Understanding Inflammation and Immune Response

Iron Engine Nerds, in this video we're going to talk about the inflammatory response. But before we do that, let's define what is inflammation. Inflammation is some type of tissue damage, right? So it's damage to the tissue that initiates a set of vascular and cellular events that are designed to be able to clean up any type of cellular debris, any type of infectious organisms, and initiate repair. So again, one more time, what is inflammation? Inflammation is any type of tissue damage or tissue infliction Right? That initiates a set of vascular events and cellular and molecular events that are designed to clean out any type of cellular debris or pathogens and initiate repair. That is its design, right? What could cause inflammation? It could be due to physical trauma. It could be due to certain types of chemical trauma. It could be due to infectious microorganisms. It could be due to certain sunlight and burns, right? There are many, many causes of inflammation. What we're going to do in this video is we're going to take a scenario. We're going to look at... gram-negative bacteria and then we're going to follow the entire inflammatory response and a sequence of actions beginning with that infectious microorganism. So let's go ahead and dive right in. Alright, so first off, let's say here I have this gram-negative bacteria right here. Here's our gram-negative bacteria. It's this gram-negative bacteria and you know that gram-negative bacteria it has on its outer outer lining it has a lipopolysaccharide layer, right, and those lipopolysaccharides are pretty pretty dangerous, right? They have lipid A which It can act as endotoxins, right? So, also, a lot of bacteria have specific types of antigens on their surface, right? And what are these red things called? These red things are called antigens. And antigens could be sugar molecules, they could be protein molecules, they could be glycoproteins. But what do antigens have to be? In order for it to be an antigen, antigen has to be two things. It has to initiate two different types of things. One is it has to be immunogenic, and the other thing is an antigen has to be reactive. What does that mean in order to be immunogenic and reactive? It means that it has to be able to, immunogenic meaning it has to be able to activate certain types of immune system cells in order for those immune system cells to start proliferating in response to that. Reactive means that the actual immune system cells, specifically the plasma cells, can produce antibodies against this antigen. So in order for it to be a complete antigen, it has to be immunogenic, initiate proliferation, and reactive, which is going to be initiating antibody production. There is what's called incomplete antigens. Incomplete antigens, for example, could be something like poison ivy or poison oak, like the ursual oil. Whenever it gets into the skin, it's actually not specifically a complete antigen, but then it binds with our skin protein, so it's called a hapten, right, an incomplete antigen. But when it binds with our skin proteins, it then becomes a complete antigen. and then it can cause that rash that we see within poison ivy, right? Anyway, just wanted to give you a little bit of information about antigens. What are antigens? They're going to be the sugar molecules or proteins or glycoproteins that are immunogenic and reactive as long as they are specifically complete antigens. All right, so now this bacteria, let's say that this bacteria is releasing endotoxins. So it's releasing its specific endotoxins. And these endotoxins, they start damaging these tissue cells. So let's say it starts damaging a lot of these tissue cells here. So look, a lot of damage to these generalized tissue cells. A lot of damage to these generalized tissue cells. And we'll talk about what happens whenever they're damaged. Also, there's a lot of other types of cells circulating right around this area that are kind of just posting up in this area. These cells right here, these green cells, are called mast cells. And these mast cells have specific types of receptors present on its cell membrane. And whenever these endotoxins either damage this mast cell or activate these receptors on the mast cell, it can initiate a specific type of inflammatory response, right? So let's say these endotoxins damage the mast cell or it activates these receptors present on the mast cell. And it sends signals to the nucleus, all right? And it starts activating a whole bunch of different types of granules. And look what starts happening. This guy starts releasing a ton of different molecules. A ton of different molecules. Let's see what these molecules are. So, really the most important one is histamines. This is a big one. Histamines are one of the most important ones that you should remember. So that's one thing that this actual mast cell will secrete. Another thing it secretes is what's called leukotrienes. It's called leukotrienes. All right, and there's many, many different types of leukotrienes. We're not going to go into each different type, but there is many types of leukotrienes. And another one is called prostaglandins, right? So a lot of different chemicals are secreted by this guy, right? All right, what else? Okay, one other thing that's really important. You know there's a lot of plasma proteins. If you remember from hemostasis, there was a specific type of collodion protein, which is called factor 12, right? In factor 12, there's specific enzymes that actually convert factor 12 into what's called pre-calichiron. And then pre-calichiron can get converted into what's called calichiron. And then calichiron is really, really interesting. So let's say that this calichiron actually gets out here into the tissue spaces. And then there's another protein out here also. This protein that's kind of hanging out here is called kyninogen. And calichiron actually converts kyninogen into what's called bradykinins. So what do we have here? Again, what is this enzyme here that's generating this step right here? This molecule is called Cali, chiron, and what is that molecule coming from? It's coming from thrombin. And again, kininogen actually could be circulating within the bloodstream just naturally and leaking out into the tissue spaces due to hydrostatic pressure or maybe due to what we're going to talk about with these gaps that are actually gonna be present within the endothelial cells. Alright, but again, these are the chemicals that are being released. You know, you know it's just not the mast cells releasing it. You know, any type of damage to a cell's membrane, you know the cell membranes made up of phospholipids? So whenever the cell membranes damaged, These phospholipids, we're going to have to utilize them. Let's utilize them and make it productive, right? So there's an enzyme right here. This enzyme, this red molecule, is called phospholipase A2. And what phospholipase A2 does is, is it starts breaking down some of the actual phospholipids. And when it breaks down these phospholipids, it breaks down the phospholipids into what's called arachidonic acid. Arachidonic acid. acid. Then arachidonic acid is actually going to be worked on by two important enzymes. One enzyme is called lipo-LPO. I'm going to put lipoxygenase. And what lipoxygenase does is it cleaves arachidonic acid and converts him into specific types of leukotrienes. All right, you see where the leukotrienes came from, from the mast cell? Same mechanism. Arachidonic acid also uses another molecule which is going to be another enzyme called COX. With COX-1 or COX-2. Now keep your mind clear it's a cyclooxygenase. Alright it's COX-1 or COX-2 and it works on arachidonic acid to be able to activate arachidonic acid into what's called prostaglandins. And again, there's many, many different types of prostaglandins like PGE2, PGF2, PGI2, PG... There's so many different types of prostaglandins. Just like leukotriene, there's leukotriene D4 and C4, and just many, many different types, right? What do all of these molecules have to do with the process of making a molecule? in common what are they gonna do I see see we have here a capillary okay this is a capillary or an arterial right there's gonna be these endothelial cells right here what is it gonna do all right so these molecules here all these molecules here are going to work on these endothelial cells. So let's say it works on this endothelial cell right here. It works on this receptor mechanism or intracellular mechanisms, whatever it might be. And it activates them. And what it does is, inside of this actual cell, you have these preformed granules. There's preformed granules in here, which are called vibopale bodies. They're not that important, just know that they're preformed granules, they're called vibopillate bodies. And what happens is, when these molecules work on this cell, it causes these granules to start migrating to the cell membrane surface. And when it migrates, look what happens. It puts these proteins up on the cell membrane. Look at these things. What are those molecules called? They're called selectins. Okay, what are these molecules called again? They're called selectins. So these green molecules are called selectins. Now, you can say they're specifically P-selectins, but we're not going to get too carried away with that. Just know that they're selectins, but if you want to know, they're called P-selectins, and they're stimulated by all these local inflammatory cytokines. What happens next? So that's one thing that happens, the P-selectins, and I'll explain what they do specifically afterwards. It also is going to We'll work on these endothelial cells. So let's say over here we have some more endothelial cells with their receptors right here. So here's another receptor. Here's another receptor. Let's say here's another receptor. What is it going to do? They're going to act on these receptors, right? So it acts on this receptor, acts on this receptor, and these molecules even act on all these endothelial cell receptors. And it causes the endothelial cells to contract. And when they contract, look what happens to the spaces now. Look at these spaces that we're going to form here now. So we're going to form a space between these cells, and we're going to form a space between these cells. So watch this. Space there. Space there. A nice little space there. and a nice little space there, right? So that's an awesome thing. So now we have spaces, big, big gaps. Let's see, we even have another one over here. A nice big gap between these endothelial cells. So now what's gonna happen? If you have a nice big gap between these endothelial cells, a lot of your plasma can start leaking out, right? So a lot of this stuff, what's out here? What's getting inside of the circulatory system? We have plasma, so we might have a lot of water, right? A lot of different types of substances here. And what's gonna happen? It's gonna start leaking out through these interstitial cells. intercellular clefts, right? These little pores here that we form. Okay, so as this fluid starts leaking out and leaking and leaking and leaking out into this area, what's going to happen? It's going to start causing a lot of swelling and swelling and swelling and accumulation. This is your interstitial space right here, right? Between the cells and the capillary bed. So as you have more fluid accumulating and accumulating, look what's happening to that space. It's getting bigger and bigger and bigger. What is that called? That's called edema. Or swelling, right? So as that fluid starts accumulating out here, it starts causing that interstitial space to start getting bigger and bigger and bigger. And that causes swelling. So remember that. Why do I say that it's important? There's signs of inflammation. I'm going to write them down here. Ready? One is swelling. Second one is specifically pain. And I'll explain that one. Third one is heat. Fourth one is redness. And sometimes people include a fifth one, and that is joint immobility. These are all the signs of inflammation. Now we've already hit one. What is one of those? We already said it was swelling, right? And what is that swelling due to? It's due to this increased vascular permeability. So again, what is this happening right here? This is an increase in vascular permeability. And that increase in vascular permeability causes a lot of leaking and causes swelling. All right? Another thing. You know what else you have a lot of out here? You have a lot of pain receptors or noiceus receptors. So there's a lot of pain receptors or noiceus receptors in this area. You see these black neurons right here? These black neurons are going to be specific types of receptors called nociceptors. Now think about this. As the fluid within the space starts increasing and increasing and increasing, what does it start doing? It starts pushing. and smashing down on those nociceptors. And as it starts compressing and pushing down on those nociceptors, what do you think's gonna happen? It's gonna activate these guys and cause pain. All right, so that's one thing, physical trauma, right, due to the fluid accumulation. You know what else? This guy right here. Bradykinins love to be able to activate these nociceptors. And when it activates these nociceptors, it initiates also a chemical event. And again, the overall response to this is pain. So, so far we've already initiated two different types of signs of inflammation, swelling and pain, all related to one similar event which is changes in the vascular permeability. Now, second thing, another thing that we're gonna have a lot of kind of hanging out in this area, let's actually draw it over here so we have a lot of room, we're gonna have a lot of smooth muscle cells. In this vicinity right here. So we're gonna have a lot of smooth muscle cells. And if you have a lot of smooth muscle cells, you know what can happen here? All of these histamines and leukotrienes and prostaglandins, all these molecules, guess what else they can do? They can come over here and bind onto these smooth muscle cells. And when they bind onto these smooth muscle cells, it causes the smooth muscle cells to relax. So it initiates relaxation. And if the smooth muscle cells are relaxing, what happens to the size of the blood vessel? It gets bigger. What is that called whenever the blood vessel gets bigger? It's called vasodilation. Okay, that is super, super important. Why? Because now we have vasodilation of this localized area. Whenever there's vasodilation of the localized area, it's called localized hyperemia. Okay, what does that mean? What does that mean? That means we're going to have a lot more blood flow coming to this area. Think about this logically. If I were to touch my, let's say I rub my arm up against like a hot stove or something like that, right? And I burn my skin. If I burn my skin, what do you notice later on after just giving it a little bit of time? It gets really, really red, right? And hot. Why? Why does it get really, really red and really, really hot? Because of this vasodilation mechanism. As the blood vessels get bigger, more blood flows through that area. As we have more blood flowing to that area, what color is our blood usually? Red. How hot is blood? Usually it's around 37, 38 degrees Celsius. That's pretty, that's kind of hot. And it's going to cause that increase in temperature to be able to help to speed up the metabolism and again, get more white blood cells to the area. Okay, so that's the next mechanism. We already talked about that. Vasodilation will cause heat and redness. Next thing, if it's a really, really, really bad sign, like really, really bad inflammation, like maybe a third degree burn. If there's a really, really bad inflammation, like a third degree burn, and it's actually near a joint, it can actually get so swollen that you can't move your joints. If I burn my arm really, really bad near my wrist, I won't be able to move my wrist that much because of the inflammation. Okay? So that's that. Now, let's keep going here. So we've already mentioned vasodilation. We mentioned vascular permeability. Let's come back and explain what the heck is going on with these selectins. What's important about them? All right, let me erase this right here so we have more room. Okay, so next thing. I already mentioned that there's going to be these selectins, right? Now, we have a lot of white blood cells circulating throughout our blood, right? Naturally, within our blood plasma. One of them that's the most abundant is our neutrophil, right? And we also have lymphocytes. But I'm going to draw another one that's also pretty abundant too. And this is our monocytes. Okay, so these guys are just circulating in the bloodstream, right? Now, naturally on their membrane, they have specific types of sugar molecules. And look at this, doesn't it look like these sugar molecules fit perfectly with these P-selectins? You'd be right. Look what happens here. Now these guys are going to come down here and they're going to interact now. So if they interact it's going to look like this now. Look at this. So now we got this white blood cell and it's interacting here like that. And then we also have this monocyte over here or this what's specifically a monocyte when it leaves the blood it becomes a macrophage, right? And look it's interacting here with these molecules. What is that going to do? Imagine blood flowing. As it's flowing through the bloodstream, right? I'm just flowing through the bloodstream. All of a sudden, my elbow gets hooked onto something. I can't keep going that way anymore, right? I'm stuck in this position. Why is that a good thing? Because we don't want the white blood cells to keep going past that area. We want them to come out here with this bacteria so he can fight with it, right? So that's what it does. It hooks them and catches them and prevents them from continuously just flowing past that area. That's a beautiful thing. Now, look what happens after that. You're going to have a ton of these different types of selectins. There is other selectins. I'll talk about them very very briefly here in a second. But now look at this. I'm gonna make this a little bit more smaller so we have room to show you what's happening here. So if you look here you got more of these selectins. These white blood cells they're just gonna go from selectin to selectin selectin. So imagine me rolling against this board right? So that one selectin hits me like this. Then I start rolling this way and I catch another selectin. Then I keep rolling this one, I catch another selectin. That's what's happening with these white blood cells. They just keep rolling and rolling and rolling along the cell membrane, right? So what is that process called when they're rolling and rolling and rolling along the cell membrane while interacting with these selectins? That process is called margination. Okay, and that's due to the interaction with the P selectins. Now there will be other ones too. But now, look at what else happens. You also have other molecules here on the surface here. They're called PCAMs. We're not going to get too crazy about this, okay? But look what happens. These white blood cells, they try to squeeze through this area while interacting with the PCAMs. So there you might have a monocyte running out here. You might even have a neutrophil squeezing through here, right? But look, they're interacting with the PCAMs because they have specific type of molecules that they interact with these PCAMs also. But look what's happening here. As they're rolling and rolling and rolling, they actually hit these other ones called PCAMs, and they can start squeezing through that capillary. And they do it like in a me-boyed motion. It's like they're pushing their way through it, right? So what is that process called whenever they're squeezing their way through the capillaries in between these spaces to get out into this area? When they're doing this and they're squeezing their way out, it's called diapodesis. Diapodesis, okay? Now, that's diapedesis, when they're trying to squeeze their way through the actual spaces between the capillaries to get out here and fight. All right? That's one thing. Now look what else happens. There's a lot of these inflammatory cytokines here. So imagine these guys are out here now. Imagine they're out here. Here's my monocyte which is now a macrophage now right and let's say over here I have my neutrophil. Okay, you know they have receptors all over their cell membrane, right? Now, what was out here before? What would we have a lot of? Histamines, leukotrienes, prostaglandins, bradykinase, leukotrienes, prostaglandins. I know I said it again, but there's a lot of different types of cytokines out here, right? There is even more, and we'll talk about those in just a second. Imagine this. You see these receptors here? All of these chemicals are going to come over here, and they're going to bind onto these receptors. They're going to bind onto these receptors and look what's going to happen. The bacteria is over here. It wants to go that way. So imagine me like this. Imagine I'm standing right here. Someone throws something at me from over and around that way, right? So someone throws, like, let's say they throw a baseball at me, right? And that's a specific type of cytokine, like prostaglandins or leukotriene. So they throw it at me. It hits me in the arm. What am I going to do? I'm going to look that way. Who the frick did that, right? So I'm going to look that way and I'm going to see, okay, that guy threw it at me. I'm going to go towards him. That's the whole purpose of this. That's what's happening. Is that these cytokines are stimulating just the right side of these white blood cells, causing them to migrate to where that action is. For example, what if the chemokines were over here? What would it do then? So if someone threw a baseball at me over there now, what's going to happen? I'll be like, who the frick did that? And I'm going to go that way now, right? That's called, whenever it's stimulating and they're following that actual chemical trail molecules towards that area, this is called Positive chemotaxis. So again, positive chemotaxis, right? Alright, so now what have we gone over so far? We've already said that there's margination due to the interaction with these P selectins, and there will be other ones. I'll talk about them, don't worry. Then after that, it goes and squeezes through these actual endothelial cells through PCAMs. Again, what do these molecules call here on the cell membrane? They're called PCAMs. Not too concerned with this right now. All right. And it'll bind on. The white blood cell will have its specific cell adhesion molecules to bind with and then start moving and squeezing through the capillary by amoeboid motion. That's called diapodesis. Then those chemical molecules will actually act as chemotactic agents and hit specific receptors on the appropriate side to cause the white blood cell to migrate to where the injury is or the bacteria is. Now, let's talk about the next thing. So let's say here we draw that bacteria over here. So let's say now look at this. Here's our bacteria. Right, and it was our gram-negative bacteria with the lipopolysaccharides and the specific antigens, the complete antigens that were immunogenic and reactive, right? So look, here's our antigens. Now look what happens here. These macrophages and these white blood cells are going to come out and they're going to start fighting with this guy. So this happened pretty quick. All these events that we just talked about, these vascular events, are very fast. But this next part is going to take a little bit longer because we've got to talk about some more selectins here. So now these white blood cells are going to come out and they're going to start trying to fight. As they start trying to fight, specifically the macrophage, he's going to come out and he's going to start trying to fight. We'll talk about this in the next video, what happens. Whenever he gets ready to start fighting these actual bacteria, he wants to alert other white blood cells that there's more bacteria in this area. So what does he do? He secretes two really important chemicals called interleukin-1 and Tumor Necrotic Factor Alpha. He also secretes another important chemical and this chemical is called Interleukin-8. Now I'm not going to spend a ton of time on this, I'm just going to mention it so that you do know that there is other types of selectins. So again, these were P selectins and these were P cams. Let's talk about what these two guys do right here. Let's make these endothelial cells bigger. Okay, first off, interleukin-1 and tumor necrotic factor alpha. Let's say that they work on this endothelial cell. When they work on this endothelial cell, it activates this endothelial cell to produce specific types of proteins in response to that. And these proteins, they're called selectins. They're called selectins, but guess what kind of selectins they're called? These selectins are called e-selectins. So it's nothing crazy, just know that interleukin-1 and tumor necrotic factor alpha, they're produced a little later on in the inflammatory response. All these histamines and leukotrienes and prostaglandins, they're produced very, very quickly because they're already preformed. Interleukin-1 and tumor necrotic factor alpha, you actually have to make those, you have to synthesize them. So it takes a little longer. So these come up later in the inflammatory response. But then again, what can they allow to happen here? They can allow for my monos... sites right here and my neutrophils to adhere with their because they have those sugar molecules right they can adhere with these e-selectants right so nothing crazy now here's where it gets a little funky another thing These actual neutrophils and specifically neutrophils and the monocytes, they have specific proteins on their cell membrane right here. So look at these proteins right here, these black proteins. They're inactive, they're not really active right now. Interleukin-8 binds on to a specific receptor here present on the endothelial cell membrane and when it does, So let's say here's interleukin-8. It's going to come and it's going to bind here on this receptor. When it binds on this receptor, it activates this actual cell and causes it to synthesize a protein. What is this protein here called? This protein here is called ICAM. There's two types, ICAM and VCAM. And I just stands for intracellular cell adhesion molecule. V stands for vascular cell adhesion molecule. But what happens here? Interleukin-8 will bind onto this receptor and then this interleukin-8 will activate this neutrophil. When it activates this neutrophil, these integrins then become activated. Now look what happens. If they're activated, let's say it moves from this E-Select and it just so happens to roll over, boom. And it perfectly interacts with that V-CAM and I-CAM. Now look. So now it's going to perfectly interact. with that V cam and the I cam. And again, this is just another way because again, what will also be within these cells too, you'll have a lot of gaps, right? Because of the endothelial cell contraction and there also will be retraction. And again, what else is going to be right here? Your P cams. And then again, what will happen, the white blood cell will actually squeeze through this capillary. And when it squeezes through this capillary by amoeboid motion, that process is called. diapedesis and then it'll follow the chemical trail molecules towards this bacteria and that's called positive chemotaxis right so there's a lot of things that are actually happening within this response before we finish this up and we go into the entire phagocytic mechanism in the next video let's do a quick quick recap alright ready so again bacteria releases endotoxins destroys the tissue activates mast cells mast cells starts producing preformed very very quickly they make them molecules like histamines, leukotrienes, prostaglandins, and bradykinins, right? And then also the actual damaged cell membrane can start producing specific types of similar molecules like leukotrienes and prostaglandins. These molecules can activate the endothelial cells to make big gaps, which increases permeability. They can also activate the smooth muscle cells to dilate, all right, to relax and then cause vasodilation, which increases blood flow. And then also this will have increased permeability. Another thing will happen is it'll stimulate these endothelial cells to expose these specific type of molecules called P-selectins, which allows for adhesion with the white blood cells and they'll roll across the surface which is margination. Then they'll interact between the cells with P-cams to squeeze through the capillaries by amoeboid motion, that's called diapedesis. Then after that they'll follow that chemical trail of molecules to where the actual infectious agent is and that's called positive chemotaxis. As the white blood cells, specifically the monocytes or macrophages, start fighting with the bacteria, they start secreting interleukin-1 and tumor necrotic factor alpha, which activate endothelial cells later in the inflammatory response, a little bit later, to produce E-selectins. And then the macrophage also produces interleukin-8, which activates the integrins to bind with ICAMs and VCAMs. And again, bind with the PCAMs and come out to this area by diapodesis. And then positive chemotaxis and fight the bacteria. All right, so last thing here I want to mention. If you know something about whenever you're really getting sick, right, if you're really sick, what happens if you're fighting off some type of infection? You have a fever, right? So usually you get really, really hot. You get a fever. What causes that fever? This mofo right here, interleukin-1 and tumor necrotic factor alpha. What do they do? If you look here, I draw three different specific organs that I want to talk about. The brain, the liver, and we're just drawing a bone marrow, right? That's what it's supposed to represent. This interleukin-1 and tumor necrotic factor alpha will track its way up to the brain, and there's a specific part of the brain it actually works on. What is that part of the brain that it works on? This area of the brain is called the hypothalamus. And when it works in the hypothalamus, this interleukin-1 and tumor necrotic factor alpha Alpha will activate the hypothalamus to start secreting a molecule called PGE2. And PGE2 resets our actual body temperature, and it initiates fever, okay? So again, what is happening here? Interleukin-1 and tumor necrotic factor alpha. So what is this chemical? It's actually shown right here, so we don't lose it. Interleukin-1 and tumor necrotic factor alpha. We're working on the hypothalamus, initiating PGE2 secretion and causing fever. What is the significance of a fever? A couple things. One thing about a fever is it makes it a harsher environment for certain types of microorganisms to survive in. It can denature some of their proteins, their DNA, right? Second thing, it speeds up our cellular metabolism. And as you speed up metabolism, you can initiate a quicker healing process. That's another thing. There is another mechanism, I'm not going to talk too much about it, but your body has a way of sequestering iron and zinc that the bacteria need in order for them to continue to multiply. It can sequester that within the iron and also within the spleen. So again, that's that mechanism. Then, we might as well show what it also does here. Look, here's our liver. It also can act on the liver. And the liver, in response to this, can produce what's called acute phase... Reactant proteins. Why is this important? Because if you actually have a really really bad infection or maybe you have cancer maybe there's actually something else wrong they actually run a test. So this is really good it's better for determining active inflammation. They run a blood test and whenever they run a blood test a specific type of acute phase reactive protein shows up. This acute phase reactive protein is called C-reactive peptide. There is many many other types of acute phase reactive proteins like ceruloplasma and haptoglobin and fibrinogen. We don't care about those, we care about this one. So high C reactive peptide levels within the blood can kind of give a doctor some type of help to diagnose, okay this person has some type of active inflammation, I don't know what it is, but we're gonna try to figure that out with other types of diagnostic test procedures, right? Okay, so that's that. Then... And there's another one that can also cause this too, didn't talk too much about it yet, interleukin 6. That can also be secreted by macrophages and by T cells. We're not going to talk too much about that, but that can also initiate that response. Then tumor necrotic factor and alpha and interleukin 1, and there is other cytokines like interleukin 3 and interleukin 5, can also act on the bone marrow. They can act on the bone marrow. What do we want to activate the bone marrow? What's in the bone marrow? Our actual cells, right? Our stem cells. What do we need a lot of? We need white blood cells right now because we have a microorganism that can cause a lot of potential damage to our tissues. So what is this tumor necrotic factor alpha and interleukin 1 and other ones like interleukin 3 and interleukin 5 going to do? They're going to stimulate the bone marrow to start blasting out more white blood cells. So we're going to start pushing out a lot more neutrophils. We're going to start pushing out a lot more monocytes. We're going to start pushing on a lot more eosinophils depending upon what the infectious organism might be. But this is called, whenever this is happening, it's called leukocytosis. Okay? It's called leukocytosis. Got it? Alright, now that we've talked about the leukocytosis mechanism, we've talked about the C-reactive peptide, and we've talked about fever, we now have a good idea now of what's happening within the inflammatory response. In the next video, I want you guys to click up on the right icon. We're going to talk about specifically continuing with the inflammatory response. Well, we're going to now focus on what's happening with these actual white blood cells and how they undergo phagocytosis.

Iron Engine Nerds, in this video we're going to talk about the inflammatory response. But before we do that, let's define what is inflammation. Inflammation is some type of tissue damage, right?

So it's damage to the tissue that initiates a set of vascular and cellular events that are designed to be able to clean up any type of cellular debris, any type of infectious organisms, and initiate repair. So again, one more time, what is inflammation? Inflammation is any type of tissue damage or tissue infliction Right? That initiates a set of vascular events and cellular and molecular events that are designed to clean out any type of cellular debris or pathogens and initiate repair.

That is its design, right? What could cause inflammation? It could be due to physical trauma. It could be due to certain types of chemical trauma.

It could be due to infectious microorganisms. It could be due to certain sunlight and burns, right? There are many, many causes of inflammation. What we're going to do in this video is we're going to take a scenario.

We're going to look at... gram-negative bacteria and then we're going to follow the entire inflammatory response and a sequence of actions beginning with that infectious microorganism. So let's go ahead and dive right in. Alright, so first off, let's say here I have this gram-negative bacteria right here. Here's our gram-negative bacteria.

It's this gram-negative bacteria and you know that gram-negative bacteria it has on its outer outer lining it has a lipopolysaccharide layer, right, and those lipopolysaccharides are pretty pretty dangerous, right? They have lipid A which It can act as endotoxins, right? So, also, a lot of bacteria have specific types of antigens on their surface, right?

And what are these red things called? These red things are called antigens. And antigens could be sugar molecules, they could be protein molecules, they could be glycoproteins. But what do antigens have to be? In order for it to be an antigen, antigen has to be two things.

It has to initiate two different types of things. One is it has to be immunogenic, and the other thing is an antigen has to be reactive. What does that mean in order to be immunogenic and reactive? It means that it has to be able to, immunogenic meaning it has to be able to activate certain types of immune system cells in order for those immune system cells to start proliferating in response to that. Reactive means that the actual immune system cells, specifically the plasma cells, can produce antibodies against this antigen.

So in order for it to be a complete antigen, it has to be immunogenic, initiate proliferation, and reactive, which is going to be initiating antibody production. There is what's called incomplete antigens. Incomplete antigens, for example, could be something like poison ivy or poison oak, like the ursual oil. Whenever it gets into the skin, it's actually not specifically a complete antigen, but then it binds with our skin protein, so it's called a hapten, right, an incomplete antigen.

But when it binds with our skin proteins, it then becomes a complete antigen. and then it can cause that rash that we see within poison ivy, right? Anyway, just wanted to give you a little bit of information about antigens. What are antigens?

They're going to be the sugar molecules or proteins or glycoproteins that are immunogenic and reactive as long as they are specifically complete antigens. All right, so now this bacteria, let's say that this bacteria is releasing endotoxins. So it's releasing its specific endotoxins.

And these endotoxins, they start damaging these tissue cells. So let's say it starts damaging a lot of these tissue cells here. So look, a lot of damage to these generalized tissue cells. A lot of damage to these generalized tissue cells.

And we'll talk about what happens whenever they're damaged. Also, there's a lot of other types of cells circulating right around this area that are kind of just posting up in this area. These cells right here, these green cells, are called mast cells.

And these mast cells have specific types of receptors present on its cell membrane. And whenever these endotoxins either damage this mast cell or activate these receptors on the mast cell, it can initiate a specific type of inflammatory response, right? So let's say these endotoxins damage the mast cell or it activates these receptors present on the mast cell. And it sends signals to the nucleus, all right? And it starts activating a whole bunch of different types of granules.

And look what starts happening. This guy starts releasing a ton of different molecules. A ton of different molecules. Let's see what these molecules are.

So, really the most important one is histamines. This is a big one. Histamines are one of the most important ones that you should remember.

So that's one thing that this actual mast cell will secrete. Another thing it secretes is what's called leukotrienes. It's called leukotrienes. All right, and there's many, many different types of leukotrienes. We're not going to go into each different type, but there is many types of leukotrienes.

And another one is called prostaglandins, right? So a lot of different chemicals are secreted by this guy, right? All right, what else? Okay, one other thing that's really important. You know there's a lot of plasma proteins.

If you remember from hemostasis, there was a specific type of collodion protein, which is called factor 12, right? In factor 12, there's specific enzymes that actually convert factor 12 into what's called pre-calichiron. And then pre-calichiron can get converted into what's called calichiron.

And then calichiron is really, really interesting. So let's say that this calichiron actually gets out here into the tissue spaces. And then there's another protein out here also.

This protein that's kind of hanging out here is called kyninogen. And calichiron actually converts kyninogen into what's called bradykinins. So what do we have here?

Again, what is this enzyme here that's generating this step right here? This molecule is called Cali, chiron, and what is that molecule coming from? It's coming from thrombin.

And again, kininogen actually could be circulating within the bloodstream just naturally and leaking out into the tissue spaces due to hydrostatic pressure or maybe due to what we're going to talk about with these gaps that are actually gonna be present within the endothelial cells. Alright, but again, these are the chemicals that are being released. You know, you know it's just not the mast cells releasing it. You know, any type of damage to a cell's membrane, you know the cell membranes made up of phospholipids?

So whenever the cell membranes damaged, These phospholipids, we're going to have to utilize them. Let's utilize them and make it productive, right? So there's an enzyme right here. This enzyme, this red molecule, is called phospholipase A2.

And what phospholipase A2 does is, is it starts breaking down some of the actual phospholipids. And when it breaks down these phospholipids, it breaks down the phospholipids into what's called arachidonic acid. Arachidonic acid. acid.

Then arachidonic acid is actually going to be worked on by two important enzymes. One enzyme is called lipo-LPO. I'm going to put lipoxygenase.

And what lipoxygenase does is it cleaves arachidonic acid and converts him into specific types of leukotrienes. All right, you see where the leukotrienes came from, from the mast cell? Same mechanism.

Arachidonic acid also uses another molecule which is going to be another enzyme called COX. With COX-1 or COX-2. Now keep your mind clear it's a cyclooxygenase. Alright it's COX-1 or COX-2 and it works on arachidonic acid to be able to activate arachidonic acid into what's called prostaglandins. And again, there's many, many different types of prostaglandins like PGE2, PGF2, PGI2, PG...

There's so many different types of prostaglandins. Just like leukotriene, there's leukotriene D4 and C4, and just many, many different types, right? What do all of these molecules have to do with the process of making a molecule?

in common what are they gonna do I see see we have here a capillary okay this is a capillary or an arterial right there's gonna be these endothelial cells right here what is it gonna do all right so these molecules here all these molecules here are going to work on these endothelial cells. So let's say it works on this endothelial cell right here. It works on this receptor mechanism or intracellular mechanisms, whatever it might be. And it activates them. And what it does is, inside of this actual cell, you have these preformed granules.

There's preformed granules in here, which are called vibopale bodies. They're not that important, just know that they're preformed granules, they're called vibopillate bodies. And what happens is, when these molecules work on this cell, it causes these granules to start migrating to the cell membrane surface. And when it migrates, look what happens.

It puts these proteins up on the cell membrane. Look at these things. What are those molecules called?

They're called selectins. Okay, what are these molecules called again? They're called selectins. So these green molecules are called selectins. Now, you can say they're specifically P-selectins, but we're not going to get too carried away with that.

Just know that they're selectins, but if you want to know, they're called P-selectins, and they're stimulated by all these local inflammatory cytokines. What happens next? So that's one thing that happens, the P-selectins, and I'll explain what they do specifically afterwards. It also is going to We'll work on these endothelial cells.

So let's say over here we have some more endothelial cells with their receptors right here. So here's another receptor. Here's another receptor. Let's say here's another receptor. What is it going to do?

They're going to act on these receptors, right? So it acts on this receptor, acts on this receptor, and these molecules even act on all these endothelial cell receptors. And it causes the endothelial cells to contract. And when they contract, look what happens to the spaces now. Look at these spaces that we're going to form here now.

So we're going to form a space between these cells, and we're going to form a space between these cells. So watch this. Space there.

Space there. A nice little space there. and a nice little space there, right?

So that's an awesome thing. So now we have spaces, big, big gaps. Let's see, we even have another one over here.

A nice big gap between these endothelial cells. So now what's gonna happen? If you have a nice big gap between these endothelial cells, a lot of your plasma can start leaking out, right?

So a lot of this stuff, what's out here? What's getting inside of the circulatory system? We have plasma, so we might have a lot of water, right?

A lot of different types of substances here. And what's gonna happen? It's gonna start leaking out through these interstitial cells. intercellular clefts, right?

These little pores here that we form. Okay, so as this fluid starts leaking out and leaking and leaking and leaking out into this area, what's going to happen? It's going to start causing a lot of swelling and swelling and swelling and accumulation.

This is your interstitial space right here, right? Between the cells and the capillary bed. So as you have more fluid accumulating and accumulating, look what's happening to that space. It's getting bigger and bigger and bigger.

What is that called? That's called edema. Or swelling, right? So as that fluid starts accumulating out here, it starts causing that interstitial space to start getting bigger and bigger and bigger.

And that causes swelling. So remember that. Why do I say that it's important?

There's signs of inflammation. I'm going to write them down here. Ready? One is swelling. Second one is specifically pain.

And I'll explain that one. Third one is heat. Fourth one is redness. And sometimes people include a fifth one, and that is joint immobility. These are all the signs of inflammation.

Now we've already hit one. What is one of those? We already said it was swelling, right? And what is that swelling due to?

It's due to this increased vascular permeability. So again, what is this happening right here? This is an increase in vascular permeability. And that increase in vascular permeability causes a lot of leaking and causes swelling.

All right? Another thing. You know what else you have a lot of out here?

You have a lot of pain receptors or noiceus receptors. So there's a lot of pain receptors or noiceus receptors in this area. You see these black neurons right here?

These black neurons are going to be specific types of receptors called nociceptors. Now think about this. As the fluid within the space starts increasing and increasing and increasing, what does it start doing? It starts pushing. and smashing down on those nociceptors.

And as it starts compressing and pushing down on those nociceptors, what do you think's gonna happen? It's gonna activate these guys and cause pain. All right, so that's one thing, physical trauma, right, due to the fluid accumulation.

You know what else? This guy right here. Bradykinins love to be able to activate these nociceptors. And when it activates these nociceptors, it initiates also a chemical event. And again, the overall response to this is pain.

So, so far we've already initiated two different types of signs of inflammation, swelling and pain, all related to one similar event which is changes in the vascular permeability. Now, second thing, another thing that we're gonna have a lot of kind of hanging out in this area, let's actually draw it over here so we have a lot of room, we're gonna have a lot of smooth muscle cells. In this vicinity right here.

So we're gonna have a lot of smooth muscle cells. And if you have a lot of smooth muscle cells, you know what can happen here? All of these histamines and leukotrienes and prostaglandins, all these molecules, guess what else they can do? They can come over here and bind onto these smooth muscle cells.

And when they bind onto these smooth muscle cells, it causes the smooth muscle cells to relax. So it initiates relaxation. And if the smooth muscle cells are relaxing, what happens to the size of the blood vessel? It gets bigger.

What is that called whenever the blood vessel gets bigger? It's called vasodilation. Okay, that is super, super important.

Why? Because now we have vasodilation of this localized area. Whenever there's vasodilation of the localized area, it's called localized hyperemia.

Okay, what does that mean? What does that mean? That means we're going to have a lot more blood flow coming to this area.

Think about this logically. If I were to touch my, let's say I rub my arm up against like a hot stove or something like that, right? And I burn my skin. If I burn my skin, what do you notice later on after just giving it a little bit of time? It gets really, really red, right?

And hot. Why? Why does it get really, really red and really, really hot? Because of this vasodilation mechanism.

As the blood vessels get bigger, more blood flows through that area. As we have more blood flowing to that area, what color is our blood usually? Red. How hot is blood? Usually it's around 37, 38 degrees Celsius.

That's pretty, that's kind of hot. And it's going to cause that increase in temperature to be able to help to speed up the metabolism and again, get more white blood cells to the area. Okay, so that's the next mechanism.

We already talked about that. Vasodilation will cause heat and redness. Next thing, if it's a really, really, really bad sign, like really, really bad inflammation, like maybe a third degree burn. If there's a really, really bad inflammation, like a third degree burn, and it's actually near a joint, it can actually get so swollen that you can't move your joints.

If I burn my arm really, really bad near my wrist, I won't be able to move my wrist that much because of the inflammation. Okay? So that's that.

Now, let's keep going here. So we've already mentioned vasodilation. We mentioned vascular permeability. Let's come back and explain what the heck is going on with these selectins.

What's important about them? All right, let me erase this right here so we have more room. Okay, so next thing. I already mentioned that there's going to be these selectins, right?

Now, we have a lot of white blood cells circulating throughout our blood, right? Naturally, within our blood plasma. One of them that's the most abundant is our neutrophil, right?

And we also have lymphocytes. But I'm going to draw another one that's also pretty abundant too. And this is our monocytes.

Okay, so these guys are just circulating in the bloodstream, right? Now, naturally on their membrane, they have specific types of sugar molecules. And look at this, doesn't it look like these sugar molecules fit perfectly with these P-selectins? You'd be right. Look what happens here.

Now these guys are going to come down here and they're going to interact now. So if they interact it's going to look like this now. Look at this. So now we got this white blood cell and it's interacting here like that. And then we also have this monocyte over here or this what's specifically a monocyte when it leaves the blood it becomes a macrophage, right?

And look it's interacting here with these molecules. What is that going to do? Imagine blood flowing. As it's flowing through the bloodstream, right?

I'm just flowing through the bloodstream. All of a sudden, my elbow gets hooked onto something. I can't keep going that way anymore, right?

I'm stuck in this position. Why is that a good thing? Because we don't want the white blood cells to keep going past that area.

We want them to come out here with this bacteria so he can fight with it, right? So that's what it does. It hooks them and catches them and prevents them from continuously just flowing past that area. That's a beautiful thing. Now, look what happens after that.

You're going to have a ton of these different types of selectins. There is other selectins. I'll talk about them very very briefly here in a second. But now look at this. I'm gonna make this a little bit more smaller so we have room to show you what's happening here.

So if you look here you got more of these selectins. These white blood cells they're just gonna go from selectin to selectin selectin. So imagine me rolling against this board right?

So that one selectin hits me like this. Then I start rolling this way and I catch another selectin. Then I keep rolling this one, I catch another selectin. That's what's happening with these white blood cells. They just keep rolling and rolling and rolling along the cell membrane, right?

So what is that process called when they're rolling and rolling and rolling along the cell membrane while interacting with these selectins? That process is called margination. Okay, and that's due to the interaction with the P selectins. Now there will be other ones too. But now, look at what else happens.

You also have other molecules here on the surface here. They're called PCAMs. We're not going to get too crazy about this, okay? But look what happens. These white blood cells, they try to squeeze through this area while interacting with the PCAMs.

So there you might have a monocyte running out here. You might even have a neutrophil squeezing through here, right? But look, they're interacting with the PCAMs because they have specific type of molecules that they interact with these PCAMs also. But look what's happening here. As they're rolling and rolling and rolling, they actually hit these other ones called PCAMs, and they can start squeezing through that capillary.

And they do it like in a me-boyed motion. It's like they're pushing their way through it, right? So what is that process called whenever they're squeezing their way through the capillaries in between these spaces to get out into this area?

When they're doing this and they're squeezing their way out, it's called diapodesis. Diapodesis, okay? Now, that's diapedesis, when they're trying to squeeze their way through the actual spaces between the capillaries to get out here and fight.

All right? That's one thing. Now look what else happens. There's a lot of these inflammatory cytokines here.

So imagine these guys are out here now. Imagine they're out here. Here's my monocyte which is now a macrophage now right and let's say over here I have my neutrophil.

Okay, you know they have receptors all over their cell membrane, right? Now, what was out here before? What would we have a lot of?

Histamines, leukotrienes, prostaglandins, bradykinase, leukotrienes, prostaglandins. I know I said it again, but there's a lot of different types of cytokines out here, right? There is even more, and we'll talk about those in just a second.

Imagine this. You see these receptors here? All of these chemicals are going to come over here, and they're going to bind onto these receptors. They're going to bind onto these receptors and look what's going to happen.

The bacteria is over here. It wants to go that way. So imagine me like this. Imagine I'm standing right here. Someone throws something at me from over and around that way, right?

So someone throws, like, let's say they throw a baseball at me, right? And that's a specific type of cytokine, like prostaglandins or leukotriene. So they throw it at me. It hits me in the arm. What am I going to do?

I'm going to look that way. Who the frick did that, right? So I'm going to look that way and I'm going to see, okay, that guy threw it at me.

I'm going to go towards him. That's the whole purpose of this. That's what's happening.

Is that these cytokines are stimulating just the right side of these white blood cells, causing them to migrate to where that action is. For example, what if the chemokines were over here? What would it do then?

So if someone threw a baseball at me over there now, what's going to happen? I'll be like, who the frick did that? And I'm going to go that way now, right?

That's called, whenever it's stimulating and they're following that actual chemical trail molecules towards that area, this is called Positive chemotaxis. So again, positive chemotaxis, right? Alright, so now what have we gone over so far?

We've already said that there's margination due to the interaction with these P selectins, and there will be other ones. I'll talk about them, don't worry. Then after that, it goes and squeezes through these actual endothelial cells through PCAMs.

Again, what do these molecules call here on the cell membrane? They're called PCAMs. Not too concerned with this right now.

All right. And it'll bind on. The white blood cell will have its specific cell adhesion molecules to bind with and then start moving and squeezing through the capillary by amoeboid motion.

That's called diapodesis. Then those chemical molecules will actually act as chemotactic agents and hit specific receptors on the appropriate side to cause the white blood cell to migrate to where the injury is or the bacteria is. Now, let's talk about the next thing. So let's say here we draw that bacteria over here.

So let's say now look at this. Here's our bacteria. Right, and it was our gram-negative bacteria with the lipopolysaccharides and the specific antigens, the complete antigens that were immunogenic and reactive, right?

So look, here's our antigens. Now look what happens here. These macrophages and these white blood cells are going to come out and they're going to start fighting with this guy.

So this happened pretty quick. All these events that we just talked about, these vascular events, are very fast. But this next part is going to take a little bit longer because we've got to talk about some more selectins here. So now these white blood cells are going to come out and they're going to start trying to fight.

As they start trying to fight, specifically the macrophage, he's going to come out and he's going to start trying to fight. We'll talk about this in the next video, what happens. Whenever he gets ready to start fighting these actual bacteria, he wants to alert other white blood cells that there's more bacteria in this area. So what does he do? He secretes two really important chemicals called interleukin-1 and Tumor Necrotic Factor Alpha.

He also secretes another important chemical and this chemical is called Interleukin-8. Now I'm not going to spend a ton of time on this, I'm just going to mention it so that you do know that there is other types of selectins. So again, these were P selectins and these were P cams. Let's talk about what these two guys do right here.

Let's make these endothelial cells bigger. Okay, first off, interleukin-1 and tumor necrotic factor alpha. Let's say that they work on this endothelial cell.

When they work on this endothelial cell, it activates this endothelial cell to produce specific types of proteins in response to that. And these proteins, they're called selectins. They're called selectins, but guess what kind of selectins they're called? These selectins are called e-selectins.

So it's nothing crazy, just know that interleukin-1 and tumor necrotic factor alpha, they're produced a little later on in the inflammatory response. All these histamines and leukotrienes and prostaglandins, they're produced very, very quickly because they're already preformed. Interleukin-1 and tumor necrotic factor alpha, you actually have to make those, you have to synthesize them.

So it takes a little longer. So these come up later in the inflammatory response. But then again, what can they allow to happen here?

They can allow for my monos... sites right here and my neutrophils to adhere with their because they have those sugar molecules right they can adhere with these e-selectants right so nothing crazy now here's where it gets a little funky another thing These actual neutrophils and specifically neutrophils and the monocytes, they have specific proteins on their cell membrane right here. So look at these proteins right here, these black proteins.

They're inactive, they're not really active right now. Interleukin-8 binds on to a specific receptor here present on the endothelial cell membrane and when it does, So let's say here's interleukin-8. It's going to come and it's going to bind here on this receptor.

When it binds on this receptor, it activates this actual cell and causes it to synthesize a protein. What is this protein here called? This protein here is called ICAM.

There's two types, ICAM and VCAM. And I just stands for intracellular cell adhesion molecule. V stands for vascular cell adhesion molecule.

But what happens here? Interleukin-8 will bind onto this receptor and then this interleukin-8 will activate this neutrophil. When it activates this neutrophil, these integrins then become activated. Now look what happens. If they're activated, let's say it moves from this E-Select and it just so happens to roll over, boom.

And it perfectly interacts with that V-CAM and I-CAM. Now look. So now it's going to perfectly interact. with that V cam and the I cam.

And again, this is just another way because again, what will also be within these cells too, you'll have a lot of gaps, right? Because of the endothelial cell contraction and there also will be retraction. And again, what else is going to be right here? Your P cams. And then again, what will happen, the white blood cell will actually squeeze through this capillary.

And when it squeezes through this capillary by amoeboid motion, that process is called. diapedesis and then it'll follow the chemical trail molecules towards this bacteria and that's called positive chemotaxis right so there's a lot of things that are actually happening within this response before we finish this up and we go into the entire phagocytic mechanism in the next video let's do a quick quick recap alright ready so again bacteria releases endotoxins destroys the tissue activates mast cells mast cells starts producing preformed very very quickly they make them molecules like histamines, leukotrienes, prostaglandins, and bradykinins, right? And then also the actual damaged cell membrane can start producing specific types of similar molecules like leukotrienes and prostaglandins. These molecules can activate the endothelial cells to make big gaps, which increases permeability.

They can also activate the smooth muscle cells to dilate, all right, to relax and then cause vasodilation, which increases blood flow. And then also this will have increased permeability. Another thing will happen is it'll stimulate these endothelial cells to expose these specific type of molecules called P-selectins, which allows for adhesion with the white blood cells and they'll roll across the surface which is margination. Then they'll interact between the cells with P-cams to squeeze through the capillaries by amoeboid motion, that's called diapedesis.

Then after that they'll follow that chemical trail of molecules to where the actual infectious agent is and that's called positive chemotaxis. As the white blood cells, specifically the monocytes or macrophages, start fighting with the bacteria, they start secreting interleukin-1 and tumor necrotic factor alpha, which activate endothelial cells later in the inflammatory response, a little bit later, to produce E-selectins. And then the macrophage also produces interleukin-8, which activates the integrins to bind with ICAMs and VCAMs.

And again, bind with the PCAMs and come out to this area by diapodesis. And then positive chemotaxis and fight the bacteria. All right, so last thing here I want to mention. If you know something about whenever you're really getting sick, right, if you're really sick, what happens if you're fighting off some type of infection?

You have a fever, right? So usually you get really, really hot. You get a fever. What causes that fever? This mofo right here, interleukin-1 and tumor necrotic factor alpha.

What do they do? If you look here, I draw three different specific organs that I want to talk about. The brain, the liver, and we're just drawing a bone marrow, right? That's what it's supposed to represent.

This interleukin-1 and tumor necrotic factor alpha will track its way up to the brain, and there's a specific part of the brain it actually works on. What is that part of the brain that it works on? This area of the brain is called the hypothalamus.

And when it works in the hypothalamus, this interleukin-1 and tumor necrotic factor alpha Alpha will activate the hypothalamus to start secreting a molecule called PGE2. And PGE2 resets our actual body temperature, and it initiates fever, okay? So again, what is happening here?

Interleukin-1 and tumor necrotic factor alpha. So what is this chemical? It's actually shown right here, so we don't lose it. Interleukin-1 and tumor necrotic factor alpha. We're working on the hypothalamus, initiating PGE2 secretion and causing fever.

What is the significance of a fever? A couple things. One thing about a fever is it makes it a harsher environment for certain types of microorganisms to survive in.

It can denature some of their proteins, their DNA, right? Second thing, it speeds up our cellular metabolism. And as you speed up metabolism, you can initiate a quicker healing process. That's another thing.

There is another mechanism, I'm not going to talk too much about it, but your body has a way of sequestering iron and zinc that the bacteria need in order for them to continue to multiply. It can sequester that within the iron and also within the spleen. So again, that's that mechanism.

Then, we might as well show what it also does here. Look, here's our liver. It also can act on the liver. And the liver, in response to this, can produce what's called acute phase... Reactant proteins.

Why is this important? Because if you actually have a really really bad infection or maybe you have cancer maybe there's actually something else wrong they actually run a test. So this is really good it's better for determining active inflammation.

They run a blood test and whenever they run a blood test a specific type of acute phase reactive protein shows up. This acute phase reactive protein is called C-reactive peptide. There is many many other types of acute phase reactive proteins like ceruloplasma and haptoglobin and fibrinogen.

We don't care about those, we care about this one. So high C reactive peptide levels within the blood can kind of give a doctor some type of help to diagnose, okay this person has some type of active inflammation, I don't know what it is, but we're gonna try to figure that out with other types of diagnostic test procedures, right? Okay, so that's that.

Then... And there's another one that can also cause this too, didn't talk too much about it yet, interleukin 6. That can also be secreted by macrophages and by T cells. We're not going to talk too much about that, but that can also initiate that response. Then tumor necrotic factor and alpha and interleukin 1, and there is other cytokines like interleukin 3 and interleukin 5, can also act on the bone marrow. They can act on the bone marrow.

What do we want to activate the bone marrow? What's in the bone marrow? Our actual cells, right? Our stem cells. What do we need a lot of?

We need white blood cells right now because we have a microorganism that can cause a lot of potential damage to our tissues. So what is this tumor necrotic factor alpha and interleukin 1 and other ones like interleukin 3 and interleukin 5 going to do? They're going to stimulate the bone marrow to start blasting out more white blood cells.

So we're going to start pushing out a lot more neutrophils. We're going to start pushing out a lot more monocytes. We're going to start pushing on a lot more eosinophils depending upon what the infectious organism might be.

But this is called, whenever this is happening, it's called leukocytosis. Okay? It's called leukocytosis. Got it? Alright, now that we've talked about the leukocytosis mechanism, we've talked about the C-reactive peptide, and we've talked about fever, we now have a good idea now of what's happening within the inflammatory response.

In the next video, I want you guys to click up on the right icon. We're going to talk about specifically continuing with the inflammatory response. Well, we're going to now focus on what's happening with these actual white blood cells and how they undergo phagocytosis.

Transcript for:Understanding Inflammation and Immune Response

Transcript for:
Understanding Inflammation and Immune Response