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Cytotoxic T cells and MHC I complexes

How damaged cells present antigens from inside the cell on MHC I and are recognized by cytotoxic T cells. Created by Sal Khan.

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  • male robot hal style avatar for user Parth Agrawal
    So MHC I complexes are kind of like whistleblowers in companies that report anything shady?
    (6 votes)
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    • leaf blue style avatar for user dysmnemonic
      Not quite, because MHC-I also presents normal cell proteins. It's a bit more like samples are sent out from the cell's protein production line for quality control testing. If all of the peptides are from normal self proteins, the cell passes quality control, but if the peptides are mutated or non-self, the CD8 T cell knows to shut it down. If the cell stops presenting MHC-I, then the NK cells know that something is wrong and they can intervene.
      (37 votes)
  • male robot hal style avatar for user Michael Zero
    I'm new to this field of study so forgive me if this is a newbie question, but are there viruses that can prevent APCs from displaying peptites on MHCIs? It sounds like the human immune system would be very vulnerable to that sort of attack. If cells can't express MHCI, then how can cytotoxic cells respond to the threat?
    (4 votes)
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    • leaf blue style avatar for user dysmnemonic
      There are! Some viruses have indeed evolved methods for blocking the presentation of peptides on MHC-I. This is where the "natural killer" (NK) cells are important. NK cells are a kind of lymphocyte that can attack other cells without being primed first. One of the ways they do this is by looking for self MHC-I on the surface of a cell. If the cell has self MHC-I, it inhibits the NK cell and stops it attacking. Otherwise, if there is no MHC-I, the NK cell is not inhibited and lyses the target cell. Immunologists call this the missing self hypothesis, and it is also thought to be important for an immune response to certain kinds of cancerous cell.
      (9 votes)
  • blobby green style avatar for user poojavasanthi
    Why aren't some cancers curable? Do the 'weird' cells somehow evade detection?
    (4 votes)
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  • leaf orange style avatar for user Jackson.Justin.W
    When a B cell internalizes a pathogen, are all parts of the pathogen attached to MHCII complexes? Is it fair to say that pretty much all epitopes are presented on a B cell after exposure to a virus or bacteria? I imagine that would require the internalization of thousands of copies rather than a single pathogen. Thanks!
    (4 votes)
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    • female robot ada style avatar for user Lidiya
      Generally, almost all parts of the pathogen are attached to MHCii complexes. It does not require the internalization of thousands of copies of the pathogen, a single pathogen can be enough. This happens because the engulfed exogenous pathogen is broken down by intracellular proteases into thousands of different 14-17 amino acid long peptides, which are random bits of the digested pathogen proteins. Each one of the fragments becomes an epitope attached to the MHCII complex.
      (3 votes)
  • aqualine ultimate style avatar for user Daniel
    At , what happens if the viruses duplicate before a cytotoxic cell gets to it?
    (3 votes)
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  • blobby green style avatar for user Linda Amato
    Do the body’s cells randomly just bump into antigens and their complementary helping cells or is there any kind of attraction during any phase of this process. Also, what is the final stage for the bits of the antigens? What happen to them?
    (4 votes)
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  • blobby green style avatar for user 4deelahmed
    At , is killing itself the process of apoptosis? or is it another mechanism specific to the immune system?
    (2 votes)
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    • aqualine ultimate style avatar for user Sebastian
      Apoptosis is where a cell receives signals in order for it to kill itself. In the immune system, the cytotoxic T cells release granzymes and other chemicals that kill the cell. For example, spores may be punctured in the cell causing an increase in water intake and eventual lysing (bursting).
      (5 votes)
  • blobby green style avatar for user nbourdoud
    so what would happen if someone lacks surface MHC I molecules? Would the immune system be affected?
    (3 votes)
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  • mr pink red style avatar for user Rahul Edassery
    So shady things presented by MHC-I protein complexes from inside of a tumor cell to outside of a tumor cell is an antigen bound to the complex?
    (3 votes)
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  • piceratops seed style avatar for user ckekec
    Actually, the example of cancer cell a little confused me. Because basically a cancer cell is the cell which had mutation MORE THAN ONCE. This means they are kinda unique cells. So how can a MEMORY cell can recognize a cancer cell? I hope I explained clearly. Thank you!
    (3 votes)
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Video transcript

Voiceover: Everything we've discussed so far involved recognizing and tagging or engulfing shady things that were found outside of cells. We've seen things like a B cell. A B cell has its membrane bound antibodies. Maybe one of these might recognize something shady out in the outside of the cell and of course this part over here as we know they all have a variable portion right over here. This is specific to this shady thing then this will be engulfed and then parts of it will be attached to an MHC two complex. Let me do that in a different color. An MHC two complex and then that will go to the surface, that will go to the membrane of the cell to present itself. That's an MHC two complex. It has little bit of the little piece of this shady thing out here we call this little shady piece, this is an antigen presenting cell here. We've seen as especially if this is a B cell then a helper T cell that it also has a variable portion that corresponds to this specific antigen. This would be helper T cell right over here. This is a helper, T helper cell. When it recognizes then it will start dividing into memory helper T cells and effector helper T cells. The effector helper T cells essentially ring the alarm bells and start kind of accelerating the B cell replication or I guess you could say that the B cell activation. The theory is that this is kind of a double handshake process. Once again this is what's occurring outside of cells. When we found stuff outside of cells, we engulf them and then we presented them on MHC two complexes. Now you're probably thinking well, I mean that's the outside of cells but there's MHC two, there's this helper T cells but we've also referred to cytotoxic T cells. What do those do? We've also, if there's MHC two, there's probably an MHC one complex. What does the MHC one complex do? We can recognize shady things that are happening outside of cells but don't shady things sometimes happen inside cells and how does our immune system respond to that? Actually as you can imagine all of those things will be answered in the rest of this video. Let's think about what happens when shady things start to happen inside the cell. For example it might not even be due to a virus or due to some type of bacteria could be the cell itself is gone awry. Let's say that this right over here is a cancer cell. It's had some mutations. It's starting to multiply like crazy. This is a cancer cell and a cancer cell because it had mutations are going to produce, it's going to produce some weird proteins. These cancer cells are going to produce some weird proteins. Every cell with a nucleus in your body and that's pretty much every cell except for red blood cells has MHC one complexes. The whole point of the MHC one complex is to bind two shady things that are produced inside of the cell, and then present them to the membrane. Even a malfunctioning cancer cell should be doing this. This MHC one complex is bound to this strange proteins that are produced by the mutations inside of the nucleus and then it can present them. You could imagine what the appropriate immune response should be. These cancer cells should be killed and actually let me label this properly. That was MHC two, you're presenting an antigen that was found, those initially found outside of the cells engulfing and taken out. MHC one, it's binding to shady things inside the cell and then presenting it out. This thing should be killed. Now as you can imagine, what's going to kill it? Well that's where the cytotoxic T cell comes into the picture. The cytotoxic T cell is going to have, that's a receptor right there. It will have a variable portion that's specific to this type of an antigen and so it will bind there. Once it does that, it says, oh boy, there's all this shady stuff here, this shady proteins that are being produce. This cell and all the other ones like it need to be killed. The cytotoxic T cell will begin to replicate once again like other types of immune cells is going to replicate into the memory cells just in case this type of thing shows up 10 years in the future and also the effector themselves. This is memory and also effector cells, effector cytotoxic T cells. As we always know the effector version is the thing that actual does something, it starts to actually affect things. What it is going to affect, it is going to start binding two things that are presenting the same antigen as part of their MR on top of their MHC one complex. This character right over here, so it's presenting that same antigen on this MHC one complex. Remember, the variable portions need to match up. Let's say that this is an effector cytotoxic T cell and actually let me draw in a little bit different. Let me draw it like this. This is effector cytotoxic T cell. Its receptor, its variable portion is the one that's compatible with this antigen that's being presented right over here. Let me just label this again. This is the MHC one complex. This is an effector cytotoxic T cell. We'll put the C there for cytotoxic and what it does is essentially kind of latches on to the cell that needs to die and it does it, not only have this receptor interfacing with the MHC one complex but actually has a whole series of proteins and I'm not drawing this to scale really. This would be much smaller or relative to the scale cell. It essentially latches on between the two and I'm not going to go in detail but essentially forms what you can call an immuno synapse which is kind of where the two things are interacting with each other. When it identifies this, it says, okay, I need to kill this thing or essentially I need to make this thing kill itself. It starts releasing all of these molecules. It can release molecules like perforins so to release this preference which will essentially cause gaps or holes to form in the membrane of the cell that needs to die and it could release other things like granzymes that can go in and essentially cause this thing to kill itself. The whole point of this video is to appreciate I guess what we haven't talked about yet. We had already talked about what happens when you identify shady things outside of the cells and then how you can kind of bring them in and then present them and then use that to further activate the immune response. Now we're talking about identifying shady things inside the cells. Those get presented by MHC one complexes and then the cytotoxic T cells recognize them and then force the cell to kill themselves. This wouldn't just be cancer cells, this could also apply to a cell that has already been affected by a virus. For example a cell like this all ready, so that's its nucleus. It's already been infected by some virus so the virus has hijacked the cell's replication machinery in order to replicate itself. The proper immune response is hey look, I'm a virus making machine. I should kill myself. It will wreck some of the antigens that are being produced inside by the viruses. They're going to bind to MHC one complexes. Pieces of the virus are going to bind to MHC one complexes and then they're going to be presented on the surface. Let me do it this way, presented on the surface. This exact process can happen again.