So what is IgE in terms of its relationship to human disease
normally, and where do we find it
and how much of it do we have?
Well, out of the five different
classes of antibody, it’s the one
that usually is present in the serum at the lowest concentration.
And in fact we only have about
100ng/ml of circulating IgE.
Contrast this with IgG where
the concentration is 15mg/ml.
So really, incredibly small
amounts of IgE in the circulation.
In fact it doesn’t last very
long at all in the circulation.
It has a half life of around
about two and a half days.
However once it becomes bound to that high
affinity FcεR1 on the surface of mast cells,
it is stabilized from being degraded and it then
has a half life of around about 12 weeks.
It is part of normal physiological
So you find IgE elevated in certain parasitic
diseases, for example schistosomiasis.
You find it in an abnormal pathological
situation, such as the hyper-IgE syndrome, which
is a primary immunodeficiency where is there--
where there is defective production of gamma
interferon, and therefore there is an increased
level of interleukin-4, because remember Th1
cells that produce gamma interferon down-regulate
the activity of Th2 cells that produce IL-4.
So in the absence of gamma interferon
production, there’ll be increased Th2
activity and therefore increased
production of the cytokine interleukin-4.
And of course we also find elevated levels of IgE in
allergy which is what we’re discussing at this moment.
Class switching to IgE is promoted by the cytokines
interleukin-4 and interleukin-13 which come from
Th2 cells, and as I’ve already mentioned, is
inhibited by gamma interferon produced by Th1 cells.
Let’s have a look at how
mast cells become activated.
The IgE is coating a resting
mast cell, nothing will happen.
Everything is absolutely fine.
But if the antigen cross links the IgE bound to the FcεR1,
there is antigen activation of the mast cell, there is
the production of histamine and lipid mediators leading to
vascular smooth muscle response and immediate reaction.
And cytokines are produced which result in
inflammation causing the late phase reaction.
The mediators that are produced, we’ve
already mentioned some of these.
The biogenic amines such as histamine
which can cause vasodilation.
The lipid mediators such as platelet
activating factor or PAF, prostaglandin D2,
leukotriene C4; these can cause
bronchoconstriction, intestinal hypermotility.
Cytokines such as TNF, lipid
mediators again - platelet activating
factor, prostaglandin D2, leukotriene C4 can cause inflammation.
And finally enzymes such as
tryptase can cause tissue damage.
The cationic granule proteins that are
released from eosinophils can also contribute.
So it’s not only mast cells that are contributing
to the pathology but also eosinophils as well.
And substances like major basic protein
and eosinophil cationic protein which
are normally there to kill parasites
can also cause death of host cells.
And enzymes such as eosinophil peroxidase
can also result in tissue damage.
If we look at the airways in chronic
allergic inflammation, we can
see that there are Th2 cells that
migrate into the bronchial wall.
We can see that smooth muscle becomes hypertrophic,
and that there is excessive mucus which reduces airflow.
Eosinophils migrate to the
bronchus and into the lumen.
And enzymes damage the