00:01
Big picture items 2.
00:03
So innate inflammation
is triggered by "danger."
And I have in quotes right now,
but we will talk in a bit
about what danger is?
Does the cell read a sign
that says danger?
Is there a siren that goes off?
No.
00:16
But there are various things
that are released
in areas of necrosis
that tell the neutrophil
and the macrophage
that there is something wrong.
00:26
So, they are brought in
and respond to, "danger."
So basically necrotic stuff.
00:34
The inflammatory response,
this innate inflammation,
proceeds in waves.
00:39
It is not...
00:41
they start, they come on,
and they go away,
that doesn't happen.
00:45
It's actually kind of
a bell-shaped curve
for over the period of time
that they occur, and they overlap.
00:52
So neutrophils
are first on the scene.
00:54
You see them spike there.
00:56
And then after a couple days,
there's not a signal that says
"More neutrophils.
We want them to come in."
In general,
we move on to the next phase,
which is going to be
the definitive cleanup,
and that's the macrophage.
01:06
So they progress in waves.
01:09
And that's important
because if we look
at a certain time point,
we may see both
neutrophils and macrophages
overlapping.
01:16
And that's okay.
01:17
That's part of how they come in
and do their job.
01:21
They do their job also
by amplification cascades.
01:25
So a single neutrophil,
or a single macrophage
can't do very much.
01:30
But a single neutrophil,
if it recruits
additional neutrophils
can do a lot
because now there's a little army
of neutrophils.
01:39
Or if a neutrophil makes a mediator
that then cleaves
other protease of proteins,
and makes other mediators,
which make other mediators,
which make other mediators,
pretty soon, we have a whole bunch
of mediators from a single cell.
01:52
So cascades, amplification cascades
are an important feature
of the immune response.
01:57
And it takes a little while
to get up to a level of activity
that we can actually see.
02:03
Really important.
02:04
This is one of those
important biological concepts.
02:07
There's a yin and a yang.
There's a pro and an anti.
02:10
And at the same moment
that we're doing
pro-inflammatory things
to clean up an area
and start the healing process,
we are also doing
anti-inflammatory things.
02:20
We are balancing that.
02:22
And if we don't have a good balance
between pro and anti,
we can have a lot of damage.
02:27
In fact, that's the last point.
02:29
These guys,
neutrophils and macrophages
make a lot of mediators,
they don't care
what they're acting on.
02:35
They're not specific for bacteria,
or any other pathogen,
or not even for necrotic debris.
02:41
They will potentially cause damage
to normal tissues in the vicinity.
02:46
So they do have
to be carefully regulated
to keep that from happening.