Allergies: When immunity goes wrong?
What do peanuts, grass, cats and latex all have in common? That might sound like a nonsensical riddle, but they really do share something: they are all allergens. Allergen is the name given to substances that in theory should be entirely harmless to humans, but some people have an adverse reaction to. The term - allergy - was introduced in 1906 by Austrian paediatrician Clemens von Pirquet.
Scientists and doctors still haven’t actually been able to determine exactly why some otherwise safe materials cause these reactions in people with allergies. There are over 300 recorded allergens, and the vast span (from milk to dust mite poo) has no obvious common denominator, making it hard to figure out why we have allergic responses. What we do know is quite a bit about the mechanisms of allergies, which we will take a look at in this article.
Or, an overexcited immune system?
You might be surprised to learn that allergies are actually immune responses in our bodies. Fighting off a cold might seem far removed from sneezing in spring, but to our immune systems it’s not so different.
Our immune systems have evolved to identify and eliminate things in our bodies that aren’t recognised as part of ourselves; foreign bodies that could be dangerous. This is generally very effective, since the immune system targets pathogens like bacteria, viruses and fungal spores that might have made their way into our bodies. Since it evolved as a relatively all-encompassing catch-all it sometimes reacts to things that are actually not a danger - but better safe than sorry!
The allergy antibody – IgE
The specific over-eager culprit that is responsible for allergies is immunoglobulin E – IgE for short. IgE is a category of antibody, with lots of randomly evolved variants that all match and bind with specific proteins. Most of those proteins are pathogens, but some are allergens that are accidentally grouped in with the “bad” intruders. Our immune systems come genetically stocked with a variety of antibodies to try and get ahead of the pathogens that are evolving to be able to infect hosts; IgE variants are produced by B cells.
When a particular IgE binds to an allergen, it is activated, triggering an immune response and storing future copies of itself to be ready for a future attack. This is called sensitisation: first exposure to an antigen that creates a response, and primes the immune system to react again. This sensitisation process results in allergen-specific IgE that circulates in the bloodstream and attaches itself to the surface of mast cells and basophils (and sometimes macrophages and B lymphocytes) – the next line of defence.
What happens physiologically?
An example of an allergy is plant pollen - tiny particles that can easily make their way into our bodies, even if they don’t mean to. If you’re outside on a spring day when the plants have started blooming, you’re quite likely to inhale pollen. The glands in our noses produce mucus (snot) that traps large particles in inhaled air. Dendritic cells in the skin inside your nose engulf the pollen and break it up into peptides, which are short protein chains that are then “checked” by the body’s recognition system once they are transported to the lymph nodes. If the peptides bind to an IgE without a “stand down” order from a T cell, the IgE continues around, telling mast cells and basophils to launch an attack on the “intruder”. Mast cells and basophils like to hang out in the mucus, so as soon as they come into contact with more of the identified allergen, they kick off their response.
Symptoms
Allergies cause a range of symptoms, from minor irritation to fatal. Sneezing, itching, tingling and swelling are all well-known struggles of anyone with hay fever. The initial response to the allergen contact with the responsive immune cells is production of histamines and cytokines, which cause our noticeable symptoms. Histamines bind to receptors all throughout the body, and cause blood vessel expansion, contraction of smooth muscle, and trigger nerve endings. Continuing our example of inhaled pollen, the nerve endings in the areas most exposed to the allergen would be irritated, causing itching, sneezing and watering. The symptoms suffered a bit later on after exposure are caused by the inflammatory cytokines trying to create an unpleasant environment for the perceived threat, but in doing so makes us pretty miserable – redness, swelling, and fatigue. Allergic inflammation tends to target cells close to the allergen, like membranes in your nose, mouth, eyes, airway or skin.
Asthma is a condition that is caused by allergies affecting the respiratory tract, prevalent in children and most commonly triggered by the faeces of tiny dust mites that live in our houses. Asthma describes the chronic inflammation of the airway that makes breathing difficult, and is a chronic, long term effect of an allergic reaction.
Allergic reactions can also affect the digestive system, particularly if the allergen is a food. Having an immune reaction is the primary differentiator between a food allergy and a food intolerance. Food allergies also typically affect the respiratory system, likely due to its close proximity to the gastric tract. Generally, if you have an allergy it will trigger a response regardless of the contact point: people with pet allergies get respiratory symptoms and itchy skin, people with peanut allergies react to eating, touching or even breathing in peanut particles.
Those severe allergies, which are typically associated with tree nuts, shellfish, certain medicines, insect stings and rubber, can cause anaphylaxis: an extreme immune reaction. This excessive form of response occurs within minutes or even seconds of exposure, and causes a flood of chemicals to be released at once, sending the body into shock. Blood pressure drops, along with narrowing of airways and swelling of tongue and throat. Anaphylaxis is treated by injecting epinephrine (a high dose of adrenaline) to reset the body, which is why anyone with an identified severe allergy should carry an EpiPen.
Why does it only affect some people?
Despite its best intentions, the immune system seems to have got it slightly wrong when it comes to allergies. It’s a trait that around 40% of adults (and half of all children) have, but although it can sometimes do more harm than good (anaphylaxis being case in point), it likely remains within our genes as a way to keep our immune systems sharp and on alert for things that could be harmful, which indicates that evolutionarily it was probably still more of a benefit than a hindrance to survival.
In 1991, Margie Profet suggested that most allergic responses are triggered by materials that sometimes or always contain poisonous substances, and so acts as a somewhat exaggerated defence mechanism against natural toxins. The theory got some traction in the 2000s with additional studies, but as of yet we just don’t know for sure.
We know that allergies are linked to genetics, but most likely they are caused by a combination of genes. It runs in families but not always as a directly inherited trait. Additionally, some people have the IgE antibody for an allergy, say cat or pollen, but don’t show any symptoms, and vice versa! The last few decades have seen a rise in allergies in industrial countries, with no clear reason. Scientists theorise that it may be due to the improved hygiene practices that mean immune systems aren’t tested and matured during our early years, resulting in more extreme reactions later on. Some people may also have more severe allergies due to a defective anti-inflammatory response to calm down the initial assault.
Mitigating measures
Allergies can’t be cured, so avoiding allergens you know give you a reaction is probably your best bet (especially for food allergies, that tend to be more severe). Sometimes, complete avoidance isn’t possible, so luckily there are some medications that can alleviate the symptoms, albeit not the allergy itself.
Antihistamines come in many formats and are bandied about frivolously during the summer months. Antihistamines are chemicals that block your histamine receptors, binding to them and taking up the space where histamines would otherwise bind and cause a reaction. Different types of antihistamines target receptors in different parts of the body. First generation (older) antihistamines, such as Benadryl, cross the blood brain barrier and block histamine receptors in the central nervous system, which means they also have sedative properties. Second and third generation antihistamines are non-sedative, and generally considered safer because they remain in the body without crossing the blood-brain barrier.
To mitigate the inflammatory symptoms, decongestants are commonly used, also available over the counter. More severe reactions are sometimes treated with corticosteroids, but only short-term. Alternative approaches that are explored is desensitisation: a form of immunotherapy similar to vaccines where doses are built up to reduce the allergenic response over time. Excitingly, scientists are also starting to produce lab-made antibodies that target IgE to occupy it before it has a chance to interact with the allergen!
Conclusion
So there we have it: hay fever sufferers and peanut allergists alike - if it’s any consolation - your allergies are the result of your immune system evolving to try to look after you. Keep tissues and EpiPens to hand, and try to stay curious about the complex (and confusing) human body.
