>>Dr. Ketchum: In part five of the immune system, we’re actually going to divide this
up into two more parts: 5A and 5B. Part 5A is going to be over adaptive immunity, but
this is going to cover the players of adapted immunity—who the players are. Okay, so here
we’re dealing with adaptive immunity. So once again, we return to your flow chart.
And specifically what we’ll be focusing on now is cell-mediated immunity. Be sure
that you remember that cell-mediated immunity involves T lymphocytes. Okay, so in a cell-mediated
response, we’re going to use different types of T cells. They’re all T cells, but there
are different types of them. These T cells are going to defend against invaders that
hide inside of cells. So you may have virally infected cells, you could have cancer cells,
you can even have intracellular bacteria. Now with T cells, they have to come directly
into contact with our target cell. The target cell being the virally infected cell or the
cancer cell or the intracellular—or the cell that’s infected with an intracellular
bacteria. And we’ll describe shortly how those T cells come into direct contact with
those cells.
The types of T cells we’ll be working with are the helper T cells, which are also known
as, or AKA, CD4 cells, cytotoxic T cells, which are also known as CD8 cells, and then
suppressor T cells. Be sure that if I mention CD4 cell to you, you understand that that’s
a helper T cell. Okay, so let’s look at the functions for these three different types
of T cells. The helper cells—think about them as being the regulators, okay? They’re
the helpers; they regulate. They do not kill, okay? Remember that these are also called
the CD4 cells. Helper cells will also secrete cytokines, and that’s actually going to
enhance the activity of your macrophages. Remember the function of the macrophages is
to phagocytose. Okay, so these cytokines will also enhance the activity of the natural killer
cells. Remember that natural killer cells secrete perforins, which create a pore in
the membrane of your infected cell. The helper T cells secrete cytokines, which will enhance
the activity of B cells. And we talked about B cells in the previous part. Remember B cells
are important in humoral immunity. Helper T cells will also secrete cytokines that will
enhance the activity of cytotoxic T cells, and we’ll talk about those below. Then it
also enhances the activity of other helper T cells, and it enhances the activity
of a suppressor T cell.
Remember what cytokines are. Back in chapter five when you were introduced to communicators,
or chemical messengers or chemical ligands, cytokines are an example of a chemical messenger.
Now the cytotoxic T cells—remember these are also called CD8 cells—are directly responsible
for cell-mediated immunity. These cells kill. They don’t regulate like a helper T cell
does. Cytotoxic T cell kills infected cells. It will kill cancer cells; it will kill transplanted
cells. Then we have the suppressor T cells. And we won’t spend a lot of time talking
about suppressor T cells, but they do produce cyko—cytokines. So again, these are chemical
messengers that are going to suppress the activity of the B cells. They’re going to
suppress the activity of the cytotoxic T cells, and they’ll suppress the activity of helper
T cells as well. So when you think about suppressor T cells, think about these in terms of turning
off an immune response.
Our main focus here is going to be on the helper T cells and the cytotoxic T cells.
So we talked earlier about how T cells have specificity, but here’s the catch, right?
There’s always more to it. Remember that the T cell has the T cell receptor. And we
said that the T cell receptor has an antigen-binding site. And this is all true. However, the only
way that a T cell will bind to an antigen using its T cell receptor is if that T cell
or the antigen is associated with an MHC molecule. So MHC molecules—these things are called
the major histocompatibility complex. Okay, so these are called self-proteins. Everybody
has MHC molecules, and everybody’s MHC molecules differ from person to person. So the self-proteins
are sometimes called self-antigens. Okay, and these self-antigens are consist of glycoproteins,
all right? So they are a protein, but they’ve got a little bit of a sugar attached to them
as well.
So let’s take a look at how these MHC molecules have to be associated with the antigen, which
therefore have to be associated with the T cell. In this particular example, here we
have at the top the plasma membrane of your cytotoxic T cell. This could also be a helper
T cell, and on the bottom we have the plasma membrane of an invaded cell. So maybe this
is a cell that’s been invaded by a virus, for example. What has to happen here in order
for the T cell to bind to the antigen? So first off, we know that there is an antigen
inside of this invaded cell. There’s also an MHC molecule that’s found inside of the
cell as well. So what has to happen then is the MHC molecule has to bind to the antigen.
Once it binds to the antigen, then this entire complex here gets presented on the surface
of the cell. So here, now what you notice is that you have the MHC cell, and then here’s
the foreign antigen. So this is the antigen that was inside of the cell, and now it’s
been brought to the surface of the cell. Once it’s been brought to the surface of the
cell, now the T cell will bind to the antigen via its T cell receptor. And then once that’s
done, something else will happen next that we’ll talk about in a little bit.
So this whole process right here is called antigen presentation. So what this means is
that we have a cell—this cell is called the antigen-presenting cell. So it’s a cell
that’s presenting the antigen to the T cell, and now that that happens, the T cell can
bind to the antigen. So let’s take a little closer look at these MHC molecules. So there’re
actually two different classes, and I’m actually going to step those through with
you. But what you are going to have to look up is the bottom bullet here: Are MHC molecules
the same for every person? And what would this have to do with a skin graft or even
an organ transplant? So let’s go ahead and look at the differed classes of MHC glycoproteins.
We have two different classes. Class one is located in the plasma membrane of all nucleated
cell; class two are restricted to the surface of just a few types of immune cells. So these
are macrophages, B cells, cytotoxic T cells, and dendritic cells. So let’s kind of take
a closer look at the relationship between these class one and class two glycoproteins
and their T cells. So class one, we said, is found on the surface of all nucleated cells.
Class one are recognized by only cytotoxic T cells. So class one will only be recognized
by a cytotoxic T cell. So cytotoxic T cells can destroy the body cells if invaded by a
foreign antigen. So this is what will happen. So cytotoxic T cells will bind to an MHC class
one molecule, then it’s response s going to be to kill that nucleated cell. Then there’s
the class two MHC glycoproteins.
These now are found on the surface of certain immune cells. Class twos are only recognized
by helper T cells. So a helper T cell will bind to an MHC two glycoprotein. And when
it does this, remember what a helper T cell does; a helper T cell regulates the immune
response. So when the helper T cell binds to MHC two, it will regulate the immune response.
Okay, so let’s take a closer look at class one MHC in cytotoxic T cells, and then we’ll
come back to class two.
The cell on top is the virally-infected cell. Remember that this could also be a tumor cell.
It could be a cell that’s been invaded by a bacteria as well, okay? Down below is a
cytotoxic T cell. So because we’re dealing with a cytotoxic T cell, right away you should
realize that it will only recognize a class one MHC molecule. So let’s look at the process
of how this is going to work. We’re going to start with a newly synthesized viral protein.
So the virus has already invaded the cell, and it’s taking over the machinery of the
cell and it’s producing it’s own proteins. So then in step two here, the proteins become
fragmented. So in other words, they start breaking apart. And then once they become
fragmented, then in step three here, the proteins will bind to the MHC class one glycoprotein.
So once that happens, then in step four the class one MHC molecule presents this antigen
fragment, right, the antigen fragment being the viral protein. And it’s presenting it
to the cytotoxic T cell. So once this happens, then, in step five, the T cell receptor will
bind to the antigen. So it’s binding to the antigen that’s bound to the class one
MHC molecule. And then here we have in step six the CD8 molecule. So the reason cytotoxic
T cells are also called CD8s is because the CD8 is a protein that actually ensures
or enhances the binding of your T cell receptor to the antigen. Because once you’ve got
it there, you don’t want to lose that cell, right? You want to be able to kill that cell.
You don’t want to lose it. So in step seven, then, the cytotoxic T cell will kill the cell.
It will kill that virally-infected cell.
So now that takes us to the class two MHCs and the helper T cells. So now what we’re
going to look at—down on, down below is the helper T cell. At the top, now, remember
that class twos are only found with certain cell types. So here for example we’ve only
listed a macrophage or a dendritic cell. So in step one, your phagocytic cell has engulfed
the antigen. Remember macrophages and dendritic cells are phagocytic. So they’ve engulfed
the antigen. The antigen in this case are viral proteins. Then those viral proteins
are fragmented, and then, once they’re fragmented, they’re going to bind to a class two MHC
molecule. And after they’ve done that then, we are going to present this antigen to the
helper T cell. Then once that happens, then in step five here, the T cell receptor will
bind to the antigen. Remember the antigen now is bound to a class two MHC molecule.
And then once that happens, the helper T cell is going to secrete cytokines to induce and
regulate the immune response. Keep in mind here which cell is the antigen-presenting
cell, okay? And that’s your macrophage or dendritic cell.
So next then we have helper T cell activation. So these are things here that you’re just
going to have to commit to memory. So we already said that helper T cells are going to secrete
cytokines, which activate the immune system. So they do not directly interact with the
antigen, though. Okay, so what helper T cell can secrete? They can secrete B cell growth
factor, and that enhances antibody secretion. That’s important right? Because once you
make antibodies—antibodies, as you learned in the previous part, can do things like neutralization
and agglutination, activate compliment system, assist with natural killer cells, and so on.
So that’s important. These helper T cells can also secrete chemicals that attract neutrophils
and macrophages. So remember, neutrophils and macrophages are very important in terms
of being of phagocytic cells. They can also enhance macrophage migration. So you need
to have macrophages in the right area if they’re going to be engulfing invaders. Helper T cells
can also activate eosinophils and promote Ig development when you have a parasitic infection,
like, for example, a roundworm or maybe a tapeworm infection. And helper T cells secrete
IL-2.
IL-2 does a number of things. IL-2 will stimulate the proliferation of helper T cells. So if
you make more helper T cells, you can induce more of an immune response. They also help
the proliferation of cytotoxic T cells. The more cytotoxic T cells you have, the more
you can kill. And then the proliferation of B cells, because the more B cells, you have
the more plasma cells you can have, which means the more antibodies and memory cells
that you will have. IL-2, which is interleukin 2, also stimulates plasma cell development.
Because remember, if you produce plasma cells, you can go onto produce antibodies. And then
helper T cells—when they secrete the interleukin 2—that also enhances the activity of natural
killer cells. So realize that when we keep talking about these cytokines, interleukin
2, IL-2, is an example of a cytokine. So it’s an example of a ligand or chemical messenger
that only ever travels through interstitial fluid. So this is where we’re going to stop,
and in part 5B I’m going to start putting all of this together for you.