Right, now having given you a little overview of those four
different types, let’s now look
in a bit more detail at each one.
So Type I hypersensitivity -
IgE-mediated mast cell degranulation.
You’ve already seen this picture.
So these Type I hypersensitivity reactions,
IgE-mediated mast cell degranulation.
That’s what we usually think of as
allergic types of responses, allergy.
And this type of response often
referred to as atopy, an inappropriate
production of IgE antibodies is caused
by a multitude of different factors.
Genetics is important, but other
factors also are important.
Regarding the genes, there is not a
single dominant allergy gene; it’s rather
that several genes contribute to the
development of the allergic process.
Amongst them, the gene encoding the FcεR1, the gene
encoding the cytokine interleukin-4 which is very important
in causing B-cells to class switch to IgE production,
CD14, HLA-DR, there are a number of different genes.
So it’s really the combination of genes that’s
important, not any one single specific gene.
And of course the environment is also very important,
it’s not a purely genetic situation we have here.
And early microbial exposure, and early allergen exposure
perhaps in the uterus seem to play an important role.
Immune responsiveness overall is abnormal, with a decreased
production of gamma interferon, and perhaps overall a more Th2
type of environment with those Th2 cells that secrete cytokines
such as interleukin-4 and interleukin-5 and interleukin-6.
They’re the more dominant population.
And remember, all of these
responses are normal responses.
So a Type I hypersensitivity reaction is based upon
something that is a normal protective immune response.
For example against a
parasitic worm infection.
If you have a parasitic worm infection in
your gut for example, you’d be very grateful
to having this sort of response because it
would help expel the worms from the gut.
However in a substantial minority of
individuals, IgE-mediated mast cell
degranulation occurs in response to what
should be a harmless environmental antigen.
And afterall, grass pollen is not going to
cause you any harm, but in a significant
number of people, there’s a response to
this that actually leads to pathology.
Maybe you yourself
suffer from allergies.
You’ll certainly know people that
do, because it’s a very common
affliction of people to suffer from these allergic reactions.
In Type I hypersensitivity, there’s an immediate IgE
response, but this resolves within around about an hour.
However it is frequently followed by
what is referred to as the late phase reaction.
This occurs around
about 4-12 hours later.
And it involves CD4+ helper T-cells,
monocytes and eosinophils becoming activated.
So there are a number of different types of atopic allergy,
that is allergy caused by excessive production of IgE.
Rhinoconjunctivitis which you may know as hay
fever, affects around about 20-35% of individuals.
Asthma affects around about 10-20%
of individuals, atopic eczema again
around about 20% of individuals,
urticaria similar kinds of numbers,
food allergy maybe around about 3-5%
of individuals develop food allergy,
and insect venom hypersensitivity
in about one in a hundred people.
We use the term anaphylaxis to describe a
severe systemic hypersensitivity to allergen
in an injection, a sting or by epithelial
exposure, for example in the gut mucosa.
It involves a rapid vasodilation which leads
to a substantial drop in blood pressure.
There is constriction of the airways, edema and
anaphylactic shock can result that is often fatal.
However, immediate administration
of epinephrine can reverse the
bronchoconstriction and vasodilation and rescue the patient.
Let’s have a look at some of the mediators that mast cells
produce that contribute towards the inflammatory process.
We can divide these
mediators into two groups.
Ones that have already been made by the mast cell
and are stored within granules within the mast cell.
And then newly synthesized mediators
that are made from arachidonic acid.
Histamine is the classical mast
cell inflammatory mediator.
It causes smooth muscle contraction and
an increase in vascular permeability.
Heparin is produced and stored in
granules, and this is an anticoagulant.
And eosinophil chemotactic factor is a
third example of a pre-made mediator stored
in the granules, and this as its name
suggests mediates eosinophil chemotaxis.
So all these substances are ready to go, and the second the
mast cell degranulates, they can mediate their effects.
Regarding the newly synthesized mediators,
prostaglandin D2, prostaglandin E2 and prostaglandin
F2α can mediate smooth muscle contraction and
increase vascular permeability just like histamine.
Leukotriene B4 is a chemotactic
factor for neutrophils.
And leukotriene C4, D4 and E4 cause
smooth muscle contraction and
vascular permeability again just like the
prostaglandins and the histamine.
Let’s look at how the leukotrienes
and prostaglandins are synthesized.
They are both produced from phospholipids, by the use
of phospholipase A2 to generate arachidonic acid.
Then either via the lipoxygenase pathway which
produces leukotrienes or via the cyclooxygenase pathway
involving COX1 and COX2 which produces prostaglandins,
these mediators are generated within the mast cell.
This is a list of allergens.
You’ll be very familiar with
many of these I am sure.
So they include things like pollens, things
associated with animals like animal dander,
house dust mites and so forth, molds, various
chemicals, and a number of food allergens.