An allergic cascade is the sequence of chemical releases that takes place in response to an allergen. The end result of this chain is the release of histamines and other chemicals that bring on typical allergy symptoms.

Individuals must first become sensitive to an allergen before an allergic reaction can take place. This process involves the immune system mistakenly perceiving an allergen to be a threat and producing a specific type of antibody to later recognize that allergen.

The allergic cascade occurs when an individual who has been sensitized to a specific substance encounters that allergen again. Links in the chain that make up an allergic cascade include:

• Proteins in the allergen, which are mistakenly recognized as threatening.
  
  
• The production of specialized antibodies to deal with this perceived threat. These antibodies attach to mast cells, which contain a variety of chemicals, including histamines.
  
  
• Histamines circulate in the body causing many of the symptoms associated with an allergic reaction, affecting the nose, lungs, throat, skin and digestive tract.

The body’s reaction to the allergic cascade depends on the individual and the allergen. Some symptoms appear immediately or within minutes, while others appear after several hours. Symptoms typically include itching, runny nose, hives, nausea, wheezing and diarrhea.

Those individuals who react most severely to allergens may be at risk for anaphylactic shock, which is a potentially life-threatening condition involving shortness of breath, a sudden drop in blood pressure and shock.

An allergic response is the body’s overreaction to some substance it believes to be a threat. The substance (called an antigen) may be completely harmless, but the body produces specific antibodies to combat this “threat” regardless. Antibodies are proteins that attach to foreign substances (e.g., bacteria, viruses) and help destroy them.

The allergic cascade refers to the chain of events that takes place when an allergen triggers an allergic response. The cascade includes the allergic response, the cellular and chemical interactions that follow, and the symptoms that usually result.

The key players in an allergic cascade include:

• Allergens. Substances that the body mistakenly perceives to be a threat. In response, the immune system reacts by producing antibodies. Allergens are a type of antigen. Examples of common allergens include pollen, mold, dust, animal dander, food and drugs.
  
  
• IgE (immunoglobulin E). A specific type of antibody that attaches to mast cells and basophils. IgE antibodies are like fuses to mast cells and basophils, waiting to be “lit” by a specific type of antigen.
  
  
• Mast cells and basophils. Types of white blood cells that reside in the mucous membranes and other tissues and contain granules of histamines and leukotrienes. They are like bombs. When IgE antibodies come in contact with an antigen, these cells release chemicals such as histamines and leukotrienes.
  
  
• Histamines and leukotrienes. Released by mast cells into surrounding tissues and the bloodstream, these chemicals directly cause allergy symptoms. They are called chemical mediators because they tell other cells to behave in a certain way. For instance, they tell blood vessels to dilate, which can cause symptoms ranging from nasal congestion to a drop in blood pressure and shock.

Other players include a type of white blood cell called TH2 cell – also called the “allergy cell” because of its central role in allergies. A brief explanation of both TH1 and TH2 cells is as follows:

• TH1 cells. These cells are not usually associated with the allergic cascade. Instead, these cells are used to fight infections by releasing chemicals that destroy microbes. TH1 cells are the body’s normal response to a foreign invader. However, when the body does not have enough TH1 cells, it is often forced to rely more heavily on TH2 cells.
  
  
• TH2 cells. These cells are responsible for sensitizing a person to a specific allergen and later, when the allergen is present in the body again, triggering an allergic response. When there are not enough TH1 cells, the body usually finds itself more sensitive to allergic reactions due to the increased reliance on TH2 cells.

The tendency toward some allergies (e.g., cow's milk, cat dander) appears to be genetic. People with a tendency for allergies are said to be atopic. Scientists are working to understand why some people are more prone to allergic reactions than others. It also appears that some types of allergies (e.g., poison ivy allergy) do not have a hereditary basis.

By understanding how these cells and chemical mediators interact, scientists can target different parts of the chain. For instance, some antihistamine medications work by preventing histamine molecules from binding with receptors in the body. Others may alter the histamine molecules themselves.

Before an allergic cascade can be put into motion, an allergic person must first have come into prior contact with an allergen (e.g., pollen, dander, food protein) and become sensitized to that allergen. This sensitizing process involves the following:

• The immune system encounters the allergen and misinterprets it as a threatening invader to the body. Lymphocytes are the specific immune system cells that actually encounter the allergen.
  
  
• The lymphocytes react to the invader by releasing a specific type of antibody known as IgE (Immunoglobulin E). The IgE antibodies contain specific information about proteins in the invading allergen – essentially a description – so that the body can remember if it ever encounters the same allergen again.
  
  
• The IgE antibodies flow through the bloodstream and eventually attach themselves to mast cells and basophils (volatile cells that can suddenly self–destruct and release powerful chemicals) and wait for months or years for another encounter with the allergen. Essentially, the IgE operates as a fuse and the mast cells and basophils operate as bombs.

This process of sensitizing a person to an allergen usually takes seven to 10 days. However, it does not produce any allergic symptoms. People do not become aware that this process has occurred until the next time that they encounter that allergen, which triggers an allergic cascade. This chain of reactions has several links, including:

• The allergen to which a person is sensitized enters the body. It may be inhaled through nasal passages, come in direct contact with the skin, be injected under the skin, or be ingested. The allergen flows through the bloodstream and encounters the IgE antibodies, which are attached to mast cells and basophils.
  
  
• The IgE antibodies recognize the invader and bind to the allergen molecule. This triggers the mast cells and basophils to which they are attached to self-destruct.
  
  
• Powerful chemicals from granules inside the mast cells and basophils are released into surrounding tissues and the bloodstream. These include histamines, leukotrienes and other allergy stimulators.
  
  
• Allergy symptoms begin to appear. These may be localized (only in the area where these chemicals were first released) or systemic (throughout the entire body). These chemicals mainly affect the blood vessels, mucous glands and bronchial tubes.

The allergens are therefore the match that lights the fuse (IgE) that triggers the bomb (mast cells and basophils) to explode.

Sometimes one substance is similar enough to another that the immune system will mistake it for a known allergen and trigger the allergic cascade. For example, a protein in latex is similar to a protein found in fresh fruits, vegetables and nuts. People with an allergy to latex often have allergic reactions to these foods. This phenomenon is known as cross reactivity.

As the allergic cascade progresses and histamines, leukotrienes and other chemicals are released, the body will begin to feel the symptoms normally associated with an allergy. The histamines are usually responsible for most of the symptoms, though leukotrienes are known to contribute by aggravating inflammation.

Symptoms can appear either in the area where the chemicals were first released or throughout the entire body. Symptoms often appear in the nose, lungs, throat, skin and digestive tract. Common allergy symptoms include:

• Itching of the skin, eyes and nose. Caused by histamine irritation of certain nerve endings.
  
  
• Sneezing, watery eyes and runny nose. Due to the leakage of fluid from the blood vessels.
  
  
• Hives. Caused by swelling and fluid leaking out of local blood vessels.
  
  

  

• Nausea and vomiting.
  
• Wheezing and coughing. Usually involves the inflammation of cells in the breathing areas.
  
• Shortness of breath. Due to the contraction of bronchial tubes.
  
• Diarrhea.

People who think they may be experiencing these symptoms as the result of an allergic cascade should contact an allergist. Allergists can help people identify the substances that trigger their allergic cascades. Once the allergens have been identified, patients can take steps to avoid the triggers and lower the odds of the cascade occurring again.

Since avoidance is not always possible, allergists may also recommend over-the-counter or prescription drugs to prevent or treat the effects of an allergic cascade.

The most severe type of reaction to an allergic cascade is anaphylactic shock. This condition involves breathing difficulties, lowered blood pressure and shock as a result of blood vessel dilation. Anaphylactic shock can be life-threatening and should be treated at the first sign of a reaction. Symptoms of this reaction include:

• Shortness of breath
• Tightness in the chest or throat
• Choking
• Dizziness, lightheadedness or fainting
• Hoarseness
• Severe itching
• Diarrhea
• Vomiting

The earliest effects of an allergic cascade may be experienced within a few minutes of exposure to an allergen. This is known as the early phase of an allergic reaction. This phase of the reaction is marked by the body’s immediate release of chemical mediators upon contact with an allergen to which the body has previously been sensitized. For this reason, this early phase reaction is typically referred to as a hypersensitive reaction. Symptoms at this point can include the full range of allergy responses, including runny nose, itching, tissue inflammation, anaphylactic shock and hives.

In about half of all allergic reactions, the early phase reaction progresses into a late phase reaction, where symptoms appear (or reappear) four to six hours after exposure. Reactions at this point typically include red and swollen inflammations, though the full range of symptoms is often produced, and can include anaphylactic shock. Individuals who are susceptible to this type of reaction are often even more sensitive to subsequent exposures. This type of reaction is commonly associated with chronic allergy symptoms. While late phase allergic reactions usually follow early phase reactions, some late-phase reactions occur without any warning.

The tendency to develop a late phase reaction depends on the type of antigen, patient sensitivity and the concentration of the allergen.

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions regarding the allergic cascade:

1. Do my symptoms indicate that I have experienced an allergic cascade?
   
   
2. What may have caused me to have the reaction?
   
   
3. Am I likely to have the reaction again in the future?
   
   
4. Is it dangerous for me to experience an allergic cascade?
   
   
5. Will I always experience the same symptoms?
   
   
6. Under what circumstances should I seek emergency medical treatment for an allergic reaction?
   
   
7. How can I prevent an allergic cascade from occurring? Will I require medication?
   
   
8. Are my children likely to inherit my allergies?
   
   
9. Am I likely to experience cross-reactivity? If so, what should I avoid?