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细胞毒性T细胞如何被I类MHC激活/抗原复合物以及继而消灭被感染的细胞. Sal Khan 创建




when we learned about antigen presenting cells we learned that they can first digest something let me draw a dendritic cell right here my best my best version of a dendritic cell maybe I should draw them simpler than that a dendritic cell is a phagocyte and it is an antigen presenting cell so after it phagocytosis some type of a pathogen it'll cut it all up and then it'll display it'll it'll present the antigen on its surface on a protein complex let me do it in a different color so it'll do it in red on a protein complex here and the part of the pathogen that it cut up it'll put up right here and we learned on the antigen presenting cell video that this complex right here was an MHC type 2 complex where MHC stands for major major histocompatibility histocompatibility compatibility complex where histor cut histocompatibility just means tissue compatibility and this was the case on antigen presenting cells so even b-cells did this so let me draw a b cell so a b cell it has its membrane bound antibody just like that it actually has many many thousands of these I could keep drawing a bunch of them but just so you know there's not more than one maybe one of these get triggered or get attached to some type of virus or or protein or bacteria floating around and what it'll do is it'll take this in it'll take this in and cut it up again and cut it up and do the same thing is what the dendritic cell did it'll cut up a part of this and present it and present it on so I've made this in pink so I'll make it in pink right here a little part of this virus it'll present it on its surface in in conjunction with an MHC 2 complex so once again this is an MHC 2 complex so these professional antigen presenting cells that go out and take things out of the fluid out of our out of the Shu roll parts of our body things just floating around they'll take them in let's say this is bad cut them up and then present them on these MHC 2 that's what we call them professional antigen presenting cells now it turns out that pretty much all cells in our bodies all cells so let me draw just a random cell on my body and I say almost all cell it's actually all nucleated cells so all cells that have a nucleus in the human body so the only cells on a human body that don't have nucleus is our red blood cells which I find fascinating it's so that they can have more space for storing hemoglobin but it all nucleated cells in our bodies have another major histocompatibility complex on it and it's called an MHC 1 mhc1 major histocompatibility type 1 and just so you know these are also nucleated cells so they're also going to have an MHC type 1 complex on them right here now the interesting thing about the MHC type 1 complex is because it's on every cell in our human body let me write that down every nucleated nucleated cell so pretty much everything but the the red blood cells have an MHC one this is where if anything wacky is going on inside the cell maybe the cell is cancerous and producing crazy proteins maybe it's been infected with a virus maybe some type of bacteria some type of weird protein has gotten in here any cell in the human body can cut those up even if it's malfunctioning and it will present them so let's say the cell is cancerous so this cell is cancerous and it has all these wacky proteins that only cancer cells present that is not normal for a normal cell that will be presented on the MHC one let's say that I have some other cell in my body let's say I have some other cell in my body that's a different type of cell it's nucleated let's say it's been infected with a virus so you have this virus so it's turning into this virus Factory those are trying I'm trying to draw hexagons same thing there are mechanisms in the cell that will take some of the pro teens that are that make up those viruses and present them on the MHC one complex so it'll present parts of the proteins on the MHC one complex so in the case of MHC two this is what triggered helper t-cells to say hey you know what I found something floating out here here's a little piece of it mr. helper t-cell why don't you bond to this and raise the alarm system now in the MHC one system says you know this isn't stuff floating around I've been infected I am cancerous I am going nuts you better kill me I'm a virus I'm a virus making machine you better kill me and that message goes to the cytotoxic T cells and that's really the topic of this video so just to make sure you understand the difference so T cells they both have T cell receptors but the helper T cells bond to MHC two complexes so if this was a helper T let me scroll up a little bit no I'm I'm space up there let's say that this is a helper T cell right here it would it would want to it's and it's not all helper T cells well only the ones that have the right combination the right variable portion right here that just perfectly bonds to this combination of an antigen and the MHC 2 complex this type of of of helper cell of helper T cell will bond here get activated and start differentiating and the effector versions of them will start raising the alarms and the memory versions of them will stick around in case this type of thing needs to happen again with MHC 1 instead of attracting a a helper T cell it will attract a cytotoxic T cell so let me draw a cytotoxic T cell right here so like helper T cells the T cell receptor it has a non variable portion it has a non variable portion but it also has a variable portion that is specific that is specific to this compensation of antigen and MHC one so maybe this type this help this cytotoxic T cell will be involved when this cell goes cancerous a different this cytotoxic T cell would be of no use or it'll just not it won't be it won't bond to this one that was attracted to a virus it's gonna have to be another cytotoxic t-cell that does that and the mechanism where we get this variability in the helper T cells are the cytotoxic T cells or you saw in the B cells on their membrane bound antibodies that all comes from when they're in their development stage there's a once they start to more in the maturation process that the the the DNA that codes for these variable portions get shuffled around intentionally so normally we're always trying to preserve DNA information here it gets shuffled around but anyway once a a cytotoxic t-cell finds one of these guys on an MHC one remember every nucleated cell in the body has an MHC one then what it does is it gets activated so let's say this guy says hey that's look shady you know you need to die so this guy gets activated and just like all other activated cells he starts to divide and divide and divide and divide and differentiate and he divides and he differentiates into memory just in case you're gonna need me again just in case this type of cancer shows up again and then also into effector T cells which are the ones that do the killing which are the ones that do the killing so this is an effect or so let's say one of these effectors they'll also bind to cancerous molecules cancerous cells just like this one so let's say I have another you know say this cell has split and there's another version of it right here that's what cancer does it divides aggressively it's producing wacky proteins it presents the wacky proteins on its MHC major histocompatibility type 1 complex that the play displays the wacky proteins and then one of these effect or cytotoxic T cells will be attracted will be attracted to it just like that and I'm not going into the details and what necessarily does the attractions and all the membrane bound proteins if you take an immunology class you'll see more on that so this is a cytotoxic T cell and it essentially forces this cell to kill itself in a couple of different ways one it dumps it actually can xoxo site owes a bunch of proteins they're called perforins that make little holes that make little holes in the membrane of this cell and then it has other proteins that it releases called granzymes that go in here and essentially start mechanisms that make the cell want to kill itself so the big picture is if you want to just take you know 20,000 feet B cells are very effective at at at at producing so when a B cell gets activated it produces antibodies that kill things that are floating around right once a B cell gets activated starts producing a bunch of antibodies these antibodies float around and then they can bond up to viruses make them ineffective or essentially tag them for pickup from macrophages or dendritic cells or other types of phagocytes while while cytotoxic T cells these are used to essentially kill cells that have gone awry for example a cancer cell that's presenting weird proteins or once the virus has entered the cell then the antibodies are really of no use the antibodies aren't gonna be able to get into those cells and though in that case instead of cleaning up the virus itself a cytotoxic T cell will come here and just kill this cell because this cell is a virus factory so you have to get it out of the way