Type II hypersensitivity is antibody
against cell surface antigens.
Examples of Type II hypersensitivity
include transfusion reactions,
autoimmune hemolytic anemia, pernicious
anemia, hemolytic disease of
the fetus and newborn, autoimmune
thrombocytopenic purpura, acute rheumatic
fever, Goodpasture syndrome, Graves’
disease and myasthenia gravis.
There are antibody-mediated effects due to
these antibodies binding to cell surfaces.
This can lead to complement activation, and the activation
of other white blood cells, in other words leukocytes.
This results in complement and Fc
receptor-mediated inflammation and tissue injury.
Alternatively, antibody-mediated effects may result in abnormal
physiological responses without cell and tissue injury.
Two examples are given here.
On the left hand side, we can see in an individual with
a particular type of autoimmune disease called thyroid
autoimmune disease, more specifically Graves’ disease
which is one type of thyroid autoimmune disease.
That this individual has antibodies that are
binding to the thyroid stimulating hormone
receptor, the TSH receptor that is present
on the surface of thyroid epithelial cells.
These autoantibodies, because they are antibodies being
produced against a self antigen, the TSH receptor.
These antibodies stimulate the receptor
without needing any TSH there at all.
So there’s a constant stimulation of the thyroid
gland and an overproduction of thyroid hormone.
On the right hand side of the slide, you
will see that in this case there are
autoantibodies to the acetylcholine receptor,
which is found at the neuromuscular junction.
And these autoantibodies result in another type of
autoimmune disease, in this instance myasthenia gravis.
The antibody inhibits binding of the
ligand to the receptor, in other
words it gets in the way of
acetylcholine binding to its receptor.
And it also has a secondary effect of causing the
loss of receptors from the surface of the muscle cell.
A very familiar situation to all of you I’m
sure, is the fact that if you need a blood
transfusion, you need cross matching of the
blood between the donor and the recipient.
And the most important blood group
antigens for eliminating transfusion
reactions is to make sure you cross
match the ABO group of antigens.
As you can see in this diagram, these antigens
are based upon sugars that are linked together.
The sugar N-acetyl-galactosamine,
N-acetyl-glucosamine, fucose and galactose.
Individuals that are blood group A have on the
surface of their red blood cells, the A antigen.
They produce antibodies, natural
antibodies, ones that occur in the
absence of any obvious stimulation,
against blood group B antigen.
So why do they do this?
Well it seems that there are many common
microorganisms that we come across that
have structures that are rather similar
and we produce these natural antibodies.
So because they are Type A, in other
words have A antigen; that’s a self
antigen, they’re tolerant to that
antigen, but they’re not tolerant to B.
So they make anti-B.
In contrast, people who are blood group B will have the B
antigen on their surface and they will make anti-A antibody.
Individuals that are group AB possess both A and B antigen, and
therefore they don’t produce any
antibodies against either A or B.
In contrast, individuals that are group O, lack both A
and B antigens, and therefore they produce these
natural antibodies that have the potential to
recognize both the A and the B blood group antigen.
So in a transfusion reaction, if an individual is blood
group A or O and therefore will possess anti-B antibodies.
If they are given blood of either type
B or of type AB which will have both the
A and also importantly in this case
the B antigen, they will cause lysis.
The IgM antibodies will cause lysis
of the transfused erythrocytes.
And likewise, an individual that is
blood group B or O will have anti-A and
therefore would lyse any transfused
cells from a blood group A or blood group AB donor.
There’s a condition that is referred to as hemolytic disease
of the fetus and newborn (Rhesus D incompatibility).
This is a situation where a
mother is Rhesus D negative.
She lacks the Rhesus D
blood group antigen.
But her partner is Rhesus D positive, and therefore
the fetus has Rhesus D positive red blood cells.
This is not a problem whatsoever
during the first pregnancy.
There is very little mixing of the fetal
and maternal circulation, and there is
not a substantial amount of fetal red cells
that enter the maternal circulation.
However, during labour there is a
significant release of fetal red blood cells
into the maternal circulation during the
rupture of the placental membranes.
Therefore, the mother gets exposed to these Rhesus D
red blood cells which to her are foreign antigens.
She’s Rhesus D negative, so she recognizes Rhesus
D as being foreign and makes an antibody response.
And the fetal red cells survive long enough
to elicit this IgG antibody response.
Now, this is also not a
problem at this point in time.
The baby has been born, so it’s now not
exposed to the maternal antibodies.
And the mother herself is Rhesus D negative, so it doesn’t
really matter that she’s got some anti Rhesus D antibody.
However, a significant problem arises, is if
during a subsequent pregnancy the partner is
again Rhesus D positive, because now the maternal
anti-D antibodies can cross the placenta.
Because one of the things that the mother does of benefit to
her fetus, is to transfer IgG antibodies across the placenta.
Most of those antibodies will be good antibodies against
common pathogens that the mother is coming across.
And obviously any pathogens that the fetus
will come across have gone through the mom.
So this will be really
But in this instance, amongst all those
good antibodies, there are also some bad
antibodies, in respect that these are anti-Rhesus
D and the infant is Rhesus D positive.
And these transferred antibodies will
attack the fetal red cells, leading to the
development of this condition called
hemolytic disease of the fetus and newborn.
However, this condition is now incredibly rare because
of a very simple procedure which is Rhesus D prophylaxis.
So at 28 weeks of pregnancy, and
then again within 72 hours of birth,
the mother is injected with antibodies against Rhesus D which is
essentially cover up the Rhesus D
antigen on the fetal erythrocytes
so that they are not able to sensitize
the mother’s immune system.