Unit 4 Video 33 Chapter 15
So in continuing our conversation about immunosuppressive drugs let’s talk about compounds that suppress the t-cell response t-cells are central to the immune system helper t-cells are required to activate b cells as well as a cytotoxic t cells cytotoxic t cells are damaging to the body they will kill cells so there are a number of instances where one would want to
Suppress t cells keep their activation low again this could occur for individuals who have organ transplants because many times tissue rejection is mediated by a low reactive t cells or it could be for individuals who have an autoimmune disorder in which t cells are playing a role in the autoimmune response so let’s look what a number of different compounds that
Suppress t cells and all of these might be used in different instances they all have pluses and minuses so they’re not all used for all types of hypersensitivity reactions they’re used in particular ones where they have been deemed successful so right now let’s look at it here the t cell a general t cell with a t cell receptor it’s got the t cell receptor alpha beta
Proteins i’m drawn in some cd3 proteins and the sata protein – which is the intracellular protein that you becomes phosphorylated on items and when the t cell receptor engages a peptide mhc complex the t cell receptor will send a signal to the nucleus so that t cell will activate so there are many compounds that inhibit t cells some of which inhibit signaling from
The t cell receptor and one compound which we’ve spoken to previously is cyclosporine which is a compound isolated from a soil fungus and that compound primarily affects t cells signaling from the t cell receptor 2a into the nucleus to either activate that t cell or trigger the t cells effector function so cyclosporine can suppress both naive t cells from activating
As well as effector t cells there’s another compound that is similar in function to cyclosporine called tacrolimus which is another compound where isolated from a soil bacterium actually this time also inhibits signaling from the t cell receptor so again can inhibit the activation of naive t cells or can inhibit the effector function of t cells the next compound
Will talk about inhibits signaling from the il-2 receptor if you recall il-2 is the cytokine and one of its main functions is to signal in a paracrine or an autocrine manner from t cells either to themselves or to neighboring t cells and induces proliferation of t cells so if we inhibit the signal from the il-2 receptor we’re going to inhibit the proliferation of
T cells and there’s a compound called repre myosin also known as a serie limas which is isolated from a soil bacterium and that inhibits the signaling from the il-2 receptor into the t cell so that would inhibit the proliferation of t cells that occurs during t cell activation what else is there well if you recall to activate a naive t cell they you need engagement
Between the b7 molecule present on the surface of antigen presenting cells specifically professional antigen presenting cells and the cd28 molecule on the surface of t cells so this is an interaction protein-protein interaction that’s required to activate naive t cells so scientists have been able to exploit this interaction blocking it and therefore inhibiting
The activation of naive t cells they’ve done this by exploiting a natural signal in the body so there’s another molecule on the surface of some cells called ctla4 that is very similar to b7 in that it also binds cd28 but it does the opposite of b7 when ctla4 the protein parent on the surface of some cells which we won’t go into when that binds cd28 that actually
Inhibits cd28 signaling into the nucleus so it’s blocking that b7 from interacting with cd28 and that t-cells don’t activate so this is a natural way in the body for the body to regulate the activation of t-cells so the body has a natural way to suppress the activation of night t-cells and that’s by using ctla4 to bind cd28 so scientists have known this for a while
And decided well what if we made a synthetic version of ctla-4 and that’s exactly what they did so there’s a protein that is now a drug it’s called bella terra septon hello bella tarr cept and it is a protein composed of this extracellular portion of ctla-4 so when this protein is administered it will bind cd28 molecules so he will prevent cd28 from binding b7 and
Therefore prevent activation of naive t-cells so these are 1 2 3 different mechanisms to inhibit t cell at t cell either function or t cell activation or both and again why wouldn’t you know we want to suppress t cell function it could be because of autoimmune reactions that are responsible for damaging self we get the t cells from decided to recognize self for
Some reason so some individuals who have autoimmune disorders they take these compounds or individuals who have other high types of hypersensitivity reactions either allergic reactions or in the case of organ transplantation if we want to suppress those a low reactive t cells that might recognize the donor organ as foreign we can just suppress t cell responses so
These compounds work on both cd4 and cd8 cells so they’re going to prevent each cd8 cells from killing cells but prevent cd4 cells from helping other cells the reduced inflammation and wiesel activation so these compounds can suppress the t-cell response isn’t that going to suppress the immune system and the answer is yes these drugs do suppress the normal immune
Cell function of t cells so individuals who take these compounds will be more susceptible to infection but that’s a cost for wanting to suppress the immune system because the immune system is hurting the body
Transcribed from video
Immunosuppressive drugs part 2 By Joe DeMasi