Cell-mediated Immunity: Cytokines, Interferons, Interleukins, and Colony Stimulating Factors

00:01 We’ve heard quite a lot about cytokines.

00:04 Let’s explore them in a little bit more detail.

00:07 What exactly are they? And what exactly do they do? And how do they do it? Well, they tend to be rather small molecules, typically kind of in the range of 8-80 kilo Daltons.

00:18 They’re secreted proteins, and really they act as messengers between cells.

00:23 We can group them into sort of, five or so major groups: the interleukins, the colony-stimulating factors, chemokines, the interferons and the tumor necrosis factors.

00:43 Some people classify chemokines independently of cytokines, but essentially they are chemotactic cytokines.

00:56 They are great at multitasking.

00:59 I don’t think there’s any example of a cytokine that just does one single job.

01:03 They tend to have multiple roles.

01:05 And they have multiple functions collectively, that include control of hematopoiesis and immune responses.

01:12 And they function by binding to specific cytokine receptors.

01:17 So for example, the cytokine interleukin-1, there’ll be an interleukin-1 receptor; the cytokine interleukin-2, there’ll be an interleukin-2 receptor and so forth.

01:25 And when the cytokine binds to its receptor, it results in initiating an intracellular signaling cascade.

01:35 And this signaling can lead either to the up-regulation or down-regulation of genes.

01:41 And those genes can encode other cytokines, may encode cell surface molecules, other secreted molecules of various types.

01:51 They may be genes that control cell proliferation or control cell differentiation, or cell survival.

01:59 So let’s just go through the different groups of cytokines and pick out a few important points.

02:07 Interferons, as their name suggests, interfere with viral replication.

02:13 And there are two main types of interferon - type I and type II.

02:18 Type I are interferon-alpha and interferon-beta.

02:22 And these two particular interferons are produced by most nucleated cells of the body.

02:28 In contrast, Type II interferon which is gamma interferon, is produced by a rather limited group of cells - natural killer cells, Th1 cells and Tc1 cells, are particularly good at producing gamma interferon.

02:45 It promotes the production of Th1 cells, but inhibits the production of Th2 cells.

02:53 It’s important in activating macrophages.

02:55 And it can increase the expression of both MHC Class I and MHC Class II on the surface of cells.

03:04 The interleukins, as their name suggests, acts between leukocytes.

03:10 So that’s where the term comes; inter- between, leukocytes, interleukins.

03:15 And there are around about 40 different interleukins.

03:18 New ones are being discovered every once in awhile, and whether a particular cytokine is given the designation interleukin or given some other designation, is to be honest rather arbitrary.

03:30 Interleukin-1 is produced by macrophages and dendritic cells, and it’s a pro-inflammatory cytokine; groups of cytokines that tend to promote inflammation.

03:41 And interleukin-1 is one of those cytokines.

03:45 Interleukin-2 is characteristically produced by Th1 cells, and it promotes both T and B-cell proliferation.

03:53 IL-4 is produced by Th2 cells, and it promotes Th2 cell differentiation and is particularly important in class switching B-cells to produce the IgE class of antibody.

04:07 IL-10 very characteristically produced by regulatory T-cells, it down-regulates responses and therefore is anti-inflammatory.

04:15 IL-12 just like IL-1 is produced predominantly by macrophages and dendritic cells, and it promotes Th1 cell differentiation.

04:24 IL-13, product of Th2 cells, promotes B-cell proliferation.

04:31 IL-17, produced by Th17 cells is pro-inflammatory and Th17 cells also produce interleukin-22, which is again pro-inflammatory.

04:42 So these are just some, picked out of those 40 or so.

04:46 Some of the more commonly discussed cytokines that are interleukins.

04:53 What about the colony-stimulating factors? Well these are secreted by a variety of cell types, including bone marrow stromal cells, that is cells like fibroblasts and macrophages.

05:04 And there are three main types: granulocyte-macrohage colony-stimulating factor (GM-CSF), which acts early in myeloid development. Monocyte macrophage colony-stimulating factor (M-CSF), which induces monocyte differentiation.

05:22 And granulocyte colony-stimulating factor (G-CSF), which induces granulocyte differentiation as its name suggests.