This can be answered in many different ways and at many different levels of detail. Here are 3 different types of answers to this question, depending on what you are looking for:

(1) The “short” answer, for those who just want the gist:

SLIT treatment engages special, tolerance-promoting immune cells in the mouth to attempt to influence and train the immune system to be more tolerant of allergens. These special cells are called oral Langerhans cells, and they are primed to suggest that the rest of the immune system choose tolerance of the substances they encounter, rather than an attack. This is presumably because they are the initial immune-system contact for our body’s vital nourishment substances – food and water – and if these cells were primed to promote attack signals like some other immune cells do, we would not be able to survive. The long-term, repetitive, slowly increasing but non-threatening exposures to allergens in this way over time begin to cause changes deeper with the immune system that can reduce the immune system’s ability and/or desire to react to exposures in the future.

(2) The “analogy” answer, for those who are interested in the overall concept:

Dr. Schroeder commonly tells patients to think of Sublingual Immunotherapy (SLIT) treatment as school for your immune system. Your immune system is the student, your SLIT allergen doses are the classes at school, and the tolerance-promoting signals your SLIT doses create for your immune system are the basic lessons being taught. The more frequently and consistently your immune system attends class (i.e. you take your SLIT doses), the more likely your immune system will begin to learn these basic lessons (i.e. to tolerate your allergens without over-reacting).

While your immune system continues to attend school (i.e. you continue on your SLIT treatment), the lessons grow and build on one another (i.e. your SLIT doses are adjusted and increase) until the main lesson (i.e. general allergen tolerance and an overall calm immune system) goes from initially having been an unknown concept to your immune system to now being a concept that is much more familiar and much better understood.

The longer your immune system continues to attend class (i.e. the longer you maintain your SLIT treatment), the more likely it is to potentially memorize the main lesson, thereby remembering it for some time after the course is completed (i.e. the more likely you may gain a period of sustained tolerance off treatment).

Many other factors also affect how well your “student immune system” learns the main lesson, such as whether or not there are stressors (i.e. major allergen exposures, illnesses, poor nutrition, lack of sleep, etc) interfering with your immune system’s ability to focus on learning this new lesson, whether classes (i.e. your SLIT doses) are regularly provided or are frequently canceled, and some additional factors outside of anyone’s control, such as whether your immune system innately learns quickly or slowly and whether it needs repetition to remember certain lessons or can memorize them.

There is generally a way to help any student learn and maintain the knowledge of an important or necessary lesson, though the route, method, and length of teaching time required will differ. Similarly, with allergy health, we can work together to find the way that works best for your immune system to learn the lessons you want it to learn.

(3) The more “technical” answer, for those who are interested in more of the medical processes:

The immune mechanisms involved in sublingual immunotherapy (SLIT), and any form of immunotherapy for that matter, are extremely complex. The full scope of this multifactorial process is not currently known, but several core mechanisms have been illuminated through study. There are some key differences between SLIT mechanisms and those of other forms of immunotherapy, such as allergy shots (SCIT) and oral immunotherapy (OIT), that suggest enhanced tolerance-promoting potential and broader immune-calming properties with SLIT.

In order to explain how SLIT can help improve your tolerance of allergens, it is first necessary to explain a little bit about how your immune system works and becomes allergic in the first place

When “messenger” immune cells (antigen-presenting cells such as dendritic cells, Langerhans cells, etc) encounter a substance in the skin, nose, stomach, etc, they process the substance, travel with it, and then share it and their suggestions about it with the “decision-making” immune cells (T and B cells). For example, if bacteria gets into a cut in the skin, the messenger immune cells in the skin will capture some of it to share with the decision-making cells and will suggest that this is an unexpected invader that needs to be removed. Next, these decision-making immune cells have to decide what they think they are looking at (a harmless substance, a piece of our own body, a virus particle, a bacterial particle, an allergen) and then how they want to respond. For the previous example, it would be recognized that the substance is a harmful bacteria, and then processes to kill the bacteria would be activated.

When the immune system decides to label a certain otherwise-harmless substance as an allergen, the B cells may go to work to “attack” it by producing something called IgE. IgE is an antibody that will bind to allergy cells to get them ready to react, and then help activate those allergy cells when the allergen is sufficiently present to bind to its IgE on those allergy cells – which causes an allergic reaction. Furthermore, these decision-making B cells also may create plasma cells that can “squat” in the body for years and just continue to mass-produce the specific IgE that can help activate allergic reactions. Additionally, the B cells can create memory B cells that can remember the earlier decision made about the substance previously encountered (that it is an allergen to be “attacked” with IgE), such that if the substance is encountered again, the “attack” response can be ramped up more quickly. These memory B cells can last years to decades. All of these layers and priming of pathways contribute to the intricate infrastructure the immune system creates over time to robustly react to allergens.

Here are the mechanisms we know of that are at play with Sublingual Immunotherapy (SLIT)

Sublingual immunotherapy uses special “messenger” immune cells in the mouth called oral Langerhans cells to capture the allergens in your treatment drops and provide tolerance-promoting signals to the “decision-making” part (T and B cells) of your immune system. These oral Langerhans cells are uniquely primed to suggest tolerance of substances they encounter, rather than an attack, presumably because they are the initial immune-system contact for our body’s vital nourishment substances – food and water. If these oral Langerhans cells were primed to promote attack signals instead, we would not be able to survive. Therefore, the sublingual (under the tongue) method of immunotherapy harnesses the natural purpose of this very special type of tolerance-promoting cell in order to attempt to train or retrain your entire immune system regarding harmless substances (allergens).

With consistent, long-term, non-overwhelming controlled allergen exposures (via SLIT), these oral Langerhans cells provide a persistent, wide-spread, tolerance-promoting influence to the immune system via their messages to T and B cells as well as the release of immune-calming natural chemicals. These natural chemicals are called cytokines, and each of them has a different effect, with some having the very important purpose of calming down the immune system. The previously built-up “attack-mode” infrastructure towards allergens (and sometimes even other inflammatory substances) begins to slowly come undone under this calming influence. If this “attack-mode” infrastructure hasn’t fully formed yet (such as with young children), these tolerance-promoting signals can help the immune system choose to change its course for the better before things get too bad (or get worse), which can remarkably prevent disease.

Once the immune system is in a tolerant state and the infrastructure to easily attack an allergen (or multiple allergens) has been broken down, the choice becomes whether or not to remain on the SLIT treatment that helped get you to this more tolerant state and may be maintaining you in it. For some people, if enough changes have settled in and if their outside influences (environment, diet, etc) do not seem like they would provide signals that would push their immune system back into attack-mode, a trial off SLIT would be appropriate. Many of these people find that they retain some or all of the benefit they were able to build while on the SLIT treatment for a prolonged period of time off of the treatment. For other people, their immune system may require the persistent calming influence of the oral Langerhans cells’ signals to keep their attack-mode immune infrastructure in check, otherwise it will start to rebuild. A longer or indefinite course on SLIT may be most beneficial to these individuals.

As the many gradual and intricate changes take place on SLIT treatment, tests like blood IgE and allergen skin tests each provide important information about one specific piece of the puzzle, but neither type of test will be able to provide enough information about the entire scope of changes that may be occurring at the time. Therefore, it is important to look at several factors including symptom relief, reactions to accidental exposures, and possibly multiple different types of test results in order to get as full of a context as possible about what may be occurring. There are some tests that have been used in research settings to measure the immune-calming chemicals released or evaluate portions of the infrastructure. However, these are not available in the clinical setting yet.