What is an Allergy?

by Dr. Kristy Wolniak, MD, PhD

Allergies are quite common and continue to rise in prevalence in the industrialized world. A room full of people in Illinois during the fall months will invariably contain at least a few individuals with the runny nose, sneezing, and itchy eyes indicative of “hay fever” season. Approximately 8% of adults in the U.S. have hay fever, and up to 40% of the world population has IgE sensitization to foreign particles in the environment, according to the American Academy of Allergy Asthma and Immunology [1].

But what is an allergy exactly?

From a medical perspective, the word allergy itself encompasses a broad range of conditions ranging from irritating seasonal allergies like hay fever to life threatening allergic reactions to bee stings. While it’s very common for people to have true allergies, the word allergy has also been widely and inaccurately adapted to apply to essentially any negative response to a substance [2]. Merriam-Webster dictionary even includes one definition of allergy as “a feeling of antipathy or aversion” [3]. Understanding the definition of a true allergy and recognizing potential misconceptions and misunderstandings about allergies is important to help determine treatment and to avoid potentially fatal allergic reactions.

Although the medical term allergy encompasses many different conditions, all of the conditions defined as true allergies have the common underlying mechanism of an abnormal immune response to a foreign substance that would normally be harmless. This foreign substance is referred to as an allergen. The formation of a true allergy begins with the creation of Immunoglobulin E (IgE) antibodies against the allergen and the subsequent triggering of an immune response. Antibodies are proteins formed by white blood cells in the immune system in response to a substance. Antibodies are designed to specifically recognize and bind to certain substances such as bacterial and viral proteins, with the normal function of protecting the host from infection. Antibodies come in different types, and IgE is the type of antibody that is implicated in allergic reactions.

“... true allergies have the common underlying mechanism of an abnormal immune response to a foreign substance that would normally be harmless.”

The normal role of IgE antibodies is to protect individuals from parasitic infections, particularly helminths. In allergic reactions, however, IgE antibodies are produced inappropriately against allergens such as food, medications, pollen, and metals. After binding its specific allergen on one end, the other end of the IgE antibody can also bind to a white blood cell called a mast cell. When multiple IgE antibodies bind to a mast cell, the mast cell releases histamine and other mediators of inflammation. These mediators of inflammation can cause dilation and leakiness of the blood vessels and drive the recruitment of more immune cells. These changes lead to the swelling and itchiness associated with different allergies. When there is a massive release of histamines, there may potentially be an overwhelming immediate immune response called anaphylaxis which can lead to potentially life-threatening closing of the airways if left untreated. Given the common mechanisms underlying allergic reactions, doctors can perform skin testing to identify a true allergy. The testing is performed by placing a small amount of the potential allergen under the skin and measuring the amount of swelling and redness that occurs. This response is indicative of the amount of IgE and therefore the immune response.

Infographic by Joo-Young Lee

The wide array of true allergic reactions is due, in part, to the different routes of exposure to allergens. Often the route of exposure to the allergen will impact the effects mediated. Some allergic reactions such as hay fever are less likely to cause massive, potentially life-threatening immune responses than other types of allergic reactions such as an allergy to ingested shellfish. An allergen such as the metal nickel can be encountered on the skin and lead to a rash (i.e., contact allergy). While inhaled allergens, such as the pollen of hay fever, can lead to respiratory symptoms such as a stuffy or runny nose, sneezing, and itchy eyes (i.e., allergic rhinitis), ingested allergens, such as those from food, can have systemic effects such as a rash and possibly intestinal effects such as abdominal pain, nausea, and diarrhea. Medication allergies involve many different types of responses as medications are delivered via many routes. Orally ingested, intravenous, and topical medications can all cause allergic reactions. For most ingested or intravenous medications, the allergic response is systemic and involves skin rash/hives, itchiness, and sometimes difficulty breathing. Allergic reactions range from mild to life-threatening, but the underlying mechanisms are similar and treatments include avoidance of the allergen, antihistamines, anti-inflammatory drugs, and in urgent situations, drugs that can dilate the airways.

The term allergy is sometimes inappropriately used to refer to an intolerance or a sensitivity, particularly when referring to food. How is food allergy different than food intolerance or sensitivity? Intolerance to food is typically due to a deficiency of an enzyme that aids in digestion of the food, such as lactose intolerance. Both food allergy and food intolerance can present with similar symptoms such as stomach pain, nausea, and diarrhea. However, a food intolerance does not lead to a systemic response such as hives or difficulty breathing. If a person has a food intolerance they may be able to ingest the food in limited quantities to avoid the negative response, but in the setting of true allergy, even a quantity of the food that is not visible to the human eye can trigger an immediate allergic reaction. Differentiating between a food allergy and food intolerance is very helpful in treatment and prevention of the negative consequences.

Understanding the mechanisms underlying true allergies helps to clarify some common misconceptions. One is that a previously mild allergic reaction means all subsequent reactions will be mild. The immune system has memory, and every exposure to the allergen can increase the amount of IgE that can potentially bind to the allergen. A mild allergic reaction after someone eats peanuts can sometimes be followed by an immediate severe allergic reaction the next time they eat peanuts, even a very tiny amount. Another common misconception is that if an individual has eaten something before without a problem, that individual will never be allergic to that substance. The inappropriate production of IgE that is able to bind a substance actually requires that there was a prior exposure and an immune response to that substance or a substance that is structurally similar. The first exposure to an allergen that generates an immune response may not cause any symptoms. In reality, an abnormal immune response to an allergen could develop at any time after exposure, and it is not possible to predict the first incidence of a symptomatic allergic reaction.

Artwork by Rachel Poli

Biography found at the end of this article

As medical science begins to uncover the mechanisms behind the development of true allergies, clues have begun to emerge about how to prevent the development of allergies. The hygiene hypothesis of allergy development proposed that early exposure in life to certain microbes could modify the development of allergies [4]. There is currently a large body of research exploring this hypothesis and the potential implications in preventing allergy development. Many studies have begun to focus on the role of the microbiome (the microbes within the body) and the effect of a person’s microbiome on the development of allergies [4]. These studies are beginning to provide the mechanisms that the environment and cleanliness behaviors of a person shape and influence the immune response to allergens.

Allergies are common and commonly misunderstood. There are still many components of allergies that are not understood by doctors and researchers. Understanding how allergy is defined and how allergies develop can help provide insight into the appropriate treatment and prevention of allergic responses.

References [1] American Academy of Allergy Asthma and Immunology. Allergy statistics. 2019. www.aaaai.org/about-aaaai/newsroom/allergystatistics. Accessed 5 July 2019. [2] Cummins, Eleanor. “You’re almost certainly using the word ‘allergies’ wrong.” 1 May, 2018. www.popsci.com/what-is-an-allergy/. Accessed 5 July, 2019. [3] Merriam-Webster’s Unabridged Dictionary. 2019. www.merriamwebster.com/dictionary. Accessed 5 July, 2019. [4] Liu, A. H. (2015). Revisiting the hygiene hypothesis for allergy and asthma. Journal of Allergy and Clinical Immunology, 136(4), 860-865. [5] [General Citation for Complete Article] Murphy, Kenneth M., et al. Janeways Immunobiology. GS, Garland Science, Taylor & Francis Group, 2017.

About the Author

Kristy Wolniak, MD, PhD, is an assistant professor in Hematopathology with a particular interest in clinical flow cytometry and education. She is the Phase I curriculum director of the Northwestern University Feinberg School of Medicine as well as the leader of the Pathology curriculum content, the coleader of the Immunology/Microbiology Foundations module, and the co-leader of the Diagnostic Testing thread. At the graduate medical education level, she is the residency associate program director (Clinical Pathology) and she has been involved in improving the laboratory medicine rotations in pathology to enhance the trainee experience and learning outcomes. Her education interests are in the use of technology in instruction at all levels (medical students, pathology trainees, faculty, and technologists) to increase learner engagement and the meaningful integration of basic science education into the clinical curriculum. She is the chair of the ASCP Specialist in Cytometry examination committee and helped to design and deploy an international specialist certification program for cytometrists. Her clinical research interest is in the design and optimization of clinical flow cytometry assays for leukemia and lymphoma evaluation.

About the Artist

As a current graduate student at the University of Illinois at Chicago’s Biomedical Visualization program, Rachel Poli started her journey in Wauwatosa, Wisconsin where she found the field of Medical Illustration. With her long-term goals in sight, she graduated from Macalester College in St. Paul, Minnesota in 2018. She received a BS in Studio Art and an honors BS in Biology by conducting research in the immunology of allergies under Dr. Devavani Chatterjea. During her first year in UIC’s BVIS program Rachel has begun research with Dr. Paul Sereno in his paleontology lab at the University of Chicago. She has also begun teaching an undergraduate level biology class where she has seen the need for her craft exemplified. You can follow Rachel through LinkedIn or through Instagram. Her Instagram handle is @polirama where you can find a selection of the work she has completed during her stay at UIC.