Why do alpha-gal allergies only occur after a tick bite if alpha-gal is already present in red meat? I just read an NPR article about allergies to red meat being caused by tick bites. That stood out to me because I thought allergies are triggered by an initial exposure to some allergen. In this case, the allergen is alpha-gal, a disaccharide found in cell membranes of most mammals; humans and apes are a notable exception. The article explains that ticks might cause this allergy by transferring alpha-gal from other animals to us when they feed on our blood. However, we also are exposed to alpha-gal every time we eat red meat. How are we protected from allergic reactions when we eat red meat but not when we eat peanuts? Why does that protection fail after alpha-gal is exposed to our bloodstream?

In order for the immune system to respond to an antigen, beyond recognition of that antigen, there needs to be a signal that there is something wrong. Co-stimulation can take a few different forms, but it requires the involvement of more than just one arm of the immune system, and generally helps prevent our immune system from what I like to call the Dr. Strangelove effect (a psychotic lone general can just decide that there is a problem and launch an attack). Here, costimulation might be from (or downstream of) the tick bite and other invaders associated with the tick bite, or from an allergy to peanuts. You can read about this in the first chapter of Sompayrac's How the Immune System Works, as well as the first chapter of Abbas Basic Immunology.