Helper T Cells - Part 2

In talking about the adaptive immune system, we've already
seen that there's a couple of actors.
You have your humoral response.
So this is responding to things that are floating
around in the fluids of the body and not necessarily
things that have infiltrated your body cells and then you
have your cell mediated response.
And then in the humoral response-- and we're talking
about specific humoral response-- this is where the B
cells, the B lymphocytes are at their most active.
And essentially what they do is, you got a B cell here.
It has a very specific antibody, specific to just
this B cell, not B cells in general.
If this happens to be the one of the billions of B cells
that happens to have the matching key-- or maybe I
should say the matching lock for the key that is the
intruding pathogen-- that pathogen will
bind to that B cell.
Maybe it's a virus, maybe it's a bacteria.
And then the B cell will get activated and we'll talk about
in this video that the activation
doesn't always happen.
In fact, it usually doesn't happen just from this, but so
far we've said it gets activated, it goes into memory
B cells, which are essentially multiple versions of this
original B cell-- just saying, hey, let's have multiple
versions of this-- because it tends to recognize this virus.
So in the future if we get this virus, those multiple
versions, those memory cells are going to be there to have
this interaction.
This interaction's going to be more likely to happen in the
future because I'm going to have more of this
variety of B cell.
And then you have effector cells.
And these are essentially-- so both of these are B cells.
So this guy, once he gets activated, he proliferates,
keeps dividing and cloning himself.
The memory cells just stick around waiting to be activated
in the future.
And I'm only drawing one of these membrane bound
antibodies, but there are actually 10,000 on them.
I mean, I could draw a bunch of these.
I don't have to just draw one.
The memories just wade around in the future, but there's
more of them now.
So in the future, if we get this virus again, this
interaction's going to happen faster and so they're going to
get activated faster.
And then the effector B cells essentially turn
into antibody factories.
This antibody goes in and it says, let me just produce--
I've been activated.
Let me produce many, many more versions
of that exact antibody.
So they get spit out.
I drew that one little wrong.
So that exact antibody, that can then be spit out to go
disable or tag antigens-- and not just any antigen-- this
antigen right here.
And we also saw that the other thing that the B cell does is
it becomes an antigen presenting cell.
So what it does is, as soon as it recognizes this, it's had
this interaction with an antigen that just matches the
variable portion of its membrane bound antibody.
It endocytosizes that.
It brings that into itself.
It's membrane facilitated so it just kind of pulls it in,
chunks it up, and then presents a piece of that
antibody on an MHC II molecule.
We saw that in the last video.
So it cuts that up and presents a piece of it right
there and that's why we call it an antigen presenting cell.
Now in this video, we're going to talk about why we even have
these MHC II molecules.
What are we presenting these antigens to?
So we're going to start talking about the cell
mediated-- and actually, even more than the cell mediated,
we're going to talk about T cells.
And I said in the first video, they're called T cells because
they mature in the thymus.
And there are two types of T cells and it's all very
confusing because you have B cells and T cells, but then
there are two types of T cells.
You have helper T cells-- and most people just write T with
a lower-case or subscript h there.
And then you have cytotoxic T cells-- or T cells that kill
other cells.
Now just so that you have a big, overarching impression of
what does what-- B cells.
When they are activated, they generate antibodies.
At 30,000 feet, that's the best summary of what an
activated B cell does.
It actually generate antibodies.
Those antibodies attach to viruses and bacteria and other
types of pathogens and disables them-- either tags
them so that macrophages can go and eat them up or just by
throwing all of those antibodies on to the surface
of the pathogen in question.
It might disable the pathogens or essentially bundle them
altogether so that it'll be easier for macrophages to pick
them up, but this is only effective for things that are
floating around.
Free floating antibodies are only effective for things that
are floating around.
Cytotoxic T cells, which I'll cover in more detail in a
future video-- these actually attack cells that have been
infiltrated.
So this is attack, kill, infiltrated cells-- and when I
say infiltrated, it could be a cell that a virus has gone
into or some bacteria has penetrated it.
And when I say infiltrated, it doesn't necessarily even mean
something from the outside.
It could even be a cancerous cell that shows itself to be
abnormal in some way and so the cytotoxic T cells will at
least attempt to kill them.
But what I want to focus on-- out of the three types of
lymphocytes-- remember, everything we've been talking
about was leukocytes, white blood cells, but lymphocytes
are a subset of that and these three are lymphocytes.
And they're called that because they began their
development in the bone marrow.
So this guy and this guy actually do stuff.
This guy generates antibodies that attach to pathogens
floating around.
This guy directly attacks cells that are
broken in some way.
They've either been infiltrated, they're abnormal,
they're cancerous-- who knows what.
And I'll do a whole video on that, but that leads us to a
very obvious question.
What does this guy do?
What does the helper T cell do if he doesn't directly
interface either with pathogens or produce things
that interface with pathogens-- or if he himself
doesn't go and directly kill cells?
And the answer is that the helper T cell's kind of the
alarm of the immune system.
And on some level, it's almost the most important.
So we talked already in the last video about antigen
presenting cells-- that either when a macrophage or a
dendritic cell takes things in, it cuts them up and
presents it on its surface as these MHC II proteins or in
complex with these MHC II complexes or proteins.
And so do B cells.
B cells are more specific.
Now, once something is presented, now the helper T
cell can come into the picture.
So this is a-- let me do a dendritic cell-- and I'm doing
dendritic cells actually on purpose because dendritic
cells are actually the best cells at
activating helper T cells.
We're going to talk about in a second what happens when a
helper T cell gets activated.
So let's say I have this dendritic cell.
It's called dendritic so it looks like it has
dendrites on it.
So I have this dendritic cell here.
It's a phagocyte.
Let's say it's already consumed some type of bacteria
or virus and it's cut it up and now it's presenting kind
of the body parts of that virus on the MHC II complex.
It's kind of its way of saying, hey, I found this
shady thing floating around in the body's tissues.
Maybe someone ought to raise an alarm.
Maybe this is part of some type of bigger thing going on
and some type of alarm bell has to be released.
And that's what the helper T cell does.
So let's say this guy-- he's presented it.
He says, I found this thing.
I killed it.
Here's a part of it.
The helper T cell has a T cell receptor on it.
Let's say this is the helper T cell right here.
And it has a T cell receptor on it and the T cell receptors
bond to-- and I'll be very particular here.
So this is the T cell receptor.
It's just like a protein, but like the membrane bound
antibodies on B cells that every B cell or almost every B
cell has a different version, different variable chain,
that's also true of helper T cells-- that just like the B
cells, this has some variation in where it binds.
So this right here is going to be variable from one helper T
cell to another.
For example, I might have another helper T cell here.
That also has a T cell receptor, but the variable
portion on that T cell receptor is different than the
variable portion on this T cell receptor.
So this helper T cell will not bind to this dendritic cell or
the MHC II complex of this dendritic cell.
Only this one would.
And the mechanism of how you get this variation is very
similar to the mechanism in how you get the variation on
the antibodies and the B cells.
During these helper T cells' development, at some point the
genes that code for this part of this receptor get shuffled
around and they get shuffled around intentionally so that
each T cell has a certain specificity to a combination
of an MHC II complex and a certain polypeptide, a certain
part of a virus.
So only this guy's going to be activated, not this guy.
So this is why we call it the specific immune system.
Now we said, what does that helper T
cell do at that point?
He said, hey, I happen to be the one helper T cell that can
bond to this guy, this antigen that's presented.
It becomes activated.
And I won't go into the details, but in general,
dendritic cells are the best ones at activating it,
especially a naive T cell.
In general, when we talk about a naive B cell or a naive
helper T cell, these are cells that are non-memory,
non-effector, that have never been touched by-- they've
never been activated, in the case of a B cell.
They've never been activated by something binding to their
membrane bound antibody-- or a naive helper T cell is a
non-effector, non-memory helper T cell that's never had
anything bound to it.
So if this guy is naive and then he finally has a reaction
with this antigen presenting cell, he becomes non-naive.
He becomes activated and when activated, two things happen.
Well, just like with B cells, he proliferates many, many,
many copies of himself and some subset of those copies
differentiate into effector cells.
And effector just means it does something.
It does something now instead of saving the memory.
And then some subset of them become memory helper T cells
after getting activated.
Now the memory T cells, just like memory B cells-- now you
have more copies of this.
So in 10 years in the future, if something like this
happens, this interaction's going to be
more likely to happen.
These guys have the same T cell receptor as their parent.
It's just that the memory T cells-- or actually even the
memory B cells-- they last longer.
They don't kill themselves.
They'll last for years so that if 10 years later, something
like this starts presenting itself, you're going to have
more of these guys around to bump into this guy so that you
can raise the alarm bells.
This guy's also going to have the same chain right there.
So you're saying, fine.
I have these memory cells.
They're going to stick around so that this reaction can
happen in the future, but I still haven't answered the
question, what does the effector T cell do?
What the effector T cell does is it raises the alarm.
So there's an effector T cell.
It has been activated.
Remember, this is very particular.
Only this version of T cells, but once it got activated, it
produced many copies of itself because it says, hey, I'm
responding to a particular type of pathogen.
So that this is a helper T cell.
This is an effector.
And what these do is they start releasing these
molecules called cytokines.
So they start releasing cytokines.
There are many, many different types of cytokines and I'm not
going to go into detail on all that, but what cytokines do is
that they really raise the alarm.
So if you have other activated lymphatic cells or other
activated immunological cells-- when the cytokines
enter those cells-- remember, cytokines
are really just proteins.
When the cytokines enter-- or polypeptides-- when they enter
those cells, it makes them get in gear.
It makes them multiply more often or it makes them get
more active in their immune response.
So what this does-- these cytokines you can view as
chemical alarm bells chemical or peptide alarm bells alarm
bells it it tells everyone to get in gear.
So that's one role, and so you can see this is actually a
very central role and it'll tell both activated cytotoxic
T cells to get in gear, which we haven't talked about yet.
And it'll also tell B cells to keep proliferating.
So when an activated B cell gets some of-- so this is an
activated B cell.
When it gets some of these cytokines, that maybe come
from a local helper T cell, it'll tell it, hey no, divide
more often.
Divide more often.
Only if you've been activated already.
And we'll talk more about why it has to be that case,
because you don't want all the B cells to be activated.
And the other thing that the effector T cell does-- in the
B cell discussion, I said, OK, if I have a B cell, and it has
its membrane bound antibody, has its
membrane bound antibody.
And remember, this is a particular version, it has its
particular variable chain right here.
And this guy binds to a pathogen.
So this binds to a pathogen.
Maybe it's a virus right there.
Up to now, I've been saying that this guy's activated.
And he's going to-- well, when he binds to the pathogen he'll
take this in and he'll take part of the pathogen and cut
it up and place it on an MHC II molecule.
And we said, then he'll be activated.
He'll proliferate and he'll differentiate into memory and
effector B cells-- but that's not quite true.
This first stage happens.
This guy bonds.
This B cell happened to be specific to this virus.
Cuts up the virus.
Puts parts of the virus on its surface and presents parts of
the antigen.
But in most cases, this B cell isn't yet activated.
You can kind of view it as in its resting state, ready to be
activated, but it hasn't started proliferating and
differentiating into effector and memory molecules yet.
And in order for that to happen, an activated helper T
cell that is also specific to this very same virus-- so you
could imagine someplace else in the cell-- this virus was
eaten by a dendritic cell.
So this exact same virus, this exact same species of virus,
is eaten by that dendritic cell and so the dendritic cell
eats it up, it cuts it up, and then it presents it-- it's
antigen presenting so it presents it just like that.
Then this will activate a very specific T
cell, maybe that one.
So a very specific T cell will come and bump into it.
Not just any T cell, the one with the
right variable portion.
So think about what's happening.
The variable portion for this T cell, it connects to this
part of the virus plus the MHC II, but it's really reacting
to the same virus.
It might be a different part.
This little part that was cut off might be someplace inside
the virus while the epitope for the B cell might be some
place on the outside of the virus, but they're both
specific to the same virus.
Now once this guy gets activated and he starts
producing memory and effector cells-- or they're descended
from him, one of those effector cells specific to
this virus are needed to come bind to this guy.
So then this guy could then go along and bump around and
eventually end up here.
And he is also specific to this virus.
So this binding site right here is the same as this
binding site.
This combination of antigen plus MHC II.
And so when this guy binds-- and remember, this binding
site is the same as this and it only binds to this
combination right here-- this is what activates the B cell
in most cases.
This is T-dependent activation, which
is usually the case.
Sometimes all you need is this first thing, but in general
you need the first thing and then you also need a T cell to
come and activate it, and only then will the B cell get
activated and start proliferating and dividing and
differentiating itself and producing-- when its effector
cells will produce a lot of antibodies.
And so there's a natural question.
Why do biological systems-- or why do we
have this double system?
And at least my sense of it is, it's a failsafe mechanism.
If every time a virus came and attached this, this guy just
started going crazy and producing antibodies against
this thing, there's some chance that maybe after
development, this chain right here or his genes for
generating these chains become specific, not for foreign
pathogens, but maybe they become specific for self
molecules, molecules that are naturally
produced within the body.
It's just a random mutation, but if he started going crazy
for that, his antibodies will start attacking molecules that
are naturally in the body and then that could really hurt.
That what causes autoimmune diseases, where your own
immune cells start activating yourself.
But if you have this double handshake system where this
has to happen and this has to happen, the likelihood of both
of these guys after they leave their development stage
becoming specific to a self protein or a self cell or a
self molecule is very unlikely.
So it kind of inhibits this guy from going wild, even if
he has some type of a mutation.
Anyway, hopefully that explains a little bit of what
helper T cells do.
We'll talk a lot more about it.
I know it can be a little bit confusing.
In the next video, we'll talk about cytotoxic T cells.