Cell-mediated Immunity: Th0, Th1, and Th2 Cells

00:01 We’ve looked at various types of T-helper cell, Th1, Th2, Th17 and so on.

00:06 But these all arise from a precursor that is called a Th0 cell.

00:14 The cytokines that are secreted by dendritic cells depend on which cell surface, cytoplasmic or endosomal Pattern Recognition Receptors are activated.

00:25 And here we can see a Th0 cell interacting with a dendritic cell.

00:32 So the optimal response is determined by the Pathogen Associated Molecular Patterns, which bind to the Pattern Recognition Receptors on the dendritic cell.

00:43 So the Th0 cell could become a Th1, Th2 or Th17 cell.

00:49 Which it becomes is determined by the pathogens that are present.

00:53 And that is detected by the Pattern Recognition Receptors on the dendritic cell.

00:57 So the dendritic cell instructs the Th0 cell, which type of cell to become to be specialized to deal with a particular type of infection that is present.

01:09 It’s also influenced by the activation of other cell types.

01:12 For example, natural killer cells secreting gamma interferon.

01:16 So depending on which Pathogen Associated Molecular Patterns are present, particular Pattern Recognition Receptors on the dendritic cell will be stimulated.

01:25 And then the dendritic cell will instruct the Th0 cell, either to become a Th1 if there is lots of interleukin-12 and gamma interferon present.

01:36 In contrast, if the predominant cytokine is interleukin-4, then the Th0 cell will be instructed to become a Th2 cell.

01:45 And if there’s lots of interleukin-6, interleukin-23 and transforming growth factor beta, then the instruction will be for the Th0 to differentiate into a Th17 cell.

01:58 Looking now at the different populations of helper T-cells; once they become specialized into particular types, starting with the Th1 cell.

02:08 So, Th1 cells typically secrete interleukin-2 that helps activate cytotoxic T-lymphocytes, gamma interferon that helps activate macrophages.

02:23 Interleukin-2, also is able to activate B-cells.

02:29 And gamma interferon down regulates the activity of Th2.

02:36 So overall, Th1 cells activate cyctotoxic T-cells, activate macrophages, activate B-cells but inhibit Th2 cells.

02:51 Let’s have a look at exactly how Th1 cells activate cytotoxic T-cells.

02:57 So here we have a Th1 cell, it’s interacting with a dendritic cell.

03:04 The Th1 cell is CD4+, so it will recognize peptides presented by MHC Class II.

03:11 In contrast, the cytotoxic T-cell is CD8+, and therefore will recognize peptides presented by MHC Class I.

03:18 And these two cell types can both be sitting on the surface of the dendritic cell, because remember dendritic cells express both MHC Class I and MHC Class II.

03:30 Following activation, the Th1 cell will secrete the cytokine interleukin-2 amongst other cytokines.

03:38 And this cytokine can be detected by interleukin-2 receptors present on the surface of the cytotoxic T-cell.

03:47 This will lead to activation of the cyctotoxic T-cell.

03:52 This cell can then leave the environment where it’s been activated, for example in a lymph node, and seek out where the infected cells are, and then subsequently kill them.

04:04 Regarding the Th1 activation of macrophages, the macrophages are also MHC Class II positive as well as being Class I. And therefore they can also present peptides to the CD4+ Th1 cells. So here we have a macrophage containing phagocytosed bacteria, and a Th1 cell releasing the cytokine gamma interferon, which again will be detected by a specific receptor for that particular cytokine that is present on the macrophage; in other words, the gamma interferon receptor. And that will lead to activation of the macrophage. And the macrophage will then up-regulate its microbicidal mechanisms, resulting in the killing of engulfed microorganisms.

04:57 Regarding Th2 cells, they typically secrete the cytokines interleukin-6, interleukin-5 and interleukin-4.

05:04 And those cytokines are very helpful in activating B-lymphocytes.

05:09 The cytokine interleukin-5 is also really good at activating eosinophils.

05:17 Just like Th1 cells can down-regulate Th2 cells, so Th2 cells by virtue of the fact that they produce interleukin-4 can down-regulate the activity of Th1 cells.