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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 margination.
- 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.