Allergic Cascade (cont.)
What about a more detailed look at the "players?"
Lymphocytes
- T's & B's
Lymphocytes are part of the white blood cell family and
consist of T and B varieties. Each T lymphocyte, or T cell,
is like a specially trained detective. The T cell examines
the evidence that is exposed by the APC. When specific T
cells come into contact with the ragweed pollen fragment on
the APC and recognize it as foreign, an army of specialized
T cells called "helper" cells (actually TH2 cells) is
activated, thus releasing chemicals (cytokines) that
stimulate B lymphocytes. B lymphocytes produce IgE
antibodies that bind to the allergens (such as the pollen
fragment).
Once the IgE is produced, it specifically recognizes the
ragweed pollen and will recognize it on future
exposure.
The balance between allergy-promoting TH2 cells and
infection-fighting TH1 cells has recently been found to be
a critical component of our immune system. Whereas allergy
reactions involve large numbers of TH2 cells, infections
generate an army of TH1 cells, which then release chemicals
that help destroy microbes.
Allergy and
asthma rates have been increasing in recent decades. One currently
favored theory
explaining the increase is that it is a consequence of
inadequately "geared up" human immune systems because of
the
relatively sterilized environment of modern man, possibly
due to
antibiotics and vaccinations! This has been referred to as
the "hygiene hypothesis." What this concept implies is that
the immune
systems of individuals who have been exposed to sufficient
microbes
make TH1 cells when stimulated. But, if an individual's
immune system
is inadequately stimulated to produce TH1 cells by exposure
to
microbes, it will instead lean toward the allergy-producing
system
and make TH2 cells. A tendency toward allergic reactions is
the
result.
Although this appears complicated, an understanding of
the different lymphocyte responses is important in treating
allergies. Ideally, we would like to respond to ragweed
pollen with TH1 lymphocytes and not TH2 lymphocytes, which
promote allergic reactions and produce IgE in large
amounts. Allergic individuals summon a large number of TH2
cells in response to allergens, whereas non-allergic people
do not.
Finally, the tendency to develop allergic conditions
(i.e., to develop strong TH2 responses to allergens) is
thought to be partially inherited from our parents. At
birth, there seems to be a balance between the
infection-fighting TH1 cells and the allergy-promoting TH2
cells.
Current thinking is that allergy develops after birth when
a child is exposed to certain substances in the
environment. The immune system is stimulated by these
exposures so that the scales are now tipped toward the
production of allergy-promoting TH2 cells. They are
especially tipped toward allergy promotion in individuals
that have inherited the genetic tendency from their
parents.
Mast Cells & Basophils
Mast cells and basophils are the next key players in the
allergic cascade. They are volatile cells with potentially
explosive behavior. Mast cells reside in tissues while
basophils are found in the blood. Each of these cells has
over 100,000 receptor sites for IgE, which binds on their
surfaces. The binding of IgE to these cells acts like the
fuse on a bomb. The cells are now sensitized or primed with
the IgE. When this allergic or sensitized individual is
exposed to ragweed pollen again, the IgE is ready to bind
to this pollen. When this occurs, the mast cells and
basophils are activated and explosively release a number of
chemicals that ultimately produce the allergic reaction we
can see and feel. Wherever these chemicals are released in
the body will display the allergy symptoms. In the ragweed
pollen example, when the mast cells are activated in the
nose by exposure to the pollen, the release of chemicals
will likely result in sneezing, nasal congestion, and a
runny nose - the typical symptoms of hay fever. Once
sensitized, mast cells and basophils can remain ready to
ignite with IgE for months or even years!
Chemical Mediators
Each mast cell and basophil may contain over 1000 tiny
packets (granules). Each of these granules holds more than
30 allergy chemicals, called chemical mediators. Many of
these chemical mediators are already prepared and are
released from the granules as they burst in an allergic
response. The most important of these chemical mediators
is histamine. Once released into the tissues or blood
stream, histamine attaches to histamine receptors (H1
receptors) that are present on the surface of most cells.
This attachment results in certain effects on the blood
vessels, mucous glands, and bronchial tubes. These effects
cause typical allergic symptoms such as swelling, sneezing,
and itching of the nose, throat, and roof of the mouth.
Some chemical mediators are not formed until 5 to 30
minutes after activation of the mast cells or basophils.
The most prominent of these are the leukotrienes.
Leukotriene D4 is 10 times more potent than histamine. Its
effects are similar to those of histamine, but leukotriene
D4 also attracts other cells to tarea, thereby
aggravating the inflammation.
Allergy Facts
- Leukotrienes were initially discovered in 1938 and
were called the "slow reacting substances of anaphylaxis
(SRS-A)." Forty years later, Samuelsen in Sweden
identified them as playing an important role in allergic
inflammation.
- Recently, a new family of medicines, called leukotriene
modifiers, have been found to be helpful in treating
asthma. Examples are Singulair (monlelukast) and Accolate
(zafirlukast).
The other group of inflammation-causing chemical
mediators that form after mast cell stimulation is the
prostaglandins. Prostaglandin D2, in particular, is a very
potent contributor to the inflammation of the lung airways
(bronchial tubes) in allergic asthma.
Next: What are cytokines? »
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