All language subtitles for Tiny Bombs in your Blood - The Complement System

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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