00:01
Welcome back.
00:03
As part of our series of
talks about the immune system,
we're going to delve a little bit
deeper into elements of innate immunity,
and talk about some of the
details because they're important,
not only to recognise about
how these various components
work as part of innate immunity,
but also to understand
potential therapeutic targets.
00:22
So this is all going to
be about innate immunity.
00:24
And we'll talk about a few cells
and we'll talk about complement.
00:28
First up are the mast cells.
00:30
So these are derived from
bone marrow precursors
that circulate and then
get into the tissue
and kind of live in the tissue
for the lifetime of the host.
00:39
You can think of
them as sentinels
that are sitting out
there in the tissue
waiting to be stimulated to
say, hey,
something's happened,
we need to respond.
00:49
So, what I'm showing you
here now is that mast cell,
and it has on its surface,
and I've specific receptor
for immunoglobulin E antibody,
so, this is the FC
epsilon receptor,
and it binds immunoglobulin E.
01:07
So, some of you will
already recognise
that immunoglobulin E
is part of allergies.
01:11
That's exactly right.
01:12
IGE will be a major element that
will drive the allergic responses,
everything from asthma, pollen,
dander, allergies, or anaphylaxis.
01:25
So, mast cells are pre loaded
with the IGE antibodies
with different specificities.
01:33
And when they recognise
a polyvalent antigen,
such as you're seeing there.
01:37
Polyvalent means
the same antigen
along a long string
of backbone protein,
such as would be
cockroach dander
or cockroach protein,
or dusts or pollens.
01:50
Then the IGE,
already pre loaded onto the
surface of the mast cell
now triggers mast
cell to degranulate.
01:57
And you can see the granules
being released into that area.
02:00
That's going to be the major
driving force for allergies,
anaphylaxis, asthma.
02:07
But there are other ways that
we can activate mast cells.
02:10
So we can do direct activation.
02:12
It turns out that
certain protein fragments
coming from the complement
activation cascade
as we'll talk about at the end
of this little series here,
can activate mast
cells directly.
02:25
Polly basic compounds,
these are things that are present
for example, in bee venom,
can activate mast
cells directly,
certain neuro peptides,
even the cold.
02:34
So those of you who go out into
the stone frolic in the snow,
but your nose runs
like a faucet.
02:39
That's because your mast
cells are degranulating,
releasing their compounds
into the adjacent tissue
and are causing increased
vascular permeability
and increased vasodilation.
02:50
So that's why your nose
runs like a faucet,
you just have wisi mast cells
that cannot hold their granules
in when you can make them cold.
02:58
So you can have specific
activation through IGE
and a variety of other pathways
to activate the mast cells.
03:04
After all,
we want them to be good sentinels
detecting potential danger
in the local environment.
03:10
So what happens when
mast cells are activated?
So they release their mediators.
03:16
There's an early a very early release
that includes histamine and serotonin.
03:21
That histamine and serotonin
will cause vasodilation
and increased
vascular permeability.
03:26
So that's one set of mediators
released by the sentinel mast cells.
03:32
They will also make leukotrienes
they will make arachidonic
acid metabolites
that can have effects
on airway tone,
and can cause
bronchoconstriction.
03:43
So those of you who suffer from
asthma or know about asthma,
that being driven
by the mast cells,
it's because it's causing the airways
to constrict and become very tight.
03:52
So the, the poor person who's
got asthma has got Airways,
that is if they are trying to breathe
through very tiny little straws.
04:03
And one of the other mediators are
a number of the other mediators
are going to cause
inflammatory cell recruitment
and their activation.
04:12
So there are cytokines
and chemokine
being elaborated over a period
of time by the mast cells
that will be also important
for recruitment and activation
of both innate and
adaptive immune elements.
04:25
So these are very good
sentinels out in the tissue
and will do a number of things
that are very important to the
early inflammatory response.
04:33
That's the mast cell.