00:01
That's been a flavour of
type two hypersensitivity.
00:06
We're going to now kind of go
into type three hypersensitivity
which will continue in
the next lecture as well.
00:12
So this is immune
complex disease
related to antigen
antibody complex formation.
00:19
I'm showing you an
example of administering
a particular antigen
at a very high level.
00:27
Then this could be in
an experimental animal,
it could be giving
them a foreign albumin.
00:34
In humans,
we actually did this back in the day
when we were
administering horse serum
that contained antibodies
against the theria.
00:43
And we were trying to
cure patients of having
diptheria toxin
induce cellular death.
00:51
And we would give
those antibodies,
and that would block the dip
there and it worked great.
00:54
It was a neutralizing
antibodies.
00:56
But in that horse serum
that we were administering to the patients
to save their lives from diptheria,
there are a lot of other horse proteins
in particular horse serum albumin.
01:07
So we would give a large
dose to the patients.
01:10
And we would notice it pretty
reliably after we did that.
01:14
Usually on the second dose,
seven to 10 days later,
we got a profound joint
inflammatory response,
a skin rash,
patients could have even
had difficulty breathing.
01:26
And it turns out, it's all due to
the formation of immune complexes.
01:30
So here at times, here, we've administered
a very large dose of a particular antigen,
let's say horse serum albumin,
and it has a long
circulating half life
and will eventually be
of various mechanisms,
including filtration,
destruction,
and formation of immune
complexes go away.
01:49
So at times zero,
we administer the antigen.
01:53
Fairly reliably because the
immune system is working,
we are developing
antibodies to that antigen.
01:59
And we will begin formulating immune
complexes by about day six to seven.
02:05
The formation of
those immune complexes
means we have less than less than
less of the free antigen circulating
and eventually everything
goes away at 14 days.
02:12
And obviously,
the immune complex is due too.
02:15
Kind of midway at that point as
we're forming immune complexes
about they can or so.
02:20
If we were measuring it,
we would see that the
complement level in this patient
who received this massive
dose of an antigen,
the complement level is
beginning to diminish.
02:30
That's because
it's being consumed
due to the formation
of immune complexes
that are activating
the complement cascade.
02:40
At about 14 days,
we have lots and lots
of free antibody,
but there's no more
antigen around.
02:47
So that's why we have free antibody
and all the antigen has gone away.
02:52
But what was noticed,
and what happens pretty reliably
is about between a date days,
eight and 14 before all
the complexes go away,
we started getting all
these immune manifestations.
03:03
We get a rash,
we get joint pain,
we have a variety of
inflammatory things.
03:09
That's due to immune
complex deposition.
03:12
So as we form immune complexes,
they're depositing in
various vascular beds,
activating complement,
recruiting FC receptor bearing cells.
03:20
Again, in a predictable way.
03:24
The reason that we're starting to
see a lot of disease at this point
is because we are in a zone where we
have a lot of small immune complexes.
03:34
Those small immune complexes
are not very easily cleared,
but they will induce complement
activation when they deposit.
03:40
They will activate FC receptor
bearing cells as they deposit.
03:46
So with that,
we've set the stage to talk about
immune complex mediated disease,
which will be part
of the next session.