Functional Modes of Cytokines and Cytokine Receptor Signaling – Cell-Mediated Immunity

by Peter Delves, PhD

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    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.

    About the Lecture

    The lecture Functional Modes of Cytokines and Cytokine Receptor Signaling – Cell-Mediated Immunity by Peter Delves, PhD is from the course Humoral Immunity and Cell-Mediated Immunity. It contains the following chapters:

    • Functional Modes of Cytokines
    • Cytokine Receptor Signaling

    Included Quiz Questions

    1. IFNγ
    2. IL-5
    3. IL-13
    4. IFNβ
    5. M-CSF
    1. Macrophage activation
    2. T cell proliferation
    3. B cell proliferation
    4. NK cell activation
    5. Enhanced adaptive immune response
    1. The JAK-STAT pathway would not be initiated and the target cell gene transcription would be unaffected.
    2. Janus kinase would be up regulated.
    3. STAT would be directly inhibited, making it incapable of effecting the target cell gene transcription.
    4. Cytokines would not be able to reach the nucleus of the target cell.
    5. STAT dimers would proliferate in the cytoplasm of the target cell.

    Author of lecture Functional Modes of Cytokines and Cytokine Receptor Signaling – Cell-Mediated Immunity

     Peter Delves, PhD

    Peter Delves, PhD

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