Inflammatory response

WEBVTT
Kind: captions
Language: en

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

00:00:03.560 --> 00:00:06.320
body, and immediately that part
of the body gets a little

00:00:06.320 --> 00:00:16.219
bit of redness, a little bit of
swelling, some heat maybe,

00:00:16.219 --> 00:00:18.800
and, of course, there'll be
some pain associated with

00:00:18.800 --> 00:00:20.040
what's going on there.

00:00:20.040 --> 00:00:24.150
And in general, this set of
symptoms that we experience,

00:00:24.150 --> 00:00:26.370
these are known as the
inflammatory response, or you

00:00:26.370 --> 00:00:29.220
might say that there's some
inflammation going on there.

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And people have known about this
I guess ever since really

00:00:32.670 --> 00:00:35.230
people have been having cuts.

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I think probably with modern
medicine, people have been a

00:00:38.250 --> 00:00:41.030
little bit more particular about
actually classifying the

00:00:41.030 --> 00:00:43.640
symptoms, but this isn't
anything new for someone to

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say that there's some type of
inflammation going on or some

00:00:45.880 --> 00:00:48.380
type of inflammatory response.

00:00:48.380 --> 00:00:51.080
But what I want to do in this
video is understand what's

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causing these-- I guess we can
call them macrosymptoms.

00:00:54.330 --> 00:00:56.130
What's happening at
a cellular level?

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Because, really, the
inflammatory response is

00:00:58.480 --> 00:01:01.140
essentially the initial
field of battle

00:01:01.140 --> 00:01:02.530
of our immune system.

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Our first line of defense is our
skin or the fluids on the

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outside of our skin or the
mucous membranes, but the

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inflammatory response is what
happens when something gets

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beyond that.

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We get punctured with a nail, or
there's some type of virus

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or bacteria gets beyond our
skin or the mucus that

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surrounds our membranes.

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This is the field of battle,
especially the

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initial field of battle.

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So let's set up an immune battle
so we can see exactly

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what's going on with the
inflammatory response.

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And I want to be very clear.

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Immunology, is still a very
under understood field.

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It's an area of active
research.

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People are still discovering
the mechanisms

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and it's hugely complex.

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I'm sure we'll probably
be studying this for a

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long time to come.

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So what I'm going to talk about
is just the overview,

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just you know the general actors
and you know in general

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what's causing the redness,
the swelling, the

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heat, and the pain.

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So let me draw some
skin cells.

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This is a gross
oversimplification of

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everything, but it's really just
to give an idea of what

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is going on.

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So I'm going to do
a cross-section.

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So those are some skin cells in
there, and then I'm going

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to-- so this is the outside
world right here.

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Then amongst those skin cells,
I'll do some other cells.

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We'll talk about what they do.

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I won't go into huge
detail about them.

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Let's call this cell right
here a mast cell.

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I'll draw a few more
mast cells.

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Maybe another one right there.

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That's a mast cell.

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And if you remember from the
videos on phagocytic action or

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phagocytes, you'll remember
there was one type called

00:02:48.480 --> 00:02:51.710
dendritic cells and they tend
to hang out near our skin.

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They kind of hang out near areas
that might interface

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with the outside world.

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I'll draw a couple of dendritic
cells and these are

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also the ones that were
really good at

00:02:59.680 --> 00:03:03.550
activating helper T-cells.

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They're called dendritic
cells.

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They have no relation to
the nervous system.

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They just look like they have
dendrites on them and that's

00:03:16.440 --> 00:03:19.170
why they call them dendritic,
but they're really phagocytes

00:03:19.170 --> 00:03:24.800
and they tend to be near
external interfaces and they

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phagocytose particles and
they're good at presenting

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them to helper T-cells so that
they can get activated and

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ring the alarm bell,
so to speak.

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So this is just a normal,
functioning, happy skin.

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So that's the outside.

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Over here, this is the
interstitial fluid.

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That's just a fancy word for the
fluid that cells are kind

00:03:46.740 --> 00:03:50.220
of being surrounded by
or that bathe cells.

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The cells aren't all directly
connected to

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the circulatory system.

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The oxygen goes from the
circulatory system to the

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interstitial fluid and
eventually finds

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its way into cells.

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So everything is directly
connected to capillaries, but

00:04:03.380 --> 00:04:05.560
capillaries play a big role
in our circulatory system.

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So let me draw that.

00:04:06.470 --> 00:04:08.815
Instead of just drawing them as
tubes, I'm actually going

00:04:08.815 --> 00:04:11.360
to draw the cells of our
circulatory system.

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So let's say that this down
here-- these are the

00:04:14.130 --> 00:04:17.670
endothelial cells of
our capillaries.

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So these are literally the cells
that make up the walls

00:04:21.310 --> 00:04:22.560
of our capillaries.

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And of course, this is
a cross-section.

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If I were to-- I would draw
it as a tube somehow.

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It's not like it's a sandwich.

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It's actually a tube.

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Everything is in
cross-section.

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So these are capillary
endothelial cells, and of

00:04:55.160 --> 00:04:58.850
course, right in here, we have
our blood flowing and we'll

00:04:58.850 --> 00:05:00.460
have red blood cells in here.

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These are red blood cells.

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Maybe they're flowing
in that direction.

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On this side, they're
oxygenated.

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This would be arteries and then
they'd become veins as

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the red blood cells
lose their oxygen.

00:05:13.580 --> 00:05:16.950
And of course, you might have
circulating white blood cells

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inside of your-- obviously, in
much lower quantity than your

00:05:21.470 --> 00:05:23.580
red blood cells, but just to
show that they're circulating

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and they're moving with your
circulatory system being

00:05:25.940 --> 00:05:27.640
pumped by the heart.

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Now under normal circumstances,
there is an

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exchange obviously of gases
between what's going on in our

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circulatory system and the
interstitial fluid and there's

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also a mild exchange of some
cells and proteins.

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What we're going to see
now is what happens

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when we have an intruder.

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So let's say someone takes a
nail, dips it in some cow

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manure, and then pokes
you with that nail.

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Let's see what happens.

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So let's say someone pokes
you with this nail

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dipped in cow manure.

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So it's got all sorts of nasty
stuff on it, pathogens on it,

00:06:07.570 --> 00:06:09.730
probably has a bunch
of bacteria

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sitting in the cow manure.

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I didn't pick cow manure
at random.

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It's probably a good
source of bacteria.

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So as soon as it pierces the
first line of defense, as soon

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as it pierces your skin,
a couple of things

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are going to happen.

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A lot of these bacteria are
immediately going to start

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floating around in your
interstitial fluid.

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The cells that it came in
contact with, it pierced them.

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It probably killed some cells.

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It's also going to damage some
of these skin cells and those

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skin cells are immediately
going to start releasing

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chemicals, the ones that are
still in a position to do so.

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They're going to start releasing
chemicals that are

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essentially chemical messengers
that move through

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the-- well, at first locally in
the interstitial fluid and

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says, something is going on.

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Something has happened to me.

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And these are called
chemokines.

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And chemokines are just a very
general word, really, for

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small molecules or small
proteins that cells release as

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a kind of signaling mechanism.

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Chemo for chemical, kine for
kinetic, for moving.

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These are messengers.

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They move.

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So these chemokines
get released.

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And this is all tremendously
complicated.

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So I'm doing very high level.

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There are many, many types
of chemokines.

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And also you have these mast
cells here, and these mast

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cells can be activated by direct
contact maybe with the

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rusty nail.

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It could be from the chemokines
released by some of

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these cells up here.

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It could be from some of the
molecules released by the

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actual bacteria.

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These bacteria are also
releasing different byproducts

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as they enter the body.

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And any of the above can
activate the mast cells and

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mast cells release histamine.

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So you can already appreciate,
I'm doing a high-level

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overview, and it already is
kind of complicated, but I

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think you get the sense
of what's going on.

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And if the word histamine sounds
vaguely familiar, it's

00:08:07.270 --> 00:08:11.040
probably because you've taken
an antihistamine sometime

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probably in the last
several months,

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especially during cold season.

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Histamine is kind of one of
the main actors in the

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inflammatory response, and when
you have a cold and a

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runny nose and stuffy nose and
all of those type of things,

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those are all byproducts of the
inflammatory response, and

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anti-histamines essentially
try to shut down that

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inflammatory response so some
of those symptoms disappear.

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But it begs the question
of is that necessarily

00:08:38.490 --> 00:08:39.419
always a good thing?

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Because, as I'm going to talk
about in this video, this is

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the first line of defense.

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This is the first part of the
battle of our immune system.

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But anyway, so the histamine--
one of the things that the

00:08:49.330 --> 00:08:54.460
histamine does is it goes to
the endothelial cells that

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line your capillaries, and it
causes them to separate away

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from each other and make the
actual capillaries larger.

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This is called vasodilation.

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Let's say that they've all been
activated with a little

00:09:17.960 --> 00:09:19.210
bit of histamine.

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The histamine has come
in so now these

00:09:24.910 --> 00:09:27.110
guys get further apart.

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They get further apart
and the actual

00:09:29.130 --> 00:09:30.400
capillary becomes larger.

00:09:35.810 --> 00:09:38.780
So this is where you get a lot
of your swelling, because all

00:09:38.780 --> 00:09:41.370
of sudden, the capillary's
larger, more fluid, and

00:09:41.370 --> 00:09:44.110
actually, it gets smaller
further down so it really

00:09:44.110 --> 00:09:47.780
encourages the fluid to collect
right around here.

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So this is called vasodilation,
just another

00:09:51.190 --> 00:09:52.960
fancy word for saying your

00:09:52.960 --> 00:09:54.470
capillaries are getting dilated.

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They're getting larger.

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Fluid is filling them up.

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Not only are things starting
to collect here-- more and

00:10:00.900 --> 00:10:03.830
more red blood cells are
collecting here, obviously

00:10:03.830 --> 00:10:06.580
there's a lot of fluid here,
the white blood cells-- but

00:10:06.580 --> 00:10:09.400
also the capillary walls are
becoming more porous.

00:10:09.400 --> 00:10:11.820
All of a sudden, things that
couldn't get through them are

00:10:11.820 --> 00:10:14.280
going to have a much easier
time getting through them.

00:10:14.280 --> 00:10:16.810
And one of those things that
are going to have an easier

00:10:16.810 --> 00:10:18.750
time getting through them-- and
once again, remember, all

00:10:18.750 --> 00:10:20.210
this other stuff is going on.

00:10:20.210 --> 00:10:24.400
You have these histamines that
are being dumped on these

00:10:24.400 --> 00:10:26.350
endothelial cells and
maybe some of it 's

00:10:26.350 --> 00:10:27.340
getting into the serum.

00:10:27.340 --> 00:10:31.530
You have these chemokines being
released locally from

00:10:31.530 --> 00:10:32.920
this area of damage.

00:10:32.920 --> 00:10:35.550
You have the actual things
being-- the green was the

00:10:35.550 --> 00:10:38.870
color of the molecules being
released by the viruses.

00:10:38.870 --> 00:10:41.330
You have the chemokines,
which are in blue.

00:10:41.330 --> 00:10:44.820
They're all being
released here.

00:10:44.820 --> 00:10:48.600
And so the first responders,
the phagocytes, and in

00:10:48.600 --> 00:10:51.590
particular, the neutrophils,
which are the most abundant of

00:10:51.590 --> 00:10:54.510
the phagocytes, a subclass of
white blood cells, they're

00:10:54.510 --> 00:10:56.730
attracted to these chemicals.

00:10:56.730 --> 00:10:58.760
They want to move in the
direction that there's more of

00:10:58.760 --> 00:10:59.660
these chemicals.

00:10:59.660 --> 00:11:03.800
And now that the space between
these capillary cells have

00:11:03.800 --> 00:11:06.440
gotten further apart, they
can get through.

00:11:06.440 --> 00:11:08.855
So what they actually do is--
let's say that this right here

00:11:08.855 --> 00:11:10.105
is a neutrophil.

00:11:13.980 --> 00:11:17.530
They start kind of rolling along
the wall right here.

00:11:17.530 --> 00:11:19.330
That's called marginalization.

00:11:19.330 --> 00:11:23.310
They roll along this wall and
eventually-- so they kind of

00:11:23.310 --> 00:11:24.600
stick to the wall.

00:11:24.600 --> 00:11:27.610
They adhere to the wall, and
then eventually they squeeze

00:11:27.610 --> 00:11:32.650
through these gaps in
the capillary wall.

00:11:32.650 --> 00:11:36.220
This is called diapedesis
or extravasation.

00:11:36.220 --> 00:11:38.110
Sometimes it's called
emigration.

00:11:38.110 --> 00:11:39.800
These are all fancy words,
but essentially it's just

00:11:39.800 --> 00:11:40.920
squeezing through the walls.

00:11:40.920 --> 00:11:42.620
So that's the neutrophil
right there.

00:11:42.620 --> 00:11:45.270
And then, of course, because of
the vasodilation, this is

00:11:45.270 --> 00:11:48.120
where the neutrophils will be
getting dumped in and this is

00:11:48.120 --> 00:11:49.800
exactly where they're needed.

00:11:49.800 --> 00:11:52.090
So these neutrophils are going
to be here and then they're

00:11:52.090 --> 00:11:52.870
going to do what they do.

00:11:52.870 --> 00:11:55.810
They're going to phagocytose
some of these bacteria and

00:11:55.810 --> 00:11:57.330
start eating up, and
maybe even some

00:11:57.330 --> 00:11:59.240
damaged cells up here.

00:11:59.240 --> 00:12:00.460
And so that's what you
want to happen.

00:12:00.460 --> 00:12:01.860
That's why I said this is
the field of battle.

00:12:01.860 --> 00:12:04.310
At the same time, your dendritic
cells, other

00:12:04.310 --> 00:12:08.430
phagocytes, they will eat up the
viruses and then they'll

00:12:08.430 --> 00:12:10.530
present them on their
surfaces.

00:12:10.530 --> 00:12:12.980
And it's not just neutrophils
that are coming in.

00:12:12.980 --> 00:12:17.240
Because this is kind of an area
of congestion and all of

00:12:17.240 --> 00:12:21.410
the fluid is coming here, you'll
also have B-cells and

00:12:21.410 --> 00:12:24.180
T-cells that'll also
make their way.

00:12:24.180 --> 00:12:27.840
They'll also experience
marginalization, where they

00:12:27.840 --> 00:12:32.130
roll up against the sides of
the capillary and then

00:12:32.130 --> 00:12:35.900
diapedesis or extravasation
where they go through, and

00:12:35.900 --> 00:12:37.670
then they'll be activated, and
they can actually do the

00:12:37.670 --> 00:12:39.490
specific immune system.

00:12:39.490 --> 00:12:41.840
So the whole point here is I
wanted to show you-- and this

00:12:41.840 --> 00:12:45.730
is why I delayed the whole
video on the inflammatory

00:12:45.730 --> 00:12:49.440
response, because it isn't just
one type of simple thing.

00:12:49.440 --> 00:12:51.830
It's actually the field of
battle where all of the actors

00:12:51.830 --> 00:12:54.400
come and play, even the first
line of defense of your skin,

00:12:54.400 --> 00:12:58.480
and then all of the actors, the
nonspecific reactions of--

00:12:58.480 --> 00:13:00.610
inflammatory response is
normally categorized as

00:13:00.610 --> 00:13:02.520
nonspecific because it's going
to happen no matter what

00:13:02.520 --> 00:13:05.450
comes, but you have the
nonspecific actors like the

00:13:05.450 --> 00:13:06.320
neutrophils.

00:13:06.320 --> 00:13:11.600
You have your specific actors
like your B-cells and T-cells

00:13:11.600 --> 00:13:13.890
and you also have the
nonspecific complement system.

00:13:13.890 --> 00:13:15.580
And I'm not going to go into
detail here, but you actually

00:13:15.580 --> 00:13:19.990
have proteins that are flowing
in your blood plasma that are

00:13:19.990 --> 00:13:23.650
normally in an inactive state,
but when the inflammatory

00:13:23.650 --> 00:13:27.050
response occurs, these proteins,
they get essentially

00:13:27.050 --> 00:13:29.940
activated and sometimes-- and
this is all not 100% well

00:13:29.940 --> 00:13:32.490
understood-- they become
activated, they get cleaved

00:13:32.490 --> 00:13:35.600
up, and then the cleaved-up
versions of those proteins are

00:13:35.600 --> 00:13:41.070
really good at, in a very
nonspecific way, helping to

00:13:41.070 --> 00:13:43.770
kill off at least some of what's
getting-- maybe the

00:13:43.770 --> 00:13:44.970
bacteria in this case.

00:13:44.970 --> 00:13:46.990
So this right here, this is the
complement system, which

00:13:46.990 --> 00:13:49.600
is really just a set of proteins
that always just

00:13:49.600 --> 00:13:53.070
floats around and they are a
good kind of first line of

00:13:53.070 --> 00:13:57.950
nonspecific fight against some
type of invading pathogen.

00:13:57.950 --> 00:14:02.470
So hopefully, this gives you a
good sense of what is going on

00:14:02.470 --> 00:14:04.410
in the inflammatory response.

00:14:04.410 --> 00:14:06.670
And as you can imagine, you have
all of this fluid coming

00:14:06.670 --> 00:14:09.210
here, all of this blood
is collecting here.

00:14:09.210 --> 00:14:13.180
You have all of this fluid
coming into-- so not just

00:14:13.180 --> 00:14:16.280
cells that are going from
our capillaries into our

00:14:16.280 --> 00:14:18.960
interstitial fluid, you'll
actually have fluid going in

00:14:18.960 --> 00:14:20.990
and that fluid that's going
in is called exudate.

00:14:23.800 --> 00:14:27.010
So this whole thing become
swelling and red and engorged

00:14:27.010 --> 00:14:30.180
and that's why you see, on kind
of a very macro level,

00:14:30.180 --> 00:14:31.970
these type of symptoms.

00:14:31.970 --> 00:14:34.550
Anyway, hopefully, you
found that useful.


PBS NewsHour on the Khan Academy

WEBVTT
Kind: captions
Language: en

00:00:00.000 --> 00:00:03.160
JUDY WOODRUFF: Now the story
of a young man teaching

00:00:03.160 --> 00:00:05.080
math to the world.

00:00:05.080 --> 00:00:08.280
NewsHour correspondent
Spencer Michels reports.

00:00:08.280 --> 00:00:11.260
SALMAN KHAN: So this is a
quadratic equation essentially.

00:00:11.260 --> 00:00:13.390
We're trying to find the 0s of--

00:00:13.390 --> 00:00:15.150
SPENCER MICHELS: This
disembodied voice

00:00:15.150 --> 00:00:17.950
is heard every day
by tens of thousands

00:00:17.950 --> 00:00:21.510
of students struggling
with math both in the US

00:00:21.510 --> 00:00:22.815
and around the world.

00:00:22.815 --> 00:00:25.660
SALMAN KHAN: So what is
x squared plus 4x plus 4?

00:00:25.660 --> 00:00:29.470
Well, it's x plus
2 times x plus 2.

00:00:29.470 --> 00:00:32.320
SPENCER MICHELS: 33-year-old
Salman Khan recently

00:00:32.320 --> 00:00:34.790
quit his job as a
hedge fund analyst

00:00:34.790 --> 00:00:37.780
to devote himself to
an unpaid job teaching

00:00:37.780 --> 00:00:39.685
math on the internet.

00:00:39.685 --> 00:00:44.520
SALMAN KHAN: Welcome to the
presentation on basic addition.

00:00:44.520 --> 00:00:47.439
These are cancers
or cancer cells.

00:00:47.439 --> 00:00:49.480
The investors in the
mortgage-backed securities--

00:00:49.480 --> 00:00:52.180
SPENCER MICHELS: He has
posted 1,200 lessons

00:00:52.180 --> 00:00:56.250
on YouTube, which appear on
an electronic blackboard,

00:00:56.250 --> 00:01:00.100
and range in subject from basic
addition and advanced calculus,

00:01:00.100 --> 00:01:01.930
to science and finance.

00:01:01.930 --> 00:01:02.920
And they are free.

00:01:02.920 --> 00:01:04.790
SALMAN KHAN: Introduction
to Trigonometry,

00:01:04.790 --> 00:01:07.730
this is where I teach people
about the trig functions.

00:01:07.730 --> 00:01:09.870
This is one of the
more popular videos.

00:01:09.870 --> 00:01:13.110
This has 179,000 views.

00:01:13.110 --> 00:01:16.820
And this is just what sine,
cosine, and tangent are,

00:01:16.820 --> 00:01:19.740
SPENCER MICHELS: Khan lives
in California's Silicon Valley

00:01:19.740 --> 00:01:23.130
with his wife, a rheumatologist
in training at Stanford,

00:01:23.130 --> 00:01:24.410
and their new baby.

00:01:24.410 --> 00:01:27.840
He got the idea for Khan
Academy four years ago

00:01:27.840 --> 00:01:29.440
when he taught a
young cousin how

00:01:29.440 --> 00:01:32.120
to convert kilograms to grams.

00:01:32.120 --> 00:01:34.650
Many American students
have trouble with math,

00:01:34.650 --> 00:01:38.300
and studies show they lag behind
their counterparts in Asia

00:01:38.300 --> 00:01:40.930
and Europe in both
math and science.

00:01:40.930 --> 00:01:44.220
With Khan's help, his
cousin got good at math,

00:01:44.220 --> 00:01:46.480
and he eventually
had a new career

00:01:46.480 --> 00:01:49.960
tapping into anxieties
around the world.

00:01:49.960 --> 00:01:53.010
Now he records his lessons
from a converted closet

00:01:53.010 --> 00:01:54.880
in the back of his bedroom.

00:01:54.880 --> 00:01:56.160
He never goes on camera.

00:01:56.160 --> 00:01:58.870
SALMAN KHAN: It kind of feels
like the voice in their head.

00:01:58.870 --> 00:01:59.940
You're looking at
it, it kind of feels

00:01:59.940 --> 00:02:02.100
like someone's over your
shoulder talking in your year

00:02:02.100 --> 00:02:03.933
as opposed to someone
at a blackboard that's

00:02:03.933 --> 00:02:06.550
distant from you. [COUGH]
Sorry for starting

00:02:06.550 --> 00:02:07.870
the presentation with a cough.

00:02:07.870 --> 00:02:11.494
But now I want to continue
with the 45-45-90 triangles.

00:02:11.494 --> 00:02:13.660
SPENCER MICHELS: Although
he is not the first person

00:02:13.660 --> 00:02:16.810
to teach on the internet,
his simple operation

00:02:16.810 --> 00:02:20.590
has attracted more eyeballs
than most university sites.

00:02:20.590 --> 00:02:22.180
And his fame has spread.

00:02:22.180 --> 00:02:25.260
The all-girl Castilleja
School in Palo Alto

00:02:25.260 --> 00:02:28.020
invited Khan to speak,
and he immediately

00:02:28.020 --> 00:02:29.664
connected to the student body.

00:02:29.664 --> 00:02:31.330
SALMAN KHAN: You tell
me that you really

00:02:31.330 --> 00:02:33.310
don't know how, dividing
decimals is still

00:02:33.310 --> 00:02:36.630
kind of this little gray
area, and if dividing decimals

00:02:36.630 --> 00:02:37.880
actually is, you're not alone.

00:02:37.880 --> 00:02:40.110
Dividing decimals is
kind of the one thing

00:02:40.110 --> 00:02:43.475
that no one wants to admit that
they kind of forgot how to do.

00:02:43.475 --> 00:02:46.010
SPENCER MICHELS: He exuded
pride in his expanding

00:02:46.010 --> 00:02:47.642
online audience.

00:02:47.642 --> 00:02:50.690
SALMAN KHAN: More and more
people kept watching it,

00:02:50.690 --> 00:02:52.830
and now it's reaching
actually on the order

00:02:52.830 --> 00:02:58.032
of 100,000 students now a month
and 40,000 video views a day.

00:02:58.032 --> 00:02:59.490
SPENCER MICHELS:
It was the concept

00:02:59.490 --> 00:03:01.550
of short, repeatable
lessons that

00:03:01.550 --> 00:03:03.500
attracted high
school senior Bridget

00:03:03.500 --> 00:03:06.960
Meany who admitted she'd had
trouble with seventh grade

00:03:06.960 --> 00:03:07.865
algebra.

00:03:07.865 --> 00:03:09.740
BRIDGET MEANY: I think
the teachers are good,

00:03:09.740 --> 00:03:15.150
but they can't go at a pace
that's perfect for everyone.

00:03:15.150 --> 00:03:20.090
But I like the concept of
knowing something in class,

00:03:20.090 --> 00:03:22.770
but then going back and
pressing pause or rewind,

00:03:22.770 --> 00:03:25.420
and actually getting a
deeper understanding of it.

00:03:25.420 --> 00:03:28.160
SPENCER MICHELS: Shy students
who don't ask questions

00:03:28.160 --> 00:03:31.580
in class may benefit the
most from Khan's videos,

00:03:31.580 --> 00:03:34.930
says Kimberly Knapp, who
teaches math at Castilleja.

00:03:34.930 --> 00:03:37.810
But his lessons aren't a
substitute for the classroom,

00:03:37.810 --> 00:03:39.560
KIMBERLY KNAPP: I don't
think that there's

00:03:39.560 --> 00:03:41.780
a perfect replacement
for the work that we do

00:03:41.780 --> 00:03:43.340
and just the kind
of conversations

00:03:43.340 --> 00:03:45.970
that students and teachers
engage in together.

00:03:45.970 --> 00:03:48.310
SPENCER MICHELS: But Khan
thinks maybe lecture halls

00:03:48.310 --> 00:03:50.750
and classrooms have
their limitations.

00:03:50.750 --> 00:03:53.080
Originally he kept
his lessons short

00:03:53.080 --> 00:03:55.410
because of YouTube restrictions.

00:03:55.410 --> 00:03:57.552
Now he thinks short is better.

00:03:57.552 --> 00:03:59.510
SALMAN KHAN: I've gotten
researchers telling me

00:03:59.510 --> 00:04:00.660
that you don't realize.

00:04:00.660 --> 00:04:02.260
10 minutes, we've
done studies, is

00:04:02.260 --> 00:04:05.504
how long someone can have a
high level of concentration,

00:04:05.504 --> 00:04:07.420
and anything beyond that,
you kind of lose it.

00:04:07.420 --> 00:04:09.750
And I think we've all had that
experience sitting in college

00:04:09.750 --> 00:04:11.850
where you can be with the
professor for about 10,

00:04:11.850 --> 00:04:12.547
15 minutes.

00:04:12.547 --> 00:04:13.755
And then you kind of lose it.

00:04:13.755 --> 00:04:16.800
SPENCER MICHELS: A lot of math
students apparently agree.

00:04:16.800 --> 00:04:19.230
I talked via the internet
with Cody Woodward

00:04:19.230 --> 00:04:23.506
in Anchorage, Alaska who uses
Khan's lessons at college.

00:04:23.506 --> 00:04:25.390
CODY WOODWARD: It has
helped me immensely

00:04:25.390 --> 00:04:28.330
in the grades for
my math classes,

00:04:28.330 --> 00:04:30.525
and I've also learned a lot.

00:04:30.525 --> 00:04:32.160
SPENCER MICHELS:
Internet instruction,

00:04:32.160 --> 00:04:35.690
be it the Khan Academy or
taped university lectures,

00:04:35.690 --> 00:04:40.220
could revolutionize education
in remote, Third World locations

00:04:40.220 --> 00:04:42.580
where access to
high-quality instruction

00:04:42.580 --> 00:04:44.800
is frequently unavailable.

00:04:44.800 --> 00:04:47.910
That's the hope of Neil
Radia, a young software

00:04:47.910 --> 00:04:50.270
programmer at Cisco Systems.

00:04:50.270 --> 00:04:53.280
He and fellow volunteers
at World Possible,

00:04:53.280 --> 00:04:56.990
working on their vacations,
are bringing online teaching

00:04:56.990 --> 00:04:59.740
to Africa and
India for starters.

00:04:59.740 --> 00:05:03.540
When Radia and Megha Jain
first traveled to Ethiopia,

00:05:03.540 --> 00:05:05.880
they found thousands
of brand new computers

00:05:05.880 --> 00:05:08.240
sitting idle because
they couldn't connect

00:05:08.240 --> 00:05:10.410
to the internet, and
therefore couldn't

00:05:10.410 --> 00:05:11.915
get online instruction.

00:05:11.915 --> 00:05:13.290
NEIL RADIA: The
great thing to do

00:05:13.290 --> 00:05:15.320
would to be putting a
lot of these resources

00:05:15.320 --> 00:05:18.840
on a single local server that
we could bring to the colleges,

00:05:18.840 --> 00:05:21.100
to the universities,
to community centers.

00:05:21.100 --> 00:05:22.780
We came across the Khan Academy.

00:05:22.780 --> 00:05:25.430
And we emailed him and asked
him if we could reproduce

00:05:25.430 --> 00:05:27.980
some of his material
on our servers,

00:05:27.980 --> 00:05:29.865
and he was very
willing to help us out.

00:05:29.865 --> 00:05:32.570
MEGHA JAIN: You'd be surprised
how fast these kids learn

00:05:32.570 --> 00:05:34.020
and take these things up.

00:05:34.020 --> 00:05:36.330
So it isn't strange to them.

00:05:36.330 --> 00:05:39.470
They've heard of this, and
they are excited to use it.

00:05:39.470 --> 00:05:41.300
SPENCER MICHELS: For
Khan, teaching math

00:05:41.300 --> 00:05:44.270
and science and finance
is just the beginning.

00:05:44.270 --> 00:05:46.650
He's ready to expand
his YouTube site

00:05:46.650 --> 00:05:48.899
to include whatever
strikes his fancy

00:05:48.899 --> 00:05:50.440
SALMAN KHAN: I want
to do everything.

00:05:50.440 --> 00:05:51.180
I want to do history.

00:05:51.180 --> 00:05:52.055
I want to do grammar.

00:05:52.055 --> 00:05:53.730
I want to do literally
every subject.

00:05:53.730 --> 00:05:56.220
SPENCER MICHELS: So far,
except for a little advertising

00:05:56.220 --> 00:05:59.650
revenue, he is donating
his time and equipment.

00:05:59.650 --> 00:06:01.800
It's a one-man
operation, but it's

00:06:01.800 --> 00:06:04.640
gotten so big he expects
to start soliciting

00:06:04.640 --> 00:06:08.680
outside support to keep
his academy growing.


Review of B cells, CD4+ T cells and CD8+ T cells

WEBVTT
Kind: captions
Language: en

00:00:00.410 --> 00:00:02.900
Now that we've touched on all
of the major players in the

00:00:02.900 --> 00:00:05.840
specific immune system, what I
thought I would do in this

00:00:05.840 --> 00:00:08.060
video is do a summary
so it all fits

00:00:08.060 --> 00:00:09.510
together a little bit.

00:00:09.510 --> 00:00:12.650
So the first person or character
we got exposed to

00:00:12.650 --> 00:00:14.770
was the B cell, which
I always do in blue.

00:00:18.610 --> 00:00:22.550
And what made that interesting
is that every B cell has its

00:00:22.550 --> 00:00:28.980
own specific-- or they have
membrane bound antibodies, but

00:00:28.980 --> 00:00:33.180
for each B cell, the membrane
bound antibodies on each

00:00:33.180 --> 00:00:36.270
specific B cell had its
own variable portion.

00:00:36.270 --> 00:00:41.770
So this B cell-- it'll be
variable right like that.

00:00:41.770 --> 00:00:45.030
And if I were to draw another
B cell right here, I would

00:00:45.030 --> 00:00:47.440
draw the variable portion
a little bit different.

00:00:47.440 --> 00:00:51.780
This is why different actual
B cells will respond to

00:00:51.780 --> 00:00:54.390
different antigens or different
pathogens that have

00:00:54.390 --> 00:00:55.640
entered our system.

00:00:55.640 --> 00:01:05.590
And a B cell gets activated--
let's talk about what happens

00:01:05.590 --> 00:01:07.445
when it gets activated or
what needs to happen.

00:01:10.800 --> 00:01:15.370
It needs binding of the pathogen
onto one of these

00:01:15.370 --> 00:01:16.863
membrane bound antibodies.

00:01:28.810 --> 00:01:29.890
But that's not all.

00:01:29.890 --> 00:01:33.480
I mean, sometimes that's all you
need, but usually you also

00:01:33.480 --> 00:01:35.450
need to be stimulated
by a T cell.

00:01:41.750 --> 00:01:44.580
And you might say, where's
the helper T cell

00:01:44.580 --> 00:01:46.070
stimulate this guy?

00:01:46.070 --> 00:01:49.390
Well, B cells were also antigen
presenting cells so

00:01:49.390 --> 00:01:53.010
he'll suck this guy in, break
him out, and present him on an

00:01:53.010 --> 00:01:54.455
MHC II complex.

00:02:00.290 --> 00:02:03.410
Let's say this is an
MHC II complex.

00:02:03.410 --> 00:02:06.750
This guy gets cut up, part of
him gets presented right here,

00:02:06.750 --> 00:02:12.500
and then an activated helper T
cell whose variable portion of

00:02:12.500 --> 00:02:15.370
their T cell receptor is
specific to this could come

00:02:15.370 --> 00:02:20.460
along and activate
this character.

00:02:20.460 --> 00:02:24.310
I'm not drawing that receptor
well, but that right there is

00:02:24.310 --> 00:02:28.340
a helper T cell and that
is the B cell.

00:02:28.340 --> 00:02:33.290
Now, once it's activated, it
starts differentiating-- and

00:02:33.290 --> 00:02:35.910
it starts cloning itself and
it can either turn into

00:02:35.910 --> 00:02:41.180
effector cells-- and this true
of B cells or T cells.

00:02:41.180 --> 00:02:43.640
Once they get activated, they
keep cloning or they either

00:02:43.640 --> 00:02:46.540
turn into effector cells
or memory cells.

00:02:46.540 --> 00:02:49.150
Memory cells stick around a
lot longer so that in the

00:02:49.150 --> 00:02:51.570
future you're going to have
many more of this

00:02:51.570 --> 00:02:52.880
version of B cells.

00:02:52.880 --> 00:02:56.790
So if you get the same antigen
or pathogen in the future, the

00:02:56.790 --> 00:02:59.780
likelihood of it bumping into
this type of B cell is going

00:02:59.780 --> 00:03:02.700
to be higher so the response
will occur faster.

00:03:02.700 --> 00:03:10.550
The effector B cells produce--
they essentially turn into

00:03:10.550 --> 00:03:12.710
antibody making machines.

00:03:12.710 --> 00:03:16.630
So they'll say, gee, this
antibody bonds to this antigen

00:03:16.630 --> 00:03:18.570
that we have in the
system now.

00:03:18.570 --> 00:03:20.290
Let me just produce
a ton of them.

00:03:20.290 --> 00:03:23.160
So it starts building up all of
the cellular machinery and

00:03:23.160 --> 00:03:26.770
it starts producing antibodies
like crazy.

00:03:26.770 --> 00:03:29.300
I want to point out one thing
that my wife pointed out to me

00:03:29.300 --> 00:03:32.490
when I was-- she overheard me
making the last video and

00:03:32.490 --> 00:03:35.890
she's a fellow in hematology
and a lot of hematology is

00:03:35.890 --> 00:03:36.570
immunology.

00:03:36.570 --> 00:03:38.640
So I definitely have
to defer to her.

00:03:38.640 --> 00:03:41.880
She is the expert on this.

00:03:41.880 --> 00:03:45.070
In the last video, I kind of
very hand-wavingly said, B

00:03:45.070 --> 00:03:47.230
cells, once they get activated,
if they're the

00:03:47.230 --> 00:03:49.800
effector B cells, they
produce antibodies.

00:03:49.800 --> 00:03:50.570
I want to be very clear.

00:03:50.570 --> 00:03:52.950
It is only the effector B
cells that produce the

00:03:52.950 --> 00:03:57.560
antibodies and the common term
for them-- if someone were to

00:03:57.560 --> 00:04:01.120
walk up to you and say, what
cells in the body are

00:04:01.120 --> 00:04:02.820
producing antibodies?

00:04:02.820 --> 00:04:05.640
You wouldn't be wrong if you
said effector B cells, but the

00:04:05.640 --> 00:04:09.030
common term that people expect
to hear are plasma cells.

00:04:12.820 --> 00:04:16.380
Plasma cells and effector B
cells are the same thing, but

00:04:16.380 --> 00:04:18.980
normally when they say, what
happens to a B cell when it

00:04:18.980 --> 00:04:20.050
starts producing antibodies?

00:04:20.050 --> 00:04:21.620
They then call it
a plasma cell.

00:04:21.620 --> 00:04:23.340
They don't call it a B cell
anymore and I want to make

00:04:23.340 --> 00:04:24.860
that very clear because my
wife's like, well, I have

00:04:24.860 --> 00:04:28.390
attendings that if they asked
me, what cell in the body

00:04:28.390 --> 00:04:29.350
produces antibodies?

00:04:29.350 --> 00:04:32.000
And if you said, B cell, they
would say, no, wrong.

00:04:32.000 --> 00:04:34.480
It's a plasma cell-- or if you
said effector B cell, they

00:04:34.480 --> 00:04:35.080
wouldn't be happy.

00:04:35.080 --> 00:04:36.920
They wanted to hear
plasma cell.

00:04:36.920 --> 00:04:44.290
This is the common term used in
immunology and apparently

00:04:44.290 --> 00:04:45.560
rheumatology circles.

00:04:45.560 --> 00:04:47.290
Did I just say my wife
is a hematologist?

00:04:47.290 --> 00:04:47.570
No, no.

00:04:47.570 --> 00:04:48.770
She's studying rheumatology.

00:04:48.770 --> 00:04:51.210
I get confused with all the
tologies sometimes.

00:04:51.210 --> 00:04:52.845
Anyway, that's what
the B cells do.

00:04:52.845 --> 00:04:55.250
And these antibodies can then
go attach things and mess up

00:04:55.250 --> 00:04:58.650
viruses and antigen-- well,
viruses or instances of

00:04:58.650 --> 00:05:02.290
antigens and bacteria-- and
tag them for pick up by

00:05:02.290 --> 00:05:04.650
macrophages or other types
of phagocytes.

00:05:04.650 --> 00:05:06.390
Those were the B cells.

00:05:06.390 --> 00:05:09.620
Then you have your T cells.

00:05:09.620 --> 00:05:11.710
And here I'm going to talk about
T cells a little bit

00:05:11.710 --> 00:05:14.310
differently than I had in
the last few videos.

00:05:14.310 --> 00:05:18.210
Just to give a little bit more
of a nuance-- so there's two

00:05:18.210 --> 00:05:19.420
types of T cells.

00:05:19.420 --> 00:05:21.740
You'll say, hey, they are helper
T cells and cytotoxic T

00:05:21.740 --> 00:05:24.710
cells-- and you're not wrong,
but what I'm going to do is do

00:05:24.710 --> 00:05:28.010
a slightly different
differentiation just so that

00:05:28.010 --> 00:05:30.600
you are familiar with these
terms. So there's

00:05:30.600 --> 00:05:33.800
two types of T cells.

00:05:33.800 --> 00:05:35.710
All T cells have T
cell receptors.

00:05:44.600 --> 00:05:50.030
But they also have these other
proteins on them and some of

00:05:50.030 --> 00:05:58.200
them have these proteins
called-- CD4 proteins and some

00:05:58.200 --> 00:06:04.590
of them have what's
called CD8.

00:06:09.530 --> 00:06:11.430
So this one right here
would be called a

00:06:11.430 --> 00:06:15.540
CD8 positive T cell.

00:06:15.540 --> 00:06:18.280
It has the CD8 proteins on it.

00:06:18.280 --> 00:06:23.770
And this would be called
a CD4 positive T cell.

00:06:23.770 --> 00:06:25.310
I've never used these
words before.

00:06:25.310 --> 00:06:27.250
You're like, gee, where
are these coming from?

00:06:27.250 --> 00:06:32.170
Now, the CD4 receptor is the
thing that wants to bind--

00:06:32.170 --> 00:06:38.760
this is the thing that helps to
go to the MHC II complexes.

00:06:38.760 --> 00:06:45.670
So most CD4 T cells are
helper T cells.

00:06:45.670 --> 00:06:47.460
Most of the time-- and I want
to make it very clear--

00:06:47.460 --> 00:06:49.940
immunology is a very-- I mean,
this field, people are

00:06:49.940 --> 00:06:51.560
discovering things on
a regular basis.

00:06:51.560 --> 00:06:53.460
So people are still
understanding these things and

00:06:53.460 --> 00:06:57.060
there's all sorts of special
cases, but usually when people

00:06:57.060 --> 00:07:00.280
talk about CD4 positive T cells,
they're talking about

00:07:00.280 --> 00:07:02.030
helper T cells.

00:07:02.030 --> 00:07:07.760
So this is normally going to
be a helper T cell-- or you

00:07:07.760 --> 00:07:10.430
could call it T helper,
just like that.

00:07:10.430 --> 00:07:13.830
Likewise, the CD8 proteins,
these are attracted

00:07:13.830 --> 00:07:15.820
to the MHC I complex.

00:07:21.340 --> 00:07:24.480
This is what brings them to
the cells that have the

00:07:24.480 --> 00:07:26.990
cancer, that have expressed
antigens

00:07:26.990 --> 00:07:28.980
on their MHC I complex.

00:07:28.980 --> 00:07:30.930
So most of the time CD8

00:07:30.930 --> 00:07:33.060
positive T cells are cytotoxic.

00:07:39.500 --> 00:07:42.170
And oftentimes, before a cell
gets activated, they just

00:07:42.170 --> 00:07:45.890
describe it as a CD4 T cell
or a CD8 cell and after it

00:07:45.890 --> 00:07:53.240
becomes activated and starts
wanting to kill things, then

00:07:53.240 --> 00:07:54.400
maybe you call it cytotoxic.

00:07:54.400 --> 00:07:56.390
But this is all wordplay.

00:07:56.390 --> 00:07:58.680
I think you get the
general idea.

00:07:58.680 --> 00:08:04.170
But just to remember what they
do, this guy-- we just said he

00:08:04.170 --> 00:08:08.520
wants to bond to the MHC
complex, so you have MHC

00:08:08.520 --> 00:08:13.580
complex plus presenting
some antigen.

00:08:13.580 --> 00:08:15.840
This is MHC I right here.

00:08:15.840 --> 00:08:19.080
We learned in the last video,
every nucleated cell in the

00:08:19.080 --> 00:08:22.870
body expresses an
MHC I complex.

00:08:22.870 --> 00:08:25.260
So this is the case where
something wacky is happening

00:08:25.260 --> 00:08:26.500
inside this cell.

00:08:26.500 --> 00:08:28.060
Maybe a virus has infected it.

00:08:28.060 --> 00:08:30.210
Maybe it's cancerous.

00:08:30.210 --> 00:08:34.909
It needs to die, otherwise it's
going to keep producing

00:08:34.909 --> 00:08:37.230
viruses if it's infected by a
virus, or otherwise it's going

00:08:37.230 --> 00:08:39.360
to keep dividing if it's
a cancer and infect

00:08:39.360 --> 00:08:40.320
the rest of the body.

00:08:40.320 --> 00:08:45.360
So the CD8 kills
infected cells.

00:08:45.360 --> 00:08:48.710
I'll just say bad cells because
I don't if you can--

00:08:48.710 --> 00:08:50.210
cancer really isn't
an infection.

00:08:50.210 --> 00:08:53.445
Kills bad cells-- cells that
are-- if you don't kill them,

00:08:53.445 --> 00:08:54.960
they're going to keep producing
viruses or keep

00:08:54.960 --> 00:09:00.110
splitting and spreading the
cancer, while T cells--

00:09:00.110 --> 00:09:03.080
they're attracted to
professional antigen

00:09:03.080 --> 00:09:04.460
presenting cells.

00:09:04.460 --> 00:09:06.950
And I always do a dendritic cell
right here because those

00:09:06.950 --> 00:09:09.360
are the best antigen
presenting cells.

00:09:09.360 --> 00:09:16.860
And they have MHC II complexes
and it's digested some antigen

00:09:16.860 --> 00:09:21.020
and it presents it right there
and then that activates the

00:09:21.020 --> 00:09:22.200
helper T cell.

00:09:22.200 --> 00:09:26.810
And then when the helper T
cell-- all of these guys, once

00:09:26.810 --> 00:09:31.620
they're activated, they all go
into effector-- they all start

00:09:31.620 --> 00:09:35.690
differentiating into effector
and memory cells.

00:09:35.690 --> 00:09:40.640
An effector helper T cell
does a couple of things.

00:09:40.640 --> 00:09:46.840
So if we're talking about a
helper T cell, it can activate

00:09:46.840 --> 00:09:51.970
B cells and it also releases
cytokines.

00:09:51.970 --> 00:09:53.080
Let's say this guy
gets activated.

00:09:53.080 --> 00:09:56.030
He'll also start releasing these
chemicals, which are

00:09:56.030 --> 00:10:00.000
really those alarm bells that
tell other people to really

00:10:00.000 --> 00:10:03.850
get in gear-- maybe B cells and
cytotoxic T cells start

00:10:03.850 --> 00:10:05.430
proliferating more rigorously.

00:10:05.430 --> 00:10:10.730
Actually, part of the cytotoxic
T cell activation

00:10:10.730 --> 00:10:14.690
can be assisted or kind of
given a boost by these

00:10:14.690 --> 00:10:17.910
cytokines-- of so by
these alarm bells.

00:10:17.910 --> 00:10:24.500
So this guy's the alarm ringer,
while the CD8 cells or

00:10:24.500 --> 00:10:27.570
the cytotoxic T cells--
in their effector

00:10:27.570 --> 00:10:31.220
mode, they kill cells.

00:10:31.220 --> 00:10:33.590
And of course in the memory
mode, there's just a bunch of

00:10:33.590 --> 00:10:36.450
copies of these originals around
that are ready and more

00:10:36.450 --> 00:10:39.120
than they were originally were,
so that in the future if

00:10:39.120 --> 00:10:41.730
something like this or something
like this occurs,

00:10:41.730 --> 00:10:43.500
they're going to be activated
faster because they're going

00:10:43.500 --> 00:10:45.150
to be bumped into faster.

00:10:45.150 --> 00:10:47.210
So hopefully that clears up a
little bit and I introduced a

00:10:47.210 --> 00:10:48.925
little bit more tough
terminology, but I really want

00:10:48.925 --> 00:10:50.750
to stress my wife's point
because she said, hey, you

00:10:50.750 --> 00:10:53.560
don't want people out there
saying B cells produce

00:10:53.560 --> 00:10:57.090
antibodies even though it is
effector B cells-- activated B

00:10:57.090 --> 00:10:59.340
cells that have differentiated
into effector B cells.

00:10:59.340 --> 00:11:01.680
Those are what are producing
antibodies-- because when they

00:11:01.680 --> 00:11:03.570
go to medical school, people
are going to want to hear

00:11:03.570 --> 00:11:05.560
plasma cell.


Cytotoxic T cells

WEBVTT
Kind: captions
Language: en

00:00:00.500 --> 00:00:03.530
When we learned about antigen
presenting cells, we learned

00:00:03.530 --> 00:00:06.130
that they can first digest
something-- let me draw a

00:00:06.130 --> 00:00:09.700
dendritic cell right here--
my best version

00:00:09.700 --> 00:00:11.450
of a dendritic cell.

00:00:11.450 --> 00:00:13.120
Maybe I should draw them
simpler than that.

00:00:13.120 --> 00:00:16.990
A dendritic cell is a phagocyte
and it is an antigen

00:00:16.990 --> 00:00:17.860
presenting cell.

00:00:17.860 --> 00:00:22.630
So after phagocytoses some type
of a pathogen, it'll cut

00:00:22.630 --> 00:00:26.550
it all up, and then it'll
display-- it'll present the

00:00:26.550 --> 00:00:35.990
antigen on its surface on a
protein complex here and the

00:00:35.990 --> 00:00:38.380
part of the pathogen that
it cut up, it'll

00:00:38.380 --> 00:00:40.040
put up right here.

00:00:40.040 --> 00:00:43.000
And we learned on the antigen
presenting cell video that

00:00:43.000 --> 00:00:49.570
this complex right here was an
MHC type II complex, where MHC

00:00:49.570 --> 00:01:02.750
stands for major
histocompatibility complex.

00:01:02.750 --> 00:01:06.800
Where histocompatibility just
means tissue compatibility.

00:01:06.800 --> 00:01:08.980
And this was the case on antigen
presenting cells.

00:01:08.980 --> 00:01:10.550
So even B cells did this.

00:01:10.550 --> 00:01:12.390
Let me draw a B cell.

00:01:12.390 --> 00:01:17.900
So a B cell-- it has
its membrane bound

00:01:17.900 --> 00:01:20.770
antibody, just like that.

00:01:20.770 --> 00:01:23.220
It actually has many, many
thousands of these.

00:01:23.220 --> 00:01:25.130
I could keep drawing a bunch of
them, but just so you know

00:01:25.130 --> 00:01:26.700
there's more than one.

00:01:26.700 --> 00:01:30.560
Maybe one of these get triggered
or get attached to

00:01:30.560 --> 00:01:36.730
some type of virus or protein
or bacteria floating around.

00:01:36.730 --> 00:01:41.340
And what it'll do is it'll take
this in and cut it up

00:01:41.340 --> 00:01:45.760
again and do the same thing as
what the dendritic cell did.

00:01:45.760 --> 00:01:56.620
It'll cut up a part of this and
present it on its surface

00:01:56.620 --> 00:02:01.170
in conjunction with
an MHC II complex.

00:02:01.170 --> 00:02:05.320
So once again, this is
an MHC II complex.

00:02:05.320 --> 00:02:09.680
So these professional antigen
presenting cells that go out

00:02:09.680 --> 00:02:13.460
and take things out of the
fluid, out of the humoral

00:02:13.460 --> 00:02:17.190
parts of our body, things
just floating around.

00:02:17.190 --> 00:02:19.860
They'll take them in, they'll
say, this is bad, cut them up,

00:02:19.860 --> 00:02:21.770
and then present them
on these MHC II.

00:02:21.770 --> 00:02:24.010
That's why we call them
professional antigen

00:02:24.010 --> 00:02:25.480
presenting cells.

00:02:25.480 --> 00:02:35.530
Now, it turns out that pretty
much all cells in our bodies--

00:02:35.530 --> 00:02:38.070
when I say almost all
cells, it's actually

00:02:38.070 --> 00:02:39.480
all nucleated cells.

00:02:39.480 --> 00:02:44.190
So all cells that have a nucleus
in the human body-- so

00:02:44.190 --> 00:02:46.370
the only cells in our human body
that don't have nucleuses

00:02:46.370 --> 00:02:48.600
are red blood cells, which I
find fascinating-- so that

00:02:48.600 --> 00:02:51.310
they can have more space
for storing hemoglobin.

00:02:51.310 --> 00:02:56.040
But all nucleated cells in our
bodies have another major

00:02:56.040 --> 00:03:05.650
histocompatibility complex on it
and it's called an MHC I--

00:03:05.650 --> 00:03:08.530
major histocompatibility
type I.

00:03:08.530 --> 00:03:10.770
And just so you know, these
are also nucleated cells.

00:03:10.770 --> 00:03:16.000
So they're also going to have an
MHC type I complex on them

00:03:16.000 --> 00:03:17.240
right here.

00:03:17.240 --> 00:03:21.040
Now the interesting thing about
the MHC type I complex

00:03:21.040 --> 00:03:30.950
is because it's on every cell in
our human body-- so pretty

00:03:30.950 --> 00:03:36.010
much everything but the red
blood cells have an MHC I--

00:03:36.010 --> 00:03:38.870
this is where if anything
wacky is going

00:03:38.870 --> 00:03:39.910
on inside the cell.

00:03:39.910 --> 00:03:43.260
Maybe the cell is cancerous and
producing crazy proteins.

00:03:43.260 --> 00:03:45.130
Maybe it's been infected
with a virus.

00:03:45.130 --> 00:03:48.430
Maybe some type of bacteria or
some type of weird protein has

00:03:48.430 --> 00:03:52.080
gotten in here-- any cell in the
human body can cut those

00:03:52.080 --> 00:03:54.460
up, even if it's malfunctioning,
and it will

00:03:54.460 --> 00:03:55.090
present them.

00:03:55.090 --> 00:03:56.930
So let's say the cell
is cancerous.

00:03:56.930 --> 00:03:59.350
So this cell's cancerous and
it has all these wacky

00:03:59.350 --> 00:04:02.140
proteins that only cancer cells
present that is not

00:04:02.140 --> 00:04:04.740
normal for a normal cell--
that will be

00:04:04.740 --> 00:04:07.140
presented on the MHC I.

00:04:07.140 --> 00:04:13.220
Let's say that I have some other
cell in my body that's a

00:04:13.220 --> 00:04:14.095
different type of cell.

00:04:14.095 --> 00:04:15.370
It's nucleated.

00:04:15.370 --> 00:04:18.865
Let's say it's been infected
with a virus.

00:04:18.865 --> 00:04:23.390
So it's turning into
this virus factory.

00:04:23.390 --> 00:04:25.980
Same thing-- there are
mechanisms in a cell that will

00:04:25.980 --> 00:04:30.230
take some of the proteins that
make up those viruses and

00:04:30.230 --> 00:04:33.245
present them on the
MHC I complex.

00:04:38.230 --> 00:04:42.250
So in the case of MHC II, this
is what triggered helper T

00:04:42.250 --> 00:04:44.130
cells to say, hey,
you know what?

00:04:44.130 --> 00:04:46.160
I found something floating
out here.

00:04:46.160 --> 00:04:48.930
Here's a little piece of
it, Mr. Helper T cell.

00:04:48.930 --> 00:04:52.290
Why don't you bond to this and
raise the alarm system?

00:04:52.290 --> 00:04:54.950
Now the MHC I system
says, this isn't

00:04:54.950 --> 00:04:55.880
stuff floating around.

00:04:55.880 --> 00:04:56.820
I've been infected.

00:04:56.820 --> 00:04:57.850
I am cancerous.

00:04:57.850 --> 00:04:58.950
I'm going nuts.

00:04:58.950 --> 00:04:59.970
You better kill me.

00:04:59.970 --> 00:05:02.280
I'm a virus, I'm a virus-making
machine.

00:05:02.280 --> 00:05:03.370
You better kill me.

00:05:03.370 --> 00:05:08.640
And that message goes to the
cytotoxic T cells and that's

00:05:08.640 --> 00:05:10.710
really the topic
of this video.

00:05:10.710 --> 00:05:12.920
So just to make sure
you understand the

00:05:12.920 --> 00:05:14.250
difference-- so T cells.

00:05:14.250 --> 00:05:17.390
They both have T cell receptors,
but the helper T

00:05:17.390 --> 00:05:20.405
cells bond to MHC
II complexes.

00:05:24.890 --> 00:05:28.680
Let's say that this is a helper
T cell right here.

00:05:28.680 --> 00:05:33.640
It would want to-- not all
helper T cells will.

00:05:33.640 --> 00:05:36.470
Only the ones that have the
right combination, the right

00:05:36.470 --> 00:05:39.960
variable portion right here that
just perfectly bonds to

00:05:39.960 --> 00:05:44.060
this combination of an antigen
and the MHC II complex-- this

00:05:44.060 --> 00:05:50.210
type of helper T cell will bond
here, get activated, and

00:05:50.210 --> 00:05:51.120
start differentiating.

00:05:51.120 --> 00:05:53.650
And the effector versions of
them will start raising the

00:05:53.650 --> 00:05:56.230
alarms and the memory versions
of them will stick around in

00:05:56.230 --> 00:05:58.550
case this type of thing
needs to happen again.

00:05:58.550 --> 00:06:03.160
With MHC I, instead of
attracting a helper T cell, it

00:06:03.160 --> 00:06:06.175
will attract a cytotoxic
T cell.

00:06:10.450 --> 00:06:14.930
So like helper T cells, the
T cell receptor has a

00:06:14.930 --> 00:06:21.540
non-variable portion, but it
also has a variable portion

00:06:21.540 --> 00:06:26.430
that is specific to this
combination of

00:06:26.430 --> 00:06:28.300
antigens and MHC I.

00:06:28.300 --> 00:06:34.400
So maybe this cytotoxic T cell
will be involved when this

00:06:34.400 --> 00:06:35.995
cell goes cancerous.

00:06:35.995 --> 00:06:41.680
This cytotoxic T cell would be
of no use-- or it won't bond

00:06:41.680 --> 00:06:43.530
to this one that was attracted
to a virus.

00:06:43.530 --> 00:06:45.360
It's going to have to be
another cytotoxic T

00:06:45.360 --> 00:06:46.720
cell that does that.

00:06:46.720 --> 00:06:49.700
And the mechanism where we get
this variability in the helper

00:06:49.700 --> 00:06:52.970
T cells or the cytotoxic T
cells or you saw in the B

00:06:52.970 --> 00:06:56.360
cells on their membrane bound
antibodies, that all comes

00:06:56.360 --> 00:07:00.750
from when-- in their development
stage or in the

00:07:00.750 --> 00:07:05.980
maturation process, the DNA that
codes for these variable

00:07:05.980 --> 00:07:08.310
portions gets shuffled
around intentionally.

00:07:08.310 --> 00:07:10.160
So normally, we're always
trying to preserve DNA

00:07:10.160 --> 00:07:12.700
information, here it gets
shuffled around.

00:07:12.700 --> 00:07:17.800
But anyway, once a cytotoxic T
cell finds one of these guys

00:07:17.800 --> 00:07:20.630
on an MHC I-- remember, every
nucleated cell in the body has

00:07:20.630 --> 00:07:25.080
an MHC I-- then what it does
is, it gets activated.

00:07:25.080 --> 00:07:27.270
So let's say this guy says,
hey, that looks shady.

00:07:27.270 --> 00:07:29.050
You need to die.

00:07:29.050 --> 00:07:31.780
So this guy gets activated and
just like all other activated

00:07:31.780 --> 00:07:33.986
cells, he starts to divide and
divide and divide and divide

00:07:33.986 --> 00:07:35.010
and differentiate.

00:07:35.010 --> 00:07:37.930
And he divides and he
differentiates into memory,

00:07:37.930 --> 00:07:41.420
just in case you're going to
need me again, just in case

00:07:41.420 --> 00:07:43.580
this type of cancer
shows up again.

00:07:43.580 --> 00:07:47.010
And then also into effector T
cells, which are the ones that

00:07:47.010 --> 00:07:48.260
do the killing.

00:07:50.740 --> 00:07:53.470
So this is an effector.

00:07:53.470 --> 00:07:56.620
So let's say one of these
effectors-- they'll also bind

00:07:56.620 --> 00:08:00.030
to cancerous molecules,
cancerous cells,

00:08:00.030 --> 00:08:00.770
just like this one.

00:08:00.770 --> 00:08:04.370
So let's say this cell has
split and there's another

00:08:04.370 --> 00:08:05.490
version of it right here.

00:08:05.490 --> 00:08:06.580
That's what cancer does.

00:08:06.580 --> 00:08:08.880
It divides aggressively.

00:08:08.880 --> 00:08:11.930
It's producing wacky proteins.

00:08:11.930 --> 00:08:15.840
It presents the wacky proteins
on its MCH-- major

00:08:15.840 --> 00:08:21.080
histocompatibility type I
complex-- it displays the

00:08:21.080 --> 00:08:25.250
wacky proteins and then one of
these effector cytotoxic T

00:08:25.250 --> 00:08:32.250
cells will be attracted
to it just like that.

00:08:32.250 --> 00:08:34.520
And I'm not going into details
on what necessarily does the

00:08:34.520 --> 00:08:36.630
attractions and all the membrane
bound proteins.

00:08:36.630 --> 00:08:38.250
If you take an immunology
class,

00:08:38.250 --> 00:08:39.289
you'll see more on that.

00:08:39.289 --> 00:08:44.310
So this is a cytotoxic T cell
and it essentially forces this

00:08:44.310 --> 00:08:46.790
cell to kill itself in a couple
of different ways.

00:08:46.790 --> 00:08:53.610
One, it actually can exocytose
a bunch of proteins.

00:08:53.610 --> 00:08:59.230
They're call perforins-- that
make little holes in the

00:08:59.230 --> 00:09:01.090
membrane of the cell.

00:09:01.090 --> 00:09:04.770
And it has other proteins that
it releases called granzymes

00:09:04.770 --> 00:09:07.160
that go in here and essentially
start mechanisms

00:09:07.160 --> 00:09:09.160
that make this cell want
to kill itself.

00:09:09.160 --> 00:09:12.970
So the big picture is, if you
want to just take 20,000 feet,

00:09:12.970 --> 00:09:17.860
these cells are very effective
at produces-- so when a B cell

00:09:17.860 --> 00:09:20.200
gets activated, it produces
antibodies that kill things

00:09:20.200 --> 00:09:21.640
that are floating
around, right?

00:09:21.640 --> 00:09:24.210
Once a B cell gets activated, it
starts producing a bunch of

00:09:24.210 --> 00:09:25.740
antibodies.

00:09:25.740 --> 00:09:28.970
These antibodies float around
and then they can bond up to

00:09:28.970 --> 00:09:31.600
viruses, make them ineffective,
or essentially

00:09:31.600 --> 00:09:34.680
tag them for pickup from
macrophages or dendritic

00:09:34.680 --> 00:09:39.900
cells, or other types of
phagocytes-- while cytotoxic T

00:09:39.900 --> 00:09:43.360
cells-- these are used to
essentially kill cells that

00:09:43.360 --> 00:09:44.390
have gone awry.

00:09:44.390 --> 00:09:46.860
For example, a cancer cell
that's presenting weird

00:09:46.860 --> 00:09:50.350
proteins or once the virus has
entered the cell, then the

00:09:50.350 --> 00:09:51.850
antibodies are really
of no use.

00:09:51.850 --> 00:09:52.880
The antibodies aren't
going to be able to

00:09:52.880 --> 00:09:54.450
get into those cells.

00:09:54.450 --> 00:09:57.270
In that case, instead of
cleaning up the virus itself,

00:09:57.270 --> 00:10:00.020
a cytotoxic T cell will come
here and just kill this cell

00:10:00.020 --> 00:10:02.300
because this cell is
a virus factory.

00:10:02.300 --> 00:10:05.160
So you have to get it
out of the way.


Helper T cells

WEBVTT
Kind: captions
Language: en

00:00:00.590 --> 00:00:04.250
In talking about the adaptive
immune system, we've already

00:00:04.250 --> 00:00:05.830
seen that there's a
couple of actors.

00:00:16.250 --> 00:00:20.070
You have your humoral
response.

00:00:20.070 --> 00:00:22.370
So this is responding to things
that are floating

00:00:22.370 --> 00:00:24.590
around in the fluids of the
body and not necessarily

00:00:24.590 --> 00:00:27.820
things that have infiltrated
your body cells and then you

00:00:27.820 --> 00:00:31.245
have your cell mediated
response.

00:00:35.740 --> 00:00:38.200
And then in the humoral
response-- and we're talking

00:00:38.200 --> 00:00:40.680
about specific humoral
response-- this is where the B

00:00:40.680 --> 00:00:45.220
cells, the B lymphocytes are
at their most active.

00:00:45.220 --> 00:00:48.540
And essentially what they do
is, you got a B cell here.

00:00:48.540 --> 00:00:52.900
It has a very specific antibody,
specific to just

00:00:52.900 --> 00:00:55.640
this B cell, not B
cells in general.

00:00:55.640 --> 00:00:59.010
If this happens to be the one
of the billions of B cells

00:00:59.010 --> 00:01:02.550
that happens to have the
matching key-- or maybe I

00:01:02.550 --> 00:01:05.920
should say the matching lock
for the key that is the

00:01:05.920 --> 00:01:09.270
intruding pathogen--
that pathogen will

00:01:09.270 --> 00:01:11.560
bind to that B cell.

00:01:11.560 --> 00:01:14.420
Maybe it's a virus, maybe
it's a bacteria.

00:01:14.420 --> 00:01:17.890
And then the B cell will get
activated and we'll talk about

00:01:17.890 --> 00:01:19.450
in this video that
the activation

00:01:19.450 --> 00:01:20.630
doesn't always happen.

00:01:20.630 --> 00:01:23.730
In fact, it usually doesn't
happen just from this, but so

00:01:23.730 --> 00:01:28.860
far we've said it gets
activated, it goes into memory

00:01:28.860 --> 00:01:31.320
B cells, which are essentially
multiple versions of this

00:01:31.320 --> 00:01:33.450
original B cell-- just saying,
hey, let's have multiple

00:01:33.450 --> 00:01:36.640
versions of this-- because it
tends to recognize this virus.

00:01:36.640 --> 00:01:39.160
So in the future if we get this
virus, those multiple

00:01:39.160 --> 00:01:42.450
versions, those memory cells are
going to be there to have

00:01:42.450 --> 00:01:43.240
this interaction.

00:01:43.240 --> 00:01:45.530
This interaction's going to be
more likely to happen in the

00:01:45.530 --> 00:01:47.210
future because I'm going
to have more of this

00:01:47.210 --> 00:01:48.640
variety of B cell.

00:01:48.640 --> 00:01:49.980
And then you have
effector cells.

00:01:53.320 --> 00:01:56.730
And these are essentially-- so
both of these are B cells.

00:01:56.730 --> 00:02:00.230
So this guy, once he gets
activated, he proliferates,

00:02:00.230 --> 00:02:02.430
keeps dividing and
cloning himself.

00:02:02.430 --> 00:02:05.910
The memory cells just stick
around waiting to be activated

00:02:05.910 --> 00:02:06.890
in the future.

00:02:06.890 --> 00:02:10.570
And I'm only drawing one
of these membrane bound

00:02:10.570 --> 00:02:13.530
antibodies, but there are
actually 10,000 on them.

00:02:13.530 --> 00:02:15.000
I mean, I could draw
a bunch of these.

00:02:15.000 --> 00:02:17.300
I don't have to just draw one.

00:02:17.300 --> 00:02:19.120
The memories just wade around
in the future, but there's

00:02:19.120 --> 00:02:19.850
more of them now.

00:02:19.850 --> 00:02:23.610
So in the future, if we get
this virus again, this

00:02:23.610 --> 00:02:26.350
interaction's going to happen
faster and so they're going to

00:02:26.350 --> 00:02:27.800
get activated faster.

00:02:27.800 --> 00:02:32.300
And then the effector B
cells essentially turn

00:02:32.300 --> 00:02:35.990
into antibody factories.

00:02:35.990 --> 00:02:39.100
This antibody goes in and it
says, let me just produce--

00:02:39.100 --> 00:02:39.870
I've been activated.

00:02:39.870 --> 00:02:42.200
Let me produce many,
many more versions

00:02:42.200 --> 00:02:44.460
of that exact antibody.

00:02:44.460 --> 00:02:46.710
So they get spit out.

00:02:46.710 --> 00:02:48.670
I drew that one little wrong.

00:02:48.670 --> 00:02:53.040
So that exact antibody, that
can then be spit out to go

00:02:53.040 --> 00:02:57.170
disable or tag antigens-- and
not just any antigen-- this

00:02:57.170 --> 00:03:00.290
antigen right here.

00:03:00.290 --> 00:03:03.550
And we also saw that the other
thing that the B cell does is

00:03:03.550 --> 00:03:06.190
it becomes an antigen
presenting cell.

00:03:06.190 --> 00:03:11.670
So what it does is, as soon as
it recognizes this, it's had

00:03:11.670 --> 00:03:14.600
this interaction with an antigen
that just matches the

00:03:14.600 --> 00:03:17.710
variable portion of its membrane
bound antibody.

00:03:17.710 --> 00:03:19.880
It endocytosizes that.

00:03:19.880 --> 00:03:22.350
It brings that into itself.

00:03:22.350 --> 00:03:25.420
It's membrane facilitated so it
just kind of pulls it in,

00:03:25.420 --> 00:03:27.770
chunks it up, and then presents
a piece of that

00:03:27.770 --> 00:03:31.920
antibody on an MHC
II molecule.

00:03:31.920 --> 00:03:33.240
We saw that in the last video.

00:03:33.240 --> 00:03:36.220
So it cuts that up and presents
a piece of it right

00:03:36.220 --> 00:03:39.520
there and that's why we call it
an antigen presenting cell.

00:03:39.520 --> 00:03:42.310
Now in this video, we're going
to talk about why we even have

00:03:42.310 --> 00:03:44.110
these MHC II molecules.

00:03:44.110 --> 00:03:47.000
What are we presenting
these antigens to?

00:03:47.000 --> 00:03:48.510
So we're going to start
talking about the cell

00:03:48.510 --> 00:03:50.360
mediated-- and actually, even
more than the cell mediated,

00:03:50.360 --> 00:03:51.765
we're going to talk
about T cells.

00:03:56.280 --> 00:03:59.120
And I said in the first video,
they're called T cells because

00:03:59.120 --> 00:04:00.440
they mature in the thymus.

00:04:07.110 --> 00:04:09.940
And there are two types of
T cells and it's all very

00:04:09.940 --> 00:04:11.810
confusing because you have B
cells and T cells, but then

00:04:11.810 --> 00:04:13.560
there are two types
of T cells.

00:04:13.560 --> 00:04:18.940
You have helper T cells-- and
most people just write T with

00:04:18.940 --> 00:04:21.440
a lower-case or subscript
h there.

00:04:21.440 --> 00:04:26.370
And then you have cytotoxic T
cells-- or T cells that kill

00:04:26.370 --> 00:04:27.620
other cells.

00:04:32.770 --> 00:04:36.560
Now just so that you have a big,
overarching impression of

00:04:36.560 --> 00:04:39.080
what does what-- B cells.

00:04:39.080 --> 00:04:43.640
When they are activated, they
generate antibodies.

00:04:43.640 --> 00:04:46.410
At 30,000 feet, that's the
best summary of what an

00:04:46.410 --> 00:04:47.620
activated B cell does.

00:04:47.620 --> 00:04:49.700
It actually generate
antibodies.

00:04:49.700 --> 00:04:53.180
Those antibodies attach to
viruses and bacteria and other

00:04:53.180 --> 00:04:55.920
types of pathogens and disables
them-- either tags

00:04:55.920 --> 00:05:02.310
them so that macrophages can go
and eat them up or just by

00:05:02.310 --> 00:05:06.040
throwing all of those antibodies
on to the surface

00:05:06.040 --> 00:05:08.510
of the pathogen in question.

00:05:08.510 --> 00:05:11.860
It might disable the pathogens
or essentially bundle them

00:05:11.860 --> 00:05:14.850
altogether so that it'll be
easier for macrophages to pick

00:05:14.850 --> 00:05:17.820
them up, but this is only
effective for things that are

00:05:17.820 --> 00:05:19.400
floating around.

00:05:19.400 --> 00:05:21.710
Free floating antibodies are
only effective for things that

00:05:21.710 --> 00:05:24.160
are floating around.

00:05:24.160 --> 00:05:27.480
Cytotoxic T cells, which I'll
cover in more detail in a

00:05:27.480 --> 00:05:32.010
future video-- these actually
attack cells that have been

00:05:32.010 --> 00:05:34.260
infiltrated.

00:05:34.260 --> 00:05:42.860
So this is attack, kill,
infiltrated cells-- and when I

00:05:42.860 --> 00:05:45.330
say infiltrated, it could be a
cell that a virus has gone

00:05:45.330 --> 00:05:47.530
into or some bacteria
has penetrated it.

00:05:47.530 --> 00:05:49.260
And when I say infiltrated, it
doesn't necessarily even mean

00:05:49.260 --> 00:05:50.110
something from the outside.

00:05:50.110 --> 00:05:53.020
It could even be a cancerous
cell that shows itself to be

00:05:53.020 --> 00:05:57.330
abnormal in some way and so the
cytotoxic T cells will at

00:05:57.330 --> 00:05:59.260
least attempt to kill them.

00:05:59.260 --> 00:06:02.500
But what I want to focus on--
out of the three types of

00:06:02.500 --> 00:06:06.626
lymphocytes-- remember,
everything we've been talking

00:06:06.626 --> 00:06:09.580
about was leukocytes, white
blood cells, but lymphocytes

00:06:09.580 --> 00:06:12.650
are a subset of that and these
three are lymphocytes.

00:06:12.650 --> 00:06:14.880
And they're called that because
they began their

00:06:14.880 --> 00:06:18.660
development in the
bone marrow.

00:06:18.660 --> 00:06:24.250
So this guy and this guy
actually do stuff.

00:06:24.250 --> 00:06:27.400
This guy generates antibodies
that attach to pathogens

00:06:27.400 --> 00:06:28.540
floating around.

00:06:28.540 --> 00:06:31.090
This guy directly attacks
cells that are

00:06:31.090 --> 00:06:32.010
broken in some way.

00:06:32.010 --> 00:06:34.700
They've either been infiltrated,
they're abnormal,

00:06:34.700 --> 00:06:36.730
they're cancerous--
who knows what.

00:06:36.730 --> 00:06:39.730
And I'll do a whole video on
that, but that leads us to a

00:06:39.730 --> 00:06:40.770
very obvious question.

00:06:40.770 --> 00:06:42.420
What does this guy do?

00:06:42.420 --> 00:06:47.650
What does the helper T cell
do if he doesn't directly

00:06:47.650 --> 00:06:50.680
interface either with pathogens
or produce things

00:06:50.680 --> 00:06:53.190
that interface with pathogens--
or if he himself

00:06:53.190 --> 00:06:55.350
doesn't go and directly
kill cells?

00:06:55.350 --> 00:06:58.520
And the answer is that the
helper T cell's kind of the

00:06:58.520 --> 00:07:01.140
alarm of the immune system.

00:07:01.140 --> 00:07:03.630
And on some level, it's almost
the most important.

00:07:03.630 --> 00:07:08.230
So we talked already in the
last video about antigen

00:07:08.230 --> 00:07:11.420
presenting cells-- that either
when a macrophage or a

00:07:11.420 --> 00:07:15.290
dendritic cell takes things
in, it cuts them up and

00:07:15.290 --> 00:07:19.760
presents it on its surface as
these MHC II proteins or in

00:07:19.760 --> 00:07:24.230
complex with these MHC II
complexes or proteins.

00:07:24.230 --> 00:07:27.070
And so do B cells.

00:07:27.070 --> 00:07:28.940
B cells are more specific.

00:07:28.940 --> 00:07:33.010
Now, once something is
presented, now the helper T

00:07:33.010 --> 00:07:34.990
cell can come into
the picture.

00:07:34.990 --> 00:07:39.990
So this is a-- let me do a
dendritic cell-- and I'm doing

00:07:39.990 --> 00:07:42.710
dendritic cells actually on
purpose because dendritic

00:07:42.710 --> 00:07:45.340
cells are actually
the best cells at

00:07:45.340 --> 00:07:46.810
activating helper T cells.

00:07:46.810 --> 00:07:49.430
We're going to talk about in a
second what happens when a

00:07:49.430 --> 00:07:51.540
helper T cell gets activated.

00:07:51.540 --> 00:07:54.090
So let's say I have this
dendritic cell.

00:07:54.090 --> 00:07:55.760
It's called dendritic so
it looks like it has

00:07:55.760 --> 00:07:57.010
dendrites on it.

00:08:01.370 --> 00:08:03.360
So I have this dendritic
cell here.

00:08:03.360 --> 00:08:06.040
It's a phagocyte.

00:08:06.040 --> 00:08:10.180
Let's say it's already consumed
some type of bacteria

00:08:10.180 --> 00:08:14.720
or virus and it's cut it up and
now it's presenting kind

00:08:14.720 --> 00:08:19.275
of the body parts of that virus
on the MHC II complex.

00:08:23.650 --> 00:08:25.830
It's kind of its way of saying,
hey, I found this

00:08:25.830 --> 00:08:29.090
shady thing floating around
in the body's tissues.

00:08:29.090 --> 00:08:32.179
Maybe someone ought
to raise an alarm.

00:08:32.179 --> 00:08:35.105
Maybe this is part of some type
of bigger thing going on

00:08:35.105 --> 00:08:37.669
and some type of alarm bell
has to be released.

00:08:37.669 --> 00:08:40.419
And that's what the helper
T cell does.

00:08:40.419 --> 00:08:42.080
So let's say this guy--
he's presented it.

00:08:42.080 --> 00:08:43.090
He says, I found this thing.

00:08:43.090 --> 00:08:43.610
I killed it.

00:08:43.610 --> 00:08:44.990
Here's a part of it.

00:08:44.990 --> 00:08:49.280
The helper T cell has a
T cell receptor on it.

00:08:49.280 --> 00:08:51.480
Let's say this is the helper
T cell right here.

00:08:55.190 --> 00:09:00.610
And it has a T cell receptor on
it and the T cell receptors

00:09:00.610 --> 00:09:03.230
bond to-- and I'll be very
particular here.

00:09:03.230 --> 00:09:04.710
So this is the T
cell receptor.

00:09:07.210 --> 00:09:11.800
It's just like a protein, but
like the membrane bound

00:09:11.800 --> 00:09:16.270
antibodies on B cells that every
B cell or almost every B

00:09:16.270 --> 00:09:18.870
cell has a different version,
different variable chain,

00:09:18.870 --> 00:09:24.240
that's also true of helper T
cells-- that just like the B

00:09:24.240 --> 00:09:27.660
cells, this has some variation
in where it binds.

00:09:27.660 --> 00:09:31.030
So this right here is going to
be variable from one helper T

00:09:31.030 --> 00:09:31.810
cell to another.

00:09:31.810 --> 00:09:35.590
For example, I might have
another helper T cell here.

00:09:35.590 --> 00:09:41.370
That also has a T cell receptor,
but the variable

00:09:41.370 --> 00:09:47.030
portion on that T cell receptor
is different than the

00:09:47.030 --> 00:09:49.100
variable portion on this
T cell receptor.

00:09:49.100 --> 00:09:55.380
So this helper T cell will not
bind to this dendritic cell or

00:09:55.380 --> 00:09:58.120
the MHC II complex of
this dendritic cell.

00:09:58.120 --> 00:09:59.500
Only this one would.

00:09:59.500 --> 00:10:02.600
And the mechanism of how you
get this variation is very

00:10:02.600 --> 00:10:05.290
similar to the mechanism in how
you get the variation on

00:10:05.290 --> 00:10:07.170
the antibodies and
the B cells.

00:10:07.170 --> 00:10:12.110
During these helper T cells'
development, at some point the

00:10:12.110 --> 00:10:15.940
genes that code for this part of
this receptor get shuffled

00:10:15.940 --> 00:10:18.800
around and they get shuffled
around intentionally so that

00:10:18.800 --> 00:10:23.090
each T cell has a certain
specificity to a combination

00:10:23.090 --> 00:10:28.180
of an MHC II complex and a
certain polypeptide, a certain

00:10:28.180 --> 00:10:29.530
part of a virus.

00:10:29.530 --> 00:10:32.720
So only this guy's going to be
activated, not this guy.

00:10:32.720 --> 00:10:35.480
So this is why we call it the
specific immune system.

00:10:35.480 --> 00:10:36.670
Now we said, what does
that helper T

00:10:36.670 --> 00:10:40.060
cell do at that point?

00:10:40.060 --> 00:10:44.050
He said, hey, I happen to be the
one helper T cell that can

00:10:44.050 --> 00:10:46.930
bond to this guy, this antigen
that's presented.

00:10:46.930 --> 00:10:49.450
It becomes activated.

00:10:49.450 --> 00:10:51.680
And I won't go into the details,
but in general,

00:10:51.680 --> 00:10:54.300
dendritic cells are the best
ones at activating it,

00:10:54.300 --> 00:10:57.060
especially a naive T cell.

00:11:02.780 --> 00:11:05.590
In general, when we talk about
a naive B cell or a naive

00:11:05.590 --> 00:11:08.370
helper T cell, these are cells
that are non-memory,

00:11:08.370 --> 00:11:11.820
non-effector, that have never
been touched by-- they've

00:11:11.820 --> 00:11:14.760
never been activated, in
the case of a B cell.

00:11:14.760 --> 00:11:18.420
They've never been activated by
something binding to their

00:11:18.420 --> 00:11:23.040
membrane bound antibody-- or
a naive helper T cell is a

00:11:23.040 --> 00:11:26.740
non-effector, non-memory helper
T cell that's never had

00:11:26.740 --> 00:11:28.180
anything bound to it.

00:11:28.180 --> 00:11:33.690
So if this guy is naive and then
he finally has a reaction

00:11:33.690 --> 00:11:37.470
with this antigen presenting
cell, he becomes non-naive.

00:11:37.470 --> 00:11:41.530
He becomes activated and when
activated, two things happen.

00:11:41.530 --> 00:11:44.870
Well, just like with B cells,
he proliferates many, many,

00:11:44.870 --> 00:11:48.830
many copies of himself and some
subset of those copies

00:11:48.830 --> 00:11:51.655
differentiate into
effector cells.

00:11:54.360 --> 00:11:56.170
And effector just means
it does something.

00:11:56.170 --> 00:11:58.140
It does something now instead
of saving the memory.

00:12:01.130 --> 00:12:08.380
And then some subset of them
become memory helper T cells

00:12:08.380 --> 00:12:12.030
after getting activated.

00:12:12.030 --> 00:12:15.020
Now the memory T cells, just
like memory B cells-- now you

00:12:15.020 --> 00:12:16.130
have more copies of this.

00:12:16.130 --> 00:12:17.960
So in 10 years in the future,
if something like this

00:12:17.960 --> 00:12:19.620
happens, this interaction's
going to be

00:12:19.620 --> 00:12:20.770
more likely to happen.

00:12:20.770 --> 00:12:25.125
These guys have the same T cell
receptor as their parent.

00:12:33.710 --> 00:12:36.270
It's just that the memory T
cells-- or actually even the

00:12:36.270 --> 00:12:38.280
memory B cells-- they
last longer.

00:12:38.280 --> 00:12:39.230
They don't kill themselves.

00:12:39.230 --> 00:12:42.380
They'll last for years so that
if 10 years later, something

00:12:42.380 --> 00:12:44.100
like this starts presenting
itself, you're going to have

00:12:44.100 --> 00:12:47.560
more of these guys around to
bump into this guy so that you

00:12:47.560 --> 00:12:49.700
can raise the alarm bells.

00:12:49.700 --> 00:12:56.910
This guy's also going to have
the same chain right there.

00:12:56.910 --> 00:12:57.630
So you're saying, fine.

00:12:57.630 --> 00:12:58.870
I have these memory cells.

00:12:58.870 --> 00:13:00.600
They're going to stick around
so that this reaction can

00:13:00.600 --> 00:13:02.390
happen in the future, but I
still haven't answered the

00:13:02.390 --> 00:13:05.800
question, what does the
effector T cell do?

00:13:05.800 --> 00:13:09.035
What the effector T cell does
is it raises the alarm.

00:13:16.410 --> 00:13:18.450
So there's an effector T cell.

00:13:18.450 --> 00:13:19.700
It has been activated.

00:13:22.430 --> 00:13:23.750
Remember, this is
very particular.

00:13:23.750 --> 00:13:27.255
Only this version of T cells,
but once it got activated, it

00:13:27.255 --> 00:13:29.310
produced many copies of itself
because it says, hey, I'm

00:13:29.310 --> 00:13:32.180
responding to a particular
type of pathogen.

00:13:32.180 --> 00:13:34.330
So that this is a
helper T cell.

00:13:34.330 --> 00:13:37.460
This is an effector.

00:13:37.460 --> 00:13:39.690
And what these do is they
start releasing these

00:13:39.690 --> 00:13:42.240
molecules called cytokines.

00:13:42.240 --> 00:13:43.800
So they start releasing
cytokines.

00:13:50.320 --> 00:13:52.620
There are many, many different
types of cytokines and I'm not

00:13:52.620 --> 00:13:56.160
going to go into detail on all
that, but what cytokines do is

00:13:56.160 --> 00:13:58.030
that they really raise
the alarm.

00:13:58.030 --> 00:14:03.080
So if you have other activated
lymphatic cells or other

00:14:03.080 --> 00:14:07.000
activated immunological cells--
when the cytokines

00:14:07.000 --> 00:14:08.600
enter those cells-- remember,
cytokines

00:14:08.600 --> 00:14:10.850
are really just proteins.

00:14:10.850 --> 00:14:14.610
When the cytokines enter-- or
polypeptides-- when they enter

00:14:14.610 --> 00:14:17.370
those cells, it makes
them get in gear.

00:14:17.370 --> 00:14:21.870
It makes them multiply more
often or it makes them get

00:14:21.870 --> 00:14:24.230
more active in their
immune response.

00:14:24.230 --> 00:14:26.740
So what this does-- these
cytokines you can view as

00:14:26.740 --> 00:14:34.430
chemical alarm bells chemical
or peptide alarm bells alarm

00:14:34.430 --> 00:14:38.030
bells it it tells everyone
to get in gear.

00:14:38.030 --> 00:14:40.310
So that's one role, and so you
can see this is actually a

00:14:40.310 --> 00:14:45.045
very central role and it'll tell
both activated cytotoxic

00:14:45.045 --> 00:14:47.760
T cells to get in gear, which
we haven't talked about yet.

00:14:47.760 --> 00:14:50.560
And it'll also tell B cells
to keep proliferating.

00:14:50.560 --> 00:14:53.940
So when an activated B cell gets
some of-- so this is an

00:14:53.940 --> 00:14:55.890
activated B cell.

00:14:55.890 --> 00:14:58.230
When it gets some of these
cytokines, that maybe come

00:14:58.230 --> 00:15:01.800
from a local helper T cell,
it'll tell it, hey no, divide

00:15:01.800 --> 00:15:02.420
more often.

00:15:02.420 --> 00:15:03.270
Divide more often.

00:15:03.270 --> 00:15:04.750
Only if you've been
activated already.

00:15:04.750 --> 00:15:07.640
And we'll talk more about why
it has to be that case,

00:15:07.640 --> 00:15:10.380
because you don't want all the
B cells to be activated.

00:15:10.380 --> 00:15:13.220
And the other thing that the
effector T cell does-- in the

00:15:13.220 --> 00:15:21.460
B cell discussion, I said, OK,
if I have a B cell, and it has

00:15:21.460 --> 00:15:24.130
its membrane bound
antibody, has its

00:15:24.130 --> 00:15:25.510
membrane bound antibody.

00:15:25.510 --> 00:15:29.370
And remember, this is a
particular version, it has its

00:15:29.370 --> 00:15:31.830
particular variable
chain right here.

00:15:31.830 --> 00:15:34.650
And this guy binds
to a pathogen.

00:15:34.650 --> 00:15:36.300
So this binds to a pathogen.

00:15:36.300 --> 00:15:38.430
Maybe it's a virus
right there.

00:15:38.430 --> 00:15:41.680
Up to now, I've been saying
that this guy's activated.

00:15:41.680 --> 00:15:44.580
And he's going to-- well, when
he binds to the pathogen he'll

00:15:44.580 --> 00:15:49.980
take this in and he'll take part
of the pathogen and cut

00:15:49.980 --> 00:15:55.760
it up and place it on
an MHC II molecule.

00:15:55.760 --> 00:15:57.410
And we said, then he'll
be activated.

00:15:57.410 --> 00:16:00.230
He'll proliferate and he'll
differentiate into memory and

00:16:00.230 --> 00:16:02.930
effector B cells-- but that's
not quite true.

00:16:02.930 --> 00:16:04.350
This first stage happens.

00:16:04.350 --> 00:16:05.600
This guy bonds.

00:16:05.600 --> 00:16:08.780
This B cell happened to be
specific to this virus.

00:16:08.780 --> 00:16:10.340
Cuts up the virus.

00:16:10.340 --> 00:16:13.830
Puts parts of the virus on its
surface and presents parts of

00:16:13.830 --> 00:16:14.730
the antigen.

00:16:14.730 --> 00:16:19.630
But in most cases, this B cell
isn't yet activated.

00:16:19.630 --> 00:16:22.390
You can kind of view it as in
its resting state, ready to be

00:16:22.390 --> 00:16:24.580
activated, but it hasn't started
proliferating and

00:16:24.580 --> 00:16:27.610
differentiating into effector
and memory molecules yet.

00:16:27.610 --> 00:16:36.620
And in order for that to happen,
an activated helper T

00:16:36.620 --> 00:16:40.580
cell that is also specific to
this very same virus-- so you

00:16:40.580 --> 00:16:45.010
could imagine someplace else in
the cell-- this virus was

00:16:45.010 --> 00:16:46.430
eaten by a dendritic cell.

00:16:52.140 --> 00:16:55.940
So this exact same virus, this
exact same species of virus,

00:16:55.940 --> 00:16:59.490
is eaten by that dendritic cell
and so the dendritic cell

00:16:59.490 --> 00:17:05.900
eats it up, it cuts it up, and
then it presents it-- it's

00:17:05.900 --> 00:17:10.339
antigen presenting so it
presents it just like that.

00:17:10.339 --> 00:17:12.760
Then this will activate
a very specific T

00:17:12.760 --> 00:17:14.569
cell, maybe that one.

00:17:14.569 --> 00:17:20.980
So a very specific T cell will
come and bump into it.

00:17:20.980 --> 00:17:23.000
Not just any T cell,
the one with the

00:17:23.000 --> 00:17:24.290
right variable portion.

00:17:24.290 --> 00:17:25.829
So think about what's
happening.

00:17:25.829 --> 00:17:33.270
The variable portion for this
T cell, it connects to this

00:17:33.270 --> 00:17:38.170
part of the virus plus the MHC
II, but it's really reacting

00:17:38.170 --> 00:17:39.290
to the same virus.

00:17:39.290 --> 00:17:40.790
It might be a different part.

00:17:40.790 --> 00:17:43.760
This little part that was cut
off might be someplace inside

00:17:43.760 --> 00:17:47.820
the virus while the epitope for
the B cell might be some

00:17:47.820 --> 00:17:50.340
place on the outside of the
virus, but they're both

00:17:50.340 --> 00:17:53.020
specific to the same virus.

00:17:53.020 --> 00:17:56.990
Now once this guy gets activated
and he starts

00:17:56.990 --> 00:17:59.770
producing memory and effector
cells-- or they're descended

00:17:59.770 --> 00:18:02.220
from him, one of those effector
cells specific to

00:18:02.220 --> 00:18:06.570
this virus are needed to
come bind to this guy.

00:18:06.570 --> 00:18:09.350
So then this guy could then go
along and bump around and

00:18:09.350 --> 00:18:11.410
eventually end up here.

00:18:11.410 --> 00:18:14.100
And he is also specific
to this virus.

00:18:14.100 --> 00:18:16.630
So this binding site right
here is the same as this

00:18:16.630 --> 00:18:17.140
binding site.

00:18:17.140 --> 00:18:21.940
This combination of antigen
plus MHC II.

00:18:21.940 --> 00:18:29.430
And so when this guy binds--
and remember, this binding

00:18:29.430 --> 00:18:31.860
site is the same as this and
it only binds to this

00:18:31.860 --> 00:18:36.320
combination right here-- this
is what activates the B cell

00:18:36.320 --> 00:18:37.880
in most cases.

00:18:37.880 --> 00:18:41.360
This is T-dependent
activation, which

00:18:41.360 --> 00:18:42.740
is usually the case.

00:18:42.740 --> 00:18:45.310
Sometimes all you need is this
first thing, but in general

00:18:45.310 --> 00:18:48.840
you need the first thing and
then you also need a T cell to

00:18:48.840 --> 00:18:52.830
come and activate it, and only
then will the B cell get

00:18:52.830 --> 00:18:55.540
activated and start
proliferating and dividing and

00:18:55.540 --> 00:18:58.240
differentiating itself and
producing-- when its effector

00:18:58.240 --> 00:19:00.240
cells will produce a
lot of antibodies.

00:19:00.240 --> 00:19:01.400
And so there's a natural
question.

00:19:01.400 --> 00:19:04.000
Why do biological systems--
or why do we

00:19:04.000 --> 00:19:05.880
have this double system?

00:19:05.880 --> 00:19:10.020
And at least my sense of it is,
it's a failsafe mechanism.

00:19:10.020 --> 00:19:13.630
If every time a virus came and
attached this, this guy just

00:19:13.630 --> 00:19:15.940
started going crazy and
producing antibodies against

00:19:15.940 --> 00:19:20.950
this thing, there's some
chance that maybe after

00:19:20.950 --> 00:19:26.440
development, this chain right
here or his genes for

00:19:26.440 --> 00:19:30.330
generating these chains become
specific, not for foreign

00:19:30.330 --> 00:19:35.180
pathogens, but maybe they
become specific for self

00:19:35.180 --> 00:19:37.180
molecules, molecules
that are naturally

00:19:37.180 --> 00:19:38.360
produced within the body.

00:19:38.360 --> 00:19:40.990
It's just a random mutation, but
if he started going crazy

00:19:40.990 --> 00:19:45.090
for that, his antibodies will
start attacking molecules that

00:19:45.090 --> 00:19:47.290
are naturally in the body and
then that could really hurt.

00:19:47.290 --> 00:19:51.240
That what causes autoimmune
diseases, where your own

00:19:51.240 --> 00:19:53.200
immune cells start activating
yourself.

00:19:53.200 --> 00:19:55.460
But if you have this double
handshake system where this

00:19:55.460 --> 00:19:59.110
has to happen and this has to
happen, the likelihood of both

00:19:59.110 --> 00:20:03.050
of these guys after they leave
their development stage

00:20:03.050 --> 00:20:09.110
becoming specific to a self
protein or a self cell or a

00:20:09.110 --> 00:20:12.010
self molecule is
very unlikely.

00:20:12.010 --> 00:20:15.380
So it kind of inhibits this guy
from going wild, even if

00:20:15.380 --> 00:20:17.180
he has some type
of a mutation.

00:20:17.180 --> 00:20:19.350
Anyway, hopefully that explains
a little bit of what

00:20:19.350 --> 00:20:20.520
helper T cells do.

00:20:20.520 --> 00:20:22.110
We'll talk a lot
more about it.

00:20:22.110 --> 00:20:23.970
I know it can be a little
bit confusing.

00:20:23.970 --> 00:20:27.365
In the next video, we'll talk
about cytotoxic T cells.