The science behind allergy immunotherapy shots

Allergic reactions range from annoying to deadly. A significant amount of modern medical research has been devoted to not just understanding how the immune system fights off pathogens, but also why it goes awry creating allergic reactions. The most effective way to stave off an allergic reaction is to avoid exposure to allergy triggers altogether, but for many of us, exposure to allergens from pollen, pets and other common sources is unavoidable.

There are a variety of medications available for the treatment of allergies, the most common being over-the-counter antihistamines. These drugs, as their name suggests, seek to inhibit histamines, which are immune system communication chemicals. Histamines are typically released in response to allergens and activate the immune system in a variety of ways including stimulating nearby tissues to inflame with blood and the production of mucus. Antihistamines are most effective when taken before the histamine is released, once the immune system has already been stimulated into action they have a limited effect.

There is a completely different approach to reduce allergic reactions. Rather than inhibit the histamine response, the idea is to change how the immune system reacts to the allergen. Typically this is done through injections of the allergen, which sounds counterintuitive. Ordinarily, repeated exposure to an allergen invokes the same or worse reaction each time. Pollen allergies, for example, aren’t thought to wear off after a while.  They are lifetime afflictions. So why or how should injection of pollen directly into the body have any kind of benefit?

Antibodies come in several flavors

The immune system is one of the most complex aspects of biology that can be considered a single system. It uses small tiny chemical differences in millions of different biomolecules to regulate several hundred cell types from memory cells to killer cells. This complexity allows it to mount a defense that’s both ready for many different threats and efficient in its use of resources.

Antibodies are one of the most impressive components of the immune system. Antibodies are also known as immunoglobulins and true to their name serve an immune function and have globular shapes. Antibodies are unique in that each one can be shaped to bind specific invaders in the blood and other bodily fluids. The body has systems to increase the presence of antibodies for known pathogens. It releases them free-floating in the blood and places them on the surface of memory cells. Different classes of antibodies are tuned to respond to different types of threats.

For example, Immunoglobulin A (IgA) is produced more than any other antibody and is mainly found in mucus in the gut and respiratory tract. IgA is the first line of antibody defense. 

Immunoglobulin G (IgG) is the second most common type and includes the antibodies mostly responsible for the acquired immunity against viruses we get from exposure like infection or vaccination. IgG is mainly found in the blood. 

Immunoglobulin E (IgE) is most important to allergies. While it is primarily responsible for defense against relatively large parasites like worms, it is also responsible for both allergic reactions and the acquisition of allergies.

Development of an allergy

Usually, the first time you are exposed to an allergen like pollen there is no allergic reaction. Instead, white blood cells digest the pollen and bring the allergens it contains to the rest of the immune system. There, a unique IgE antibody will recognize it, which stimulates the production of more pollen-specific IgE.  These will mount a response the next time pollen shows up. This response involves releasing histamines, which stimulate the body to produce mucus and inflame tissues. This response is great to flush foreign matter out of the mucous membranes or mire an invading worm in a pool of mucus, but if in response to pollen can be overblown. This overblown response is called hypersensitivity to an allergen. 

 

A) The allergen enters the body. B) An antigen-presenting cell takes up the allergenic substance and presents the unique allergens on its surface. The activated antigen presenting cell then migrates to the nearest lymph node. C) T cells recognize the allergen, which differentiate into Th2 cells. D) B cells recognize the allergen through the Th2 cell. E) B cells are activated by allergens. F) B cells differentiate into plasma cells, at which point they actively synthesize antibodies of IgE from the allergen. G) The IgE antibody that now recognizes the allergen molecule circulates around the body and attaches to mast and basophil cells. H) When the allergen re-enters the body at a later time it binds to the IgE resulting in an release of pre-formed chemicals. One of these chemicals is histamine which causes the 5 symptoms of allergic inflammation: heat, pain, swelling, redness and itchiness. Another mediator is IL-4, which tells more B cells to differentiate into plasma cells and produce more IgE and continue the vicious cycle.

Because of the interconnected nature of the immune system the individual genetics of each person can result in very different diverse responses to allergens from person to person. The acquisition of allergies is also subject to the vagaries of the chemistry that govern the extremely unique nature of antibodies. 

Hypersensitization can have varying levels depending on three factors.  The first two are how much and how many different forms of IgE have been stimulated and to what levels.  Lastly, it can vary to the extent that the body has started storing histamine in preparation for stimulation by IgE. Many different versions of IgE along with histamine ready to be dumped out are key characteristics of people with severe allergies.

Shifting the response

The idea of immunotherapy is to stimulate the immune system to produce antibodies other than IgE to react to allergens. IgE is the antibody class that releases histamines, which are best used to defend against worms and other large parasites. If IgG could react to the allergen instead, it would stimulate a different reaction that didn’t involve excess mucus or inflammation. IgG responds by recruiting offensive white blood cells more appropriate to kill a small virus or bacterium.

Immunotherapy involves injecting the allergen beneath the skin, taking it orally, or otherwise getting a small amount of it into the body in some way other than the exposure route that leads to IgE-based sensitivity. Instead, the allergens are digested and presented to IgG. 

Since they are designed for totally different threats, IgG mounts a response that counteracts the histamine-based methods that IgE uses. If allergy immunotherapy is effective, eventually the IgE response will be suppressed by the IgG response, and no or very little histamines are released when exposed to the allergen. This will also draw down the body’s stores of histamines as they are stimulated less and less.

A mast cell releasing histamine into the blood in the presence of allergens

Given that inflammation can be so destructive to bodily tissues, immunotherapy can be a great addition to other methods of reducing the impact of allergies. For allergy sufferers, any way they can reduce stimulation of IgE or histamine can have an impact on reducing the severity of the reaction.

Typically, allergy immunotherapy takes several months or even years to be effective. It starts with a build-up phase of very small and frequent treatments (a few times a week) to get the IgG response and lasts three to six months. Then a longer maintenance period of less frequent treatments with a steady amount of allergen determined by the response to the build-up phase. 

They aren’t effective for everyone, constant exposure to allergens by the normal route can keep the IgE response robust, or it might be challenging to identify the right allergen to use. For some people, their IgE responses may be so entrenched that the IgG response can’t even be initiated. There is also a risk of a massive reaction just from the therapy, which is why it is administered in doctor’s offices where future complications can be quickly addressed.

Allergies may be getting worse, so be sure to leave allergens outside by changing your clothes when you get indoors. This includes the mask you are wearing during the pandemic, pulling air through it all day will certainly saturate it with allergens. 

Indoor air purification can reduce airborne allergens, as well. Airborne pollen particles can be as small as 30 nanometers (0.03 microns) so be sure your purifier can capture very small particles. Alternatively, an air purifier that destroys organic substances might help to reduce the tiny fragments in the air.

Keep an eye on this blog, and our Facebook, Instagram, and Twitter for more information on what’s in your air.

 

Allergy sensitization diagram courtesy of Wikimedia Commons.

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