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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11 thoughts on “Tiny Bombs in your Blood – The Complement System

  1. Our Complement System is super complex and fascinating and we can’t get enough of it – so we also made a poster and postcards with its core workings step by step.
    Get it here: http://shop.kurzgesagt.org

  2. Hey guys great video! I was recently stung by a hive of yellow jackets and it was enough to give me a fever and nausea symptoms. I'd love for you guys to explain the body's process of neutralizing venom!

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