00:01
I’ve already mentioned that genetics are
important in the development of allergy.
00:06
So let’s take a couple of minutes to look at
some of the genes that have been identified.
00:13
Polymorphisms of genes encoding Pattern Recognition
Receptors have been described in patients with allergy.
00:22
So have polymorphisms in the gene encoding
the cytokine thymic stromal lymphopoietin.
00:30
Polymorphisms of the MHC
particularly HLA-DQ polymorphisms.
00:37
And polymorphisms in the
transcription factor SMAD3.
00:42
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.
00:54
As well as polymorphisms of the genes for the
interleukin-33 receptor and for interleukin-33.
01:02
And as these reactions get going with the
dendritic cell stimulating Th2 cells.
01:09
And with the involvement perhaps of induced regulatory
T-cells trying to dampen down the allergic response.
01:17
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.
01:29
Eosinophils will be stimulated,
B-cells will be stimulated.
01:33
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.
01:47
This will then bind to the FCεR1,
the high affinity IgE receptor.
01:53
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.
02:02
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.
02:16
And again, TSLP is influential in modulating the activity
of mast cells, just like it can act on dendritic cells.