 Welcome back to our meds smarter lecture series where we're taking a smarter approach to preparing future physician Before we get started if you'll take just a quick minute and click that like button and also Subscribe and turn the bell on so that you'll be notified when we post new videos Let's continue on in our discussion of T cells and talk about the differentiation of T cells So T cells undergo two different types of selection They undergo positive selection and then in a minute we'll talk about it what it undergoes is negative selection so positive selection occurs in the thymic cortex and what we're seeing here is T cells that express the TCRs that are capable of binding the self MHC's on cortical epithelial cells will survive So that is a positive selection saying we are selecting you to continue to survive, okay Negative selection occurs in the thymic medulla. So when the cortex is positive selection in the medulla is Negative selection and here we're seeing T cells expressing the TCRs that have a high affinity for self antigens undergoing apoptosis or becoming a regulatory T cell So in this case our tissue restricted self antigens are expressed in the thymus Due to the action of our autoimmune regulator or air AIR-E That deficiency leads to autoimmune polyendocrine syndrome one. What is autoimmune polyendocrine syndrome one? Well, you can remember that using C-H-A-R and I'm actually gonna give you another mnemonic in just a second to help you wrap this all together but C in Char for autoimmune polyendocrine syndrome one is a chronic mucocutaneous Candidiasis so mucocutaneous candidiasis that's chronic alongside of hypoparathyroidism Adrenal insufficiency and recurrent Canada infections So C-H-A-R chronic mucocutaneous candidiasis hypoparathyroidism Adrenal insufficiency and recurrent candida infections. So that little mnemonic without air your body will char so air AIR-E is our autoimmune regulator and Char is the symptoms associated with autoimmune polyendocrine syndrome So let's look at T cells and how they differentiate So we start here in the thymus and we have for the most part We're gonna talk about is our native T cells here the native T cells can differentiate in several different ways But for the most part what we're gonna be focusing on here is that we have different interleukens or ILS that will Give us the signal For those T cells a differentiate into different types of T cells Okay, so with the help of IL-4 and IL-33 our native T cell or our naive T cell Will come in and we'll transform into an I a T helper 2 cell Okay, that T helper 2 cell can then give off IL-10 IL-5 and IL-4 All right, if the naive T cell comes in and it comes into contact with IL-12 or interferon gamma That will transform it into a T helper 1 cell which can then get off off more interfere on gamma So this is actually how we can get that positive section where it gives off more and more and more Naive T cells Come in contact with interleukin 1b Tgf beta IL-6 IL-23 can become a different type of T helper cell T or for 17 Which gives off IL-17 and IL-6 and then finally if it comes into contact with IL-6 and IL-21 We can become a tfh Which gives off IL-4 IL-21 Let's look at this one particular section in general the naive T cell becoming T helper 1 cells that gives off interfere on gamma So in this slide, you'll see that the T helper 1 cells Secret interfere on gamma and what that does is enhances the ability of monocytes and macrophages to kill microbes that they ingest All right, this is enhanced by the use of cd 40l Along with cd 40 on the macrophages Which macrophages come in play here also because they activate the lymphocytes using antigen presentation cytotoxic T cells are involved here because the cytotoxic T cells actually kill virus infected cells They also kill the tumors or neoplastic cells as well as donor grafts By inducing apoptosis. So this is a key thing here. How to cytotoxic T cells kill They kill with apoptosis. Okay, there's many different ways that immune cells can kill various structures diseases viruses bacteria cytotoxic T cells work by inducing apoptosis How do they work? They're going to release their cytotoxic granules that contain preform proteins perforin and granzyme B They do have cd8 on their surface. So what that means is as we've saw before using the rule of eight cytotoxic T cells also bind on mhc1 on our virus infected cells If you found this material helpful for your studying, please like and consider subscribing to the channel Also, share this video so that more people can benefit from it like you have