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辅助性 T 细胞

辅助性T细胞和B细胞的活化作用简介。 Sal Khan 创建




in talking about the adaptive immune system we've already seen that there's a couple of actors let me write this down adaptive or specific immune system adaptive immune system you have your humoral response humoral so this is responding to things that are floating around in the fluids of the body and not necessarily things that have infiltrated your body cells and then you have your cell mediated cell mediated response so mediated and then in the humoral response and we're talking about specific humoral response this is where the B cells the B lymphocytes are at their most active and essentially what they do is you got a B cell here it has a very specific antibody specific to just this B cell not B cells in general if this happens to be the one of the billions of B cells that happens to have the matching key or maybe I should say the matching lock for the key that is the intruding pathogen that pathogen will bind to that B cell maybe it's a virus maybe it's a bacteria and then the B cell will get activated and we'll talk about in this video that the activation doesn't always happen in fact it usually doesn't happen just from this but so far we've said it gets activated it goes into memory cells memory B cells which are essentially multiple versions of this original B cell just saying hey let's have multiple versions of this because it tends to recognize this virus so in the future if we get this virus those multiple versions those memory cells are going to be there to do to have this interaction this interaction is going to be more likely to happen in the future because I'm gonna have more of this variety of B cell and then you have effector cells effector cells and these are essentially so both of these are B cells so this guy's once he gets activated he proliferate he keeps dividing and cloning himself the memory cells just stick around waiting to be activated in the future and I'm only drawing one of these membrane bound antibodies but they're actually 10,000 on I mean I could draw a bunch of these you know I don't have to just draw one the memories just wait around in the future but there's more of them now so in the future if we get this virus again there's the reaction the this interaction is going to happen faster and so they're going to get activated faster and then the effector B cells essentially turn into antibody factories so they just start this antibody goes in alright it says let me just produce I've been activated let me produce many many more versions of that exact antibody so they get spit out let me add I drew that one a little wrong so that exact antibody that can then be spit out to go disable or tag antigens and not just any antigen this antigen this antigen right here and we also saw that the other thing that the B cell does is it becomes an antigen presenting cell so what it does is as soon as it recognizes this it's been it's been it's had this interaction with an antigen just matches the variable portion of its membrane bound antibody it endocytosis that it brings that into itself it's getting membrane facilitated so it just kind of pulls it in chunks it up and then presents a piece of that antibody on an MHC 2 molecule we saw that in the last video so it takes a cut set up and presents a piece of it right there and that's why we call it an antigen presenting cell now in this video we're going to talk about why we even have these MHC 2 molecules what are we presenting these antigens to and so we're gonna start talking about the cell mediated and actually even more than the cell mediated we're gonna talk about T cells so we're gonna talk about T cells and I said in the first video they're called T cells because they mature in the thymus mature in the thymus and there are two types of T cells and it's all very confusing you have B cells and T cells but then there are two types of T cells you have helper T cells helper T cells and most people just write T with a lowercase or subscript H there and then you have cytotoxic T cells or T cells that kill other cells cytotoxic t cell and that's T with the subscript C now just so that you have a big overarching impression of what does what B cells when they are activated they generate antibodies that's if 30,000 feet that's the best summary of what an activated b-cell does it actually generates antibodies those antibodies attach to viruses and bacteria and other types of pathogens and disables them either tags them so that other so that macrophages can go and eat them up or it just by throwing all of those antibodies onto the surface onto the surface of the pathogen in question it might disable the pathogens or essentially bundle them all together so that'll be easier for macrophages to pick them up but this is only effective for things that are floating around antibodies free floating antibodies are only effective for things that are floating around side of toxic t-cells which I'll cover in more detail in a future video these actually attack cells that have been infiltrated so this is attack kill infiltrated infiltrated cells and when I say infiltrated it could be a cell that a virus has gone into or some bacteria has penetrated it and when I say infiltrate it doesn't necessarily even mean something from the outside it could even be a cancerous cell that shows itself to be abnormal in some way and so the cytotoxic T cells will at least attempt to kill them but what I want to focus on this so if you wanted out of the three types of lymphocytes these aren't remember all all of everything we've talked about is leukocytes white blood cells but lymphocytes are a subset of that and these three are lymphocytes and they're called that because they began their development in in in the bone marrow so this guy so this guy and this guy actually do stuff this guy generates antibodies that to attach to pathogens floating around this guy directly attacks cells that are broken in some way they've either been infiltrated they're abnormal they are cancerous who knows what and I'll do a whole video on that but that that leads us to a very obvious question what does this guy do what does the helper the helper t-cell do if if he doesn't directly interface either with pathogens or produce things and interface with pathogens or if he himself doesn't go and directly kill cells and the answer is that the helper t-cells kind of the the alarm of the immune system and it on some level it's almost the most important so we talked already about in the last video about antigen presenting cells that either when a macrophage or dendritic cell takes things in it cuts them up and presents it on its surface as these MHC 2 proteins or in complex with these MHC 2 complexes or proteins and so do B cells B cells they get attached but B cells are more specific now once something is presented now the helper T cell can come into the picture so this is a let's draw a let me just do a dendritic cell because and I'm doing genetic cells actually on purpose because gender it excels are actually the best cells at activating helper T cells so we're gonna talk about in a second what happens when a helper T cell gets activated so let's say I have this dendritic cell it's called dendritic so it looks like it has dendrites on it so dendritic cell looks like that so I have this dendritic cell here it's a phagocyte it's already consumed let's say it's already consumed a some type of bacteria or virus and it's cut it up and now it's presenting the kind of the body parts of that virus on the MHC 2 complex so this is M H c2 it's kind of its way of saying hey I found this shady thing floating around in the body's tissues maybe someone ought to raise an alarm maybe something maybe this is part of some type of bigger thing going on and some type of alarm bell has to be released and that's what the helper T cell does so let's say this guy he's presented it he says I found this thing I killed it here's a part of it the helper T cell has a T cell receptor on it so let me do let's say this is the helper T cell right here so this is a t-helper and it has a t-cell receptor on it and the t-cell receptors bond to and I'll be very particular here so this is the T cell receptor draw it like that it's just a protein but like the the membrane bound antibodies on B cells that are very that every B cell or almost every B cell has a different version different variable chain that's also true of helper T cells that just like just like the B cells this has some variation in where it bounds so this right here is going to be variable from one helper T cell to another for example I might have another helper T cell here that also has a T cell receptor that also has a T cell receptor but the variable portion on that T cell receptor the variable portion on that T cell receptor is different than the variable portion on this T cell receptor so this helper T cell will not bond or not bind to this genetic cell or the MHC 2 complex of this dendritic cell only this one would and the mechanism of how you get this variation is very similar to the mechanism and how do you get the variation on the antibodies and the b-cells during these helper T cells development at some point they're the genes that code for this part of this receptor gets shuffled around and they get shuffled around intentionally so that each T cell has a certain specificity to a combination of an MHC 2 complex and a certain polypeptide a certain part of a virus so only this guy is going to be activated not this guy so this is why we call it the specific immune system now we said what does the helper T cell do at that point well at this point once he says hey gee I happen to be the the the one helper T cell that can bond to this guy this antigen that's presented it becomes activated and I won't go into the details but in general dendritic cells are the best ones that activating it especially a naive t-cell meu that words important naive and naive helper T cell in general when we talk about a naive b-cell or an IE helper t-cell these are cells that are non memory non effector that have never been touched by they've never been activated in the case of a B cell they've never been activated by something bonding binding to their membrane bound antibody or a naive T helper T cell is a non effector non memory helper T cell that's never had anything bound to it so if this guy is naive and then he gets he finally gets he has a reaction with this this this antigen presenting cell he becomes non naive he becomes activated and when activated two things happen well just like with B cells they he proliferate s-- many many many copies of themselves and some subset of those copies differentiate into effector cells effect or an effector just means it does something it does something now instead of saving the memory effect our helper T cells and then some subset of them become memory memory helper T cells after getting it after getting activated now the memory T cells just like memory b-cells now you have more copies of this on 10 years in the future something like this happens this interaction is going to be more likely to happen this guys have the same T cell receptor as their parent this guy has the same T cell receptor as the parent actually both of these guys do this guy does as well it's just that the memory T cells or actually even the memory b-cells they last longer they don't kill themselves they'll last for years so that if 10 years later something like this starts presenting itself you're gonna have more of these guys around to bump into this guy so that you can raise the alarm bells and this guy's also going to have he's also going to have the same chain right there so you're saying fine I have these memory cells they're gonna stick around so this reaction can happen in the future but I still haven't answered the question what does the effector T cell do what the effector T cell does is it raises the alarm it starts releasing let me draw an effector T cell that same effectors T cell up there it's been activated so there's an effector T cell it has been act faded and it's remember this is very particular only this version of t-cells but once it got activated produced many copies of itself because it says hey I'm responding to a particular type of pathogen so that this is a helper t-cell this is an effect or and what these do is they start releasing these molecules called cytokines so they start releasing cytokines so it starts releasing cytokines let me write that down cytokines and there are many many different types of cytokines and I'm not going to go into detail and all of that but what cytokines do is that they really raise the alarm so if you have other activated other activated lymphatic cells or other activated immunological cells when they get when the cytokines entered those cells remember cytokines are really just proteins when when the cytokines enter or or polypeptides when when they enter those cells it makes them get in gear it makes them multiply more often or it makes them get more active in their immune response so what this does these cytokines you can view as chemical alarm bells chemical or peptide alarm bells alarm bells it it tells everyone to get get in gear so that's one role and so you can see this is actually a very central role and it'll it'll tell both activated cytotoxic T cells to get in gear which we haven't talked about yet and it'll also tell B cells to keep pleura frating so when in an activated b-cell gets some of so this is an activated b-cell when it gets some of these cytokines that are maybe come from a local helper T cell it'll tell it hey no divide more often divide more often only if you've been activated already and we'll talk more about why you know it has to be that case because you don't want all the B cells to be activated and then the other thing that the effector T cell does in the B cell discussion I said okay you know if I have a B cell if I have a B cell and it has its membrane bound antibody has its membrane bound antibody and remember this is a particular version it has its particular variable chain right here and that this guy binds to pathogen so this binds to a pathogen maybe it's a virus right there up to now I've been saying that this guy is activated and he's going to well when he binds to the pathogen he'll take this in and he'll take part of the pathogen he'll take part of the pathogen and cut it up and place it on an MHC 2 molecule and we've said then he'll be activated he'll proliferate and he'll differentiate into memory and effector b-cells but that's not quite true this first stage happens this guy bonds this b-cell happened to be specific to this virus cuts up the virus up puts parts of the virus on its surface and presents parts of the antigen but in most cases this b-cell isn't yet activated it's just in kind of this you can kind of view it as in this resting state ready to be activated but it hasn't started proliferating and differentiating into effector and memory molecules yet and in order for that hat to happen in order to for that to happen a helper t-cell a helper t-cell an activated helper t-cell that is also specific to this very same virus so you could imagine someplace else in the cell this virus was eaten by a dendritic cell was eaten by a dendritic cell so I'll draw an intruder excel like that so this exact same virus this exact same species of virus is eaten by that rendered Excel and so the dendritic cell eats it up it cuts it up and then it presents it on an mhm it's an antigen presenting so it presents it just like that then this will activate a very specific t-cell maybe that one so then that so the a very specific T cell will come and bump into it not just any t-cell the one with the right variable portion so think about what's happening the variable portion for this t-cell the variable portion for this t-cell it's really this part of the virus plus the MHC 2 but it's really reacting to the same virus it might be a different part this little part that was cut off might be someplace inside the virus while the epitope for the beast might be some place on the outside of the virus but they're both specific to the same virus now the once this guy gets activated and he starts producing memory and effector cells or they descended from him one of those affect yourself specific to this virus are needed to come bind to this guy so then this guy can then go along and bump around and then eventually end up here and then he is also specific to this virus so this binding site right here is the same as this binding site this combination of antigen plus MHC 2 and so when this guy binds so just like that when he binds and remember this binding site is the same as this and it only binds to this combination right here this is what activates the b-cell in most cases summed this is TT dependent activation which is usually the case there sometimes all you need is this first thing but in general you need the first thing and then you also need a t-cell to come and activate it and only then will the b-cell get activated and start proliferating and dividing and differentiating itself and producing when its effector cells will produce a lot of antibodies and so there's a natural question why why do biological systems or why do we have this double system and at least my sense of it is it's a fail-safe mechanism because if you only if every time a virus came and attached this this guy's just started going crazy and producing antibodies against this thing there is some chance there's some chance that maybe after development this guy this this chain right here or his genes for generating these chains become specific not for foreign pathogens but maybe they become specific for self molecules molecules that are naturally produced within the body and it's just a random mutation but if he started going crazy for that then he'll start his antibodies will start attacking molecules that are naturally in the body and then that could really hurt that that's that that's what causes autoimmune diseases where your own immune cells start activating yourself but if you have this double handshake system where this has to happen and this has to happen the likelihood of both of these guys become after they leave their development stage becoming specific to a self to a self protein or a self cell or a self molecule is very unlikely so it kind of inhibits this guy is just going from wild even if he has some type of mutation anyway hopefully that explains a little bit of what helper t-cells do we'll talk a lot more about it I know there can be a little bit confusing in the next video we'll talk about cytotoxic t-cells this is cytotoxic I spelled it wrong in the first cytotoxic T cell