How an Allergic Reaction Works

With 2.5% of the world's population sufering from a food allergy, we explore how the body's own defense mechanism causes the allergic reaction
Produced by National Geographic for Bayer

In 1859, Charles Harrison Blackley sneezed. A doctor in Manchester, England, Blackley suffered from what were called summer colds, with seasonal sneezing, watery eyes, and a runny nose. The idea of hay fever had been around for some time, but Blackley was passionate about discovering its cause: heat was one popular theory of the time, ozone another. However, Blackley realized that it was neither ozone nor heat making him sneeze but pollen, and he went on to prove it—largely by experimenting on himself.

Allergies are not new. It’s possible that our immune systems have always overreacted to certain innocuous substances, going into overdrive and producing allergic symptoms such as swelling, rashes, red eyes, runny noses, and shortness of breath. Such reactions have been described in historical documents with asthma symptoms recorded in ancient China, Rome, Egypt, and Greece, from where the word “asthma” comes, meaning panting. But while allergies are not new, our modern understanding of them is.

Amidst the scientific progress that characterized the 19th century, an understanding of allergies was slow to develop. In 1819, John Bostock wrote a detailed description of hay fever. Over the following decades, Charles Harrison Blackley identified pollen as the cause, however no effective treatments were found and most allergic conditions remained unidentified. Despite great advances in immunology, the pieces of the allergy puzzle were not being put together. In the early 1900s that began to change.

In 1905 Clemens von Pirquet, an Austrian pediatrician, noticed that patients vaccinated for smallpox using horse serum reacted quickly and severely to a second dose. Pirquet correctly deduced that the symptoms of what he called serum sickness were being caused by the immune system producing antibodies to fight antigens, or foreign substances contained in the serum. In 1906, he coined a new term for this antibody-antigen interaction: allergy.

Over the next few years this hypersensitive reaction of the immune system was proposed as the cause of hay fever, asthma, some skin diseases, and anaphylaxis—the extreme whole-body allergic reaction that can cause death. A link was also made between asthma and anaphylaxis, and between anaphylaxis and the body’s production of the chemical histamine. As interest in allergies rocketed, allergy clinics sprang up across Europe and America while experiments began into immunotherapy, building up a person’s immune system through gradual exposure to the antigen.

After the Second World War, the term allergy was being applied to many conditions, including reactions to synthetic chemicals such as cosmetics, and to some common foods. As early as the first century A.D., the Roman philosopher Lucretius had noted that “what is food to one man is bitter poison to others.” However, food allergies were difficult to prove as they are notoriously inconsistent and often mimic unrelated ailments. In an important breakthrough, exhaustive studies of cases previously dismissed as medical anomalies were demonstrated to be food allergies. The floodgates opened, and as diagnoses surged many medical practitioners derided food allergies as a passing fad.

Meanwhile, the production of drugs to treat allergies accelerated. In 1948, the steroid corticosteroid was successfully used to reduce the inflammation in asthma attacks, and specific anti-allergy products were developed, such as non-biological washing powder that answered growing fears about the enzymes in biological soaps. Food labeling also became widespread and warnings about potential allergies began to appear.

Our understanding of allergies made a leap in the early 1950’s with the discovery of mast cells. These are found in some of the most sensitive parts of the body, including the skin, blood vessels, and respiratory system. A mast cell contains 500 to 1,500 granules, each packed with different chemicals, such as histamine, designed to attack antigens. It’s these chemicals that produce the symptoms of an allergic reaction.

Then in 1967, researchers identified immunoglobulin E (IgE), the antibody responsible for most allergic reactions. When someone is exposed to an antigen, peanuts for example, their body produces a specific IgE antibody in a process called sensitization. People prone to allergies produce disproportionate amounts of IgE that remain dormant until the allergen is detected again; they then go berserk, triggering the mast cells to release their allergy-causing chemicals.

Further discoveries followed: blood tests to detect IgE levels; the EpiPen to treat anaphylactic shock; and in 1982, the Nobel Prize in Medicine and Physiology was awarded for work on leukotrienes, which cause asthma and inflammatory responses to antigens. Today, allergies are the sixth leading cause of chronic illness in the United States, costing around $18 billion a year. And so the research continues. Advances are being made in immunotherapy and the management of some symptoms, but a cure for any allergy remains as elusive as ever.

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