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Welcome.
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The topic for today is to begin
looking at the inflammatory response
that occurs
in the setting of injury,
and specifically necrosis.
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Acute inflammation
is going to be the first step.
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And so for this topic,
we're going to do kind of
an overview to understand
where acute inflammation fits
into the total scheme of things.
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Inflammation is actually divided
into two components:
Innate immunity,
and adaptive immunity.
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Adaptive immunity are
T and B cells.
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And we'll come back to those
in a subsequent set of discussions.
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Today, we're going to be talking
mostly almost exclusively about
innate immunity.
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And the components
of innate immunity
are acute and chronic.
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Okay, easy enough.
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And that really has to do with
when they appear?
And how long they last?
And are they early or are they late?
So there are various components
in the acute and chronic
inflammatory response.
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That's where we're headed today.
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Inflammation: Innate immunity
is happens because it anticipates
that if we have necrosis,
if we have injury
that has caused cell death,
that was one,
either caused by an infection,
and there are nasty infectious
pathogens roaming around,
or that zone of necrosis
can be very soon infected.
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Necrotic tissue
is a beautiful culture medium.
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And if we don't get rid of that,
bacteria that are in the environment
can set up shop in there
and then we're in a world
of trouble.
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So we have this innate immunity
to deal with necrosis.
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Again, assuming that
it's either caused by infection
or will soon be infected.
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So the goals of innate immunity.
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The goals of this
inflammatory response
is to subdue any infection
that might be there. That's one.
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Number two,
it's to remove necrotic debris
because we don't want to leave
dead stuff lying around,
because that could be a source
for subsequent infection.
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So we want to
clean up the mess.
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And then if at all possible,
number three,
restore normal function.
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So that's the goal of inflammation.
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And it works pretty well
for about 90% of infections,
and works pretty well
for a lot of necrotic injury.
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Too cool.
That's where we are.
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Okay, so acute inflammation.
Big picture things.
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It's the first responder.
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It occurs within hours to days
after an injury.
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The major cell
that's going to be involved
is shown on the right hand side.
It's the neutrophil.
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It's called a neutrophil
because the granules within it
in this white blood cell,
don't stain well
with our typical stains,
so they are neutral.
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The neutrophil is also called
a polymorphonuclear leukocyte.
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that's because
the nuclear component,
as you see there
can be in multiple forms and shapes.
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So it's a polymorphonuclear cell.
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And it can also be called a PMN
polymorphonuclear, or a poly.
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So there are lots of different names
that we will use.
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And I'll try to stick
with neutrophil
as we're going through this,
but just so you're aware.
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So the neutrophil is the major cell
that's involved
in the acute inflammatory response.
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It's the major player.
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Here, it's shown
in the bloodstream.
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It's shown amongst
a bunch of red blood cells,
but it actually can crawl out
and do its job in the tissue.
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So it has the ability
to have mobility.
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The acute inflammatory response
getting back over
to our bulleted points,
there's an
initial vascular change.
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The vessels in an area
where there is inflammation
where there's been necrosis
become dilated,
and they have
increased permeability.
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This is to improve blood flow
into that area.
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To deliver more neutrophils
and more of the mediators
that neutrophils will provide.
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The cells that are there,
the neutrophils
are very short-lived.
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In fact, they die within a day
after they're synthesize
on the bone marrow.
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They die within 10 hours
after they crawl out
of the bloodstream
and start doing their job.
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So they're
very short lived cells.
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And that's part of the beauty
of the acute inflammatory response,
it goes away pretty quickly
because the length of the cells
that get the length and duration
of survivability of the cells
that crawl out,
is pretty short.
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They do their job
in part by eating
but in part by making
very potent short-lived mediators.
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Important point about this
is that those short-lived mediators
don't care
what they're acting on.
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They will do damage
not only to bugs, pathogens,
but they can also potentially
do damage to host tissues.
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So they work really well
for sterilizing the wound,
but they can cause
a lot of bystander injury.
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They sterilize the site,
that's why they're there.
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And they also begin the process
of degrading the debris.
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They release a lot of proteases.
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Again, proteases don't care
what protein they're acting on,
they're just going to be
degrading them.
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So you can have specific destruction
of things that are necrotic.
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But you may also get destruction
of normal tissues
that are in the vicinity.
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So there may be bystander injury.
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The neutrophils
are going to set the stage
for the subsequent
chronic inflammation
that's on the next slide.
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So they are first on the scene
and they kind of set the stage.
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Next players in the sequence.
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And these form the major cells
of chronic inflammation
are the monocyte-macrophage lineage.
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So it's the second response,
chronic inflammation comes later.
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That's why it's chronic,
and it persists.
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It can last for days, or weeks,
or months or even years,
depending on the circumstance.
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It is driven largely by
the monocyte.
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Here we see the monocyte,
which is the precursor
to the macrophage.
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In the bloodstream,
it circulates as this kind of
bilobed larger cell,
that once it crawls out of the
bloodstream and into the tissue
can become a very
long-lived macrophage.
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And the macrophage
in the tissues can live
for the lifespan of the host.
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So these as opposed
to neutrophils,
which only live
a very short period of time,
these can live potentially forever.
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This is a macrophage.
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After it's crawled out
into the tissue,
and it's out there
with a variety of other cell types,
it's a very granular cell.
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We will spend
a whole bunch of time
talking about the macrophage.
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So never fear,
we will revisit this cell,
and he will become
your good friend.
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Macrophages
do part of their job
by making potent,
short-lived mediators.
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So much like the neutrophil,
they secrete proteases and
a variety of other mediators
that can be extremely potent
in doing their job.
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And are usually short-lived,
but they have the potential
for bystander injury.
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They are the definitive
clean-up crew.
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So the first ones on the scene,
the neutrophils do a lot of it,
but not all of it.
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And then the macrophages
will be the final ultimate cleaner.
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They also will orchestrate
subsequent stages.
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So we've now cleaned up
all the necrotic mess.
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Now what?
Well, we either have
to heal and regenerate that tissue
if we can,
or we need to make scar.
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We can't just leave a vacuum.
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And the people who are
going to coordinate this...
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the cell that's going to
coordinate this, orchestrate this
be the field marshal
is going to be the macrophage.
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Okay, so we will spend as they say,
a lot more time
talking about macrophages
when we talk about
the inflammatory process.