Direct Action Against Drugs

Transcription

We've all had cuts on our finger or wherever else on our body, and immediately that part of the body gets a little bit of redness, a little bit of swelling, some heat maybe, and, of course, there'll be some pain associated with what's going on there. And in general, this set of symptoms that we experience, these are known as the inflammatory response, or you might say that there's some inflammation going on there. And people have known about this I guess ever since really people have been having cuts. I think probably with modern medicine, people have been a little bit more particular about actually classifying the symptoms, but this isn't anything new for someone to say that there's some type of inflammation going on or some type of inflammatory response. But what I want to do in this video is understand what's causing these-- I guess we can call them macrosymptoms. What's happening at a cellular level? Because, really, the inflammatory response is essentially the initial field of battle of our immune system. Our first line of defense is our skin or the fluids on the outside of our skin or the mucous membranes, but the inflammatory response is what happens when something gets beyond that. We get punctured with a nail, or there's some type of virus or bacteria gets beyond our skin or the mucus that surrounds our membranes. This is the field of battle, especially the initial field of battle. So let's set up an immune battle so we can see exactly what's going on with the inflammatory response. And I want to be very clear. Immunology, is still a very under understood field. It's an area of active research. People are still discovering the mechanisms and it's hugely complex. I'm sure we'll probably be studying this for a long time to come. So what I'm going to talk about is just the overview, just you know the general actors and you know in general what's causing the redness, the swelling, the heat, and the pain. So let me draw some skin cells. This is a gross oversimplification of everything, but it's really just to give an idea of what is going on. So I'm going to do a cross-section. So those are some skin cells in there, and then I'm going to-- so this is the outside world right here. Then amongst those skin cells, I'll do some other cells. We'll talk about what they do. I won't go into huge detail about them. Let's call this cell right here a mast cell. I'll draw a few more mast cells. Maybe another one right there. That's a mast cell. And if you remember from the videos on phagocytic action or phagocytes, you'll remember there was one type called dendritic cells and they tend to hang out near our skin. They kind of hang out near areas that might interface with the outside world. I'll draw a couple of dendritic cells and these are also the ones that were really good at activating helper T-cells. They're called dendritic cells. They have no relation to the nervous system. They just look like they have dendrites on them and that's why they call them dendritic, but they're really phagocytes and they tend to be near external interfaces and they phagocytose particles and they're good at presenting them to helper T-cells so that they can get activated and ring the alarm bell, so to speak. So this is just a normal, functioning, happy skin. So that's the outside. Over here, this is the interstitial fluid. That's just a fancy word for the fluid that cells are kind of being surrounded by or that bathe cells. The cells aren't all directly connected to the circulatory system. The oxygen goes from the circulatory system to the interstitial fluid and eventually finds its way into cells. So everything is directly connected to capillaries, but capillaries play a big role in our circulatory system. So let me draw that. Instead of just drawing them as tubes, I'm actually going to draw the cells of our circulatory system. So let's say that this down here-- these are the endothelial cells of our capillaries. So these are literally the cells that make up the walls of our capillaries. And of course, this is a cross-section. If I were to-- I would draw it as a tube somehow. It's not like it's a sandwich. It's actually a tube. Everything is in cross-section. So these are capillary endothelial cells, and of course, right in here, we have our blood flowing and we'll have red blood cells in here. These are red blood cells. Maybe they're flowing in that direction. On this side, they're oxygenated. This would be arteries and then they'd become veins as the red blood cells lose their oxygen. And of course, you might have circulating white blood cells inside of your-- obviously, in much lower quantity than your red blood cells, but just to show that they're circulating and they're moving with your circulatory system being pumped by the heart. Now under normal circumstances, there is an exchange obviously of gases between what's going on in our circulatory system and the interstitial fluid and there's also a mild exchange of some cells and proteins. What we're going to see now is what happens when we have an intruder. So let's say someone takes a nail, dips it in some cow manure, and then pokes you with that nail. Let's see what happens. So let's say someone pokes you with this nail dipped in cow manure. So it's got all sorts of nasty stuff on it, pathogens on it, probably has a bunch of bacteria sitting in the cow manure. I didn't pick cow manure at random. It's probably a good source of bacteria. So as soon as it pierces the first line of defense, as soon as it pierces your skin, a couple of things are going to happen. A lot of these bacteria are immediately going to start floating around in your interstitial fluid. The cells that it came in contact with, it pierced them. It probably killed some cells. It's also going to damage some of these skin cells and those skin cells are immediately going to start releasing chemicals, the ones that are still in a position to do so. They're going to start releasing chemicals that are essentially chemical messengers that move through the-- well, at first locally in the interstitial fluid and says, something is going on. Something has happened to me. And these are called chemokines. And chemokines are just a very general word, really, for small molecules or small proteins that cells release as a kind of signaling mechanism. Chemo for chemical, kine for kinetic, for moving. These are messengers. They move. So these chemokines get released. And this is all tremendously complicated. So I'm doing very high level. There are many, many types of chemokines. And also you have these mast cells here, and these mast cells can be activated by direct contact maybe with the rusty nail. It could be from the chemokines released by some of these cells up here. It could be from some of the molecules released by the actual bacteria. These bacteria are also releasing different byproducts as they enter the body. And any of the above can activate the mast cells and mast cells release histamine. So you can already appreciate, I'm doing a high-level overview, and it already is kind of complicated, but I think you get the sense of what's going on. And if the word histamine sounds vaguely familiar, it's probably because you've taken an antihistamine sometime probably in the last several months, especially during cold season. Histamine is kind of one of the main actors in the inflammatory response, and when you have a cold and a runny nose and stuffy nose and all of those type of things, those are all byproducts of the inflammatory response, and anti-histamines essentially try to shut down that inflammatory response so some of those symptoms disappear. But it begs the question of is that necessarily always a good thing? Because, as I'm going to talk about in this video, this is the first line of defense. This is the first part of the battle of our immune system. But anyway, so the histamine-- one of the things that the histamine does is it goes to the endothelial cells that line your capillaries, and it causes them to separate away from each other and make the actual capillaries larger. This is called vasodilation. Let's say that they've all been activated with a little bit of histamine. The histamine has come in so now these guys get further apart. They get further apart and the actual capillary becomes larger. So this is where you get a lot of your swelling, because all of sudden, the capillary's larger, more fluid, and actually, it gets smaller further down so it really encourages the fluid to collect right around here. So this is called vasodilation, just another fancy word for saying your capillaries are getting dlated. They're getting larger. Fluid is filling them up. Not only are things starting to collect here-- more and more red blood cells are collecting here, obviously there's a lot of fluid here, the white blood cells-- but also the capillary walls are becoming more porous. All of a sudden, things that couldn't get through them are going to have a much easier time getting through them. And one of those things that are going to have an easier time getting through them-- and once again, remember, all this other stuff is going on. You have these histamines that are being dumped on these endothelial cells and maybe some of it 's getting into the serum. You have these chemokines being released locally from this area of damage. You have the actual things being-- the green was the color of the molecules being released by the viruses. You have the chemokines, which are in blue. They're all being released here. And so the first responders, the phagocytes, and in particular, the neutrophils, which are the most abundant of the phagocytes, a subclass of white blood cells, they're attracted to these chemicals. They want to move in the direction that there's more of these chemicals. And now that the space between these capillary cells have gotten further apart, they can get through. So what they actually do is-- let's say that this right here is a neutrophil. They start kind of rolling along the wall right here. That's called marginalization. They roll along this wall and eventually-- so they kind of stick to the wall. They adhere to the wall, and then eventually they squeeze through these gaps in the capillary wall. This is called diapedesis or extravasation. Sometimes it's called emigration. These are all fancy words, but essentially it's just squeezing through the walls. So that's the neutrophil right there. And then, of course, because of the vasodilation, this is where the neutrophils will be getting dumped in and this is exactly where they're needed. So these neutrophils are going to be here and then they're going to do what they do. They're going to phagocytose some of these bacteria and start eating up, and maybe even some damaged cells up here. And so that's what you want to happen. That's why I said this is the field of battle. At the same time, your dendritic cells, other phagocytes, they will eat up the viruses and then they'll present them on their surfaces. And it's not just neutrophils that are coming in. Because this is kind of an area of congestion and all of the fluid is coming here, you'll also have B-cells and T-cells that'll also make their way. They'll also experience marginalization, where they roll up against the sides of the capillary and then diapedesis or extravasation where they go through, and then they'll be activated, and they can actually do the specific immune system. So the whole point here is I wanted to show you-- and this is why I delayed the whole video on the inflammatory response, because it isn't just one type of simple thing. It's actually the field of battle where all of the actors come and play, even the first line of defense of your skin, and then all of the actors, the nonspecific reactions of-- inflammatory response is normally categorized as nonspecific because it's going to happen no matter what comes, but you have the nonspecific actors like the neutrophils. You have your specific actors like your B-cells and T-cells and you also have the nonspecific complement system. And I'm not going to go into detail here, but you actually have proteins that are flowing in your blood plasma that are normally in an inactive state, but when the inflammatory response occurs, these proteins, they get essentially activated and sometimes-- and this is all not 100% well understood-- they become activated, they get cleaved up, and then the cleaved-up versions of those proteins are really good at, in a very nonspecific way, helping to kill off at least some of what's getting-- maybe the bacteria in this case. So this right here, this is the complement system, which is really just a set of proteins that always just floats around and they are a good kind of first line of nonspecific fight against some type of invading pathogen. So hopefully, this gives you a good sense of what is going on in the inflammatory response. And as you can imagine, you have all of this fluid coming here, all of this blood is collecting here. You have all of this fluid coming into-- so not just cells that are going from our capillaries into our interstitial fluid, you'll actually have fluid going in and that fluid that's going in is called exudate. So this whole thing become swelling and red and engorged and that's why you see, on kind of a very macro level, these type of symptoms. Anyway, hopefully, you found that useful.