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Role of phagocytes in innate or nonspecific immunity

Video transcript
The whole point of the immune system is to keep out shady things from your body-- or, if they get in, to kill them. So those shady things would include shady proteins that can do damage to your body, viruses, bacteria, even eukaryotic parasites, and then even fungi. So all sorts of things that if they were to enter your body, they would cause some form of disease. These are collectively called pathogens. So the whole point of the immune system is, on a first line of defense, keep these things out-- and then if they were to get into your body, to kill and eliminate them from our system so that we don't get sick and so that we don't die. So I already just mentioned that there's kind of two lines of defense and even with those, there's kind of subclassifications. The first line of defense-- I'll just call that the first line-- which is essentially just to keep things out-- keep all of these pathogens out. And there's some obvious ones. There's our skin. Our skin keeps pathogens out and actually even the oils on our skin are a little bit more acidic and it's hard for some types of bacteria to thrive in that type of environment. You have your mucus membranes and in the mucus, there's there's some chemicals that maybe make it a little bit more difficult for bacteria to survive. And then you even have acidic environments like your stomach acid. You might not view your stomach as the outside of you, but it fundamentally is. Your whole digestive tract, which I'll make videos on in the near future, is really on the outside of you. You can simply model really most vertebrate bodies as kind of a doughnut our digestive tract is the inside of the doughnut. So stomach acid is on the outside of our real bodies and you can imagine, that's a hard environment for a lot of these pathogens to survive in. So that's the first line of defense, but we know that that's not good enough, that sometimes these things can get into our bodies, and there we have to start thinking about the second line of defense. What do we do once things are actually in our body? And here, in both the first and second line, I'm talking about non-specific immunity-- and this is going to make a lot of sense when we start talking about specific immunities. So both of these are non-specific. And when I say non-specific-- or you can also call them innate-- it means that they just generally respond to things that appear bad. They don't remember the bad things that came before. They don't respond to a particular type of virus or a particular-- well, they do respond to every type of virus or every type of bacteria, but they don't say, this is virus type A, B, C, or this is bacteria type A, B, C. They just say, this is a virus. Let me get rid of it, or let me not let it in. This is a bacteria. Let me get rid of it or let me not let it in. It doesn't know what type of bacteria it's dealing with. So this is all the non-specific or innate immune system. And we'll go into a lot of detail on the specific immune system because you can imagine, it becomes very complicated or interesting when you start thinking about your body somehow remembering a virus that it's seen before and being able to respond better to that virus or that bacteria or that protein the second time it sees it. So we're dealing with non-specific in this case. And the the second line of your non-specific immunity, there are two things. One is an inflammatory response. And I'm going to do a whole video on this, but in general, we've all experienced inflammatory responses. When you see blood flowing to a certain part of an area and you see there's pus and there's-- and I'm going to go into a lot more detail on what an inflammatory response actually is, but that's one of your-- and what it really is doing is bringing blood and bringing cells that can fight whatever type of infection you have. It's bringing them to the site where maybe you got a cut or maybe where a lot of the bacteria or whatever the pathogen is. So inflammatory response is all about bringing fluid and fighters to the fight. I'm going to do a whole video on that. But the byproduct is, that part of your tissue or that part of you body gets inflamed-- a lot of fluid there, a lot of byproducts of the battle that goes on there. We'll do a whole video on that. And the other second line of defense is, and it's actually part of the inflammatory response-- are phagocytosis or phagocytes. And really, what I want to do over the rest of this video is talk in a little bit more detail about phagocytes because once we understand what phagocytes do, that's a pretty good building block for going into the specific immune system-- and actually, it'll help lead into the discussion on the inflammatory response as well because phagocytes are really part of the inflammatory response. So phagocytes are just a class of cell that can eat up pathogens. They can eat up other things really, but when we talk about the immune system, we're talking about pathogens. So let's say that this is a phagocyte right here. This is a phagocyte right there. It has some kind of a nucleus, whatever. I don't have to focus on the inside of the phagocyte. It's a traditional eukaryotic cell, but what I want to do is see what happens when a phagocyte encounters a foreign particle or a foreign bacteria. So let me say this is a foreign bacteria right here. So the phagocyte, we've already said, is non-specific. What it does is, it has receptors that respond to just things that it knows are bad. You could imagine these are super sensors. Maybe these are super sensors for bacteria. The bacteria have proteins on their surface that maybe look something like that. Obviously they don't look exactly like that. I'm just drawing them as kind of a Y and a triangle so you can see that they fit. But once these two guys connect-- let me draw the situation where they have connected. So this is the bacteria. This is the pathogen. And it's really the same idea with a virus or any other type of thing. And we'll actually see in future videos that these guys can actually be tagged by other molecules, which makes these phagocytes want to attack them even more. Once they're bonded-- that's my bacteria, the invading pathogen. And now it is bonded. It has triggered the receptor on this phagocyte. This phagocyte will start to engulf-- it'll wrap around this pathogen. And these two ends are eventually going to meet. But then once these two meet, what's it going to look like? Then all of a sudden, that bacteria is going to be completely engulfed. It's going to be inside of the cell. So now the cell-- once these two ends meet and these membranes merge, then this guy is going to be in his own little membrane bubble-- or you can almost imagine, it's in its own little vesicle. So this is the pathogen, the bacteria in this case-- but phagocytosis-- the process is completely identical in terms of how it engulfs things. If it was a virus or some type of other foreign protein or any type of really foreign molecule-- actually, sometimes it doesn't even occur to foreign stuff. It can occur to dying molecules that are not foreign, that just need to be cleared out. But we'll just focus on the immune system, on foreign things right now. So this membrane right here will completely merge and go around this guy like this. And of course, you had your receptors and who knows if they're still there. By the time-- let's just draw them there so you see that that part is that part. But once it's fully engulfed, this thing is called a phagosome, on which is really just a vesicle that contains that foreign particle that you want to get rid of. And then other fluid or vesicles that contain things that can eat up this phagosome-- so let's say that this is some vesicle that contains things-- lysozymes and it contains really reactive species of oxygen. And if this comes in contact with, really, almost any biological compound, it's going to do some damage. But once the pathogen is completely merged inside the cell, this little package will merge over here and it will dump its contents into this phagosome, into this vesicle containing the pathogen, and then break it up. It's essentially digesting it. So obviously the first role is, it just got it out of the way and it killed it. And then the second role-- and I'm just going to give a little tidbit right here. We're going to do it in a lot more detail in future videos. It breaks it up. So now the thing is all broken up. So that thing is broken up into constituent proteins and another molecules. And then what the phagocyte does-- it'll actually take some subset of these molecules, some subset of the proteins. It'll break them out. Proteins are just sequences of amino acids. Normally when people say proteins, they're talking about long sequences of amino acids. When people talk about short sequences of amino acids or a protein that's broken up a lot, they refer to it as a peptide chain. A peptide chain is a shorter chain of amino acids. So this guy will take some special peptide chains, some special pieces from the thing it just killed, attach them to some other proteins. So it'll take maybe a little piece of this bacteria right now, attach it to other protein, which is called a major histocompatibility complex-- and if we're talking about phagocytes, this will be a major histocompatibility complex type II. It sounds very-- a strange word, but we're going to see this a lot. So they abbreviate it MHC. This is a protein and it bonds with this peptide that was kind of chunked off or digested off of this invading pathogen and then this phagocyte will then present it onto its membrane. So this combination-- the complex of the MHC-- in this case, it's going to be an MHC II protein. We're going to talk about Type II in the future. It's going to take this complex and then present it on its surface. And the reason why I'm going through all this pain of explaining this process-- you're like, hey, we already got rid of the thing and killed it. Why is Sal worried about what we do with the peptides? This is crucial to our immune system because we'll see other specific parts of our immune system. Remember, so far everything is non-specific. This guy just said, this is an invader. It doesn't know the type of an invader. It just says, hey, let me bond to this thing and kill it. It's one of these things that I know are foreign to my body. So it kills it, but now it can leave it on its surface and now the specific parts, the parts that actually have memory and attack specific things, can say, gee, Mr. Phagocyte, look, you've killed something. Let me see if I have some specific reactions that can be triggered by this thing that you're presenting. So, many phagocytes are also called antigen presenting cells. And I'm going to go into more detail on what exactly an antigen is. I called this thing a pathogen. An antigen is essentially-- you can view it as a protein or a peptide chain that will trigger or that can be dealt with within the immune system. I'll be a little bit-- the specific immune system. And I'm going to be a little bit more nuanced about it when I talk-- I'll make a whole video on antigens and antibodies, but right now you can just view it as a peptide chain right there. An antigen is just a protein or part of a protein. So this is presenting an antigen on its surface that can later be used by other parts. Now, the one thing that-- there are many, many types of phagocytes. And just to give you-- just so when you see different words, you don't get confused by the different types of phagocytes. I'll do a little review of those right now. You have neutrophils. These are actually the most common of the phagocytes. And these are the fast and numerous respondors. So these get to a location of infection very fast. Phagocytes don't necessarily just have to kill in this way. I mean, they're called phagocytes because they engulf this way, but we'll in future videos talk about other ways that they can release chemicals or even DNA nets to ensnare pathogens, but neutrophils are fast and abundant. And then you have macrophages, which are-- on some level, they're the most versatile and do the heavy lifting, but they're also phagocytes. And then you dendritic cells. And when you first see the word dendritic cell, you think, hey, does this somehow relate to dendrites of the nervous system? And no, they have nothing to do with the nervous system. The reason why they're called dendritic cells is because they look like they have dendrites. So they look like neurons on some level, but they don't participate in the nervous system at all. And these tend to be the best activators of the specific immune system that we'll talk about in future videos. So anyway, I'll leave you there and we'll talk more about all of this in the next few videos.