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  • 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.

We've all had cuts on our finger or wherever else on our

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