Download Tips to Remember: What is an allergic reaction

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Histamine1
WHAT IS HISTAMINE?
Histamine is an important protein involved in many
allergic reactions. Allergies are caused by an immune
response to a normally innocuous substance (i.e. pollen,
dust) that comes in contact with lymphocytes specific
for that substance, or antigen. In many cases, the
lymphocyte triggered to respond is a mast cell. For this
response to occur, a free-floating IgE (an immunoglobulin
associated with allergic response) molecule specific to
the antigen must first be attached to cell surface
receptors on mast cells. Antigen binding to the mast
cell-attached IgE then triggers the mast cell to respond.
This response often includes the release of histamine
(Janeway et al 1999).
WHAT DOES HISTAMINE DO?
The release of histamine (hist = because it's made up of histidine residues, amine = because it's a
vasoactive amine) causes several allergic symptoms. 1) It contributes to an inflammatory
response. 2) It causes constriction of smooth muscle.
Histamine can cause inflammation directly as well as indirectly. Upon release of histamine by an
antigen activated mast cell, permeability of vessels near the site is increased. Thus, blood fluids
(including leukocytes, which participate in immune responses) enter the area causing swelling. This
is accomplished due to histamine’s ability to induce phosphorylation of an intercellular adhesion
protein (called (VE)-cadherin) found on vascular endothelial cells (Andriopoulou et al 1999). That is
why histamine is known as being vasoactive. Gaps between the cells in vascular tissue are created
by this phosphorylation, allowing blood fluids to seep out into extracellular space. Indirectly,
histamine contributes to inflammation by affecting the functions of other leukocytes in the area.
It has been suggested by Marone et al that histamine release triggers the release of cytokines and
inflammatory mediator by some neighboring leukocytes (1999). These chemicals in turn increases
the inflammatory response.
Histamine's second type of allergic response is one of the major causes for asthma. In response
to an allergen (a substance that triggers an allergic reaction), histamine, along with other
chemicals, causes the contraction of smooth muscle (Schmidt et al 1999). Consequently, the
muscles surrounding the airways constrict causing shortness of breath and possibly complete
trachial-closure, an obviously life-threatening condition. If the effects of histamine during an
allergic reaction are inhibited, the life of an allergic person can be eased (in the case of
inflammation) or even saved by preventing or shortening asthma attacks. Thankfully, many
effective drugs have been developed to hinder histamine's allergic response activities.
1
Adapted from http://www.bio.davidson.edu/courses/Immunology/Students/spring2000/lamar/mfirp.htm
Antihistamines
Allergies are frequently treated by drugs called antihistamines (because they inhibit the activity
of histamine). Some contemporary examples are Claritin and Allegra, but antihistamines have been
in use since as early as the 1930s and they continue to be an effective way to deal with the
problems of allergies (Emanuel 1999). One effect antihistamines have is the inhibition of the
histamine-mediated release of inflammatory mediators by leukocytes (Cuss 1999). Other
antihistamine effects result in the neutralization of histamine, preventing it from binding and
activating immune-related cells in the area. An allergic reaction is an immune response that should
not be occurring because the substance that triggers it should not be dangerous to us. Allowing
our immune system to run its course against allergens means living with annoying and potentially
dangerous symptoms. The use of antihistamines allows us to live more safely and comfortably by
counteracting the body's immunological “mistakes”.
References
Andriopoulou P, Navarro P, Zanetti A, Lampugnani MG, Dejana E. 1999 Oct. Histamine induces tyrosine
phosphorylation of endothelial cell-to-cell adherens junctions. Arteriosclerosis Thrombosis and
Vascular Biology 19(10): 2286-2297.
Cuss FM. 1999 July. Beyond the histamine receptor: effects of antihistamines on mast cells. Clinical and
Experimental Allergy 29: 54-59.
Emanuel, MB. 1999 July. Histamine and the antiallergic antihistamine: a history of their discoveries. Clinical
and Experimental Allergy 29: 1-11.
Janeway CA, Travers P, Walport M, Capra JD. Immunobiology: the Immune System in Health and Disease.
4th ed. London: Current Biology Publication; 1999. p 602.
Marone G, Granata F, Spadaro G, Onorati AM, Triggiani M. 1999. Antiinflammatory effects of oxatomide.
Journal of Investigational Allergology and Clinical Immunology 9(4): 207-214.
Protein Data Bank. Structure Explorer - 1AVN. <http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1AVN>
Accessed 2000 Mar 2.
Schmidt D, Ruehlmann E, Branscheid D, Magnussen H, Rabe KF. 1999 Aug. Passive sensitization of human
airways increases responsiveness to leukotriene C4. European Respiratory Journal 14(2): 315-319.
Questions
Tips to Remember: What is an allergic reaction?2
Approximately 50 million Americans suffer from some form of allergic disease, and
the incidence is increasing. When most of us think of allergies, we think of
sneezing, a runny nose or watery eyes. While those are symptoms of some types of
allergic disease, an allergic reaction is actually a product of several events
occurring within your immune system.
The immune system
The immune system serves as the body's defense mechanism against the countless
different substances present in the air we breathe, the foods we eat, and the
things we touch. Within this immense group of materials, the term “allergen”
refers to any antigen which is any substance that can trigger an allergic response.
2
http://www.aaaai.org/patients/publicedmat/tips/whatisallergicreaction.stm
Common allergens include pollen, mold, animal dander, and cockroach and house dust mite droppings.
Antibodies circulate in the bloodstream and are present in almost all bodily fluids. They help to
capture unwanted invaders. People who have allergies have an antibody called Immunoglobulin E, or
IgE. When allergens first enter the body of a person predisposed to allergies, a series of reactions
occurs and allergen-specific IgE antibodies are produced. Following IgE production, these
antibodies travel to cells called mast cells, which are particularly plentiful in the nose, eyes, lungs
and gastrointestinal tract. The IgE antibodies attach themselves to the surface of the mast cells
and wait for their particular allergen.
Each type of IgE has specific “radar” for one type of allergen only. That's why some people are
only allergic to cat dander (they only have the IgE antibodies specific to cat dander) and others
seem to be allergic to everything (they have many more types of IgE antibodies.)
The next time an allergic individual comes into contact with the allergens to which he or she is
sensitive, the allergens will be captured by the IgE. This initiates the release of chemical
“mediators” such as histamine and other chemicals from the mast cells. These mediators produce
the symptoms of an allergic reaction, such as swelling of tissues, sneezing, wheezing, coughing and
other reactions.
The allergic reaction typically continues: these newly released mediators recruit other
inflammatory cells to that site, resulting in additional inflammation. Many symptoms of chronic
allergic disease—such as swelling, excessive mucus and hyperresponsiveness to irritating stimuli—
are the result of tissue inflammation due to ongoing exposure to allergens.
It is not yet fully understood why some substances trigger allergies and others do not, nor why
every person does not develop an allergic reaction after exposure to allergens. A family history of
allergies is the single most important factor that predisposes a person to develop allergic disease.
If one parent has allergic disease, the estimated risk of the child to develop allergies is 48%; the
child's risk grows to 70% if both parents have allergies.
Types of allergic disease
The existence of IgE antibodies is common to all forms of allergic disease. But the physical
symptoms differ depending on the type of mediator released and where they act. When a person
with allergies begins to experience symptoms, key questions are: What allergens am I reacting to?
When, and how much, am I exposed to these substances?
Major allergic diseases include:
 Allergic rhinitis, or “hay fever”
 Allergic conjunctivitis (an eye reaction)
 Asthma
 Atopic dermatitis, or allergic skin reactions
 Urticaria, also known as hives
 Severe allergic reactions to substances such as food, latex, medications, and insect stings
 Problems commonly resulting from allergic rhinitis—sinusitis and otitis media (ear
infections)
Symptoms of allergic rhinitis, commonly referred to as “hay fever,” occur when allergens touch the
lining of the nose—called the mucus membranes—of a person who is sensitive to that particular
allergen. Allergic rhinitis is characterized by congestion, itching and dripping of the nose and itchy,
watery eyes. If the person continues to have daily, ongoing exposure to the responsible allergen(s),
the symptoms will continue. Similar to allergic rhinitis, allergic conjunctivitis occurs when the eyes
react to allergens with symptoms of reddening, itching and swelling.
Symptoms of atopic dermatitis, also called eczema, often result from allergen exposure to the
skin. Dermatitis symptoms include itching, reddening, and flaking or peeling of the skin. Symptoms
begin in childhood for 80% of those with atopic dermatitis. Dermatitis often precedes other
allergic disorders; over 50% of those with atopic dermatitis also develop asthma.
Urticaria, or hives, another allergic skin reaction, is characterized by itchy red bumps that can
occur in clumps and be either large or small. Hives are often triggered by infection, certain foods
or medications. Foods commonly associated with hives include nuts, tomatoes, shellfish and berries.
Medications include penicillin, sulfa, anti-seizure medications, phenobarbital and aspirin.
Asthma is a chronic lung disease that affects more than 17 million Americans and is characterized
by coughing, chest tightness, shortness of breath and wheezing. Allergic rhinitis is considered a
risk factor in developing asthma: up to 78% of those with asthma also have allergic rhinitis.
When an individual experiences asthma symptoms, the inflamed airways become constricted so it
becomes more difficult to breathe through the narrowed air passages. For people with allergies,
inhaling allergens may produce increased inflammation of the airway lining and further narrowing of
the air passages. Asthma may also occur as a result of other stimuli, such as respiratory tract
infections or exposure to irritants.
Individuals who have allergies to specific foods may have severe and possibly life-threatening
reactions if they eat them. The most common food allergy triggers are the proteins in cow's milk,
eggs, peanuts, wheat, soy, fish, shellfish and tree nuts. Food allergy occurs more frequently in
children than adults. Many of these children may lose their sensitivity to particular foods over
time.
Foods and other allergens, including penicillin, insect stings and latex, can trigger a severe,
systemic allergic reaction called anaphylaxis. Anaphylaxis is caused by swelling throughout the
body, and can involve several organ systems. Symptoms of anaphylaxis include a feeling of warmth,
flushing, tingling in the mouth or a red, itchy rash. Other symptoms may include feelings of lightheadedness, shortness of breath, severe sneezing, anxiety, stomach or uterine cramps, and/or
vomiting and diarrhea. In severe cases, patients may experience a drop in blood pressure that
results in a loss of consciousness and shock. Without immediate treatment with an injection of
epinephrine (adrenalin), anaphylaxis may be fatal.
Sinusitis and otitis media are other common allergic diseases that often are triggered by allergic
rhinitis. Sinusitis is an acute or chronic inflammation of the nasal sinuses, which are hollow cavities
within the cheek bones found around the eyes and behind the nose. This condition affects over
15% of the U.S. population. Otitis media—or ear infections—is the most common childhood disease
requiring physician care. If not properly treated, it can affect a child's speech and language
development.
You can learn more about various allergic diseases by reading the appropriate Tips brochures in
this series.
Diagnosing and treating allergic reactions
An allergist is best qualified to treat allergic diseases. To determine if you have an allergy, your
allergist will take a thorough medical history and perform an exam. If indicated, he or she will then
perform allergy skin testing, or sometimes blood testing, to determine precisely which substance is
causing your allergy. Once your allergy triggers are identified, your physician can help you establish
a treatment program. The first step is to minimize your exposure to your particular allergens to
whatever extent possible. Your physician may also prescribe medications to reduce allergic
symptoms as well as inflammation.
Immunotherapy, also known as allergy shots, may also be recommended to modify your immune
response. For many patients, immunotherapy can help diminish their reactions to allergens. Please
see the Tip brochure in this series for more information on allergy shots.
In summary, an allergic reaction is a complex chain of events that involves many cells, chemicals
and tissues throughout the body. While there is not yet a cure for allergic disease, there are many
treatments available to lessen symptoms. See your allergist to determine the best course of
treatment.
Your allergist/immunologist can provide you with more information on allergic reactions. Tips to Remember
are created by the Public Education Committee of the American Academy of Allergy, Asthma and
Immunology. The content of this brochure is for informational purposes only. It is not intended to replace
evaluation by a physician. If you have questions or medical concerns, please contact your
allergist/immunologist.
American Academy of Allergy,
Asthma and Immunology
555 East Wells Street, Suite 1100
Milwaukee, WI 53202
Additional information: http://www.nlm.nih.gov/medlineplus/allergy.html