Original subtitles

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 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.​

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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