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.
The lecture Cell-mediated Immunity: Functional Modes of Cytokines and Cytokine Receptor Signaling by Peter Delves, PhD is from the course Humoral Immunity and Cell-mediated Immunity. It contains the following chapters:
Which of the following terms is a form of cell signaling in which the hormones secreted by a cell bind to receptors on that same cell, leading to changes in the cell?
Which of the following cytokines promotes class switching of B cells to produce immunoglobulin E?
Which of the following cytokines can suppress B-cell class switching recombination to immunoglobulin E?
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helped me alot, wouldnt be able to pass without these