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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. Autocrine
    2. Paracrine
    3. Endocrine
    4. Exocrine
    1. Interleukin 4
    2. Interferon gamma
    3. Tumor necrosis factor alpha
    4. Interleukin 2
    5. Granulocyte colony stimulating factor
    1. Interferon gamma
    2. Granulocyte colony stimulating factor
    3. Interleukin 2
    4. Interleukin 4
    5. Tumor necrosis factor alpha

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

     Peter Delves, PhD

    Peter Delves, PhD


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