Previously we talked about
immediate type hypersensitivity
or type 1 hypersensitivity
driven by immunoglobulin E.
Now we're going to talk about type 2,
which are due to immunoglobulin antibody
bound to fixed
So type two hypersensitivity.
Let's see how this happens.
If I have a cell that I happen
to have antibody bind to,
that will activate complement and we
will get on the surface of the cell C3b.
Remember C3b is
one of those fragments
that gets generated during
the activation of complement.
Antibody binding either to
the C3b or to the initial antigen
is going to cause
opsonization and lisis.
So, here we have a macrophage,
that's got an Fc receptor,
bound now to the antibody that
is recognised a particular antigen
or via the C3b receptor
and that macrophage
is going to ingest,
degrade and kill that cell.
So, we can imagine
that if this orange blob
all the way on the
left is a red cell,
then I'm going to have
the loss of those red cells
by having an antibody
that binds to it.
Which is exactly
what we have here.
When we talk about
autoimmune hemolytic anaemia.
We have a red cell, it's got
a variety of surface antigens.
And if we break tolerance, or if we have
antibodies to those surface molecules,
we will bind the antibody.
How might that happen?
Well, in fact, if we give
the wrong blood group,
we've give an A type
blood to a B type person,
they will have
circulating A antibodies,
which will bind to the
surface of the red cell.
That binding of the antibody
will cause complement activation
and deposition with
rupture the cells.
So that's the autoimmune
but we've also made
these cells tasty.
We've opsonized them by
binding complements C3b
and by having an antibody
present with a rearranged Fc portion,
and it will be pulled out.
Those cells will be
pulled out by macrophages
as they go through
the liver and the spleen.
So that's what happens if we
have antibodies against red cells.
And it can be a
It can be due to mom having
antibodies against baby's Rh.
Or it could be a primary autoimmune
disorder, autoimmune hemolytic anaemia.
What does this look like?
Not only is the patient anaemic,
we're destroying red cells,
were eating up red cells,
were fragmenting red cells.
So there's lower numbers of red
cells, but we're also getting fragments.
And the arrow that's pointing to
that funny looking red cell at the top
is actually identifying a cell that
was coated with antibody and C3b.
And as it went through the gauntlet of
macrophages in the red pulp in the spleen,
bits and pieces of that
red cell got nibbled away at.
And so we have, in
fact, just the sides.
We've got fragmented red cells, and that's
just an example on our peripheral smear.
Okay, that's on
That one's pretty easy
to wrap our minds around.
But what about antigen that's on a
tissue, such as a basement membrane.
So here we have a basement
membrane that's indicated along the bottom
and we have particular
proteins that are inserted into it.
And oh my goodness, now we have
antibodies that are bound to those.
Those antibodies will have
rearrangement of the Fc portion
and now neutrophils
things that have Fc
receptors will be able to bind.
We will also by virtue of having that
antibody bound activate complement.
So we're going to get
that will settle down onto the surface
including C3b and bind to those proteins,
while also make
So C3a and C5a that will activate
mast cells and recruit neutrophils
So we'll get neutrophils that come
in response to the complement.
But we will also have
the cells trying to ingest
what is functionally a very large
surface and they won't be able to do so.
So they'll be dumping their
mediators, their proteases,
their arachidonic acid
metabolites directly onto the tissue,
potentially causing damage.
Remember, our old
friend the natural killer cell,
has on its surface Fc receptors
that can bind to bound antibody
on the surface of a target.
So the NK cell,
as you see there,
is interacting with the orange
blob in the upper right hand corner
so called antibody dependent
cell mediated cytotoxicity.
So binding antibody to tissues will
cause cell death in that way as well.
And this notion of frustrated phagocytosis
is pretty important to understand.
So here, this is a normal
neutrophil with something it can eat.
It can get its
So it's recognised that
microbe via antibody bound to it,
or via complement
And it now will
and it will be able to get
it completely enclosed.
And now, it can fuse lysosomes with that
phagosomes and destroy whatever it ate.
That's great for smaller things but if
we an antibody binding to big things,
like a basement membrane, neutrophil
comes up, and wants to do same thing.
It's binding through its Fc receptor
and its complement receptor
and it's ready to rock and roll except
that it can't ever get it all inside.
So now what it does is it basically
spews its lysosomal content
on to the surface.
It's frustrated phagocytosis,
it can't get its arms around it.
And now I will get damaged because
of the release of extracellular enzymes
and other mediators
on to the tissue.
Oh my god, does this happen?
Oh yes, it does.