Professional antigen presenting cells (APC) and MHC II complexes

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Kind: captions
Language: en

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In the very first immunology
video, where we talked about

00:00:02.740 --> 00:00:05.580
nonspecific defense mechanisms,
we said if we had

00:00:05.580 --> 00:00:09.400
some type of a pathogen-- let's
say it's a bacteria--

00:00:09.400 --> 00:00:14.040
that our phagocytes can
recognize either proteins on

00:00:14.040 --> 00:00:16.770
the bacteria or maybe it was
some other type of pathogen--

00:00:16.770 --> 00:00:18.095
some other marker
on the pathogen.

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It doesn't know what type of
pathogen it is, but that's

00:00:20.780 --> 00:00:23.820
enough for the phagocyte.

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It'll engulf the pathogen.

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So let's say this is
the phagocyte.

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Somehow one of their receptors
touches one of the proteins

00:00:32.060 --> 00:00:36.560
that's on the surface of this
bacteria in this case and

00:00:36.560 --> 00:00:38.800
says, gee, that's not a good
thing to have around and so

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it'll engulf it.

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So the membrane is just going to
surround the pathogen-- and

00:00:44.830 --> 00:00:46.060
this part is going to go in.

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It's going to kind of pinch in
and the pathogen is going to

00:00:48.440 --> 00:00:50.290
get surrounded and
get engulfed--

00:00:50.290 --> 00:00:53.570
phagocytozed by the phagocyte.

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So the end product-- we saw this
on the first video where

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I talked about phagocytes-- is
we're going to end up-- so

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then the membrane's going
to be completely around.

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This is going to pinch in and
bubble around this thing and

00:01:05.349 --> 00:01:08.970
so we're going to have
the pathogen sitting

00:01:08.970 --> 00:01:11.100
inside of the phagocyte.

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It's going to be surrounded
by a membrane.

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That membrane's called
a phagosome.

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And we learned there's
different types of

00:01:17.560 --> 00:01:22.380
phagocytes-- could be a
macrophage, could be a

00:01:22.380 --> 00:01:28.280
neutrophil, could be a dendritic
cell-- and we have

00:01:28.280 --> 00:01:30.250
it like this and then we also
saw in that video, it's not

00:01:30.250 --> 00:01:32.460
just done-- the macrophage
doesn't

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just digest this thing.

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That by itself is very useful.

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It got this bacteria
out of the way.

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If this was a virus, it got
that virus out of the way.

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But it does even
more than that.

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It takes that and then it lyses
it-- or it breaks it up.

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It doesn't have to actually
use-- well, it breaks it up.

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There's several ways it can do
it, but the bottom line is, it

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processes it.

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It'll break up the pathogen--
and we saw that first video on

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phagocytes that we'll actually
have a lysosome bond to it and

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dump all sorts of particles that
are going to break up and

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cut up this bacteria,
in this case, into

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its constituent molecules.

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And then some subset of the
leftovers, particular chains

00:02:24.250 --> 00:02:27.060
of the peptides-- and remember,
proteins are long

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chains of amino acids.

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Polypeptides are short chains.

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So you take short chains of
those and they're going to

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bond to special proteins.

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And this is essentially the
topic of this video.

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So let's say they bond to that
special protein, bond to that

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special protein.

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And then those proteins get
transported or get to the

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membrane or the outer surface
of the cell and they present

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themselves along with the
piece of the pathogen.

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So the end product after
phagocytozed this pathogen is

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that the phagocyte will look
something like this and it

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will have these antigen
presenting proteins, I guess

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we can call them, that had
bound to parts of that

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original pathogen.

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Let me do it right here.

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So it has a little bit of the
original pathogen on it that I

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drew in green right here.

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And these proteins right here,
these are called-- it's a

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fancy word and I talked about
it in the previous video--

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these are called major
histocompatibility complexes,

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or MHC for short.

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And when we're talking about
phagocytes or macrophages or

00:03:58.170 --> 00:04:00.270
dendritic cells that are
particular cases of

00:04:00.270 --> 00:04:03.600
phagocytes, the major
histocompatibility complexes

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that they present after
they've digested this

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molecule-- this is
an MHC class II.

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Let me write this down.

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This is an MHC class
II protein.

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It might seem like I'm really
going into the minutiae of

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what these proteins are, but
we're going to see this is key

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for activating other parts of
the immune system, especially

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the cell mediated parts
of the immune system.

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So this was the case with a
macrophage or a dendrite.

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They engulf something, they chew
it all up, and then parts

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of the chewed up thing that they
ate, they attach to these

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MHC II proteins and these
MHC proteins go to the

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surface of the cell.

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The same thing-- or actually not
the quite the same thing--

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a very similar thing happens
with B cells.

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So if we have a B cell--
that's a good color.

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B for blue.

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We know B stands for bursa, but
it could stand for bone

00:04:57.590 --> 00:04:58.940
marrow just as well.

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Let's say we have a B cell and
it's got its membrane bound

00:05:02.560 --> 00:05:03.910
antibody on it.

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Remember, it's very specific
to that B cells.

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So all of the membrane bound
antibodies, all 10,000 or so

00:05:10.910 --> 00:05:14.500
of them on this B cell, they
all expressed the same

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variable part.

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So this is a particular
B cell.

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So remember, this
was nonspecific.

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When we talked about
phagocytosis, these guys just

00:05:23.450 --> 00:05:24.440
say, you're a bacteria.

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You're a virus.

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I don't know what
kind you are.

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I'm just going to eat you up.

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You look shady.

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I'm going to eat you up.

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I don't know what type
you are or whether

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I've seen you before.

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When we're talking about B
cells, we're talking about the

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adaptive or the specific
immune system.

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And so these-- the variable ends
of these membrane bound

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antibodies are specific to
certain parts of certain

00:05:43.060 --> 00:05:45.650
pathogens, to certain
epitopes.

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Remember, epitopes were the
parts of certain pathogens

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that these specific chains can
recognize and bond to.

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So let's say that we're
dealing with a

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virus in this situation.

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And let's say the virus
just happens to

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bond to this B cell.

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Remember, there might be
other-- in fact, there

00:06:02.760 --> 00:06:08.910
definitely are tons of other
B cells around, but their

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variable portions are
all different.

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And that's what I always find
amazing about B cells is that

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they come from the same genetic
line, their genes have

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been shuffled around in their
development so that they can

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produce billions of combinations
of these

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proteins, or the variable ends
of their antibodies.

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So let's say we have
some virus.

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Let me say it's a bacteria.

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When I did the other B cell
example, I said we're dealing

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with viruses.

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But let's say some new bacteria
and just some part of

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its surface just happens to
bind to only this B cell--

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because this B cell has just
the right combination.

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So some part of his surface
binds just to that B cell

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right there.

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That part of the surface that
binds, remember, that was

00:06:59.760 --> 00:07:01.000
called the epitope.

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That's that part of the pathogen
that binds to our

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variable sequencer.

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It won't bind to this B cell
or this B cell because they

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have different sequences here,
but it binds to this B cell

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and then that starts the
activation process.

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We'll go into-- sometimes this
by itself can get the B cell

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activated, but you normally
need help from helper T

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cells-- and we'll talk
more about that.

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And we said, once this
happens, once you get

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activated or the activation
process starts, this guy

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actually gets engulfed-- and I
didn't talk about that in the

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last video just because I didn't
want to go into too

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much detail.

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So this whole thing gets
engulfed by the B cell.

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And then when it gets activated,
it proliferates

00:07:46.870 --> 00:07:49.960
itself and you normally need
the T cells there and some

00:07:49.960 --> 00:07:52.245
part of them become plasma B
cells, some part of them

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become memory B cells.

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Remember, the plasma B cells
say, gee, I've been activated.

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I'm just going to produce a
ton of these antibodies.

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So the plasma B cell will just
produce tons of these

00:08:07.850 --> 00:08:10.720
antibodies and start spitting
them out so that they can

00:08:10.720 --> 00:08:14.020
attach to more and more of that
pathogen and just mess

00:08:14.020 --> 00:08:18.650
them up in different ways,
either tag them so that other

00:08:18.650 --> 00:08:23.070
macrophages or phagocytes eat
them up-- or tag two of them

00:08:23.070 --> 00:08:25.380
so you bundle them up so that
they can't operate properly.

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Whatever.

00:08:25.700 --> 00:08:27.120
I'm not going to go into
detail on that.

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That's when it gets activated.

00:08:28.390 --> 00:08:31.860
But the interesting thing is
that the B cell will also do

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what the phagocytes do.

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The B cell will also take
this guy into the cell.

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Maybe he's initially attached
to the antibody-- and break

00:08:47.100 --> 00:08:55.140
him up, take pieces of this
pathogen and attach it to MHC

00:08:55.140 --> 00:08:59.790
II proteins and then present
them on the surface.

00:08:59.790 --> 00:09:03.495
So a B cell will also
present the antigen.

00:09:06.970 --> 00:09:11.220
So this is also an MHC
II complex-- a major

00:09:11.220 --> 00:09:13.790
histocompatibility complex--
and just so you know, histo

00:09:13.790 --> 00:09:14.700
means tissue.

00:09:14.700 --> 00:09:17.050
So this is related to whether
something is compatible with

00:09:17.050 --> 00:09:19.260
the tissue in your body and
we'll talk more about that and

00:09:19.260 --> 00:09:21.380
how it relates to transplants
and all of that.

00:09:21.380 --> 00:09:25.750
So this is also an
MHC class II.

00:09:25.750 --> 00:09:28.250
In both cases, whether we're
talking about B cells that

00:09:28.250 --> 00:09:31.950
recognize a very specific
pathogen-- and it could be a

00:09:31.950 --> 00:09:37.090
specific virus, a specific
protein, a specific bacteria,

00:09:37.090 --> 00:09:40.350
or in the cases of phagocytes,
they'll just say,

00:09:40.350 --> 00:09:41.210
oh, you look shady.

00:09:41.210 --> 00:09:42.050
Let me take you in.

00:09:42.050 --> 00:09:44.300
I don't know what type of
bacteria or virus or protein

00:09:44.300 --> 00:09:47.940
you are, but in either case,
they both engulf them, take

00:09:47.940 --> 00:09:50.190
pieces of them, cut them up,
and present them on their

00:09:50.190 --> 00:09:52.580
surface in a complex
with the major

00:09:52.580 --> 00:09:57.040
histocompatibility complexes.

00:09:57.040 --> 00:10:01.450
So cells that do this are called
professional antigen

00:10:01.450 --> 00:10:02.700
presenting cells.

00:10:05.080 --> 00:10:07.770
This is what they do for a
living, although they do other

00:10:07.770 --> 00:10:09.430
things, as we've seen.

00:10:09.430 --> 00:10:10.750
The phagocytes eat things.

00:10:10.750 --> 00:10:14.640
The B cells generate antibodies
or memories so that

00:10:14.640 --> 00:10:17.355
they can later be activated to
generate antibodies, but these

00:10:17.355 --> 00:10:25.730
are called professional antigen
presenting cell.

00:10:25.730 --> 00:10:29.630
And the antigen in question is
this little piece of the

00:10:29.630 --> 00:10:35.420
actual thing that you're trying
to track, that little

00:10:35.420 --> 00:10:38.720
piece-- the actual part of the
pathogen, that's what the

00:10:38.720 --> 00:10:40.520
antigen-- so it's presenting
the antigen.

00:10:40.520 --> 00:10:48.630
It's professional because it
takes pathogens from in the

00:10:48.630 --> 00:10:51.940
fluid of our system and then
engulfs them, breaks them up,

00:10:51.940 --> 00:10:53.510
and then presents them.

00:10:53.510 --> 00:10:57.810
Now there are also
nonprofessional antigen

00:10:57.810 --> 00:10:58.530
presenting cells.

00:10:58.530 --> 00:11:00.910
And in fact, most
cells are this.

00:11:00.910 --> 00:11:02.600
In fact, even these guys.

00:11:02.600 --> 00:11:03.770
Actually, I'm going to wait
for the next video.

00:11:03.770 --> 00:11:05.960
I realize all of my videos
are getting long.

00:11:05.960 --> 00:11:10.280
So you're probably thinking,
these guys in either case

00:11:10.280 --> 00:11:12.030
engulf them, cut them
up, present them,

00:11:12.030 --> 00:11:13.320
what is it good for?

00:11:13.320 --> 00:11:18.690
You'll see these MHC II, these
are what are recognized by

00:11:18.690 --> 00:11:20.290
helper T cells.

00:11:20.290 --> 00:11:23.830
It'll all form part of the
puzzle of how our immune

00:11:23.830 --> 00:11:24.420
system works.

00:11:24.420 --> 00:11:28.160
So in the next video, I'll talk
about MHC I presenting

00:11:28.160 --> 00:11:31.450
cells, which is pretty
much all body cells.


B lymphocytes (B cells)

WEBVTT
Kind: captions
Language: en

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Let's just talk about the
humoral response right now,

00:00:04.880 --> 00:00:08.180
that deals with B lymphocytes.

00:00:08.180 --> 00:00:15.340
So B lymphocytes or B cells--
let me do them in blue.

00:00:15.340 --> 00:00:18.200
So let's say that that
is a B lymphocyte.

00:00:18.200 --> 00:00:21.720
It's a subset of white blood
cells called lymphocytes.

00:00:21.720 --> 00:00:25.360
It comes from the bone marrow
and that's where the-- well,

00:00:25.360 --> 00:00:27.360
the B comes from bursa of
Fabricius, but we don't want

00:00:27.360 --> 00:00:28.450
to go into detail there.

00:00:28.450 --> 00:00:30.760
But they have all of these
proteins on their surface.

00:00:30.760 --> 00:00:34.280
Actually, close to
10,000 of them.

00:00:34.280 --> 00:00:35.890
I get very excited about
B cells and I'll tell

00:00:35.890 --> 00:00:36.550
you why in a second.

00:00:36.550 --> 00:00:39.390
It has all of these proteins
on them that look

00:00:39.390 --> 00:00:41.760
something like this.

00:00:41.760 --> 00:00:43.120
I'll just draw a
couple of them.

00:00:46.240 --> 00:00:48.740
These are actually protein
complexes, you can

00:00:48.740 --> 00:00:49.320
kind of view them.

00:00:49.320 --> 00:00:52.380
They actually have four separate
proteins on them and

00:00:52.380 --> 00:00:57.215
we can call these proteins
membrane bound antibodies.

00:01:10.990 --> 00:01:13.460
And I'll talk a lot more
about antibodies.

00:01:13.460 --> 00:01:14.920
You've probably heard
the word.

00:01:14.920 --> 00:01:17.860
You have antibodies for such and
such flu, or such and such

00:01:17.860 --> 00:01:20.800
virus, and we're going to talk
more about that in the future,

00:01:20.800 --> 00:01:25.060
but antibodies are
just proteins.

00:01:25.060 --> 00:01:27.330
They're often referred to
as immunoglobulins.

00:01:36.130 --> 00:01:39.360
These are essentially
equivalent words.

00:01:39.360 --> 00:01:44.000
Antibodies or immunoglobulins--
and they're

00:01:44.000 --> 00:01:45.560
really just proteins.

00:01:45.560 --> 00:01:50.640
Now, B cells have these on the
surface of their membranes.

00:01:50.640 --> 00:01:52.290
These are membrane bound.

00:01:52.290 --> 00:01:54.050
Usually when people talk about
antibodies, they're talking

00:01:54.050 --> 00:02:00.140
about free antibodies that are
going to just be floating

00:02:00.140 --> 00:02:01.260
around like that.

00:02:01.260 --> 00:02:03.410
And I'm going to go into
more detail on

00:02:03.410 --> 00:02:04.770
how those are produced.

00:02:04.770 --> 00:02:08.009
Now what's really, really,
really, really, really

00:02:08.009 --> 00:02:11.980
interesting about these membrane
bound antibodies and

00:02:11.980 --> 00:02:17.220
these B cells in particular is
that a B cell has one type of

00:02:17.220 --> 00:02:19.240
membrane bound antibody
on it .

00:02:27.200 --> 00:02:29.730
It's going to also have
antibodies, but those

00:02:29.730 --> 00:02:32.160
antibodies are going
to be different.

00:02:32.160 --> 00:02:34.920
So we'll focus on where
they're different.

00:02:34.920 --> 00:02:37.360
Let me just draw them the same
color first and then we'll

00:02:37.360 --> 00:02:38.805
focus on where they're
different.

00:02:45.530 --> 00:02:46.840
These are both B cells.

00:02:46.840 --> 00:02:49.190
They both have these
antibodies on them.

00:02:49.190 --> 00:02:54.130
The interesting thing is that
from one B cell to another B

00:02:54.130 --> 00:03:00.200
cell, they have a variable part
on this antibody that

00:03:00.200 --> 00:03:02.780
could take on a bunch of
different forms. So this one

00:03:02.780 --> 00:03:06.960
might look like that and that.

00:03:06.960 --> 00:03:09.720
So these long-- I'll go into
more detail on that.

00:03:17.070 --> 00:03:19.600
The fixed portion, you can
imagine is green for any kind

00:03:19.600 --> 00:03:22.500
of antibody, and then there's
a variable portion.

00:03:22.500 --> 00:03:24.710
So maybe this guy's variable
portion is--

00:03:24.710 --> 00:03:25.900
I'll do it in pink.

00:03:25.900 --> 00:03:28.520
And every one of the antibodies
bound to his

00:03:28.520 --> 00:03:32.220
membrane are going to have that
same variable portion.

00:03:32.220 --> 00:03:34.100
This different B cell
is going to have

00:03:34.100 --> 00:03:36.310
different variable portions.

00:03:36.310 --> 00:03:38.640
So I'll do that in a
different color.

00:03:38.640 --> 00:03:40.270
Maybe I'll do it in magenta.

00:03:40.270 --> 00:03:42.690
So his variable portions are
going to be different.

00:03:47.850 --> 00:03:50.410
Now he has 10,000 of these on
a surface and every one of

00:03:50.410 --> 00:03:53.170
these have the same variable
portions, but they're all

00:03:53.170 --> 00:03:57.600
different from the variable
portions on this B cell.

00:03:57.600 --> 00:04:00.110
There's actually 10 billion
different combinations of

00:04:00.110 --> 00:04:01.360
variable portions.

00:04:14.580 --> 00:04:16.779
So the first question-- and I
haven't even told you what the

00:04:16.779 --> 00:04:19.640
variable portions are good for--
is, how do that many

00:04:19.640 --> 00:04:21.149
different combinations arise?

00:04:21.149 --> 00:04:23.990
Obviously these proteins-- or
maybe not so obviously-- all

00:04:23.990 --> 00:04:27.420
these proteins that are part of
most cells are produced by

00:04:27.420 --> 00:04:29.200
the genes of that cell.

00:04:29.200 --> 00:04:32.200
So if I draw-- this
is the nucleus.

00:04:32.200 --> 00:04:34.050
It's got DNA inside
the nucleus.

00:04:34.050 --> 00:04:35.240
This guy has a nucleus.

00:04:35.240 --> 00:04:37.360
It's got DNA inside
the nucleus.

00:04:37.360 --> 00:04:41.410
If these guys are both B cells
and they're both coming from

00:04:41.410 --> 00:04:46.000
the same germ line, they're
coming from the same, I guess,

00:04:46.000 --> 00:04:49.180
ancestry of cells, shouldn't
they have the same DNA?

00:04:57.930 --> 00:05:01.300
If they do have the same DNA,
why are the proteins that

00:05:01.300 --> 00:05:03.530
they're constructing
different?

00:05:03.530 --> 00:05:04.800
How do they change?

00:05:04.800 --> 00:05:08.090
And this is why I find B cells--
and you'll see this is

00:05:08.090 --> 00:05:11.720
also true of T cells-- to be
fascinating is, in their

00:05:11.720 --> 00:05:17.940
development, in their
hematopoiesis-- that's just

00:05:17.940 --> 00:05:20.610
the development of these
lymphocytes.

00:05:20.610 --> 00:05:22.960
At one stage in their
development, there's just a

00:05:22.960 --> 00:05:25.990
lot of shuffling of the portion
of their DNA that

00:05:25.990 --> 00:05:30.200
codes for here, for these
parts of the protein.

00:05:30.200 --> 00:05:33.990
There's just a lot of shuffling
that occurs.

00:05:33.990 --> 00:05:36.080
Most of when we talk about
DNA, we really want to

00:05:36.080 --> 00:05:38.510
preserve the information, not
have a lot of shuffling.

00:05:38.510 --> 00:05:42.110
But when these lymphocytes,
when these B cells are

00:05:42.110 --> 00:05:46.270
maturing, at one stage of their
maturation or their

00:05:46.270 --> 00:05:50.120
development, there's intentional
reshuffling of the

00:05:50.120 --> 00:05:52.490
DNA that codes for this
part and this part.

00:05:52.490 --> 00:05:56.160
And that's what leads to all
of the diversity in the

00:05:56.160 --> 00:05:58.980
variable portions on these
membrane bound

00:05:58.980 --> 00:05:59.770
immunoglobulins.

00:05:59.770 --> 00:06:02.620
And we're about to find out why
there's that diversity.

00:06:02.620 --> 00:06:07.890
So there's tons of stuff that
can infect your body.

00:06:07.890 --> 00:06:12.220
Viruses are are mutating and
evolving and so are bacteria.

00:06:12.220 --> 00:06:14.490
You don't know what's going
to enter your body.

00:06:14.490 --> 00:06:18.480
So what the immune system has
done through B cells-- and

00:06:18.480 --> 00:06:22.200
we'll also see it through T
cells-- it says, hey, let me

00:06:22.200 --> 00:06:24.940
just make a bunch of
combinations of these things

00:06:24.940 --> 00:06:28.470
that can essentially bind
to whatever I get to.

00:06:28.470 --> 00:06:33.010
So let's say that there's
just some new virus

00:06:33.010 --> 00:06:34.900
that shows up, right?

00:06:34.900 --> 00:06:40.190
The world has never seen this
virus before this B cell,

00:06:40.190 --> 00:06:42.940
it'll bump into this virus and
this virus won't attach.

00:06:42.940 --> 00:06:44.750
Another B cell will bump
into this virus

00:06:44.750 --> 00:06:45.740
and it won't attach.

00:06:45.740 --> 00:06:49.370
And maybe several thousands of
B cells will bump into this

00:06:49.370 --> 00:06:52.620
virus and it won't attach, but
since I have so many B cells

00:06:52.620 --> 00:06:55.620
having so many different
combinations of these variable

00:06:55.620 --> 00:06:59.570
portions on these receptors,
eventually one of these B

00:06:59.570 --> 00:07:00.650
cells is going to bond.

00:07:00.650 --> 00:07:01.900
Maybe it's this one.

00:07:06.120 --> 00:07:09.620
He's going to bond to part of
the surface of this virus.

00:07:09.620 --> 00:07:13.440
It could also be to part of a
surface of a new bacteria, or

00:07:13.440 --> 00:07:16.630
part of a surface for some
foreign protein.

00:07:16.630 --> 00:07:21.080
And part of the surface that it
binds on the bacteria-- so

00:07:21.080 --> 00:07:24.050
maybe it binds on that part of
the bacteria-- this is called

00:07:24.050 --> 00:07:25.300
an epitope.

00:07:28.350 --> 00:07:33.200
So once this guy binds to some
foreign pathogen-- and

00:07:33.200 --> 00:07:35.730
remember, the other B cells
won't-- only the particular

00:07:35.730 --> 00:07:37.790
one that had the particular
combination, one of

00:07:37.790 --> 00:07:38.760
the 10 to the 10th.

00:07:38.760 --> 00:07:41.000
And actually, there aren't 10
to the 10th combinations.

00:07:41.000 --> 00:07:43.310
During their development,
they weed out all of the

00:07:43.310 --> 00:07:48.760
combinations that would bind to
things that are essentially

00:07:48.760 --> 00:07:52.070
you, that there shouldn't be
an immune response to.

00:07:52.070 --> 00:08:00.350
So we could say self-responding
combinations

00:08:00.350 --> 00:08:02.550
weeded out.

00:08:02.550 --> 00:08:04.950
So there actually aren't 10
to the 10th, 10 billion

00:08:04.950 --> 00:08:06.690
combinations of these--
something smaller than that.

00:08:06.690 --> 00:08:08.940
You have to take out all the
combinations that would have

00:08:08.940 --> 00:08:12.770
bound to your own cells, but
there's still a super huge

00:08:12.770 --> 00:08:15.000
number of combinations that are
very likely to bond, at

00:08:15.000 --> 00:08:17.460
least to some part of some
pathogen of some

00:08:17.460 --> 00:08:19.200
virus or some bacteria.

00:08:19.200 --> 00:08:22.680
And as soon as one of these B
cells binds, it says, hey

00:08:22.680 --> 00:08:26.650
guys, I'm the lucky guy who
happens to fit exactly this

00:08:26.650 --> 00:08:28.110
brand new pathogen.

00:08:28.110 --> 00:08:36.909
He becomes activated after
binding to the new pathogen.

00:08:36.909 --> 00:08:39.630
And I'm going to go into more
detail in the future.

00:08:39.630 --> 00:08:43.880
In order to really become
activated, you normally need

00:08:43.880 --> 00:08:46.210
help from helper T cells,
but I don't want to

00:08:46.210 --> 00:08:47.610
confuse you in the video.

00:08:47.610 --> 00:08:50.550
So in this case, I'm going to
assume that activation can

00:08:50.550 --> 00:08:54.690
only occur-- or that it just
needs to respond, it just

00:08:54.690 --> 00:08:57.080
needs to essentially
be triggered by

00:08:57.080 --> 00:08:59.200
binding with the pathogen.

00:08:59.200 --> 00:09:00.670
In most cases, you
actually need the

00:09:00.670 --> 00:09:01.785
helper T cells as well.

00:09:01.785 --> 00:09:03.420
And we'll discuss why
that's important.

00:09:03.420 --> 00:09:05.280
It's kind of a fail
safe mechanism

00:09:05.280 --> 00:09:07.090
for your immune system.

00:09:07.090 --> 00:09:11.830
But once this guy gets
activated, he's going to start

00:09:11.830 --> 00:09:13.060
cloning himself.

00:09:13.060 --> 00:09:17.500
He's going to say, look, I'm
the guy that can match this

00:09:17.500 --> 00:09:20.390
virus here-- and so he's going
to start cloning himself.

00:09:20.390 --> 00:09:24.810
He's going to start dividing
and repeating himself.

00:09:24.810 --> 00:09:28.010
So there's just going to be
multiple versions of this guy.

00:09:41.640 --> 00:09:45.240
So they all start to replicate
and they also differentiate--

00:09:45.240 --> 00:09:48.110
differentiate means they start
taking particular roles.

00:09:48.110 --> 00:09:51.350
So there's two forms
of differentiation.

00:09:51.350 --> 00:09:54.100
So many, many, many hundreds
or thousands of these are

00:09:54.100 --> 00:09:55.270
going to be produced.

00:09:55.270 --> 00:10:01.210
And then some are going to
become memory cells, which are

00:10:01.210 --> 00:10:05.850
essentially just B cells that
stick around a long time with

00:10:05.850 --> 00:10:09.660
the perfect receptor on them,
with the perfect variable

00:10:09.660 --> 00:10:11.500
portion of their receptor
on them.

00:10:21.810 --> 00:10:23.440
So some will be memory cells
and they're going to be in

00:10:23.440 --> 00:10:25.140
higher quantities than
they were originally.

00:10:25.140 --> 00:10:28.770
So if if this guy invades our
bodies 10 years in the future,

00:10:28.770 --> 00:10:31.120
they're going to have more of
these guys around that are

00:10:31.120 --> 00:10:34.540
more likely to bump into them
and start and get activated

00:10:34.540 --> 00:10:35.710
and then some of them
are going to turn

00:10:35.710 --> 00:10:36.760
into effector cells.

00:10:36.760 --> 00:10:38.640
And effector cells are generally
cells that actually

00:10:38.640 --> 00:10:39.890
do something.

00:10:44.900 --> 00:10:50.580
What the effector cells do is,
they turn into antibody-- they

00:10:50.580 --> 00:10:53.050
turn into these effector B
cells-- or sometimes they're

00:10:53.050 --> 00:10:55.030
called plasma cells.

00:10:55.030 --> 00:10:59.175
They're going to turn into
antibody factories.

00:11:03.630 --> 00:11:06.690
And the antibodies they're going
to produce are exactly

00:11:06.690 --> 00:11:10.800
this combination, the date that
they originally had being

00:11:10.800 --> 00:11:12.050
membrane bound.

00:11:12.050 --> 00:11:15.230
So they're just going to start
producing these antibodies

00:11:15.230 --> 00:11:19.650
that we talk about with the
exact-- they're going to start

00:11:19.650 --> 00:11:22.260
spitting out these antibodies.

00:11:22.260 --> 00:11:24.670
They're going to start spitting
out tons and tons of

00:11:24.670 --> 00:11:28.660
these proteins that are uniquely
able to bind to the

00:11:28.660 --> 00:11:32.340
new pathogen, this new
thing in question.

00:11:35.240 --> 00:11:40.430
So an activated effector cell
will actually produce 2,000

00:11:40.430 --> 00:11:41.590
antibodies a second.

00:11:41.590 --> 00:11:43.270
So you can imagine, if you have
a lot of these, you're

00:11:43.270 --> 00:11:46.290
going to have all of a sudden
a lot of antibodies floating

00:11:46.290 --> 00:11:49.500
around in your body and going
into the body tissues.

00:11:49.500 --> 00:11:52.600
And the value of that and why
this is the humoral system is,

00:11:52.600 --> 00:11:54.560
all of a sudden, you have all
of these viruses that are

00:11:54.560 --> 00:12:01.020
infecting your system, but now
you're producing all of these

00:12:01.020 --> 00:12:01.820
antibodies.

00:12:01.820 --> 00:12:05.680
The effector cells are these
factories and so these

00:12:05.680 --> 00:12:08.960
specific antibodies will
start bonding.

00:12:08.960 --> 00:12:10.510
So let me draw it like this.

00:12:16.140 --> 00:12:22.370
The specific antibodies will
start bonding to these viruses

00:12:22.370 --> 00:12:28.360
and that has a couple
of values to it.

00:12:28.360 --> 00:12:31.180
One is, it essentially tags
them for pick up.

00:12:31.180 --> 00:12:33.700
Now phagocytosis-- this is
called opsonization.

00:12:40.370 --> 00:12:42.730
When you tag molecules for
pickup and you make them

00:12:42.730 --> 00:12:51.260
easier for phagocytes to eat
them up, this is what--

00:12:51.260 --> 00:12:53.600
antibodies are attaching and
say, hey phagocytes, this is

00:12:53.600 --> 00:12:54.290
going to make it easier.

00:12:54.290 --> 00:12:56.760
You should pick up these
guys in particular.

00:12:56.760 --> 00:12:59.180
It also might make these viruses
hard to function.

00:12:59.180 --> 00:13:01.240
I have this big thing hanging
off the side of it.

00:13:01.240 --> 00:13:04.110
It might be harder for them to
infiltrate cells and the other

00:13:04.110 --> 00:13:09.110
thing is, on each of these
antibodies you have two

00:13:09.110 --> 00:13:13.460
identical heavy chains
and then two

00:13:13.460 --> 00:13:14.710
identical light chains.

00:13:17.120 --> 00:13:20.250
And then they have a very
specific variable portion on

00:13:20.250 --> 00:13:25.450
each one and each of these
branches can bond to the

00:13:25.450 --> 00:13:29.760
epitope on a virus.

00:13:29.760 --> 00:13:31.970
So you can imagine, what happens
if this guy bonds to

00:13:31.970 --> 00:13:34.760
one epitope and this guy
bonds to another virus?

00:13:34.760 --> 00:13:37.110
Then all of a sudden, these
viruses are kind of glued

00:13:37.110 --> 00:13:38.950
together and that's even
more efficient.

00:13:38.950 --> 00:13:40.680
They're not going to be able to
do what they normally do.

00:13:40.680 --> 00:13:43.910
They're not going to be able
to enter cell membranes and

00:13:43.910 --> 00:13:45.340
they're perfectly tagged.

00:13:45.340 --> 00:13:48.650
They've been opsonized so
that phagocytes can come

00:13:48.650 --> 00:13:49.520
and eat them up.

00:13:49.520 --> 00:13:51.770
So we'll talk more about B cells
in the future, but I

00:13:51.770 --> 00:13:53.480
just find it fascinating that
there are that many

00:13:53.480 --> 00:13:56.100
combinations and they have
enough combinations to really

00:13:56.100 --> 00:14:00.210
recognize almost anything that
can exist in the fluids of our

00:14:00.210 --> 00:14:02.760
body, but we haven't solved
all of the problems yet.

00:14:02.760 --> 00:14:04.950
We haven't solved the problem
of what happens when things

00:14:04.950 --> 00:14:08.060
actually infiltrate cells
or we have cancer cells?

00:14:08.060 --> 00:14:11.270
How do we kill cells that have
clearly gone astray?


Types of immune responses: Innate and adaptive, humoral vs. cell-mediated

WEBVTT
Kind: captions
Language: en

00:00:00.500 --> 00:00:02.340
In the last video, we
talked a little bit

00:00:02.340 --> 00:00:04.650
about the immune system.

00:00:04.650 --> 00:00:09.930
In that video, we focused on the
nonspecific or the innate

00:00:09.930 --> 00:00:10.695
immune system.

00:00:10.695 --> 00:00:11.945
So let me write that.

00:00:17.100 --> 00:00:20.310
And even in the nonspecific
immune system, we subdivided

00:00:20.310 --> 00:00:24.870
that into kind of the
first line barriers.

00:00:24.870 --> 00:00:30.030
And those were things like the
skin, or the stomach acid, or

00:00:30.030 --> 00:00:33.420
the acidity of the oils on
the outside of your skin.

00:00:33.420 --> 00:00:35.640
These are just natural barriers
to not allowing

00:00:35.640 --> 00:00:38.210
things inside of your body, but
then once they get in-- so

00:00:38.210 --> 00:00:39.520
you can almost imagine
these were the

00:00:39.520 --> 00:00:42.830
first line of defense.

00:00:42.830 --> 00:00:45.730
And then you had your second
line of defense, but these are

00:00:45.730 --> 00:00:48.970
still nonspecific-- and when we
say nonspecific, it means

00:00:48.970 --> 00:00:51.680
that they don't necessarily know
what type of virus, what

00:00:51.680 --> 00:00:53.460
type of protein, what
type of bacteria.

00:00:53.460 --> 00:00:55.430
They just know that this
thing looks shady.

00:00:55.430 --> 00:00:56.260
Let me eat it up.

00:00:56.260 --> 00:00:56.950
Let me kill it.

00:00:56.950 --> 00:00:59.450
Let me have an inflammatory
response.

00:00:59.450 --> 00:01:01.710
So in there, we said, well,
there's an inflammatory

00:01:01.710 --> 00:01:06.230
response, which I'm actually
going to talk about after we

00:01:06.230 --> 00:01:09.470
do videos on the specific
immune system.

00:01:09.470 --> 00:01:11.580
You have your inflammatory
response, which really just

00:01:11.580 --> 00:01:14.990
gets things to where the action
is at and then you also

00:01:14.990 --> 00:01:20.070
have your phagocytes, which
are these cells that are

00:01:20.070 --> 00:01:22.810
engulfing things.

00:01:22.810 --> 00:01:24.940
And just so you know, all the
phagocytes that we talked

00:01:24.940 --> 00:01:29.070
about in the last video, these
are all instances of white

00:01:29.070 --> 00:01:30.530
blood cells or leukocytes.

00:01:35.380 --> 00:01:38.670
These phagocytes right here,
these are all-- I talk about

00:01:38.670 --> 00:01:43.320
dendritic cells and macrophages
and neutrophils.

00:01:43.320 --> 00:01:45.900
These were all white
blood cells.

00:01:45.900 --> 00:01:47.740
These weren't all the kinds
of white blood cells.

00:01:47.740 --> 00:01:50.310
We're about to talk about more--
and the other word for

00:01:50.310 --> 00:01:51.920
white blood cell is
also leukocyte.

00:01:55.560 --> 00:01:57.620
So that is nonspecific.

00:01:57.620 --> 00:01:59.660
Well, one, it just doesn't let
you in, but then when you're

00:01:59.660 --> 00:02:01.920
in, it says, hey, you're
just shady.

00:02:01.920 --> 00:02:02.880
I'm going to eat you up.

00:02:02.880 --> 00:02:03.980
I have receptors.

00:02:03.980 --> 00:02:06.170
You have some double stranded
DNA floating around.

00:02:06.170 --> 00:02:08.030
Only viruses have double
strand DNA.

00:02:08.030 --> 00:02:08.949
I'm going to eat you up.

00:02:08.949 --> 00:02:10.550
I don't know what type
of virus you are.

00:02:10.550 --> 00:02:12.400
I don't know if I've seen
you before or not.

00:02:12.400 --> 00:02:14.000
That's why it's nonspecific.

00:02:14.000 --> 00:02:16.130
Now the really interesting
thing about our immune

00:02:16.130 --> 00:02:22.240
system-- and this nonspecific,
this exists across many, many,

00:02:22.240 --> 00:02:28.290
many species and types of
organisms. But the specific is

00:02:28.290 --> 00:02:32.020
kind of a-- it's thought to
be a newer adaptation.

00:02:32.020 --> 00:02:34.450
What I'm going to talk about is
the specific immune system

00:02:34.450 --> 00:02:35.705
that's particular to humans.

00:02:41.120 --> 00:02:42.470
That's our other
classification.

00:02:42.470 --> 00:02:45.060
Let me do it like that.

00:02:45.060 --> 00:02:50.070
So then you have your specific--
or you can imagine

00:02:50.070 --> 00:02:52.690
it's an adaptive
immune system.

00:02:52.690 --> 00:02:54.850
You've probably heard
of things like that.

00:02:54.850 --> 00:03:00.690
I have resistance to that
bacteria or that virus.

00:03:00.690 --> 00:03:03.800
So this is adaptive.

00:03:03.800 --> 00:03:06.800
And it's really all based on
having exposure to things.

00:03:06.800 --> 00:03:12.580
And within the specific immune
system, we talked a little--

00:03:12.580 --> 00:03:16.600
when we talked about the antigen
presenting molecules

00:03:16.600 --> 00:03:18.810
that phagocytes do-- that
plays a role in this.

00:03:18.810 --> 00:03:20.430
We're going to go into more
detail, but I don't want to

00:03:20.430 --> 00:03:21.230
confuse you.

00:03:21.230 --> 00:03:24.300
But the main actors here are
called lymphocytes, not to be

00:03:24.300 --> 00:03:26.570
confused with leukocytes--
because they still are

00:03:26.570 --> 00:03:28.180
leukocytes.

00:03:28.180 --> 00:03:29.430
So let me write this down.

00:03:38.940 --> 00:03:40.060
These are specific.

00:03:40.060 --> 00:03:44.180
Phagocytes, for the most part,
are nonspecific, but both of

00:03:44.180 --> 00:03:45.860
these are white blood cells.

00:03:45.860 --> 00:03:47.630
Lymphocytes are another
type of white

00:03:47.630 --> 00:03:49.850
blood cell or leukocyte.

00:03:49.850 --> 00:03:53.150
Don't want to confuse you with
this convoluted diagram, but I

00:03:53.150 --> 00:03:54.510
just want to make the
terminology clear.

00:03:54.510 --> 00:03:56.350
When someone talks about a
white blood cell, they're

00:03:56.350 --> 00:03:58.380
really just talking about a set
of cells that when people

00:03:58.380 --> 00:04:01.100
first tried to separate the
components of blood-- you'd

00:04:01.100 --> 00:04:03.470
have your red blood cells that
would kind of settle in the

00:04:03.470 --> 00:04:06.040
bottom, then you'd have this
layer of white frothy stuff in

00:04:06.040 --> 00:04:08.840
the middle that was really made
of white blood cells, and

00:04:08.840 --> 00:04:11.660
then on the top, you had the
fluid, the plasma from your

00:04:11.660 --> 00:04:13.000
blood, kind of the
watery part.

00:04:13.000 --> 00:04:15.290
So that's where the name came
from, but they have different

00:04:15.290 --> 00:04:17.350
roles, but they interact
with each other.

00:04:17.350 --> 00:04:24.890
Now lymphocytes can be divided
into B lymphocytes, usually

00:04:24.890 --> 00:04:28.380
referred to as B cells--
and T lymphocytes.

00:04:36.430 --> 00:04:39.350
And the B and T just come from
where they're developed.

00:04:39.350 --> 00:04:42.820
B lymphocytes were first
recognized in

00:04:42.820 --> 00:04:44.820
the bursa of Fabricius.

00:04:44.820 --> 00:04:45.810
That's why it's called B.

00:04:45.810 --> 00:04:48.520
That's actually a part of birds
that participate in the

00:04:48.520 --> 00:04:49.410
immune system.

00:04:49.410 --> 00:04:52.520
And so the B came from bursa,
but B also applies to the

00:04:52.520 --> 00:04:56.380
human immune system because it's
produced in bone marrow.

00:04:56.380 --> 00:04:58.790
So that might be an easier
way to remember.

00:04:58.790 --> 00:05:01.920
It's produced in bone marrow.

00:05:01.920 --> 00:05:08.500
It's developed in bone marrow,
but historically, the B came

00:05:08.500 --> 00:05:11.290
from the bursa of Fabricius,
just in case you want to know.

00:05:11.290 --> 00:05:12.420
But it's easy to remember.

00:05:12.420 --> 00:05:14.720
The B could also stand for bone
marrow because that's

00:05:14.720 --> 00:05:16.000
where it's produced.

00:05:16.000 --> 00:05:18.490
T lymphocytes actually do start
off in the bone marrow,

00:05:18.490 --> 00:05:22.760
but they mature and become what
they are in the thymus.

00:05:22.760 --> 00:05:24.110
So that's where the
T comes from.

00:05:26.780 --> 00:05:29.130
Now in this video, I'm going
to focus just on the B

00:05:29.130 --> 00:05:31.260
lymphocytes-- because frankly,
if I focused on everything, it

00:05:31.260 --> 00:05:32.530
would be an hour-long video.

00:05:32.530 --> 00:05:36.570
But the B lymphocytes frankly on
some level-- well, I don't

00:05:36.570 --> 00:05:39.230
want to pick and choose
favorites, but something in my

00:05:39.230 --> 00:05:41.930
brain-- I just really like
the B lymphocytes.

00:05:41.930 --> 00:05:44.570
So the B lymphocytes participate
in what's called

00:05:44.570 --> 00:05:45.820
the humoral response.

00:05:49.190 --> 00:05:51.050
And I'll tell you what humoral
means in a second.

00:05:58.360 --> 00:06:00.810
You'll see that T lymphocytes
participate in what's called

00:06:00.810 --> 00:06:02.910
the cell mediated response and
we're going to do that in a

00:06:02.910 --> 00:06:04.160
future video.

00:06:07.410 --> 00:06:10.770
They actually do certain classes
of T lymphocytes.

00:06:10.770 --> 00:06:15.470
We'll see that there are helper
T cells and there are

00:06:15.470 --> 00:06:16.950
cytotoxic T cells.

00:06:16.950 --> 00:06:19.370
I know it's all very confusing
the first time you see it, but

00:06:19.370 --> 00:06:21.180
that's why I just want
to focus on just

00:06:21.180 --> 00:06:22.180
this part right here.

00:06:22.180 --> 00:06:25.240
We're going to see in the future
that the helper T cells

00:06:25.240 --> 00:06:28.710
play a role in amplifying
and really activating

00:06:28.710 --> 00:06:30.400
this humoral response.

00:06:30.400 --> 00:06:33.540
But a simple way to think about
the difference between

00:06:33.540 --> 00:06:36.480
the humoral response and the
cell mediated response is,

00:06:36.480 --> 00:06:38.470
when I get infected--
let's say I get

00:06:38.470 --> 00:06:40.485
infected by a virus, right?

00:06:45.610 --> 00:06:48.230
At first, when a virus comes
into my system, it's just

00:06:48.230 --> 00:06:51.710
floating around in the
fluids in my system.

00:06:51.710 --> 00:06:54.330
The fluids of our system--
that's really what humoral

00:06:54.330 --> 00:06:59.800
responds to, into the humoral
fluids of your body.

00:06:59.800 --> 00:07:01.050
So you have your viruses.

00:07:05.050 --> 00:07:08.270
These are little viruses
floating around.

00:07:08.270 --> 00:07:11.740
So while they're floating around
and they're not sitting

00:07:11.740 --> 00:07:17.710
inside of cells, that's where
the humoral response

00:07:17.710 --> 00:07:18.600
can come into play.

00:07:18.600 --> 00:07:22.070
Same thing if we have little
bacteria floating around and

00:07:22.070 --> 00:07:23.860
they haven't infiltrated
cells yet.

00:07:23.860 --> 00:07:27.320
They're just floating around in
the fluid, then the humoral

00:07:27.320 --> 00:07:31.130
response can be useful
for that.

00:07:31.130 --> 00:07:37.730
Now if all of a sudden, these
guys have infiltrated cells--

00:07:37.730 --> 00:07:40.580
so if the cells are now infected
with the virus and

00:07:40.580 --> 00:07:43.570
they're producing the viruses
using the mechanisms of the

00:07:43.570 --> 00:07:46.940
cell to produce more, then all
of a sudden we have to be a

00:07:46.940 --> 00:07:49.950
little bit more sophisticated
in how we deal with these

00:07:49.950 --> 00:07:52.180
cells and how we deal with the
viruses because they're not

00:07:52.180 --> 00:07:53.580
just going to be floating
around anymore.

00:07:53.580 --> 00:07:56.230
We probably want to just kill
this cell even though it was

00:07:56.230 --> 00:07:59.010
one of our own, but now it's
helping to make viruses.

00:07:59.010 --> 00:08:02.260
Or maybe it's been colonized
by bacteria.

00:08:02.260 --> 00:08:03.490
So in either case, you
want to kill this.

00:08:03.490 --> 00:08:07.010
And we'll talk more about that
in the cell mediating.


Role of phagocytes in innate or nonspecific immunity

WEBVTT
Kind: captions
Language: en

00:00:00.650 --> 00:00:08.170
The whole point of the immune
system is to keep out shady

00:00:08.170 --> 00:00:10.950
things from your body-- or, if
they get in, to kill them.

00:00:10.950 --> 00:00:15.680
So those shady things would
include shady proteins that

00:00:15.680 --> 00:00:23.670
can do damage to your body,
viruses, bacteria, even

00:00:23.670 --> 00:00:31.290
eukaryotic parasites,
and then even fungi.

00:00:31.290 --> 00:00:34.770
So all sorts of things that if
they were to enter your body,

00:00:34.770 --> 00:00:37.050
they would cause some
form of disease.

00:00:37.050 --> 00:00:38.500
These are collectively
called pathogens.

00:00:41.730 --> 00:00:44.620
So the whole point of the immune
system is, on a first

00:00:44.620 --> 00:00:47.710
line of defense, keep these
things out-- and then if they

00:00:47.710 --> 00:00:51.480
were to get into your body, to
kill and eliminate them from

00:00:51.480 --> 00:00:53.450
our system so that we don't
get sick and so

00:00:53.450 --> 00:00:54.970
that we don't die.

00:00:54.970 --> 00:00:57.470
So I already just mentioned that
there's kind of two lines

00:00:57.470 --> 00:00:59.510
of defense and even with
those, there's kind of

00:00:59.510 --> 00:01:01.340
subclassifications.

00:01:01.340 --> 00:01:03.800
The first line of defense-- I'll
just call that the first

00:01:03.800 --> 00:01:10.140
line-- which is essentially just
to keep things out-- keep

00:01:10.140 --> 00:01:12.940
all of these pathogens out.

00:01:12.940 --> 00:01:14.260
And there's some obvious ones.

00:01:14.260 --> 00:01:15.410
There's our skin.

00:01:15.410 --> 00:01:19.540
Our skin keeps pathogens out and
actually even the oils on

00:01:19.540 --> 00:01:22.040
our skin are a little bit more
acidic and it's hard for some

00:01:22.040 --> 00:01:27.410
types of bacteria to thrive in
that type of environment.

00:01:27.410 --> 00:01:35.330
You have your mucus membranes
and in the mucus, there's

00:01:35.330 --> 00:01:37.550
there's some chemicals that
maybe make it a little bit

00:01:37.550 --> 00:01:40.310
more difficult for bacteria
to survive.

00:01:40.310 --> 00:01:43.640
And then you even have acidic
environments like

00:01:43.640 --> 00:01:44.890
your stomach acid.

00:01:48.000 --> 00:01:52.120
You might not view your stomach
as the outside of you,

00:01:52.120 --> 00:01:53.310
but it fundamentally is.

00:01:53.310 --> 00:01:55.810
Your whole digestive tract,
which I'll make videos on in

00:01:55.810 --> 00:01:58.840
the near future, is really
on the outside of you.

00:01:58.840 --> 00:02:04.130
You can simply model really most
vertebrate bodies as kind

00:02:04.130 --> 00:02:07.270
of a doughnut our digestive
tract is the

00:02:07.270 --> 00:02:08.289
inside of the doughnut.

00:02:08.289 --> 00:02:14.020
So stomach acid is on the
outside of our real bodies and

00:02:14.020 --> 00:02:16.870
you can imagine, that's a hard
environment for a lot of these

00:02:16.870 --> 00:02:18.570
pathogens to survive in.

00:02:18.570 --> 00:02:20.720
So that's the first line of
defense, but we know that

00:02:20.720 --> 00:02:24.820
that's not good enough, that
sometimes these things can get

00:02:24.820 --> 00:02:27.760
into our bodies, and there we
have to start thinking about

00:02:27.760 --> 00:02:30.750
the second line of defense.

00:02:30.750 --> 00:02:33.540
What do we do once things are
actually in our body?

00:02:44.980 --> 00:02:48.550
And here, in both the first and
second line, I'm talking

00:02:48.550 --> 00:02:51.660
about non-specific immunity--
and this is going to make a

00:02:51.660 --> 00:02:54.290
lot of sense when we start
talking about specific

00:02:54.290 --> 00:02:54.840
immunities.

00:02:54.840 --> 00:02:57.020
So both of these are
non-specific.

00:03:00.630 --> 00:03:03.840
And when I say non-specific--
or you can also call them

00:03:03.840 --> 00:03:09.430
innate-- it means that they
just generally respond to

00:03:09.430 --> 00:03:11.050
things that appear bad.

00:03:11.050 --> 00:03:13.840
They don't remember the bad
things that came before.

00:03:13.840 --> 00:03:16.690
They don't respond to a
particular type of virus or a

00:03:16.690 --> 00:03:20.060
particular-- well, they do
respond to every type of virus

00:03:20.060 --> 00:03:23.270
or every type of bacteria, but
they don't say, this is virus

00:03:23.270 --> 00:03:26.660
type A, B, C, or this is
bacteria type A, B, C.

00:03:26.660 --> 00:03:27.990
They just say, this
is a virus.

00:03:27.990 --> 00:03:30.120
Let me get rid of it, or
let me not let it in.

00:03:30.120 --> 00:03:31.180
This is a bacteria.

00:03:31.180 --> 00:03:33.390
Let me get rid of it or
let me not let it in.

00:03:33.390 --> 00:03:36.950
It doesn't know what type of
bacteria it's dealing with.

00:03:36.950 --> 00:03:39.320
So this is all the
non-specific or

00:03:39.320 --> 00:03:41.630
innate immune system.

00:03:41.630 --> 00:03:44.370
And we'll go into a lot of
detail on the specific immune

00:03:44.370 --> 00:03:45.850
system because you can imagine,
it becomes very

00:03:45.850 --> 00:03:48.760
complicated or interesting when
you start thinking about

00:03:48.760 --> 00:03:51.710
your body somehow remembering a
virus that it's seen before

00:03:51.710 --> 00:03:53.930
and being able to respond better
to that virus or that

00:03:53.930 --> 00:03:57.240
bacteria or that protein the
second time it sees it.

00:03:57.240 --> 00:03:59.580
So we're dealing with
non-specific in this case.

00:03:59.580 --> 00:04:04.080
And the the second line of your
non-specific immunity,

00:04:04.080 --> 00:04:04.790
there are two things.

00:04:04.790 --> 00:04:06.760
One is an inflammatory
response.

00:04:16.910 --> 00:04:20.250
And I'm going to do a whole
video on this, but in general,

00:04:20.250 --> 00:04:23.110
we've all experienced
inflammatory responses.

00:04:23.110 --> 00:04:26.000
When you see blood flowing to a
certain part of an area and

00:04:26.000 --> 00:04:28.010
you see there's pus and
there's-- and I'm going to go

00:04:28.010 --> 00:04:30.280
into a lot more detail on what
an inflammatory response

00:04:30.280 --> 00:04:33.090
actually is, but that's one of
your-- and what it really is

00:04:33.090 --> 00:04:37.250
doing is bringing blood and
bringing cells that can fight

00:04:37.250 --> 00:04:41.450
whatever type of infection you
have. It's bringing them to

00:04:41.450 --> 00:04:45.030
the site where maybe you got a
cut or maybe where a lot of

00:04:45.030 --> 00:04:47.370
the bacteria or whatever
the pathogen is.

00:04:47.370 --> 00:04:50.810
So inflammatory response is all
about bringing fluid and

00:04:50.810 --> 00:04:52.570
fighters to the fight.

00:04:55.210 --> 00:04:56.500
I'm going to do a whole
video on that.

00:05:07.190 --> 00:05:10.070
But the byproduct is, that part
of your tissue or that

00:05:10.070 --> 00:05:12.030
part of you body gets inflamed--
a lot of fluid

00:05:12.030 --> 00:05:16.960
there, a lot of byproducts of
the battle that goes on there.

00:05:16.960 --> 00:05:18.000
We'll do a whole
video on that.

00:05:18.000 --> 00:05:20.100
And the other second line of
defense is, and it's actually

00:05:20.100 --> 00:05:24.940
part of the inflammatory
response-- are phagocytosis or

00:05:24.940 --> 00:05:26.190
phagocytes.

00:05:28.730 --> 00:05:31.120
And really, what I want to do
over the rest of this video is

00:05:31.120 --> 00:05:34.300
talk in a little bit more
detail about phagocytes

00:05:34.300 --> 00:05:37.110
because once we understand what
phagocytes do, that's a

00:05:37.110 --> 00:05:42.350
pretty good building block for
going into the specific immune

00:05:42.350 --> 00:05:45.010
system-- and actually, it'll
help lead into the discussion

00:05:45.010 --> 00:05:47.850
on the inflammatory response as
well because phagocytes are

00:05:47.850 --> 00:05:51.740
really part of the inflammatory
response.

00:05:51.740 --> 00:05:54.460
So phagocytes are just
a class of cell

00:05:54.460 --> 00:05:56.430
that can eat up pathogens.

00:05:56.430 --> 00:05:59.020
They can eat up other things
really, but when we talk about

00:05:59.020 --> 00:06:00.970
the immune system, we're talking
about pathogens.

00:06:00.970 --> 00:06:04.710
So let's say that this is
a phagocyte right here.

00:06:04.710 --> 00:06:07.620
This is a phagocyte
right there.

00:06:07.620 --> 00:06:09.310
It has some kind of a
nucleus, whatever.

00:06:09.310 --> 00:06:12.550
I don't have to focus on the
inside of the phagocyte.

00:06:12.550 --> 00:06:16.210
It's a traditional eukaryotic
cell, but what I want to do is

00:06:16.210 --> 00:06:20.840
see what happens when a
phagocyte encounters a foreign

00:06:20.840 --> 00:06:22.590
particle or a foreign
bacteria.

00:06:22.590 --> 00:06:26.850
So let me say this is a foreign
bacteria right here.

00:06:26.850 --> 00:06:29.940
So the phagocyte, we've already
said, is non-specific.

00:06:29.940 --> 00:06:32.620
What it does is, it has
receptors that respond to just

00:06:32.620 --> 00:06:34.380
things that it knows are bad.

00:06:34.380 --> 00:06:36.426
You could imagine these
are super sensors.

00:06:43.050 --> 00:06:45.410
Maybe these are super sensors
for bacteria.

00:06:45.410 --> 00:06:48.010
The bacteria have proteins on
their surface that maybe look

00:06:48.010 --> 00:06:48.860
something like that.

00:06:48.860 --> 00:06:50.270
Obviously they don't look
exactly like that.

00:06:50.270 --> 00:06:53.240
I'm just drawing them as kind
of a Y and a triangle so you

00:06:53.240 --> 00:06:54.430
can see that they fit.

00:06:54.430 --> 00:06:59.810
But once these two guys
connect-- let me draw the

00:06:59.810 --> 00:07:02.100
situation where they
have connected.

00:07:02.100 --> 00:07:03.310
So this is the bacteria.

00:07:03.310 --> 00:07:04.600
This is the pathogen.

00:07:04.600 --> 00:07:06.670
And it's really the same idea
with a virus or any

00:07:06.670 --> 00:07:07.600
other type of thing.

00:07:07.600 --> 00:07:10.070
And we'll actually see in future
videos that these guys

00:07:10.070 --> 00:07:13.250
can actually be tagged by other
molecules, which makes

00:07:13.250 --> 00:07:17.100
these phagocytes want to
attack them even more.

00:07:17.100 --> 00:07:20.720
Once they're bonded--
that's my bacteria,

00:07:20.720 --> 00:07:21.900
the invading pathogen.

00:07:21.900 --> 00:07:25.590
And now it is bonded.

00:07:25.590 --> 00:07:28.850
It has triggered the receptor
on this phagocyte.

00:07:28.850 --> 00:07:34.540
This phagocyte will start to
engulf-- it'll wrap around

00:07:34.540 --> 00:07:35.790
this pathogen.

00:07:44.140 --> 00:07:48.125
And these two ends are
eventually going to meet.

00:08:00.230 --> 00:08:03.690
But then once these two meet,
what's it going to look like?

00:08:03.690 --> 00:08:09.320
Then all of a sudden, that
bacteria is going to be

00:08:09.320 --> 00:08:10.350
completely engulfed.

00:08:10.350 --> 00:08:11.880
It's going to be inside
of the cell.

00:08:11.880 --> 00:08:15.760
So now the cell-- once these
two ends meet and these

00:08:15.760 --> 00:08:19.070
membranes merge, then this guy
is going to be in his own

00:08:19.070 --> 00:08:21.410
little membrane bubble-- or you
can almost imagine, it's

00:08:21.410 --> 00:08:23.820
in its own little vesicle.

00:08:23.820 --> 00:08:28.370
So this is the pathogen, the
bacteria in this case-- but

00:08:28.370 --> 00:08:31.950
phagocytosis-- the process is
completely identical in terms

00:08:31.950 --> 00:08:33.340
of how it engulfs things.

00:08:33.340 --> 00:08:37.390
If it was a virus or some type
of other foreign protein or

00:08:37.390 --> 00:08:42.010
any type of really foreign
molecule-- actually, sometimes

00:08:42.010 --> 00:08:43.620
it doesn't even occur
to foreign stuff.

00:08:43.620 --> 00:08:47.780
It can occur to dying molecules
that are not

00:08:47.780 --> 00:08:49.310
foreign, that just need
to be cleared out.

00:08:49.310 --> 00:08:51.190
But we'll just focus on the
immune system, on foreign

00:08:51.190 --> 00:08:52.440
things right now.

00:08:54.870 --> 00:08:58.930
So this membrane right here will
completely merge and go

00:08:58.930 --> 00:09:01.520
around this guy like this.

00:09:01.520 --> 00:09:03.800
And of course, you had your
receptors and who knows if

00:09:03.800 --> 00:09:04.910
they're still there.

00:09:04.910 --> 00:09:07.740
By the time-- let's just draw
them there so you see that

00:09:07.740 --> 00:09:08.800
that part is that part.

00:09:08.800 --> 00:09:11.220
But once it's fully engulfed,
this thing is called a

00:09:11.220 --> 00:09:20.240
phagosome, on which is really
just a vesicle that contains

00:09:20.240 --> 00:09:22.740
that foreign particle that
you want to get rid of.

00:09:22.740 --> 00:09:33.660
And then other fluid or vesicles
that contain things

00:09:33.660 --> 00:09:38.800
that can eat up this phagosome--
so let's say that

00:09:38.800 --> 00:09:43.360
this is some vesicle that
contains things-- lysozymes

00:09:43.360 --> 00:09:46.905
and it contains really reactive
species of oxygen.

00:09:50.420 --> 00:09:52.920
And if this comes in contact
with, really, almost any

00:09:52.920 --> 00:09:55.240
biological compound, it's
going to do some damage.

00:09:55.240 --> 00:10:00.360
But once the pathogen is
completely merged inside the

00:10:00.360 --> 00:10:06.530
cell, this little package will
merge over here and it will

00:10:06.530 --> 00:10:11.130
dump its contents into this
phagosome, into this vesicle

00:10:11.130 --> 00:10:15.380
containing the pathogen,
and then break it up.

00:10:15.380 --> 00:10:18.990
It's essentially digesting it.

00:10:18.990 --> 00:10:21.190
So obviously the first role is,
it just got it out of the

00:10:21.190 --> 00:10:22.530
way and it killed it.

00:10:22.530 --> 00:10:24.910
And then the second role-- and
I'm just going to give a

00:10:24.910 --> 00:10:26.230
little tidbit right here.

00:10:26.230 --> 00:10:28.660
We're going to do it in a lot
more detail in future videos.

00:10:28.660 --> 00:10:29.910
It breaks it up.

00:10:38.490 --> 00:10:40.550
So now the thing is
all broken up.

00:10:45.330 --> 00:10:48.930
So that thing is broken up into
constituent proteins and

00:10:48.930 --> 00:10:50.590
another molecules.

00:10:50.590 --> 00:10:57.550
And then what the phagocyte
does-- it'll actually take

00:10:57.550 --> 00:11:02.050
some subset of these
molecules, some

00:11:02.050 --> 00:11:02.990
subset of the proteins.

00:11:02.990 --> 00:11:04.170
It'll break them out.

00:11:04.170 --> 00:11:06.860
Proteins are just sequences
of amino acids.

00:11:06.860 --> 00:11:08.350
Normally when people say
proteins, they're talking

00:11:08.350 --> 00:11:10.580
about long sequences
of amino acids.

00:11:10.580 --> 00:11:13.760
When people talk about short
sequences of amino acids or a

00:11:13.760 --> 00:11:16.820
protein that's broken up a lot,
they refer to it as a

00:11:16.820 --> 00:11:17.710
peptide chain.

00:11:17.710 --> 00:11:20.360
A peptide chain is a shorter
chain of amino acids.

00:11:20.360 --> 00:11:22.880
So this guy will take some
special peptide chains, some

00:11:22.880 --> 00:11:28.160
special pieces from the thing it
just killed, attach them to

00:11:28.160 --> 00:11:29.920
some other proteins.

00:11:29.920 --> 00:11:37.020
So it'll take maybe a little
piece of this bacteria right

00:11:37.020 --> 00:11:45.060
now, attach it to other protein,
which is called a

00:11:45.060 --> 00:11:48.800
major histocompatibility
complex-- and if we're talking

00:11:48.800 --> 00:11:52.650
about phagocytes, this will be
a major histocompatibility

00:11:52.650 --> 00:11:54.140
complex type II.

00:11:59.810 --> 00:12:01.900
It sounds very-- a strange word,
but we're going to see

00:12:01.900 --> 00:12:03.150
this a lot.

00:12:17.110 --> 00:12:20.110
So they abbreviate it MHC.

00:12:20.110 --> 00:12:24.580
This is a protein and it bonds
with this peptide that was

00:12:24.580 --> 00:12:27.510
kind of chunked off or digested
off of this invading

00:12:27.510 --> 00:12:32.820
pathogen and then this phagocyte
will then present it

00:12:32.820 --> 00:12:33.910
onto its membrane.

00:12:33.910 --> 00:12:37.590
So this combination-- the
complex of the MHC-- in this

00:12:37.590 --> 00:12:40.420
case, it's going to be
an MHC II protein.

00:12:44.960 --> 00:12:46.820
We're going to talk about
Type I in the future.

00:12:46.820 --> 00:12:49.920
It's going to take this complex
and then present it on

00:12:49.920 --> 00:12:51.170
its surface.

00:13:01.780 --> 00:13:05.060
And the reason why I'm going
through all this pain of

00:13:05.060 --> 00:13:06.930
explaining this process-- you're
like, hey, we already

00:13:06.930 --> 00:13:08.340
got rid of the thing
and killed it.

00:13:08.340 --> 00:13:11.240
Why is Sal worried about what
we do with the peptides?

00:13:11.240 --> 00:13:14.780
This is crucial to our immune
system because we'll see other

00:13:14.780 --> 00:13:16.590
specific parts of our
immune system.

00:13:16.590 --> 00:13:19.590
Remember, so far everything
is non-specific.

00:13:19.590 --> 00:13:21.290
This guy just said, this
is an invader.

00:13:21.290 --> 00:13:22.900
It doesn't know the type
of an invader.

00:13:22.900 --> 00:13:26.900
It just says, hey, let me bond
to this thing and kill it.

00:13:26.900 --> 00:13:30.270
It's one of these things that I
know are foreign to my body.

00:13:30.270 --> 00:13:33.880
So it kills it, but now it can
leave it on its surface and

00:13:33.880 --> 00:13:36.460
now the specific parts, the
parts that actually have

00:13:36.460 --> 00:13:40.450
memory and attack specific
things, can say, gee, Mr.

00:13:40.450 --> 00:13:42.600
Phagocyte, look, you've
killed something.

00:13:42.600 --> 00:13:46.260
Let me see if I have some
specific reactions that can be

00:13:46.260 --> 00:13:48.420
triggered by this thing that
you're presenting.

00:13:48.420 --> 00:13:51.000
So, many phagocytes
are also called

00:13:51.000 --> 00:13:52.590
antigen presenting cells.

00:14:00.120 --> 00:14:03.260
And I'm going to go into more
detail on what exactly an

00:14:03.260 --> 00:14:04.640
antigen is.

00:14:04.640 --> 00:14:06.340
I called this thing
a pathogen.

00:14:06.340 --> 00:14:10.950
An antigen is essentially-- you
can view it as a protein

00:14:10.950 --> 00:14:15.750
or a peptide chain that will
trigger or that can be dealt

00:14:15.750 --> 00:14:16.830
with within the immune system.

00:14:16.830 --> 00:14:19.720
I'll be a little bit-- the
specific immune system.

00:14:19.720 --> 00:14:22.170
And I'm going to be a little bit
more nuanced about it when

00:14:22.170 --> 00:14:24.150
I talk-- I'll make a whole
video on antigens and

00:14:24.150 --> 00:14:27.810
antibodies, but right now you
can just view it as a peptide

00:14:27.810 --> 00:14:28.620
chain right there.

00:14:28.620 --> 00:14:31.660
An antigen is just a protein
or part of a protein.

00:14:31.660 --> 00:14:34.390
So this is presenting an antigen
on its surface that

00:14:34.390 --> 00:14:37.220
can later be used
by other parts.

00:14:37.220 --> 00:14:41.720
Now, the one thing that-- there
are many, many types of

00:14:41.720 --> 00:14:42.470
phagocytes.

00:14:42.470 --> 00:14:45.300
And just to give you-- just so
when you see different words,

00:14:45.300 --> 00:14:48.250
you don't get confused by the
different types of phagocytes.

00:14:48.250 --> 00:14:50.860
I'll do a little review
of those right now.

00:14:50.860 --> 00:14:52.110
You have neutrophils.

00:14:54.850 --> 00:14:58.340
These are actually the most
common of the phagocytes.

00:14:58.340 --> 00:15:01.120
And these are the fast and
numerous respondors.

00:15:01.120 --> 00:15:10.880
So these get to a location
of infection very fast.

00:15:10.880 --> 00:15:13.900
Phagocytes don't necessarily
just have to kill in this way.

00:15:13.900 --> 00:15:15.620
I mean, they're called
phagocytes because they engulf

00:15:15.620 --> 00:15:17.930
this way, but we'll in future
videos talk about other ways

00:15:17.930 --> 00:15:20.840
that they can release chemicals
or even DNA nets to

00:15:20.840 --> 00:15:23.540
ensnare pathogens,
but neutrophils

00:15:23.540 --> 00:15:25.210
are fast and abundant.

00:15:25.210 --> 00:15:30.610
And then you have macrophages,
which are-- on some level,

00:15:30.610 --> 00:15:32.800
they're the most versatile and
do the heavy lifting, but

00:15:32.800 --> 00:15:34.560
they're also phagocytes.

00:15:34.560 --> 00:15:38.130
And then you dendritic cells.

00:15:38.130 --> 00:15:40.460
And when you first see the
word dendritic cell, you

00:15:40.460 --> 00:15:42.520
think, hey, does this somehow
relate to dendrites of the

00:15:42.520 --> 00:15:43.390
nervous system?

00:15:43.390 --> 00:15:46.740
And no, they have nothing to
do with the nervous system.

00:15:52.720 --> 00:15:54.100
The reason why they're called
dendritic cells is because

00:15:54.100 --> 00:15:55.350
they look like they
have dendrites.

00:16:03.190 --> 00:16:05.640
So they look like neurons on
some level, but they don't

00:16:05.640 --> 00:16:08.130
participate in the nervous
system at all.

00:16:08.130 --> 00:16:11.610
And these tend to be the best
activators of the specific

00:16:11.610 --> 00:16:14.920
immune system that we'll talk
about in future videos.

00:16:14.920 --> 00:16:16.680
So anyway, I'll leave you there
and we'll talk more

00:16:16.680 --> 00:16:19.690
about all of this in the
next few videos.


Anatomy of a muscle cell

WEBVTT
Kind: captions
Language: en

00:00:00.000 --> 00:00:03.170
I think we have a respectable
sense of how muscles contract

00:00:03.170 --> 00:00:04.520
on the molecular level.

00:00:04.520 --> 00:00:08.080
Let's take a step back now and
just understand how muscles

00:00:08.080 --> 00:00:10.720
look, at least structurally, or
how they relate to things

00:00:10.720 --> 00:00:12.375
that we normally associate
with muscles.

00:00:12.375 --> 00:00:16.140
So let me draw a flexing
bicep right here.

00:00:18.890 --> 00:00:21.940
That's their elbow and
let's say that's

00:00:21.940 --> 00:00:23.540
their hand right there.

00:00:23.540 --> 00:00:25.435
So this is their bicep
and it's flexing.

00:00:28.130 --> 00:00:30.890
I think we've all seen diagrams
of what muscles look,

00:00:30.890 --> 00:00:33.820
at least on kind of a macro
level and it's connected to

00:00:33.820 --> 00:00:36.010
the bones at either end.

00:00:36.010 --> 00:00:39.090
Let me draw the bones.

00:00:39.090 --> 00:00:41.060
I'm not going to detail where--
so it's connected to

00:00:41.060 --> 00:00:43.060
the bones at either
end by tendons.

00:00:43.060 --> 00:00:49.610
So this right here would
be some bone.

00:00:49.610 --> 00:00:52.910
Right there would be another
bone that it's connected to.

00:00:52.910 --> 00:00:56.330
And then this is tendons, which
connects the bones to

00:00:56.330 --> 00:00:57.580
the muscles.

00:01:02.620 --> 00:01:04.560
We have the general sense--
connected to two bones, when

00:01:04.560 --> 00:01:07.310
it contracts it moves some part
of our skeletal system.

00:01:07.310 --> 00:01:09.025
So we're actually focused
on skeletal muscles.

00:01:12.780 --> 00:01:15.660
The other types are smooth
muscles and cardiac muscles.

00:01:15.660 --> 00:01:19.280
Cardiac muscles are those, as
you can imagine, in our heart.

00:01:19.280 --> 00:01:23.000
And smooth muscles are-- these
are more involuntary, slow

00:01:23.000 --> 00:01:25.610
moving muscles and things like
our digestive tract.

00:01:25.610 --> 00:01:27.740
And I'll do video on that in
the future, but most of the

00:01:27.740 --> 00:01:30.330
time when people say muscles,
we associate them with

00:01:30.330 --> 00:01:33.545
skeletal muscles that move our
skeletal system around, allow

00:01:33.545 --> 00:01:38.720
us to run and lift and talk
and do and bite things.

00:01:38.720 --> 00:01:40.940
So this is what we normally
associate-- let's dig in a

00:01:40.940 --> 00:01:41.960
little bit deeper here.

00:01:41.960 --> 00:01:45.670
So if I were to take a cross
section of this bicep right

00:01:45.670 --> 00:01:50.130
there-- if I were to take a
cross section of that muscle

00:01:50.130 --> 00:01:52.285
right there-- so let
me do it big.

00:02:06.760 --> 00:02:11.400
And then it looks something
like this.

00:02:11.400 --> 00:02:16.020
This is the inside of this
muscle over here.

00:02:16.020 --> 00:02:17.960
Now I said back here,
we had our tendon.

00:02:22.400 --> 00:02:25.880
And then there's actually a
covering; there's no strict

00:02:25.880 --> 00:02:29.100
demarcation or dividing line
between the tendon and the

00:02:29.100 --> 00:02:35.100
covering around this muscle,
but that covering is called

00:02:35.100 --> 00:02:42.060
the epimysium and it's really
just connective tissue that

00:02:42.060 --> 00:02:45.450
covers the muscle, kind of
protects it, reduces friction

00:02:45.450 --> 00:02:49.120
between the muscle and the
surrounding bone and other

00:02:49.120 --> 00:02:52.620
tissue that might be in this
person's arm right there.

00:02:52.620 --> 00:02:56.960
And then within this muscle, you
have connective tissue on

00:02:56.960 --> 00:02:57.980
the inside.

00:02:57.980 --> 00:02:59.570
Let me do it in another color.

00:02:59.570 --> 00:03:00.820
I'll do it in orange.

00:03:17.600 --> 00:03:21.460
This is called a perimyseum,
and that's also just

00:03:21.460 --> 00:03:23.860
connective tissue inside
of the actual muscle.

00:03:28.980 --> 00:03:32.780
And then each of these things
that the perimysium is

00:03:32.780 --> 00:03:37.700
dividing off-- let me say if we
were to take one of these

00:03:37.700 --> 00:03:40.410
things and allow it to go a
little bit further-- so if we

00:03:40.410 --> 00:03:43.870
were to take this thing right
here-- what this perimysium is

00:03:43.870 --> 00:03:45.800
dividing off-- and if we were to
pull it out-- actually, let

00:03:45.800 --> 00:03:47.260
me do this one right here.

00:03:47.260 --> 00:03:51.600
If we were to pull this one out
just like that-- so you

00:03:51.600 --> 00:03:55.050
have the perimysium surrounding
it, right?

00:03:55.050 --> 00:03:57.840
This is all perimysium, and
it's just a fancy word for

00:03:57.840 --> 00:04:00.630
connective tissue.

00:04:00.630 --> 00:04:01.600
There's other stuff in there.

00:04:01.600 --> 00:04:03.940
You could have nerves and you
could have capillaries, all

00:04:03.940 --> 00:04:07.920
sorts of stuff because you have
to get blood and neuronal

00:04:07.920 --> 00:04:10.150
signals to your muscles of
entry so it's not just

00:04:10.150 --> 00:04:10.680
connective tissue.

00:04:10.680 --> 00:04:13.800
It's other things that have to
be able to eventually get to

00:04:13.800 --> 00:04:14.950
your muscle cells.

00:04:14.950 --> 00:04:19.320
So each of these-- I guess you'd
call it subfibers, but

00:04:19.320 --> 00:04:23.220
these are pretty big subfibers
of the muscle.

00:04:23.220 --> 00:04:24.470
This is called a fascicle.

00:04:35.650 --> 00:04:39.600
The connective tissue inside of
the fascicle is called the

00:04:39.600 --> 00:04:40.850
endomysium.

00:04:45.320 --> 00:04:48.680
So once again, more connective
tissues, has capillaries in

00:04:48.680 --> 00:04:52.650
it, has nerves in it, all of
the things that have to

00:04:52.650 --> 00:04:57.370
eventually come in contact
with muscle cells.

00:04:57.370 --> 00:05:00.015
We're inside of a
single muscle.

00:05:04.850 --> 00:05:07.320
All this green connective
tissue is endomysium.

00:05:12.740 --> 00:05:16.220
And each of these things that
are in the endomysium are an

00:05:16.220 --> 00:05:18.240
actual muscle cell.

00:05:18.240 --> 00:05:20.150
This is an actual muscle cell.

00:05:20.150 --> 00:05:21.320
I'll do it in purple.

00:05:21.320 --> 00:05:24.700
So this thing right here-- I can
pull it out a little bit.

00:05:30.380 --> 00:05:37.110
If I pull this out, this is
an actual muscle cell.

00:05:37.110 --> 00:05:38.990
This is what we wanted to get
to, but we're going to go even

00:05:38.990 --> 00:05:43.610
within the muscle cell to see,
understand how all the myosin

00:05:43.610 --> 00:05:45.920
and the actin filaments fit
into that muscle cell.

00:05:45.920 --> 00:05:48.595
So this right here is a muscle
cell or a myofiber.

00:05:51.440 --> 00:05:53.970
The two prefixes you'll see
a lot when dealing with

00:05:53.970 --> 00:05:58.010
muscles-- you're going to see
myo, which you can imagine

00:05:58.010 --> 00:05:59.710
refers to muscle.

00:05:59.710 --> 00:06:01.990
And you're also going to see
the word sarco, like

00:06:01.990 --> 00:06:05.930
sarcolemma, or sarcoplasmic
reticulum.

00:06:05.930 --> 00:06:09.970
So you're also go see the
prefix sarco and that's

00:06:09.970 --> 00:06:13.980
flesh-- so sarcophagus-- or you
can think of other things

00:06:13.980 --> 00:06:14.900
that start with sarco.

00:06:14.900 --> 00:06:16.850
So sarco is flesh.

00:06:16.850 --> 00:06:18.760
Muscle is flesh and
myo is muscle.

00:06:18.760 --> 00:06:20.220
So this is myofiber.

00:06:20.220 --> 00:06:22.650
This is an actual muscle cell
and so let's zoom in on the

00:06:22.650 --> 00:06:23.320
actual muscle.

00:06:23.320 --> 00:06:27.490
So let me actually draw it
really a lot bigger here.

00:06:27.490 --> 00:06:30.570
So an actual muscle cell
is called a myofiber.

00:06:30.570 --> 00:06:34.760
It's called a fiber because it's
longer than it is wide

00:06:34.760 --> 00:06:37.380
and they come in various--
let me draw the

00:06:37.380 --> 00:06:38.880
myofiber like this.

00:06:45.600 --> 00:06:48.200
I'll take a cross section of
the muscle cell as well.

00:06:52.620 --> 00:06:57.110
And these can be relatively
short-- several hundred

00:06:57.110 --> 00:07:00.520
micrometers-- or it could be
quite long-- at least quite

00:07:00.520 --> 00:07:02.500
long by cellular standards.

00:07:02.500 --> 00:07:06.340
We're talking several
centimeters.

00:07:06.340 --> 00:07:07.160
Think of it as a cell.

00:07:07.160 --> 00:07:08.330
That's quite a long cell.

00:07:08.330 --> 00:07:10.760
Because it's so long,
it actually has to

00:07:10.760 --> 00:07:12.770
have multiple nucleuses.

00:07:12.770 --> 00:07:15.280
Actually, to draw the nucleuses,
let me do a better

00:07:15.280 --> 00:07:17.470
job drawing the myofiber.

00:07:17.470 --> 00:07:21.510
I'm going to make little lumps
in the outside membranes where

00:07:21.510 --> 00:07:25.740
the nucleuses can fit
on this myofiber.

00:07:25.740 --> 00:07:29.330
Remember, this is just one of
these individual muscle cells

00:07:29.330 --> 00:07:32.760
and they're really long so they
have multiple nucleuses.

00:07:32.760 --> 00:07:34.600
Let me take its cross section
because we're going to go

00:07:34.600 --> 00:07:36.800
inside of this muscle cell.

00:07:36.800 --> 00:07:40.210
So I said it's multinucleated.

00:07:40.210 --> 00:07:43.340
So if we kind of imagine its
membrane being transparent,

00:07:43.340 --> 00:07:46.930
there'd be one nucleus over
here, another nucleus over

00:07:46.930 --> 00:07:49.200
here, another nucleus
over here, another

00:07:49.200 --> 00:07:50.170
nucleus over there.

00:07:50.170 --> 00:07:53.630
And the reason why it's
multinucleated is so that over

00:07:53.630 --> 00:07:55.830
large distances, you don't have
to wait for proteins to

00:07:55.830 --> 00:07:57.980
get all the way from this
nucleus all the way over to

00:07:57.980 --> 00:07:59.090
this part of the muscle cell.

00:07:59.090 --> 00:08:03.020
You can actually have the DNA
information close to where it

00:08:03.020 --> 00:08:03.680
needs to be.

00:08:03.680 --> 00:08:04.850
So it's multinucleated.

00:08:04.850 --> 00:08:08.735
I read one-- I think it was 30
or so nucleuses per millimeter

00:08:08.735 --> 00:08:10.700
of muscle tissue is what
the average is.

00:08:10.700 --> 00:08:12.680
I don't know if that's actually
the case, but the

00:08:12.680 --> 00:08:17.370
nucleuses are kind of right
under the membrane of the

00:08:17.370 --> 00:08:19.610
muscle cell-- and you remember
what that's called from the

00:08:19.610 --> 00:08:21.010
last video.

00:08:21.010 --> 00:08:23.040
The membrane of the muscle
cell is the sarcolemma.

00:08:31.380 --> 00:08:32.630
These are the nucleuses.

00:08:36.770 --> 00:08:43.690
And then if you take the cross
section of that, there are

00:08:43.690 --> 00:08:47.070
tubes within that called
myofibrils.

00:08:47.070 --> 00:08:53.300
So here there's a bunch
of tubes inside

00:08:53.300 --> 00:08:54.210
of the actual cell.

00:08:54.210 --> 00:08:56.380
Let me pull one of them out.

00:08:56.380 --> 00:08:58.050
So I've pulled out one
of these tubes.

00:08:58.050 --> 00:08:59.300
This is a myofibril.

00:09:04.390 --> 00:09:07.360
And if you were to look at this
under a light microscope,

00:09:07.360 --> 00:09:11.380
you'll see it has little
striations on it.

00:09:11.380 --> 00:09:14.190
the striations will look
something like that, like

00:09:14.190 --> 00:09:17.560
that, like that, and there'll
be little thin ones

00:09:17.560 --> 00:09:19.110
like that, like that.

00:09:19.110 --> 00:09:24.200
And inside of these myofibrils
is where we'll find our myosin

00:09:24.200 --> 00:09:25.260
and actin filaments.

00:09:25.260 --> 00:09:28.170
So let's zoom in over here
on this myofibril.

00:09:28.170 --> 00:09:31.910
We'll just keep zooming until we
get to the molecular level.

00:09:31.910 --> 00:09:36.300
So this myofibril, which is--
remember, it's inside of the

00:09:36.300 --> 00:09:39.220
muscle cell, inside
of the myofiber.

00:09:39.220 --> 00:09:41.090
The myofiber is a muscle cell.

00:09:41.090 --> 00:09:45.640
Myofibral is a-- you can view
it as a tube inside of the

00:09:45.640 --> 00:09:46.580
muscle cell.

00:09:46.580 --> 00:09:48.390
These are the things that
are actually doing the

00:09:48.390 --> 00:09:49.600
contraction.

00:09:49.600 --> 00:09:53.270
So if I were to zoom in on a
myofibril, you're going to see

00:09:53.270 --> 00:09:56.830
it-- it's going to look
something like that and it's

00:09:56.830 --> 00:09:59.020
going to have those
bands in it.

00:09:59.020 --> 00:10:01.040
So the bands are going to look
something like this.

00:10:01.040 --> 00:10:05.445
You're going to have these
short bands like that.

00:10:09.710 --> 00:10:14.170
Then you're going to have wider
bands like that, like

00:10:14.170 --> 00:10:18.020
these little dark-- trying my
best to draw them relatively

00:10:18.020 --> 00:10:20.410
neatly and there could be a
little line right there.

00:10:20.410 --> 00:10:24.670
Then the same thing
repeats over here.

00:10:24.670 --> 00:10:26.100
So each of these units of

00:10:26.100 --> 00:10:30.030
repetition is called a sarcomere.

00:10:37.050 --> 00:10:39.550
And these units of repetition go
from one-- this is called a

00:10:39.550 --> 00:10:43.490
Z-line to another Z-line.

00:10:43.490 --> 00:10:46.060
And all of this terminology
comes out of when people just

00:10:46.060 --> 00:10:48.430
looked under a microscope and
they saw these lines, they

00:10:48.430 --> 00:10:50.070
started attaching names to it.

00:10:50.070 --> 00:10:52.450
And just so you have the other
terminology-- we'll talk about

00:10:52.450 --> 00:10:55.060
how this relates to the myosin
and the actin in a second.

00:10:55.060 --> 00:10:57.330
This right here is the A-band.

00:11:00.720 --> 00:11:03.410
And then this distance right
here or these parts right

00:11:03.410 --> 00:11:06.850
here, these are called
the I-bands.

00:11:06.850 --> 00:11:09.380
And we'll talk about really in a
few seconds how that relates

00:11:09.380 --> 00:11:12.610
to the mechanisms or the units
that we talked-- or the

00:11:12.610 --> 00:11:14.300
molecules that we talked about
in the last video.

00:11:14.300 --> 00:11:17.710
So if you were to zoom in here,
if you were to go into

00:11:17.710 --> 00:11:20.440
these myofibrils, if you were
to take a cross section of

00:11:20.440 --> 00:11:24.060
these myofibrils, what you'll
find is-- if you were to cut

00:11:24.060 --> 00:11:28.960
it up, maybe slice it-- if you
were slice it parallel to the

00:11:28.960 --> 00:11:32.190
actual screen that you're
looking at, you're going to

00:11:32.190 --> 00:11:33.660
see something like this.

00:11:33.660 --> 00:11:35.390
So this is going to
be your Z-band.

00:11:41.110 --> 00:11:42.540
This is your next Z-band.

00:11:42.540 --> 00:11:45.160
So I'm zooming in on
sarcomere now.

00:11:45.160 --> 00:11:49.560
This is another Z-band.

00:11:49.560 --> 00:11:53.290
Then you have your
actin filaments.

00:11:53.290 --> 00:11:54.920
Now we're getting to that
molecular level

00:11:54.920 --> 00:11:56.170
that I talked about.

00:12:17.000 --> 00:12:20.250
And then in between the actin
filaments, you have your

00:12:20.250 --> 00:12:22.910
myosin filaments.

00:12:27.700 --> 00:12:30.540
Remember, the myosin filaments
had those two heads on them.

00:12:30.540 --> 00:12:36.670
They each have two heads like
that, that crawl along the

00:12:36.670 --> 00:12:37.390
actin filaments.

00:12:37.390 --> 00:12:39.260
I'm just drawing a couple of
them and then they're attached

00:12:39.260 --> 00:12:41.810
at the middle just like that.

00:12:41.810 --> 00:12:43.680
We'll talk about in a second
what happens when the muscle

00:12:43.680 --> 00:12:46.650
actually contracts.

00:12:46.650 --> 00:12:48.070
And I could draw it
again over here.

00:12:51.060 --> 00:12:53.440
So it has many more heads than
what I'm drawing, but this

00:12:53.440 --> 00:12:55.070
just gives you an idea
of what's happening.

00:13:00.010 --> 00:13:03.320
These are the myosin, I guess,
proteins and they all

00:13:03.320 --> 00:13:05.660
intertwined like we saw in the
previous video and then

00:13:05.660 --> 00:13:08.460
there'll be another
one over here.

00:13:08.460 --> 00:13:09.950
I don't have to draw
in detail.

00:13:09.950 --> 00:13:12.890
So you can see immediately that
the A-band corresponds to

00:13:12.890 --> 00:13:15.032
where we have our myosin.

00:13:15.032 --> 00:13:17.260
So this is our A-band
right here.

00:13:20.100 --> 00:13:23.680
And there is an overlap.

00:13:23.680 --> 00:13:27.780
They do overlap each other, even
in the resting state, but

00:13:27.780 --> 00:13:30.070
the I-band is where you
only have actin

00:13:30.070 --> 00:13:31.740
filaments, no myosin.

00:13:36.070 --> 00:13:39.410
And then the myosin filaments
are held in place by titin,

00:13:39.410 --> 00:13:44.460
which you can kind of imagine
as a springy protein.

00:13:44.460 --> 00:13:46.186
I want to do it in a different
color than that.

00:13:52.020 --> 00:13:54.520
So the myosin is held
in place by titin.

00:13:58.310 --> 00:14:00.790
It's attached to the
Z-band by titin.

00:14:00.790 --> 00:14:01.760
So what happened?

00:14:01.760 --> 00:14:07.340
So we have all of these-- when
a neuron excites-- so let me

00:14:07.340 --> 00:14:10.600
draw an endpoint of a neuron
right here, the endpoint of an

00:14:10.600 --> 00:14:12.470
axon of a neuron right there.

00:14:12.470 --> 00:14:13.280
It's a motor neuron.

00:14:13.280 --> 00:14:14.960
It's telling this
guy to contract.

00:14:14.960 --> 00:14:16.670
You have the action potential.

00:14:16.670 --> 00:14:21.460
The action potential travels
along the membrane, really in

00:14:21.460 --> 00:14:22.580
all directions.

00:14:22.580 --> 00:14:24.860
And then it eventually, if we
look at it from this view,

00:14:24.860 --> 00:14:29.690
they have those little
transverse or T-tubules.

00:14:29.690 --> 00:14:35.860
They essentially go into the
cell and continue to propagate

00:14:35.860 --> 00:14:37.140
the action potential.

00:14:37.140 --> 00:14:41.980
Those trigger the sarcoplasmic
reticulum to release calcium.

00:14:41.980 --> 00:14:46.580
The calcium attaches to the
troponin that's attached to

00:14:46.580 --> 00:14:50.340
these actin filaments that moves
the tropomyosin out of

00:14:50.340 --> 00:14:52.290
the way, and then the
crawling can occur.

00:14:52.290 --> 00:14:55.130
The myosin can start
using ATP to crawl

00:14:55.130 --> 00:14:57.060
along these actin filaments.

00:14:57.060 --> 00:15:03.210
And so as you can imagine, as
they crawl along, their power

00:15:03.210 --> 00:15:07.050
stroke is going to push-- you
can either view it as the

00:15:07.050 --> 00:15:10.130
actin filaments in that way or
you can say that the myosin is

00:15:10.130 --> 00:15:12.490
going to want to move in that
direction, but you're pulling

00:15:12.490 --> 00:15:14.440
on both sides of
a rope, right?

00:15:14.440 --> 00:15:18.040
So the myosin is going to stay
in one place and the actin

00:15:18.040 --> 00:15:19.715
filaments are going to
be pulled together.

00:15:22.610 --> 00:15:25.740
And that's essentially how the
muscle is contracting.

00:15:25.740 --> 00:15:28.830
So we've, hopefully, in this
video, connected the big

00:15:28.830 --> 00:15:32.230
picture from the flexing muscle
all the way over here

00:15:32.230 --> 00:15:34.920
to exactly what's happening at
the molecular level that we

00:15:34.920 --> 00:15:36.000
learned in the last
few videos.

00:15:36.000 --> 00:15:39.500
And you can imagine, when this
happens to all of the

00:15:39.500 --> 00:15:42.850
myofibrils inside of the muscle,
right, because the

00:15:42.850 --> 00:15:45.550
sarcoplasmic reticulum's
releasing calcium generally

00:15:45.550 --> 00:15:49.690
into the cytoplasm of-- which
is also called myoplasm,

00:15:49.690 --> 00:15:52.110
because we're dealing with
muscle cells-- the cytoplasm

00:15:52.110 --> 00:15:54.370
of this muscle cell.

00:15:54.370 --> 00:15:57.210
The calcium floods all
of these myofibrils.

00:15:57.210 --> 00:16:00.910
It's able to attach to all of
the troponin-- or at least a

00:16:00.910 --> 00:16:05.305
lot of the troponin on top of
these actin filaments and then

00:16:05.305 --> 00:16:07.000
the whole muscle contracts.

00:16:07.000 --> 00:16:11.340
And then when that's done, each
muscle fiber, myofiber,

00:16:11.340 --> 00:16:13.030
or each muscle cell
will not have that

00:16:13.030 --> 00:16:14.350
much contracting power.

00:16:14.350 --> 00:16:16.930
But when you couple it with all
of them that are around

00:16:16.930 --> 00:16:19.040
it-- if you just have one,
actually, working, or a few of

00:16:19.040 --> 00:16:20.240
them, you'll just
have a twitch.

00:16:20.240 --> 00:16:22.710
But if you have all of them
contracting together, then

00:16:22.710 --> 00:16:25.270
that's actually going to create
the force to actually

00:16:25.270 --> 00:16:28.420
do some work, or actually pull
your bones together, or lift

00:16:28.420 --> 00:16:28.920
some weights.

00:16:28.920 --> 00:16:31.980
So hopefully you found
that mildly useful.