A few months ago, I talked to you about The Science of Anaphylaxis. We started our exploration of an allergic reaction with a mast cell that had IgE antibody to a food allergen on its surface, learned how allergic reactions are initiated, and ended the conversation with the signs, symptoms, and treatment of anaphylaxis. But how did the mast cell get that IgE antibody to a specific food on its surface in the first place? How did the mast cell get primed, so to speak, for an allergic reaction? How do we become allergic? Well, we become allergic through a process called sensitization. So here, my friends, is the foreword to The Science of Anaphylaxis, it is The Science of Sensitization. We will discuss in depth one of the ways that an individual can become allergic. I think you are ready for this, but just like the last science post, you may need to read it a few times. (I had to write it a few times!)
Okay, here we go. When an individual eats a food, (let’s use peanut as our example again), it enters the gastrointestinal (GI) tract and begins to be digested. At some point during this process, the tiny peanut protein passes through the wall of the GI tract. Through a series of events, the protein finds its way to cells in the blood stream and lymphoid tissues. This is where the peanut protein stumbles upon a type of cell called an antigen-presenting cell. Antigen-presenting cells do exactly that – they present (or show) antigens (allergenic food proteins, for example) to other cells. An antigen is a foreign substance that initiates an immune response by the body. This immune response usually includes the creation of antibodies that help to rid the body of this foreign substance. Many types of cells can act as antigen-presenting cells. In this example, the antigen-presenting cell will be a B cell.
When a B cell (seen in blue in the figure below) encounters peanut protein, it takes the protein from the outside and internalizes it. It processes the protein and then puts it on a molecule that resides on the surface of its cell (see the B cell with peanut protein on its surface molecule below). The peanut protein on the surface of this B cell will then get presented to a T cell (shown in green). Believe it or not, this T cell has on its surface a peanut-specific receptor, as well as receptors for so many other proteins. When this receptor on the T cell sees this peanut protein on the surface of the B cell, the cells realize that they have something in common and they begin to communicate. The conversation between the B cell and the T cell is intense and complicated. There is an automatic connection between them. They come into contact with each other’s surface molecules and engage in other receptor-based physical interactions. They also spew out cytokines (chemicals) as another way to converse with each other and boy, do they have a lot to say! The T cell specifically releases IL-4 and IL-13 and these cytokines cause the B cell to undergo several changes. These changes eventually lead to its secretion of peanut-specific IgE antibody represented by the blue Y’s in the figure below. (IgE stands for immunoglobulin type E. It is a type of antibody that aids in ridding the body of parasites and plays an important role in allergic reactions.)
This is tough. Try picturing the B cell and T cell in the figure above like two people. They meet each other in the middle of a huge crowd and they have instant chemistry. They recognize something in the other person that they are attracted to. They share a good handshake, a strong hug. They have a common interest in food. They talk easily. They effortlessly exchange information. Their interaction ultimately is so powerful that it changes their lives forever. This is romantic stuff.
Now back to the science… we left the B cell churning out peanut-specific IgE antibody while under the influence of IL-4 and IL-13. It has the ability to secrete antibody specific to whatever food protein that it originally encountered. It could be egg, wheat or cow’s milk, for example. Remember from The Science of Anaphylaxis that an antibody looks like an arm with a hand on the end (shown in blue and attached to a mast cell in the figure below). These peanut-specific IgE antibodies are now flowing in the blood stream in an attempt to find and bind to high-affinity (very sticky) IgE receptors on mast cells. These IgE receptors on mast cells are perfect, sticky landing pads for the circulating IgE antibodies. When the peanut-specific IgE antibodies bind to the IgE receptors on mast cells, this marks the completion of the process of sensitization.
The process that I described occurs in atopic individuals (those with a propensity to become allergic). In the case of these allergic and now-sensitized individuals, once the mast cell has the peanut-specific IgE attached to its surface, it is primed for a reaction the next time the peanut protein appears in the body. This means that the next time a peanut-sensitized individual encounters a peanut, the signs and symptoms of an allergic reaction or anaphylaxis can occur.
Now I am going to confuse things a bit but only in hopes of answering some questions that may have come up for you. It is good to keep in mind that the process I have described does not end in sensitization in non-allergic people. An individual without a genetic predisposition to allergy will likely undergo what is called, tolerance, instead. They will have similar cellular communications that result in that individual’s ability to safely eat (tolerate) a potentially allergenic food.
Imagine it like this… When two people meet, there is a better chance that they will simply and happily co-exist with each other (or tolerate each other) than there is a chance that they will instantly hit it off. These two people may exchange small talk but they do not cause a radical change in the lives of one another. They don’t move the other one into action. Tolerance is what normally happens. Allergic sensitization is the exceptional response.
You should also know that there are some individuals who undergo sensitization but do not react the next time their cells encounter the allergenic food. They are not clinically allergic. See, I told you this was confusing! These individuals go through this process but do not react to foods. This group of individuals is fascinating and likely holds a key piece of information in the search for the treatment or cure of food allergy. I mention this in order to teach you that not every positive blood test indicates that an individual will have an allergic reaction to that food. So think twice before you ask your physician to draw extensive “panels” of blood tests (food specific IgE antibody levels, also referred to as RASTs or ImmunoCAPs) to foods that there is no history of a reaction to in order to diagnose food allergies. This practice can lead to an over-diagnosis of food allergy and thus, an unnecessary over-avoidance of food. It can also lead, perhaps, to the avoidance of food that the person was eating safely just the day before.
I hope that piece gives you a deeper understanding of how some of us become allergic. I have left many of the nitty-gritty details out of this explanation because it is simply not easy material, but I am confident that you will be able to get the big picture. If you want to work through this whole story, read this post and follow it up with The Science of Anaphylaxis. It will bring the allergic puzzle together for you – sensitization followed by allergic reaction.
Please share this post with your friends! Even if they don’t have food allergies, the process of sensitization is basically the same for those people who are allergic to pet dander, tree pollen, ragweed or other environmental allergens. And we all know someone who is sneezing and rubbing their eyes as spring draws to a close and summer grass pollen fills the air!
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