00:01
Okay, so kind of a
big broad overview.
00:04
If at times zero here
on the left hand side,
we have some sort of injury or
infection or damage, whatever,
we will start with the
innate immune response.
00:15
And the innate immune response
is a number of kind of barriers
and inflammatory components.
00:24
Notably too, on this slide,
you'll see at the top,
a microbe has come in and
presumably started an infection.
00:30
I could also
equally put in there
a new allograft, a new heart,
it would be the same pathways,
or I could put up there,
I could put a foreign body,
a hip implant,
it would be similar pathways.
00:44
Okay, but I'm just gonna be
talking about microbes for now.
00:47
But keep in mind,
it could be anything at the beginning.
00:51
The microbes first has to get
past the epithelial barrier,
that's part of the
innate immune system.
00:57
And there are a number of proteins that
are elaborated by epithelial barriers,
that can be a first kind of barrier
in the way of a microbial infection,
there are a number of cells
that are going to be important.
01:10
And these are going
to be the phagocytes,
neutrophils and macrophages
that are going to be a very important
part of the initial innate response.
01:20
There are also proteins as we're going
to learn about complement proteins.
01:24
A series of over 20
different proteins
that end up providing us with
protective responses to pathogens.
01:32
And then one final cell type
that doesn't always get mentioned
is the natural killer
cell or the NK cell.
01:39
And I've liken this to
a very deranged person
who has somehow got
their hands on an AK-47.
01:46
If they do not see
a friendly face,
they will fire indiscriminately,
so they can cause,
they can very quickly eliminate some
infections and potentially cause damage.
01:57
Those are our innate
immune elements,
and they are first on the scene.
02:01
And within the first 24 hours are
pretty effective against 90, maybe 95%,
of whatever trauma is going on
and we never need to get the
adaptive immune system into the fray.
02:13
But if they're not able to
get things taken care of,
then over the next days,
the stage will be set for the
recruitment and activation
of the specific or
adaptive immune system.
02:28
The top part of that
are B lymphocytes,
so they will be able
to respond to antigen
to proliferate and
to make antibody.
02:38
And T lymphocytes,
whether they're killer T cells,
or helper T cells in the various
helper T cell populations,
they will be able to respond.
02:47
And then make cytokines to
drive the effector functions
of the innate immune system.
02:54
So it is a collaboration,
it starts first with the
innate immune system.
02:59
And if they're not
able to finish the job,
they set the stage and instruct
the adaptive immune
responses that will follow.
03:07
Now, there's also
feedback the other way.
03:10
So the adaptive immune
response is very good.
03:12
It's incredibly selective,
we can generate 10 to the 10th
different antigenic specificities.
03:20
That's pretty remarkable.
03:23
It's specific, but it's not
entirely completely powerful.
03:28
And the way that the
two systems work in,
in synchrony together is that
the adaptive immune system
will rely upon the
innate immune system
to provide the heavy lifting,
to do a lot the bulk of the,
of the microbial
destruction, for example.
03:47
So what's been shown up here
now, in the upper left corner,
is kind of the activation of complement
that occurs at a very low level,
but at a reasonably good
level for most pathogens.
04:00
And that occurs through interactions
with bacterial cell wall components.
04:05
So the bacteria is that
little green thing,
and now we've killed it
by binding compliment,
that occurs at some efficiency,
it's not great, it's not bad.
04:13
It's not terrific, however,
if we bind antibody first.
04:17
So the little green antibodies,
if we bind antibody
made from AB cell first
to that microbe,
we get much, much, much 10 to 10,000
fold better activation the complement.
04:33
And when that occurs,
we get a much better bang for our buck.
04:37
So it's the same pathways.
04:39
It's the same
complement activation,
but it's just much
more efficient
if we have an
antibody bound first.
04:46
Similarly,
for the cellular components,
so macrophages at a
reasonably good level
will ingest recognise and ingest
phagocytized and degrade microbes.
04:58
But I can do that 10,000 times.
Better
if I activate a T cell and it makes
cytokines such as interferon gamma
that will drive the macrophages
to do their job better.
05:09
So, the innate immune
system comes first,
handles the majority
of the cases.
05:16
If it doesn't complete the job,
it then sets the stage for
the adaptive immune system
and even instructs the
adaptive immune system
about whether it's going
to make more antibody
or more cytotoxic T
lymphocyte response.
05:29
And then once the innate immune
system has set the stage,
the T cells and the B cells are on board
and they're starting their activity.
05:38
They in turn,
cross talk back to
the innate system
to do the heavy lifting.
05:44
So with that broad overview,
hopefully I've
whetted your appetite.
05:48
You're going to be very excited about
hearing about immune mediated injury
and we will move on.