Cell-mediated Injury: Polyclonal Activation by Superantigens

00:01 Very quickly, we'll talk about polyclonal activation.

00:04 So, there is a form of type four hypersensitivity that is related to proteins that are elaborated by certain microbes, this will lead to polyclonal activation, these are the so called super antigens.

00:20 What is shown here on the slide is the surface of an antigen-presenting cell (APC), it has on its surface MHC class II, and it has been processing happily all the proteins around it, and taking peptides and putting it in to its new class two molecule.

00:38 And then it presents it to T cells.

00:41 And the T cells have their receptors formed of alpha and beta components that are going to recognise the peptide and MHC class II.

00:51 And if all of the peptides in the MHC class II, ourself, then we let them go, and if they are recognised as foreign, if they come from a foreign object, that microbe or whatever, then we will elicit a helper T cell response.

01:06 Well, there's a certain class of molecules called superantigens.

01:11 Normally elaborated by bacteria, these super antigens bind outside of the peptide groove, and bind independently of any particular peptide that might be associated with MHC class II.

01:26 And what they will do is will bind to a particular subset of the V beta elements, so the variable region, beta chain of the T cell receptor, and it will cross link all of the class to on APCs and all of the V betas of that particular kind on every T cell.

01:45 Well, because T cells only have maybe six or seven V beta chains to choose from., what that means is if you make a superantigen, dump it into the system, you're going to get activation of somewhere between 10 to 20% of all the T cells, but that superantigen glueing everything together.

02:04 So as a result, the T cells are cranking out now cytokines but you're not just having a little bit here a little bit there, you're having a lot everywhere.

02:15 20% of the T cells firing all at once, and you get a resulting cytokine storm.

02:22 Examples of this are toxic shock syndrome, associated with Staphylococcus aureus, and staph scalded skin syndrome, all because those bacteria make a super antigen that can fit outside the antigen binding groove and can activate a whole bunch of T cells all at once.

02:40 So another form of T cell mediated injury.