Adaptive Immunity: T Cells

00:01 So let's talk about the effector functions from T cells.

00:05 And there are going to be two flavours of T cells that we need to deal with.

00:08 There are cytotoxic T cells and there are helper T cells.

00:12 And they will respond in different ways to dealing with infectious agents.

00:18 So, the first thing we have to deal with our infectious agents that are intracellular.

00:25 Viruses, certain intracellular bacteria, we need to be able to kill the cell that is harbouring them.

00:31 That's our only way to respond.

00:33 To kill an infected cell, we bring in cytotoxic T lymphocytes, killer T cells.

00:40 They are identified on their surface by a marker called CD8.

00:46 And I apologise for the immunologists, who named these various markers.

00:51 CD stands for cluster of differentiation.

00:54 And just knowing the number doesn't help you figure out what cell type it is.

01:00 You just have to memories it.

01:02 So cytotoxic T lymphocytes or killer T cells are also CD8+.

01:08 So that's how we recognise them.

01:11 So that CD8+ T cell needs to somehow recognise that that orange blob on the left hand side has become infected with a virus and to kill it.

01:21 How does it do that? Well, that blob on the left, any any cell in the body, is constantly surveilling its internal environment.

01:31 It's constantly breaking down proteins into peptides, and then presenting them out on their surface.

01:38 If everything that's inside the cell is normal, and is self, we leave it alone.

01:42 However, if there's an invading pathogen, an intracellular virus, those viral proteins will be broken down into little peptides, and they're presented on the surface of that cell via MHC class 1.

01:59 MHC stands for major histocompatibility complex, and it's class 1.

02:05 It's a specific kind of the MHC molecules.

02:10 So that infected orange blob is now expressing on surface MHC class 1 a normal molecule, but in it, bound to it, is a little tiny peptide that is derived from the virus.

02:22 And now specific cytotoxic T lymphocytes can recognise it.

02:27 And when they do, what they do is they release in a vectorial way vacuoles that contain granzyme and perforin.

02:38 The perforin punches holes in the target cell and the granzymes induce a proptosis.

02:44 So, the goal here is that we need to be able to recognise intracellular pathogens.

02:51 We do so via the generation of peptides bound to class 1 that can be recognised by CD8 cytotoxic T lymphocytes that will kill.

03:01 Great. Now we've identified a way to deal with intracellular pathogens.

03:05 What about extracellular pathogens? That's on the right hand side.

03:10 In this particular case, there are cells that run around the body, macrophages, dendritic cells, some endothelial cells a variety of antigen presenting cells.

03:22 So their job is to surveil the extracellular space and look for pathogens, look for microbes, look for invaders, and they're constantly surveilling the extracellular environment.

03:36 Everything that they swallow, gulp, eat, they will process into peptides that they will express on their surface with MHC class II.

03:46 So major histocompatibility complex class two molecules.

03:50 And those little peptides bound to MHC class II potentially allow helper T cells to recognise it.

03:57 If the outside world doesn't contain any new molecules, no new microbes, then all the proteins that are presented ourself, and we leave them alone.

04:08 However, if there's a microbe out there, a bacterium or fungus or whatever, the antigen presenting cell will gobble that up, sample it, put the peptide on MHC class two and display it so that helper T cells can come along.

04:23 So remember we said there are two flavours of T cells: the cytotoxic T lymphocytes on the left hand side, the helper T cells in the right hand side.

04:32 The marker for helper T cells or TH cells is CD4.

04:37 That's a way that we can tell when we do even a histochemical staining or flow cytometry, which population we're talking about.

04:45 Now the helper T cells recognise this newly processed peptide in association with MHC class II and will respond.

04:55 Now we don't want to kill the messenger.

04:56 We don't want to kill the antigen presenting cell.

04:59 Antigen presenting cell just saying, "Hey dude, there's infection going on out here." So, we want to have the T cell respond when it sees that process peptide plus class II, we want it to make cytokines, that will bring in other inflammatory cells.

05:15 So, the cytokines that are elaborated by that helper T cells are going to coordinate, regulate, activate macrophages and neutrophils and other elements of the immune system to go after that extracellular pathogen.

05:30 So two different flavours: killer T cells - recognising peptide plus class 1 on target cells and killing them.

05:39 And helper T cells CD4+, that are recognising extracellular peptide on edge of presenting cells and then orchestrating a response through cytokine production.

05:55 Cytotoxic T lymphocytes.

05:57 So they are recognising intracellular pathogen plus MHC class 1 and will kill.

06:04 And that's their major job in life, but they also will do additional things such as making cytokines.

06:13 Important point about the cytotoxic T lymphocyte is its specific killing.

06:19 Only the target will die as a result of the T cell interacting with it.

06:25 As opposed to the helper T cells.

06:28 So the helper T cells recognising extracellular pathogen peptide, in association with MHC class II on an antigen presenting cell make a whole variety of cytokines.

06:39 Those cytokines, however, just turn on the macrophages and neutrophils.

06:44 They're very potent, but they're pretty dumb.

06:47 And potentially once they get turned on, turn all their activities towards itself.

06:53 So you can have a lot of innocent by standard damage.

06:57 So the cytokines produced in this process will activate macrophages and neutrophils will recruit those effectors but there's potentially important nonspecific killing that's going on.