Cell-mediated Immunity: Functional Modes of Cytokines and Cytokine Receptor Signaling

00:01 The way in which cytokines function, can be looked at in a variety of ways.

00:08 First of all, which cells produce cytokines, and which cells respond? Well, sometimes the same cell that produces the cytokine, responds to that cytokine.

00:19 In other words, the cytokine acts in autocrine way.

00:22 So we can see here, a lymphocyte that’s producing a cytokine and its also has the receptor for that cytokine.

00:30 So not only will it produce the cytokine but that single cell itself will respond to that particular cytokine.

00:37 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.

00:50 But do remember, in order to respond to a cytokine, you need to have a cytokine receptor.

00:56 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.

01:04 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.

01:14 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.

01:24 So for example, gamma interferon as we’ve already heard, very potent macrophage activator.

01:31 As a result of that stimulation by gamma interferon, the macrophage releases interleukin-12.

01:39 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.

01:52 So this is a cascade type of system.

01:55 But there are other ways in which cytokines interact with each other, and other types of activity of cytokines.

02:03 So let’s have a look at those.

02:06 Pleiotropism is where a single cytokine has multiple effects, and this is probably true for all cytokines; give you just one example.

02:15 Interleukin-2, it can cause T-cells to proliferate, it can cause B-cells to proliferate and it can activate natural killer cells.

02:27 Conversely, there is also some degree of redundancy within the cytokine networks.

02:32 So for example, both interleukin-4 and interleukin-5 can cause B-cells to proliferate.

02:39 Some cytokines act synergistically, in other words they work together in a much stronger way than you would imagine just from the summative effect.

02:48 So TNF alpha and gamma interferon act synergistically in the inhibition of viral replication.

02:56 And in contrast, some cytokines antagonize the activity of others.

03:00 And this can be seen with interleukin-4 and gamma interferon.

03:04 So interleukin-4 will cause B-cells to class switch to IgE production, but gamma interferon will prevent that happening - antagonist.

03:14 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.

03:24 So why don’t we look at cytokine receptors for a few seconds.

03:29 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.

03:42 But here we have a dimeric cytokine receptor.

03:48 When the cytokine binds, it causes dimerisation of the receptor as we can see here.

03:55 And that will initiate a signaling cascade.

03:59 So JAK kinase will cause phophorylation of sequences within the cytoplasmic region of the cytokine receptors.

04:09 This leads to the recruitment of STAT, and further phosphorylation events occur.

04:16 STAT then dimerizes and ultimately, the result will be gene transcription.