The way in which cytokines function,
can be looked at in a variety of ways.
First of all, which cells produce
cytokines, and which cells respond?
Well, sometimes the same cell that produces
the cytokine, responds to that cytokine.
In other words, the cytokine
acts in autocrine way.
So we can see here, a lymphocyte that’s producing a
cytokine and its also has the receptor for that cytokine.
So not only will it produce the cytokine but that single
cell itself will respond to that particular cytokine.
And that often happens, but perhaps even more
commonly is a paracrine function, in other
words one particular cell produces a cytokine
and a different cell responds to it.
But do remember, in order to respond to a
cytokine, you need to have a cytokine receptor.
We can then look at the way in which
cytokines work in a kind of network,
because there are lots and lots and
lots and lots of different cytokines.
And the ultimate response will
depend upon the mixture of cytokines
that’s present in a particular local
environment at any one point in time.
So they can act in a cascade way,
so here we have an example of a
Th1 cell secreting a cytokine that’s
going to activate macrophages.
So for example, gamma interferon as we’ve
already heard, very potent macrophage activator.
As a result of that stimulation by gamma
interferon, the macrophage releases interleukin-12.
And one of the effects of interleukin-12 is
to stimulate Th1 cells which in turn go on
and secrete more gamma interferon, plus
interleukin-2 and tumor necrosis factor beta.
So this is a cascade type of system.
But there are other ways in which cytokines interact with
each other, and other types of activity of cytokines.
So let’s have a look at those.
Pleiotropism is where a single
cytokine has multiple effects, and
this is probably true for all
cytokines; give you just one example.
Interleukin-2, it can cause T-cells
to proliferate, it can cause
B-cells to proliferate and it can activate natural killer cells.
Conversely, there is also some degree of
redundancy within the cytokine networks.
So for example, both interleukin-4 and
interleukin-5 can cause B-cells to proliferate.
Some cytokines act synergistically,
in other words they work together in a
much stronger way than you would imagine
just from the summative effect.
So TNF alpha and gamma interferon act synergistically
in the inhibition of viral replication.
And in contrast, some cytokines
antagonize the activity of others.
And this can be seen with
interleukin-4 and gamma interferon.
So interleukin-4 will cause B-cells
to class switch to IgE production,
but gamma interferon will prevent that happening - antagonist.
I’ve mentioned that it doesn’t really matter how
much cytokine is around, nothing’s going to happen
at all unless the cell is expressing on its cell
surface, a receptor for that particular cytokine.
So why don’t we look at cytokine
receptors for a few seconds.
So here we have a typical cytokine receptor
on the surface of a cell and many of these
cytokine receptors are dimers or sometimes
even consists of more chains than that.
But here we have a dimeric
When the cytokine binds, it causes dimerisation
of the receptor as we can see here.
And that will initiate
a signaling cascade.
So JAK kinase will cause phophorylation of sequences
within the cytoplasmic region of the cytokine receptors.
This leads to the recruitment of STAT,
and further phosphorylation events occur.
STAT then dimerizes and ultimately,
the result will be gene transcription.