Voiceover: The purpose of the immune system
is to fight things.
To fight bacteria and viruses and other things
that you don't want in your body.
That's what it does.
The question we can ask is
how does the immune system know not
to attack your own body,
and that might seem like a strange question
or an obvious question
but it's actually not obvious the answer to it.
In this video we're gonna go into why it's not obvious
and then how the body actually
does prevent its immune system from attacking itself.
Another way of saying is this
how does the body distinguish self versus non-self?
By that we mean how does it tell the difference
between your own body, your own proteins,
your own cells
and foreign proteins or cells
or things that shouldn't be in your body.
How does it know to attack these
and not to attack this.
To find out why the question itself is not obvious
let's go back to B cells and talk about B cells.
Here we have a B cell
and here is its nucleus with some DNA
and the most important part of the B cell
that we care most about is its B cell receptor
which later if it becomes active
can be released as an antibody.
Now this B cell receptor is what's gonna bind
to foreign, pieces of foreign bacteria or viruses
and these antibodies are gonna bind to those things
and help your body get rid of them.
The important thing to remember about B cells
is that these antibodies
or these B cell receptors are coded
in the DNA of the B cell,
but that they're different for every B cell.
Every B cell has a unique set of antibodies
and B cell receptors that it makes.
We'll give them slightly different colors
to make that obvious.
Here's one with slightly different DNA
and a slightly different B cell receptor.
The really critical point to remember
is that these B cell receptors that will become antibodies
are generated at random.
Your body kind of shuffles the DNA here
and creates a unique B cell receptor
and antibody for each B cell.
It's precisely that fact
which is that they're created at random
which means that your body is in danger of creating
B cell receptors and antibodies
that can react to your own body
because while this guy might be good,
while he might react to let's say
a bacteria out here that you want to get rid of,
while that's good.
This guy might easily create a B cell receptor
and later an antibody that can react
to something you don't want it to react to.
For example, let's say this is
an important protein in your body
maybe it's insulin.
You would not want a B cell to be created
which will react to insulin
because then maybe it will start creating antibodies
that bind all the insulin in your blood
and if you don't know what insulin does
don't worry about it but by binding to insulin
it will prevent insulin from doing its function
which is very important.
How can you keep your body from making B cells
that would react to yourself?
In fact there's no way to do it
because as I said,
this process of creating different
B cell receptors and antibodies is totally random.
There's no way to keep your body
from making B cell receptors
or B cells that will react to yourself.
What does that mean?
That means that you're gonna make them
but you need to find a way to figure out
which ones are reacting to you
and to get rid of them.
You need to figure out a way
to kill the ones you don't want.
By the way we're talking about B cells here.
B cells.
Everything we're saying is equally applicable to T cells.
Let me draw one here.
T cells it's equally applicable
because T cells also have a T cell receptor
that's generated at random
and you only want that T cell receptor
to react to foreign things.
To non-self things and not to self things.
The processes we're gonna talk about are
equally true, maybe even in some cases
more so true for T cells and B cells.
Let's go to the bone marrow
to figure out how this process works,
and we're going to the bone marrow
because that's where B cells come from.
It's where they get their unique antibody,
your B cell receptor.
They get that by changing their DNA
a tiny little bit by shuffling pieces around.
Let's look at a couple of these B cells
which are still young.
They haven't yet been allowed out of the bone marrow.
They haven't been vetted
to see if they should be allowed out.
Each one has its unique receptor.
Let's draw a few of those receptors here.
Let's say that one of these guys reacts to self.
One of them reacts to some protein in your own body
that you don't want it to.
Again, that just happened at random
because you're creating these receptors
really at random.
Let's say that the guy
that we're gonna want to get rid of this one
because he reacts to let's say it's insulin again
like up there.
Really we should have drawn insulin in yellow
to show that it goes with this receptor.
Let's say this guy reacts to insulin.
How can you figure out that this guy reacts to self?
The answer is actually quite simple.
The answer is that you just need to keep around
the various proteins that your body uses.
You need to keep them around in the bone marrow
while these B cells are being vetted.
For example here you'll have a little insulin.
Very small amount but it will be there.
You'll have a little bit of some other protein.
Let's say maybe hemoglobin.
You'll have some other protein here.
You'll have yet another protein over here.
All these proteins will be around.
What your body does at this stage and development
is it says whatever B cell binds to something,
wherever B cell binds to something
with its B cell receptor
in the bone marrow will be killed.
This B cell right here
that recognizes this insulin protein
the fact that it recognizes it,
it means that it will bind
and that will cause a little bit of a chemical change
in the B cell or something,
and one thing will lead to another
and the whole system will be programmed
so that as a result this guy will die.
Every B cell that recognizes self
if it sees that self molecule in the bone marrow
it will be killed.
This works because your bone marrow
will have most of the abundant proteins in your body.
They'll be present there so that you can make sure
that you weed out all the B cells that react to self.
Now what happens after this step is that
these guys who have been vetted
they can proceed onwards to maybe a lymph node.
Somewhere where they can begin to actually be active
now that they've sort of gone through
basic training here in the bone marrow.
You might ask yourself, well, what about here?
What about here when one of these B cells
that doesn't react to self,
what about when it interacts with a bacteria
that you actually want it to fight?
Is the same thing gonna happen?
Is it going to die just because it recognizes
the molecule that its made to bind to?
The answer is obviously not.
You don't want this guy to die because you need him.
Because you want to fight this bacteria.
The reason why he doesn't die is because
well, we're in a different environment.
There are different rules,
there are different other cells around
and this B cell has matured and become different.
The rules are different
and he's not going to die.
This weeding out of B cells
that react to self proteins is
sort of the first of two mechanisms
that I'd like to talk about that the body uses
to not react to self.
Actually the same thing exact thing happens for T cells
except it doesn't happen in the bone marrow,
it happens in the thymus
because that's where T cells mature.
In the thymus we have really the identical process
where T cells differentiate
and each one has a unique receptor
and the ones that reacts to self in the thymus
too strongly are killed.
It's not a foolproof method
or else we wouldn't need step two.
Every once in a while a B cell will get out there.
A B cell will escape which reacts to self.
It's just because every process has its mistakes
and maybe you don't have
every single protein here in the bone marrow
and enough abundance to find the B cells
that reacts to a protein of your own body.
Let's say this is a B cell that escaped the bone marrow
even though it reacts to self.
What's gonna happen now?
It's gonna find that protein
that it was sort of made at random to react with.
It's gonna find that protein
that your body makes and that your body needs
and it's going to bind to it.
What's it gonna do now?
If you remember it's now going to take that protein
ingest it, break it up into little pieces
and then present it on an MHC II molecule.
If you recall it will just present
a small piece of that protein on the MHC II molecule.
Maybe it will present a different piece of protein
on a different MHC II molecule over here,
something like that.
The reason it does this is
because it needs a T cell to come along.
Here's a T cell.
It needs a T cell to come along
that will recognize that same piece
that is put there on its surface.
It needs that in order to activate it.
It's going to sit there
and wait for this T cell to come along
who has the perfect receptor.
Here's that T cell.
They're going to interact
and they're gonna have some kind of
intracellular kiss
that's going to finally allow this B cell to activate.
Usually without the T cell coming
and recognizing the antigen that the B cell reacts to
the B cell cannot activate.
It needs this T cell to recognize it.
This is exactly the second mechanism of defense
that I'd like to bring to your attention
which is that even if a B cell escapes
that reacts to self.
Almost always it's also going to need a T cell
that reacts to self to come and activate it.
You need both the B cell to escape
the weeding out in the bone marrow
and the T cell to escape the weeding out in the thymus
for you to get an active B cell
that's now going to start putting out antibodies
that react to self.
By the way, this cellular kiss here
is usually going on in the lymph node.
Looking at this whole process
you might have a few complaints.
I encourage you think about how it might go wrong.
One way you might think it could go wrong is
what if bacteria got into the bone marrow
and certainly that's very, very possible
because when you get infections
the thing that's infecting you
can move around your body.
If this bacterium gets into your bone marrow
does that mean that now this B cell
is going to bind to it
and therefore it's going to be killed?
Because at this stage whenever the B cells
bind to something they're killed.
The answer is yes.
This is exactly what happens.
The reason why it's not too much of a problem is that
even if you have this bacterium here in the bone marrow
for a week or two or maybe a month,
after that once this bacterium goes away or it's killed
then it won't be there anymore
and you can start producing these B cells
that react to that bacterium again.
Hopefully you already had a bunch of these B cells
that could react to this bacterium
that you had made previously
and that were already out in the lymph nodes.
Those guys will be there to fight the infection
while maybe the infection might be in your bone marrow
preventing you from making more of those B cells
to kill it.
You already have some of those B cells
out there in the lymph nodes
and they can proliferate out there
and sort of lead the battle from there.
Now even though your body has these mechanisms
to keep your immune system
from reacting to yourself
it still happens sometimes.
The process still goes wrong sometimes
and the result is autoimmune disease.
It's called autoimmune because you're immune to yourself.
Your immune system basically starts attacking your own body
and some pretty terrible disease can result.
To kind of bring it to life
where I'd like to tell you about one example of this.
This is a muscle fiber
and the way your muscle fibers are activated
because you don't want to be flexing
all of your muscles all the time
the way that they're activated is that
they have a little receptor which I'll draw here.
This receptor is ready to receive
little molecules from a neuron, part of a nerve.
It receives little molecules from this neuron
that activate this receptor
and therefore activate the muscle fiber.
If you want to tighten this muscle fiber
you just need to send the signal down a neuron
and they'll release the little molecules
which will activate the muscle fiber.
In one example of autoimmune disease
you get antibodies against this receptor here on the muscle.
They bind to it
and that either stops it from functioning.
It makes it impossible for it to react to the neuron signals
or causes that receptor to be destroyed.
Those are two mechanisms that have been seen.
In this autoimmune disease what do you think will happen?
What happens is that
your body can no longer
activate muscle fibers as easily.
The disease is called myasthenia gravis
and the etymology of that is "my" it means muscle
and "asthenia" means weakness.
Muscle weakness and gravis just means it's serious
because it gets serious over time.
If you can't activate the muscle fibers in your body
you slowly become paralyzed.
You don't need to remember this exact mechanism.
That's not really important
but I just wanted to give an example of
one kind of autoimmune disease and how it works.