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hypersensitivity
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Hypersensitivity.Allergy and hypersensitivity.
Allergy is one type of hypersensitivity.
Allergic reactions (hypersensitivity reactions) are increasing in the western world.
This could be due to improved hygiene in certain areas of the world.
This is called the hygiene hypothesis.
Where our very clean environment, as a result of improved hygiene, of vaccination,
of antibiotics, means that we don’t have to defend ourselves against normal immune
challenges, infectious immune challenges.
Because of this our immune system will overrespond to imaginary foes, things that it
does not really need to respond to, innocuous antigens.
Where parasites are endemic, these are the areas where allergies are rare.
Allergies are mediated by IgE, which is normally developed within us to respond to
parasites.
In those areas of the world where there are no parasites, or very few parasites, we
tend to get an increase in allergic reactions.
Hypersensitivity.
Hypersensitivity happens in two ways:
1st. Sensitization- this is when you first see the antigen, you will mount an immune
response.
You will get an IgM mediated immune response.
As you see the antigen again, you can start to class-switch the antibody type.
If you are a TH2 type of individual, you may get more IgE formed against those
antigen, that then allows a reaction to happen, that is a hypersensitivity reaction.
There are multiple types of hypersensitivity reactions.
Allergies are a type 1 hypersensitivity.
There are 4 types of hypersensitivity based on a number of features:
Their effector mechanisms, the molecules that mediate and the antigens that they
are responding to
Four classes of hypersensitivity.
4 types of hypersensitivity.
The 4 types of hypersensitivies are named: 1,2,3 and 4.
Type 1 is antibody mediated, but it specifically uses IgE as the antibody.
Type 2 and Type 3 are also antibody mediated, but they use IgG.
Type 1 is allergic reactions.
It is IgE mediated, it is a response to soluble antigen, it results in activation of mast
cells.
Type 1 hypersensitivity.
Type 1 hypersensitivity is sometimes called an immediate hypersensitivity.
This is because it is very rapid in its onset.
Some of the allergens are inhaled material, like pollen, faeces, house dust mite.
, The key feature for all the common sources of allergens for type 1 hypersensitivities
is that the effector mechanism is mast cells degranulating.
Allergy- generally thought of as a type 1 hypersensitivity.
However, sometimes people consider allergy as any hypersensitivity reaction.
Atopy- genetic tendency amongst individuals to have immediate type 1
hypersensitivity reactions.
These individuals are atopic. They have an increased tendenciey to these
hypersensitivies such as atopic dermatitis, exezma and asthma
IgE.
IgE is a major class of antibody within the body.
They are important in protection against parasite diseases.
And they crucially sensitize mast cells.
The antibody itself is not very good at neutralizing or opsonizing but it is very good at
sensitizing mast cells, by binding to a receptor on mast cells, called FCepsilonR1.
It binds FC region of IgE, we know it’s the receptor for IgE because of the epsilon.
The Fcepsilonreceptor is on mast cells, and it is on basophils and activated
eosinophils as well.
Mast cells.
Mast cells play a physiological role in inflammation.
They are full of granules.
Because the granules are ready made, once they are released through
degranulation, you get the immediate effects.
This is why type 1 hypersensitivies are considered an immediate hypersensitivity.
These mast cells carry FCepsilonR1.
This means that they can carry antibody on their surface.
There is a distinction between mast cells carrying antibody and B cells that also carry
surface antibody.
Figure 1. B cell that carries a single type of antibody, against a single antigen.
Figure 2. another B cell that carries a different antibody, to a different antigen.
Figure 3. for mast cells, with its green FCepsilonR1 (green Fc receptors for IgE), one
of the FC receptor molecules can bind to the anti-herring worm antibody, another
can bind an anti-blood fluke antibody, another can bind an anti-hookworm and an
anti-roundworm.
Figure 4. this may continue until we have a mast cell that carries an antibody for
pollen, for cat dandruff, peanuts and venom.
This means that mast cells can multitask.
One mast cell can carry multiple different IgE molecules for many different antigens.
This means that they can easily, be degranulated by lots of different allergens.
Once they degranulate.
We see the FC receptor carrying the IgE.
As you get the FC receptors being cross-linked by this antigen, you get an activated
signal, that can result in degranulation of these pre-formed granules.
This will lead to very rapid responses that will do a lot of the features that you will
see in a normal inflammatory response.
, Inflammation is usually good, but in this case it is unwelcome.
This will cause, muscular contraction.
If you have eaten an allergen, you might be sick or you might get diarrhea.
Inappropriate response.
Hypersensitivies are inappropriate responses to inocuous antigens.
They are mediated through an IgE antibody that is bound to Fc receptors on mast
cells.
These are called the FCepsilonR1.
The preformed granules within the mast cell, with an FCepsilonR1 receptor that has
bound an IgE molecule onto each of its copies.
These could be many different types of IgE binding to many different antigens.
When you are first exposed to an antigen, you have primary immune response.
In the context of hypersensitivity this is called sensitization.
In these early responses, you respond to that antigen, and you start to produce IgE.
This is the nature of some individuals, as they have more of a TH2 skew to their
production of antibody and if they produce IgE, they are more likely to have allergic
reactions.
The IgE that is made, can then be used to coat, VIA the FCepsilonR1, the mast cells.
So, when you get a repeated exposure, you start to get allergic reactions, which are
immediate hypersensitivity reactions.
Where you get degranulation of mast cells, and all of the complications that arise
with that.
Mast cells are a cell that is designed, that is developed within us to be able to
promote inflammation, which is a physiological response for us to deal with trauma.
But in this situation, it is an unwelcomed inflammatory response that happens in
which ever tissues are affected by the allergic reaction.
The degranulation can lead to problems.
A mast cell is now recognizing an antigen.
You will get cross linking of the FC receptors, through the IgE molecule.
And you get degranulation.
Mast cell activation.
On this degranulation, you see lots of different factors being released.
These are categorized into different classes to provide simplicity.
Enzymes are released, these enzymes have many biological effects.
But they activate other enzymes, these can then mediate breakdown and damage of
tissue that come with chronic repeated allergic reactions.
It can be very damaging to the tissue.
EG. If you have allergic asthma, you can get chronic inflammatory damage as a result
of that.
We see cytokines and chemokines.
They are both protein type molecules, which can activate other cells.
They can drive inflammation and they can recruit other leukocytes into tissues to
help drive an inflammatory response.
An inflammatory response in an allergy is unwelcome.
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