I’ve already mentioned that genetics are
important in the development of allergy.
So let’s take a couple of minutes to look at
some of the genes that have been identified.
Polymorphisms of genes encoding Pattern Recognition
Receptors have been described in patients with allergy.
So have polymorphisms in the gene encoding
the cytokine thymic stromal lymphopoietin.
Polymorphisms of the MHC
particularly HLA-DQ polymorphisms.
And polymorphisms in the
transcription factor SMAD3.
Other polymorphisms that have been described
are ones for the genes encoding the
interleukin-2 receptor β-chain, and indeed
for the cytokine itself interleukin-2.
As well as polymorphisms of the genes for the
interleukin-33 receptor and for interleukin-33.
And as these reactions get going with the
dendritic cell stimulating Th2 cells.
And with the involvement perhaps of induced regulatory
T-cells trying to dampen down the allergic response.
If the balance goes towards the development
of an allergic response, the Th2 cells will become
dominant with the production of cytokines such
as interleukin-4, interleukin-5, interleukin-13.
Eosinophils will be stimulated,
B-cells will be stimulated.
Those B-cells will class switch to IgE production
differentiate into plasma cells that will
secrete the IgE antibody that is so characteristic
of the Type I hypersensitivity reaction.
This will then bind to the FCεR1,
the high affinity IgE receptor.
And maybe you won’t be too surprised
to hear that polymorphisms in that
particular receptor have also been linked
to the development of allergic disease.
And again, mast cells just like Th2 cells have
a receptor for interleukin-33 and therefore
that polymorphism is acting at several
different levels during the allergic response.
And again, TSLP is influential in modulating the activity
of mast cells, just like it can act on dendritic cells.