical barriers, defense cells, and weapons factories.​

  • like physical barriers, defense cells, and weapons factories.​

  • But one of the most important defenses of our body is largely unknown:​

  • But one of the most important defenses of our body is largely unknown:​

  • But one of the most important defenses of our body is largely unknown:​

  • The Complement System

  • The Complement System

  • The Complement System

  • It evolved over 700 million years ago and is an army of over 30 different proteins

  • It evolved over 700 million years ago and is an army of over 30 different proteins

  • It evolved over 700 million years ago and is an army of over 30 different proteins

  • that work together in a complex and elegant dance to stop intruders.​

  • that work together in a complex and elegant dance to stop intruders.​

  • that work together in a complex and elegant dance to stop intruders.​

  • All in all, about 15 quintillion of them are saturating every fluid in your body right now.​

  • All in all, about 15 quintillion of them are saturating every fluid in your body right now.​

  • All in all, about 15 quintillion of them are saturating every fluid in your body right now.​

  • Guided by nothing but chemistry,​

  • Guided by nothing but chemistry,​

  • Guided by nothing but chemistry,​

  • these proteins are one of the most effective weapons we have against invaders.​

  • these proteins are one of the most effective weapons we have against invaders.​

  • these proteins are one of the most effective weapons we have against invaders.​

  • Many other parts of the immune system are just tools to activate the Complement System.​

  • Many other parts of the immune system are just tools to activate the Complement System.​

  • Many other parts of the immune system are just tools to activate the Complement System.​

  • But it's also really dangerous.​

  • But it's also really dangerous.​

  • But it's also really dangerous.​

  • Imagine having trillions of little bombs inside your blood that could go off at any moment.​

  • Imagine having trillions of little bombs inside your blood that could go off at any moment.​

  • Imagine having trillions of little bombs inside your blood that could go off at any moment.​

  • So our cells use numerous mechanisms to prevent​ ​complement from accidentally attacking ​​them​.​

  • So our cells use numerous mechanisms to prevent​ ​complement from accidentally attacking ​​them​.​

  • So our cells use numerous mechanisms to prevent​ ​complement from accidentally attacking ​​them​.​

  • Okay, what exactly does it do and what makes it so dangerous?​

  • Okay, what exactly does it do and what makes it so dangerous?​

  • Okay, what exactly does it do and what makes it so dangerous?​

  • In a nutshell, The Complement System does three things:​

  • In a nutshell, The Complement System does three things:​

  • In a nutshell, The Complement System does three things:​

  • it cripples enemies, it activates the immune system, and it rips holes in things until they die.​

  • it cripples enemies, it activates the immune system, and it rips holes in things until they die.​

  • it cripples enemies, it activates the immune system, and it rips holes in things until they die.​

  • But, how?​

  • But, how?​

  • But, how?​

  • After all, these are mindless proteins randomly drifting around without will or direction.​

  • After all, these are mindless proteins randomly drifting around without will or direction.​

  • After all, these are mindless proteins randomly drifting around without will or direction.​

  • Well, this is actually part of the strategy.​

  • Well, this is actually part of the strategy.​

  • Well, this is actually part of the strategy.​

  • Complement proteins float around in a sort-of passive mode.​

  • Complement proteins float around in a sort-of passive mode.​

  • Complement proteins float around in a sort-of passive mode.​

  • They do nothing, until they get activated and change their shape.​

  • They do nothing, until they get activated and change their shape.​

  • They do nothing, until they get activated and change their shape.​

  • In the world of proteins, your shape determines what you can and cannot do.​

  • In the world of proteins, your shape determines what you can and cannot do.​

  • In the world of proteins, your shape determines what you can and cannot do.​

  • Because shape determines what you can interact with and in what way.​

  • Because shape determines what you can interact with and in what way.​

  • Because shape determines what you can interact with and in what way.​

  • For example, in your passive shape you might do nothing.​

  • For example, in your passive shape you might do nothing.​

  • For example, in your passive shape you might do nothing.​

  • In your active shape, however, you might, for example, change the shape of other proteins

  • In your active shape, however, you might, for example, change the shape of other proteins

  • In your active shape, however, you might, for example, change the shape of other proteins

  • activating them so they can activate others.​

  • activating them so they can activate others.​

  • activating them so they can activate others.​

  • Mechanisms like this one can start cascades that spread very quickly.​

  • Mechanisms like this one can start cascades that spread very quickly.​

  • Mechanisms like this one can start cascades that spread very quickly.​

  • Imagine the complement proteins as being like millions of matches very close together.​

  • Imagine the complement proteins as being like millions of matches very close together.​

  • Imagine the complement proteins as being like millions of matches very close together.​

  • Once one catches fire, it ignites the ones around it.​

  • Once one catches fire, it ignites the ones around it.​

  • Once one catches fire, it ignites the ones around it.​

  • They ignite more and suddenly you have a big fire.​

  • They ignite more and suddenly you have a big fire.​

  • They ignite more and suddenly you have a big fire.​

  • To show the actual mechanisms of The Complement System is a tad complicated and overwhelming.​

  • To show the actual mechanisms of The Complement System is a tad complicated and overwhelming.​

  • To show the actual mechanisms of The Complement System is a tad complicated and overwhelming.​

  • So, we'll simplify here.​

  • So, we'll simplify here.​

  • So, we'll simplify here.​

  • Now, let's imagine you cut yourself and a bunch of bacteria enter the wound

  • Now, let's imagine you cut yourself and a bunch of bacteria enter the wound

  • Now, let's imagine you cut yourself and a bunch of bacteria enter the wound

  • and make it into the surrounding tissue.​

  • and make it into the surrounding tissue.​

  • and make it into the surrounding tissue.​

  • Our complement attack begins with C3.​

  • Our complement attack begins with C3.​

  • Our complement attack begins with C3.​

  • C3 is the first match, the initial spark that will start our fire.​

  • C3 is the first match, the initial spark that will start our fire.​

  • C3 is the first match, the initial spark that will start our fire.​

  • And to do that, C3 needs to switch from passive to active.​

  • And to do that, C3 needs to switch from passive to active.​

  • And to do that, C3 needs to switch from passive to active.​

  • How this happens is complex, but let's just say it can happen randomly

  • How this happens is complex, but let's just say it can happen randomly

  • How this happens is complex, but let's just say it can happen randomly

  • through other complement proteins that bind to enemies or through antibodies.​

  • through other complement proteins that bind to enemies or through antibodies.​

  • 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 virusinfects a cell,​

  • For example, when the ​​vaccinia virusinfects a cell,​

  • For example, when the ​​vaccinia virusinfects 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.​

  • A beautiful example of how many mindless things can do smart things together.​

  • A beautiful example of how many mindless things can do smart things together.​

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  • And it's hard to overstate how grateful we are for that.​

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  • ​​

Every living being needs to fight off other living beings that want to feast on them.​

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