>>Dr. Ketchum: Okay, so this is part 5B. There is no separate notes for this, but if you
look at the part 5A, you’ll have the slides for part 5B. I just divided it up into two
parts so that the lecture wasn’t so long. Okay, so this going to be still on adaptive immunity,
and we’re going to be talking about putting it together. And we’re going to start looking
at the mechanism for cytotoxic T cells first, then we’ll put it all together.
Okay, so in step one we’re going to have a virus, and the virus invades a host cell.
So here’s the virus, and you can see here the virus—how it’s invading the host cell.
When the virus invades the host cell, the virus will take over the genetic machinery,
right? They’ll take over the cell, and the virus will produce viral proteins, and those
viral proteins will become fragmented. Notice on this cell here we have these self-antigens,
which are MHC molecules. Those are already on the cell surface, just hanging out, waiting
there. After that virus has invaded the cell and it’s produced it’s proteins
and the proteins have been fragmented, now we can have your MHC molecule present the
antigen on the surface of the cell. We’re talking about cytotoxic T cells here that
are going to have to bind to this viral antigen, so what class MHC molecule should be binding
to this antigen and presenting it to this cytotoxic T cell? Hopefully you said class
one. Class one MHCs will present antigens to cytotoxic T cells.
So the next step then is for the cytotoxic T cell to come in and bind to the antigen-presenting
cell. So here’s your cytotoxic T cell, and it binds to the antigen. So what this slide
does not show is the protein that’s going to ensure or enhance the binding of the cytotoxic
T cell to the virally-invaded host cell. What protein, what protein is going to enhance this binding?
Remember that your cell, we’re dealing with cytotoxic T cells. So this protein that’s
enhancing the binding must be a CD8 protein. When the cytotoxic T cell—and this is something
new, so it’s very important to pay attention. When the cytotoxic T cell recognizes and binds
to the class one, okay, and then you get the CD8 enhancing the binding. At the same time
that this happens, at the time of your cytotoxic T cell binding to the antigen, the cytotoxic
T cell is going to receive a signal from the helper T cell. This signal is in the form
of a chemical messenger called interleukin 2.
Once we have this occurring, okay, and we’ll talk more about this helper T and where this
IL-2 thing came from here in just a moment, but let’s talk about what the cytotoxic
T cell does. We know that cytotoxic T cells—think about the name, cytotoxic. “Cyto” is cell,
“toxic,” kill. So we want to kill the virally-invaded cell. So how does that happen?
Well the cytotoxic T cell is going to release chemicals called perforins. And you already
know that natural killer cells release perforins as well. And perforins will create a pore
or a hole, right, in the membrane of the virally-infected cell. So once that pore gets
created, then we know this increases the permeability of the cell to water and ions and the cell
will lyse. Now just to ensure that this cell is killed, something else happens. The cytotoxic
T cell not only releases perforins, also releases a chemical called fragmentins. So this is
a chemical that enters the cell via the pore that was created by the perforins. What the
fragmentins do when they get into this cell is that they induce apoptosis—
programmed cell death. They tell that cell to commit suicide. So here we have sort of
a backup system, right? If the perforins that created the pore don’t get the cell to lyse
very quickly? Well, you can also rely on apoptosis or programmed cell death, and that cell will
kill itself.
So now let’s put all of this information together. You have a cell; it’s been infected
or invaded by a virus. We are going to begin with a macrophage. All right, so remember what
macrophages do—macrophages engulf. So they, in this case, have engulfed viral fragmented
proteins. So remember this macrophage could also be a dendritic cell, okay, it could be
other cell types, because guess what? You find class two MHC molecules associated with
them. So what other cell types could this be? Go back and review what class two MHC
molecules are associated with. So when the macrophage engulfs these virally fragmented
proteins, then the class two MHC will present the antigen (remember the antigen is the fragmented
protein) to the helper T cell. Because remember, it’s a helper T cell that always recognizes
class two.
So once the class two presents the antigen to the helper T cell, at this moment when
they bind—so here we have binding, and you’re also going to be using a CD4 to enhance the
binding just like we talked about earlier. So now once this happens, your macrophage
will secrete a chemical messenger. It’s going to secrete interleukin 1. And when macrophages
secrete interleukin 1, that’s going to cause a couple of things to happen. That’s going
to cause your helper T cells to proliferate. And when they proliferate, they’re going
to proliferate into IL-2 secreting helper T cells, and they’re going to proliferate
into memory cells. So the IL-2 helper T cells go on, and they’re going to secrete IL-2—interleukin2,
this chemical messenger. Memory cells, we know what memory cells do. Memory cells are
going to sit there and hang out until you get exposed again to the same viral antigen.
All right, so now focusing on this IL-2 secreting helper T cell. So IL-2 then, once it get’s
secreted that’s going to cause—and if you think back a few slides to part 5A, you
think about the functions of secreting IL-2. One of those functions is to cause the B cells
to proliferate. So we activate the B cells, and when we activate the B cells, they can
go on to produce antibodies and memory cells.
What IL-2 also does is it activates cytotoxic T cells. So here we are here, and we activate
cytotoxic T cells. And when they’re activated, now they can bind to a class one MHC molecule.
So remember, class ones are on the surface of all nucleated cells, and they’re presenting
some antigen to the cytotoxic T cell. And so what we need to do here is we need to kill
the infected cell. So we know how cytotoxic T cells do that. Cytotoxic T cells will release
perforins—perforins and also fragmentins, right? You can see both of them being released
by a cytotoxic T cell. That will create—the perforins create the pore, the fragmentins
enter through the pore, the perforins can cause lyses of the cell, and fragmentins can
cause apoptosis.
Now cytotoxic T cells can then go on and kill other cells as well. So their job is not done
once they’ve caused the death of this cell. So again, here’s a nice little flow chart
that puts all of this information together for you. So once again, now—now what we
have done is we’ve gone through the innate immune response, we’ve covered the adaptive
immune response, which is the one that has the memory, right? And the one that’s very
specific to certain microbes or certain pathogens or tumor cells. We’ve kind of ended here
at a point where we’ve put all of this information together and how the innate response and how
the adaptive response actually have to work together in order to do this. So the next—or
the last—which is going to be a part six video, is on the immune responses in health
and disease.