Immunology | T- Cell Development

all right Niners what we're going to do in this video is we're going to talk about te- cell development all right before we do that let's understand where is the actual te- cells being made okay so if we look here in this diagram just give you kind of a look at the anatomical structures here we're going to have our red bone mirror here where the actual tea cells are being produced and then we're going to have our blood vessel which is going to be our sinusoidal capillaries that they could be pushed into but then we're

going to take this what's going to happen is we're going to follow this t- cell over here into this blue structure right here which is called the thymus gland right and then we got the thymus gland uh specifically we'll talk about this in just a second actually we'll come back to this but again what we're going to need to know is that the te- cells are produced within the red bone marrow and then what's going to happen is they're going to have to get sent to a primary lymphoid organ which is called the thymus gland

where they're going to be able to mature and undergo specific types of selective processes which we'll explain in detail all right so let's go ahead and dive right into this right so we have here in the red bone marrow if you remember we had that lymphoid stem cell and when it went over to all these different types of Divisions It produced your B cells and your t- cells let's follow our T cells out of here so let's say right here I have this t- cell right here so this is our t- cell but it's going

to be kind of like a precursor so this is our t- cell but it's like a precursor t- cell so it's not completely mature yet it's it's not at the point where we can actually put that thing into specific secondary lymphoid organs and we'll talk about that so what happens is this t- cell it's going to get put into the bloodstream but how does it know to go to the thymus gland that's what's going to be cool so if we come over to the thymus gland for a second so here again this is our thymus

gland and where would we find the thymus gland the thymus gland is actually located it overlies the heart so it's located within this mediastinum right which is like a cavity that's located within the thoracic cavity right and it houses the esophagus it houses the heart it houses the trachea and the other different types of structures right so again this is going to be located within the medyum and it overlies the heart now the thymus gland is what's called a primary lymphoid organ so it's a primary lymphoid organ what does that mean so this is the

one that's actually going to allow for tea cells to develop completely the other primary lymph oid organ is the red bone marrow that's where the B cells develop right okay so this primary lymphoid organ it's primarily going to be functioning during the younger ages of life so during the infancy and during the childhood and up to early early adolescence right but once we hit to the early early ages of adolescence the thymus gland activities begins to decline and then it starts to atrophy and then it just becomes filled with fibrous tissue and becomes pretty much

non-functional so again remember that that the thymus gland is specifically functional at Young ages like during infancy and childhood and early early adolescence but as you start to get older it atrophies means it getting smaller and then on top of that it gets filled with fibrous tissue and actually becomes nonfunctional so let's see what does the thymus gland do that kind of draws these te- cells over to him so that they can undergo specific types of selection and maturation it secretes specific types of chemo kindes right so these chemotactic agents what are these chemotactic agents

that it's secreting that are drawing these te- cells into this area these chemotactic agents there's a couple of them one is actually going to be called thymosin another one can be called thyoxin another one can be called thop potin and then there's other ones that because thop you actually you know specifically uh actually we put thop because thop potin no yeah we can put thop I'm sorry I'm think I was thinking about throp but thop potin specifically he also helps to be able to draw these t- cells to the thymus clam another one that's really

really important is just generalize thymic factors okay so what are these chemicals right here these chemicals are acting to be able to draw this t- cell towards the thymus gland so they're initiating what's called this chemo taxis if you will right so this chemotax is trying to draw this T Cell precursor into the thymus gland so now this T cell is actually going to start tracking its way to the thymus Clan so now that it's got received the stimulus from these certain chemicals it's now going to start moving its way where towards the thymus Clan

where it's going to undergo specific maturation processes okay so now now that we know exactly what's happening with this T cell and how it's getting to the thus gland to mature now we can go ahead and zoom in and see exactly what's happening at the molecular and cellular level okay okay so if you look here guys we have our thymus gland and we're just really really zoomed in on it now okay so we have our thymus gland here which again is a primary lymphoid organ and then if you look over here I just basically have

the spleen okay which is a secondary lymphoid organ and a lymph node which is another secondary FOID organ let's go ahead and start right here and work our way towards the left going with each type of event all right so we have our T Cell right here right now this te- cell it has its DNA and it's basically it's a te- cell it hasn't undergone any different no mechanisms have been acted on upon it yet right so it has it doesn't really have any different types of receptors on it and I'll explain what those receptors

are those proteins but what happens is if you remember those chemicals that the thymic cells were secreting so here's our thymic cell this is a thymic cell or an epithelial cell within the thymus right it's secreting those chemicals if you remember them again thymosin thop potin thymic factors so many many different types of chemicals what is that doing that's acting on this T Cell so when it acts on this te- cell it stimulates the te- cell's genes a specific cell of genes though and these genes produce a very very very important product and these enzymes

that they're actually produced are called rag one and rag two why did I mention these all right here's why when these genes get activated and they produce these proteins called recombinases so rag one and rag 2 what recombinases do is they basic basically Shuffle the DNA so when they Shuffle that d they produce different types of proteins for different types of antigens so what is it going to produce on its actual surface so these rag ones and rag twos are going to act on specific genes Shuffle the DNA and lead to the production of a

specific protein which is called a TCR so this is called a TCR which stands for T Cell receptor now why did I mention this rag one or rag two what's the specificity of it if I have an antigen here some type of foreign antigen and it's circular if I have some type of antigen and it's a square antigen or a triangular antigen and this is foreign this TCR that we're making has to be able to recognize any of these foreign antigens so the recombinases might activate and Shuffle the genes to produce a TCR that fits

this circular antigen then it might make a TCR to fit this Square antigen and then it might make a TCR to fit this triangular antigen right but all of these TC RS are different from one another and unique and that's because of these recombination enzymes all right that's enough about that these chemicals are also activating other genes and these genes are they're uh let's say that we have another line coming down here activating another set of genes and these genes are producing what's called CD proteins or cluster differentiation proteins so let's draw one here in

Black let's say this protein right here is actually going to be let's say this is cd8 so cluster differentiation eight and let's say that this uh red protein right here that we're going to draw is going to be another cluster differentiation protein but this one's called CD4 so what's happened here in this first step here this is where most of the stuff is actually occurring this these chemicals thymos and thop thymic factors are stimulating this T Cell precursor to make tcrs but different types because of the rag one and rag two cd8 molecules and CD4

molecules now this t- cell comes over here look at it it's such a beautiful thing right this whole process it's unbelievable how all these things happen but again what will this guy have on his membrane he'll have a CD 8 he'll have a CD4 and I'll mention why these proteins are really significant so it has a CD4 and then it also has a TCR looks like a bunny all right so now this thyx cell is going to present some specific types of molecules on its cell membrane so let's say one of them it presents specifically

binds with cd8 all right so this molecule specifically binds and only with CD and this molecule is called mhc1 okay and CDA binds with them perfectly it's a good binding it's not too not too strong but it's just the right type of binding right then CD4 it comes and it perfectly bonds with CD4 and this molecule is called mhc2 and these MHC stands for major hysto compatibility complex type one and type two these two molecules have recognized and interacted with these MHC molecules if they do interact with these MHC molecules that's a good thing they've

positively selected did this so this right here this event where they recognize them is called positive selection because they recognized these t- cells recognized the thymic cells mhc1 and mhc2 molecules appropriately okay if it doesn't recognize this what's going to happen this cell will undergo apoptosis because we need these cells to be able to recognize these mhc1 and mhc2 so again if this TC it cd8s and it cd4s don't bind with the mhc1 and mhc2 then it'll undergo apoptosis so again if this guy does not if this t- cell if it cd4s and cd8s don't

recognize these MHC molecules appropriately and respectively what's going to happen it's going to undergo apoptosis how does that happen well these thymic cells we're not really concerned with the whole mechanism but just know that it secretes these specific chemicals I'll just mention it anyway it's called f and f basically works on this specific receptor here on the actual t- cell and triggers the genes to undergo what activate specific genes to produce apoptosis okay but that's if it does not recognize class one and class two all right but he survives let's say this guy survives like

hooray okay we go to the next step so what's the next step okay now it's this guy's turn now I didn't show show it specifically here but I'm going to show it now so let's say here I draw mhc1 molecule right so here's this MHC one molecule same thing from over there this blue molecule right here that I'm going to draw is still the same thing it's the MHC 2 molecule right now these guys are going to have always like a self peptide that's a part of these MHC molecules and usually they put it like

right here right so let's say goes specifically right there now this t- cell if you remember what did it have I'm going to draw the CD protein a little bit different now so this red one is going to be CD4 and again this black one is going to be cd8 which are interacting appropriately with the class one and the class two but if you remember what other structure do we have we had that TCR now the tcrs of this t- cell if it recognizes these self antigens or these self peptides that is not a good

thing that means that in the future these tea cells could go and interact with our own tissues and then if it does interact with our own tissues and it causes damage to our tissues that can lead to autoimmune disorders so we don't want that so in other words I don't want these tcrs to recognize my own self- peptides or self antigens I only want it to recognize foreign things so what does it do so again so for example that one was circular let's say that this structure right here is like jaggedy so it's not interacting

perfectly right so that's a good thing and again let's say that this one was circular right here and this one was jaggedy and that TCR doesn't fit this self antigen it doesn't interact with it and if it doesn't interact with it that's a good thing that's called negative selection okay but if this TCR fits perfectly in binds to that self peptide that's not a good thing and that cell will undergo apoptosis right so again why will it undergo apoptosis if this te- cell has its TCR recognized these self peptides and again how will it cause

apoptosis it'll secrete the chemical called f and f will bind onto a specific receptor and Trigger this Pathway to lead to apoptosis so it's finished such a great thing here we've gone through how many steps so Far We've gone through the first step we've gone through the Second Step it's got one more thing that has to do before it can finally be a functional t- cell so it's done all of this test perfectly it comes to this last Point here and at this last Point here we're going to draw these molecules again let's say I

have this th let's actually say I have two thymic cells one here one down here and this t- cell has a choice it's got his choice but really it's random so let's say down here I draw an MHC C1 molecule okay so that's my MHC one molecule and let's say up here I draw specifically a mhc2 molecule if you remember what's this cell right now this cell that we had he is TCR positive CD4 positive and cd8 positive so he has all of these different things that he needs to interact he comes over here and

let's say just by perfectly random chance I know it seems crazy but just by perfectly random chance the CD4 molecule on this t- cell interacts with the mhc2 so just perfectly this CD4 molecule here interacts perfectly with the mhc2 molecule but it doesn't it CDA doesn't interact with the class one this T cell is going to specifically what's going to happen is if it interacts with the class two the genes will downregulate the cd8 molecule so if you remember here was the cd8 but let's say that this interaction doesn't happen and that this T Cell

only has a CD4 interact with mhc2 if that reaction only happens you'll upregulate these CD4 molecules and you'll down regulate these cd8 molecules what does downregulate mean you'll decrease the number of cd8s what does U regulate me you'll increase the number of cd4s so what would this cell look like for example and I'm not going to draw all the CD4 for is perfectly I'm just going to draw red markers on this I'm just going to draw little red dots here there's a whole bunch of red dots there representing the cd4s and we might have at

this point in time maybe one cd8 right that's it this is this cell right here if it has all of these nice little beautiful cd4s and again what else would it have here I'm just going to draw these in purple these tcrs these T cell receptors and it down regulates all these cd8s and up regulates all these cd4s this cell is specifically a t helper cell okay now let's say that this let's say another T Cell comes through so another t- cell comes through and it's by random chance I know it seems crazy but by

random chance this cd8 molecule perfectly interacts with the mhc1 molecule and this interaction between the CD4 and the mhc2 interaction doesn't occur this cell will downregulate his CD4 molecule so in other words he'll decrease the amount of cd4s and he'll upregulate his cd8s because he interacted with the class one so now let's draw this molecule here so again what we have all out of on the surface these cd8 molecules there and again he'll start down regulating he shouldn't have I'm just showing it for an example this T helper cell shouldn't have any cd8 molecules I'm

just giving you the idea that it should downregulate the cd8s for this t- helper same thing with this guy he shouldn't have any CD4 molecules I'm showing it to you as an example that these CD4 molecules will be downregulated and completely diminished right but again it'll have a lot of these cd8s and it'll also have a lot of tcrs right so this is our TCR T Cell receptor this cell specifically called a t cyto toxic cell okay one last one but it's the easiest one some of these cells it's it's really weird these cells some

of these t- helper cells can become T regulatory cells and some of these cytotoxic te- cells can become t-regulatory cells so I'm going to draw this right up here then and on what I'm saying here again is that some of these cells some of the CD4 cells and some of the the actual CDH cells can literally become so let's say I have two of them over here they can become T regulatory cells in these T regulatory cells again what can they have on their membrane they could have CD4 molecules and what else would they have

tcrs you have to have the tcrs these purple molecules right here but this other cell he would have cd8 molecules and these cd8 molecules as well as TCR molecules now I know this seems weird because I just said this was a t- helper cell and this was a t-cytotoxic cell through certain types of cyto kindes these actual T helper cells and T cytotoxic te- cells can differentiate into a specific type of cell and this is called a t regulatory um sometimes they call them suppressor also Al cells and these are very very important for being

able to regulate um prevent these uh regulate the activity the te Helper and the tea cytotoxic to prevent autoimmune diseases little piece of it there is a specific mechanism of how these guys can go into forming te regulatory I'm not going to hit too much into it but they say it's due to certain types of proteins that's present on this guy like maybe the cd25 and certain chemicals like interlukin um 2 that can regulate this activity but nonetheless just know t- helper cells and T cytotoxic te- cells some of these guys can get converted into

T regulatory okay so we formed all our three cells all of our three T cells that we need now what happens now these guys go and get specifically put into different lymphoid organs what is some of them let's just say I draw with one cell here one cell it could be any of these these guys coming right in here so what are these little black cells right here these little black cells are called te- cells and they can go to the lymph node and they can park themselves right there in the Deep part of the

cortex of the lymph node where else could they go they could come in here into the spleen and in the spleen what's important is that these te- cells literally form right around these red blood vessels that we have drawn right here these capillaries called sinusoidal capillaries they come and Surround these blood vessels and form what's called periarteriolar lymphatic sheaths and or specifically they just call it white pulp they make What's called the white pulp so again what can happen these te- cells can go to the lymph nodes and park into the deep part of the

cortex or they can surround these uh specific cido capillaries and form what's called White pulp or periarteriolar lymphatic sheaths and another place you see these t-regulatory cells there's a specific place for them they literally come into this specific area into the thymus gland where they're primarily going to be this where a good concentration of them could be but they can be again they could be all over the place too they could be in the uh the spleen as well as the lymph noid lymph node but they've been found to be concentrated in the thymus gland

in a specific area which is called the hassal cor pusles or the uh thic cor pusles okay so again in brief it would undergo this T Cell will undergo positive selection it'll undergo negative selection positive meaning it recognize mhc1 and mhc2 negative selection meaning it does not recognize the self peptide or the self antigen then after that by random chance it'll either get if it CD4 interacts with mhc2 it'll form a CD4 cell or a t- helper if by random chance the cd8 interacts with the mhc1 it'll actually turn into a t-cytotoxic and then some

of these t- helper cells and t-cytotoxic te- cells can be converted into T regulatory cells maybe through a cd25 interlukin 2 interaction right and then these cells all of these cells can be sent to secondary lymphoid organs like the core deep part of the cortex in the lymph node or the white pulp within the spleen or the hassal Cor pusles in the thymus and there's other different areas too besides that they can go to the tonsils they can go into the um the mucosa Associated lymphatic tissue which could be in your respiratory tract your urogenital

tract they can be all over the place right but again know that this is the entire process starting from where where do we start and an overall Outlook starting in the red bone marrow that's where they're made they're made within the red bone marrow but they mature in the thymus and then from there where can they go they can go to secondary lymphoid organs where they'll carry out their functional processes all right Engineers I hope that helped take it easy