Food allergy

A food allergy is a medical condition where there’s an abnormal immune reaction to some food. Now, a variety of food proteins can cause food allergies, but the most common are known as the big eight, these include proteins within milk, eggs, peanuts, tree nuts, seafood, shellfish, soy, and wheat.

Food is essential to life, and normally food doesn’t cause an allergic reaction - in fact, the process that allows for that is called oral tolerance. Let’s see how that works. Normally, when food travels through the stomach and intestines, the proteins within them are broken down by gastric acid and proteases into tiny fragments, called oligopeptides - small strings of amino acids. These oligopeptides reach the Peyer’s patches which are bits of tissue along the intestinal wall where M-cells live. M-cells are intestinal epithelial cells in the gut that grab protein fragments from the intestines and then transfer them to antigen-presenting cells like dendritic cells. Dendritic cells present them on their cell surface to a nearby helper T cell. The protein fragments are presented by the dendritic cell using an MHC class II molecule, which is basically a serving platter for the helper T cells. The helper T cell is key because it largely controls the immune response. Now here’s the catch, even if a helper T cell binds to that oligopeptide, another type of T cell called a regulatory T cell can release cytokines so that the helper T cell undergoes anergy. Anergy is a bit like turning off that helper T cell so that it doesn’t induce an immune response. In other words, regulatory T cells release cytokines in the lining of the intestines to help prevent the helper T cells from ever getting stimulated by food.

Now, in food allergy, this process doesn’t work properly. An allergic reaction towards food happens in two steps, a first exposure, or sensitization, and then a subsequent exposure, which usually gets a lot more serious. So, let’s say a person eats shrimp for the first time, and for some reason the helper T cell is able to generate an immune response towards the proteins within shrimp. Now, once shrimp proteins reach the small intestines, M cells grab the shrimp proteins and transfer them to dendritic cells that present shrimp proteins on their MHC class II molecules to helper T cells. Helper T cells that recognize this antigen will bind to it with their T cell receptors, and based on the cytokines that are floating around they mature into type 2 helper T cell, or TH2 cells. TH2 cells release a variety of cytokines like interleukin 4. This interleukin 4 gets nearby B cells that also recognize the protein to switch from making IgM antibodies to making IgE antibodies which are specific to the shrimp protein. These shrimp-specific IgE antibodies are able to attach to the surface of mast cells and basophils. At this point, the sensitization phase has come to an end and the mast cells and basophils are ready for action.

Now, let’s say that the same person eats shrimp again, a few months later. That’s the second exposure leads to a type I hypersensitivity reaction. Specifically, the IgE on the surface of the sensitized mast cells and basophils will bind to the shrimp antigen. When two IgE antibodies that are near one another both bind to the same antigen, it’s called crosslinking. When two IgE antibodies crosslink on the surface of a mast cell or basophil it sends a signal down into the cell, which makes that cell degranulate and release a bunch of pro-inflammatory molecules like histamine. This histamine gets into the intestinal tissue as well as into the blood. The histamine often binds to H1 receptors stimulating free nerve endings near the skin, which causes hives and itching. It also causes blood vessel dilation and increases the permeability of the walls of the blood vessel, which causes fluid to leak out into space between cells, which causes edema and swelling of the lips. In a severe case can cause so much fluid to leak out of the vessels that it leads to hypotension. Histamine can cause the smooth muscles around the bronchi in the lungs to contract, which means the airways get smaller, and it makes breathing difficult. All of this happens within minutes to hours of the second exposure. When all of these symptoms occur and breathing is affected it’s called anaphylaxis, and sometimes there can be a biphasic reaction which is when the symptoms improve and then get worse again over the course of a few hours.