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Professional antigen presenting cells (APC) and MHC II complexes

Video transcript
In the very first immunology video, where we talked about nonspecific defense mechanisms, we said if we had some type of a pathogen-- let's say it's a bacteria-- that our phagocytes can recognize either proteins on the bacteria or maybe it was some other type of pathogen-- some other marker on the pathogen. It doesn't know what type of pathogen it is, but that's enough for the phagocyte. It'll engulf the pathogen. So let's say this is the phagocyte. Somehow one of their receptors touches one of the proteins that's on the surface of this bacteria in this case and says, gee, that's not a good thing to have around and so it'll engulf it. So the membrane is just going to surround the pathogen-- and this part is going to go in. It's going to kind of pinch in and the pathogen is going to get surrounded and get engulfed-- phagocytozed by the phagocyte. So the end product-- we saw this on the first video where I talked about phagocytes-- is we're going to end up-- so then the membrane's going to be completely around. This is going to pinch in and bubble around this thing and so we're going to have the pathogen sitting inside of the phagocyte. It's going to be surrounded by a membrane. That membrane's called a phagosome. And we learned there's different types of phagocytes-- could be a macrophage, could be a neutrophil, could be a dendritic cell-- and we have it like this and then we also saw in that video, it's not just done-- the macrophage doesn't just digest this thing. That by itself is very useful. It got this bacteria out of the way. If this was a virus, it got that virus out of the way. But it does even more than that. It takes that and then it lyses it-- or it breaks it up. It doesn't have to actually use-- well, it breaks it up. There's several ways it can do it, but the bottom line is, it processes it. It'll break up the pathogen-- and we saw that first video on phagocytes that we'll actually have a lysosome bond to it and dump all sorts of particles that are going to break up and cut up this bacteria, in this case, into its constituent molecules. And then some subset of the leftovers, particular chains of the peptides-- and remember, proteins are long chains of amino acids. Polypeptides are short chains. So you take short chains of those and they're going to bond to special proteins. And this is essentially the topic of this video. So let's say they bond to that special protein, bond to that special protein. And then those proteins get transported or get to the membrane or the outer surface of the cell and they present themselves along with the piece of the pathogen. So the end product after phagocytozed this pathogen is that the phagocyte will look something like this and it will have these antigen presenting proteins, I guess we can call them, that had bound to parts of that original pathogen. Let me do it right here. So it has a little bit of the original pathogen on it that I drew in green right here. And these proteins right here, these are called-- it's a fancy word and I talked about it in the previous video-- these are called major histocompatibility complexes, or MHC for short. And when we're talking about phagocytes or macrophages or dendritic cells that are particular cases of phagocytes, the major histocompatibility complexes that they present after they've digested this molecule-- this is an MHC class II. Let me write this down. This is an MHC class II protein. It might seem like I'm really going into the minutiae of what these proteins are, but we're going to see this is key for activating other parts of the immune system, especially the cell mediated parts of the immune system. So this was the case with a macrophage or a dendrite. They engulf something, they chew it all up, and then parts of the chewed up thing that they ate, they attach to these MHC II proteins and these MHC proteins go to the surface of the cell. The same thing-- or actually not the quite the same thing-- a very similar thing happens with B cells. So if we have a B cell-- that's a good color. B for blue. We know B stands for bursa, but it could stand for bone marrow just as well. Let's say we have a B cell and it's got its membrane bound antibody on it. Remember, it's very specific to that B cells. So all of the membrane bound antibodies, all 10,000 or so of them on this B cell, they all expressed the same variable part. So this is a particular B cell. So remember, this was nonspecific. When we talked about phagocytosis, these guys just say, you're a bacteria. You're a virus. I don't know what kind you are. I'm just going to eat you up. You look shady. I'm going to eat you up. I don't know what type you are or whether I've seen you before. When we're talking about B cells, we're talking about the adaptive or the specific immune system. And so these-- the variable ends of these membrane bound antibodies are specific to certain parts of certain pathogens, to certain epitopes. Remember, epitopes were the parts of certain pathogens that these specific chains can recognize and bond to. So let's say that we're dealing with a virus in this situation. And let's say the virus just happens to bond to this B cell. Remember, there might be other-- in fact, there definitely are tons of other B cells around, but their variable portions are all different. And that's what I always find amazing about B cells is that they come from the same genetic line, their genes have been shuffled around in their development so that they can produce billions of combinations of these proteins, or the variable ends of their antibodies. So let's say we have some virus. Let me say it's a bacteria. When I did the other B cell example, I said we're dealing with viruses. But let's say some new bacteria and just some part of its surface just happens to bind to only this B cell-- because this B cell has just the right combination. So some part of his surface binds just to that B cell right there. That part of the surface that binds, remember, that was called the epitope. That's that part of the pathogen that binds to our variable sequencer. It won't bind to this B cell or this B cell because they have different sequences here, but it binds to this B cell and then that starts the activation process. We'll go into-- sometimes this by itself can get the B cell activated, but you normally need help from helper T cells-- and we'll talk more about that. And we said, once this happens, once you get activated or the activation process starts, this guy actually gets engulfed-- and I didn't talk about that in the last video just because I didn't want to go into too much detail. So this whole thing gets engulfed by the B cell. And then when it gets activated, it proliferates itself and you normally need the T cells there and some part of them become plasma B cells, some part of them become memory B cells. Remember, the plasma B cells say, gee, I've been activated. I'm just going to produce a ton of these antibodies. So the plasma B cell will just produce tons of these antibodies and start spitting them out so that they can attach to more and more of that pathogen and just mess them up in different ways, either tag them so that other macrophages or phagocytes eat them up-- or tag two of them so you bundle them up so that they can't operate properly. Whatever. I'm not going to go into detail on that. That's when it gets activated. But the interesting thing is that the B cell will also do what the phagocytes do. The B cell will also take this guy into the cell. Maybe he's initially attached to the antibody-- and break him up, take pieces of this pathogen and attach it to MHC II proteins and then present them on the surface. So a B cell will also present the antigen. So this is also an MHC II complex-- a major histocompatibility complex-- and just so you know, histo means tissue. So this is related to whether something is compatible with the tissue in your body and we'll talk more about that and how it relates to transplants and all of that. So this is also an MHC class II. In both cases, whether we're talking about B cells that recognize a very specific pathogen-- and it could be a specific virus, a specific protein, a specific bacteria, or in the cases of phagocytes, they'll just say, oh, you look shady. Let me take you in. I don't know what type of bacteria or virus or protein you are, but in either case, they both engulf them, take pieces of them, cut them up, and present them on their surface in a complex with the major histocompatibility complexes. So cells that do this are called professional antigen presenting cells. This is what they do for a living, although they do other things, as we've seen. The phagocytes eat things. The B cells generate antibodies or memories so that they can later be activated to generate antibodies, but these are called professional antigen presenting cell. And the antigen in question is this little piece of the actual thing that you're trying to track, that little piece-- the actual part of the pathogen, that's what the antigen-- so it's presenting the antigen. It's professional because it takes pathogens from in the fluid of our system and then engulfs them, breaks them up, and then presents them. Now there are also nonprofessional antigen presenting cells. And in fact, most cells are this. In fact, even these guys. Actually, I'm going to wait for the next video. I realize all of my videos are getting long. So you're probably thinking, these guys in either case engulf them, cut them up, present them, what is it good for? You'll see these MHC II, these are what are recognized by helper T cells. It'll all form part of the puzzle of how our immune system works. So in the next video, I'll talk about MHC I presenting cells, which is pretty much all body cells.