00:01
So those are different
types of helper T-cells.
00:03
What about the regulatory T-cells?
Well these suppress immune responses.
00:07
In fact, they’d probably be better called
suppressor T-cells rather than regulatory T-cells.
00:13
And they act in a number
of different ways.
00:16
One of the ways in which they function
is by releasing immunosuppressive
cytokines such as interleukin-10 and
transforming growth factor beta (β).
00:25
And these cytokines can down-regulate
the activity of eosinophils,
basophils, mast cells, helper T-cells and cytotoxic T-cells.
00:39
So really, suppressing a very
broad range of immune responses.
00:44
There is a second way in which
regulatory T-cells can suppress immune
responses, and that’s a cell contact-dependant mechanism whereby
molecules on the surface of the regulatory T-cell interact with
molecules on the surface of the cell
that is going to be suppressed.
01:00
And cell surface CTLA-4 and LAG-3, are functional
in down-regulating the activity of dendritic cells.
01:11
What about cytotoxic T-cells?
Well, as their name suggests, they
can kill; cytotoxic cell killing.
01:19
They can kill infected
cells and also tumor cells.
01:24
They can also secrete cytokines; in fact virtually
all cells in the body can secrete cytokines.
01:29
And cytotoxic T-cells have been divided into different
subpopulations, just like the helper T-cells have.
01:36
So, we can identify Tc1 cells that secrete
gamma interferon, just like Th1 cells secrete
gamma interferon, Tc2 cells that secrete
IL-4 and so forth just like Th2 cells do.
01:48
So there are also subpopulations
of cyctoxic T-cells.
01:55
The killing of an infected cell by cytotoxic
T-cell depends upon peptides from the pathogen
being presented by MHC Class I to the T-cell
receptor on the surface of the cytotoxic T-cell.
02:12
This will lead to the activation
of the cytotoxic T-cell.
02:17
And there are two ways in which
the killing process can function.
02:23
First of all, infected cells have on their
cell surface, the molecule Fas, and this can
interact with the molecule Fas ligand or
FasL on the surface of the cytotoxic T-cell.
02:37
So when Fas is engaged by Fas ligand, a signal is
sent into the infected cell which activates caspases.
02:48
And these are enzymes that are involved in
inducing apoptotic cell death in the infected cell.
02:56
There is a second pathway by which
cytotoxic T-cells can kill infected cells.
03:01
And this relies on the release of enzymes called
granzymes from the cytotoxic T-cell, and also molecules
called perforin which as their name suggests, cause pores
to be formed in the membrane of the infected cell.
03:21
Again, just like Fas-Fas ligand
interaction, the granzyme-perforin pathway
leads to caspase activation and apoptotic
cell death of the infected cell.
03:34
This killing of infected cells may
seem like a rather brutal strategy.
03:39
I mean the cytotoxic T-cell
is killing our own cells.
03:44
But the problem is, as we’ve already heard, that antibody and
complement can’t get at pathogens once they’re inside a cell.
03:50
So, this strategy of killing our own cells removes the ability
of viruses and other pathogens to replicate within our cells.
04:00
And as long as that happens very early on
in the immune response, it’s not a problem.
04:03
We can regenerate a few of our own cells,
and the infected cells can be got rid of.
04:09
And the way in which the killed cells are
removed is by using macrophages to recognize
the fact that these cells have been killed
and to take them up and then destroy them.
04:21
So here we can see a cytotoxic T-cell that
has interacted with a virus infected cell.
04:26
And when those apoptotic signals are sent into the cell,
either via the Fas-Fas ligand pathway or the perforin-granzyme
pathway; one of the things that happens is that there is a
flipping of the membrane on the outside of the apoptotic cell.
04:43
So bits of the membrane that… surface
membrane of the cell that were
on the inside of the cell now become on the outside of the cell.
04:50
And molecules associated with the inside layer of the
cell membrane, now become exposed to the outside.
04:56
Previously they weren’t on
the outside but now they are.
04:59
An example of such a molecule
is phosphatidylserine.
05:03
And this is normally not present on
the outside of the cell but following
apoptotic cell death, the phosphatidylserine
appears on the outside of the cell.
05:14
And macrophages have on their cell surface,
receptors for phosphatidylserine.
05:22
And that means that they can recognise the fact that this is
a dead or dying cell, and they will engulf it and destroy it.
05:31
I’m sure you’re fairly clear that infections
often enter the body via mucosal surfaces.
05:36
So you won’t be surprised to hear that there are many
immune system cells associated with mucosal surfaces.
05:43
And one group of lymphocytes that has
been identified as being important
in protection of mucosal surfaces, are
the intra-epithelial lymphocytes.
05:53
And on this diagram you can see
them highlighted by the red boxes.
05:58
So they are resident within the intestinal epithelium, and they
are one of the first lines of defence of the immune system.
These intra-epithelial lymphocytes are a mixed
population of antigen-experienced cells.
So they’re not naïve cells, they’ve
already encountered antigen previously.
And they comprise both, gamma-delta
T-cells and alpha-beta T-cells.
06:24
Some of them are CD4+,
but others are CD8+.
06:29
And very unusually, many of the
CD8+ cells, have a… not the normal
form if you like, of the CD8,
which is an alpha-beta heterodimer.
06:41
But they have a alpha-alpha
homodimer version of CD8.