Allergic Cascade (cont.)
In this Article
- Who are the "players" in the allergic cascade?
- What about a more detailed look at the "players?"
- What are cytokines?
- What is the "early phase" of an allergic reaction?
- What is the "late phase" of an allergic reaction?
- What are the consequences of the allergic cascade?
- How does understanding the allergic cascade help?
- Allergic Cascade At A Glance
What about a more detailed look at the "players?"
- 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!
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.
- 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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