This post initially appeared on Science Blogs

One of my favorite places on the internet is r/askscience, a place on reddit where people come and ask questions, and a panel of scientists answer. People can ask follow-up questions, and there is often some great back-and forth (to be honest, part of the reason I haven't been writing as much here is because I'm using up all my time over there). Recently, an number of people have been asking questions about allergies - Can people grow out of allergies? Why is the incidence of allergies increasing? Can eating honey cure allergies?

You can check out those threads if you want answers to those specific questions (I'm commenting as "KeScoBo"), but I decided I wasn't done after my semen allergy posts, and thought it would be a good idea to go back to basics. From the perspective of the immune system, what are allergies, and how do they arise?

At its most basic level, an allergy is an inappropriate immune response to a non-harmful substance. But there are many ways the immune system can respond that wouldn't cause problems - they key to allergies is that your immune system thinks that pollen is a worm.

To back up a sec - as soon as a pathogen breaches the barriers of our skin or epithelial tissue, the immune system kicks into gear. Receptors on the surface of specialized immune cells or on the inside of normal cells fire off, indicating the presence of an infectious agent. Macrophages do their best to clear out the invades, dendritic cells run off and sound the alarm in nearby lymph nodes, and signaling molecules called cytokines and chemokines activate and recruit a massive influx of immune cells from the blood. But not all infections are created equal. Depending on the type of pathogen, different receptors will be triggered, and the immune system will tailor its response appropriately. Broadly speaking, there are three major types of pathogens that the immune system needs to respond to:

  1. Intracellular - these pathogens (all viruses and some bacteria like Listeria) live most or all of their life inside our own cells. In order to deal with them, the immune system needs to be able to identify and kill infected cells, while preventing new cells from becoming infected.
  1. Small extracellular - These pathogens (mostly bacteria, some fungi) live outside of cells. They are small enough to be eaten by phagocytes, but often reproduce very quickly and produce toxins that can kill or manipulate healthy cells.
  1. Large extracellular - Pathogens like worms can't be eaten by our own cells, and they can't be neutralized with antibodies. They only way to deal with them is to make their living environment terrible and try to flush them from the body.

One of the differences between these different immune responses is the selection of antibody isotypes. The binding sites of all antibodies are generated in the same way, but during an immune response, the B-cells that are participating are instructed to choose a particular butt depending on what type of pathogen their attacking. IgG is good at binding and neutralizing viruses and toxins, IgA can be shuttled across mucosal barriers, and IgE is good at making your life miserable.

Actually, IgE is the antibody isotype (butt) most associated with allergic reactions, and its "natural" job is to fight worms. Worms are mutlicellular, and often WAAAAAY bigger than our own immune cells. Because of this, the combat strategies that work well for viruses and bacteria are useless against worms - it'd be like trying to fight off a grizzly bear with a fly swatter. Instead, IgE arms the hand grenades - immune cells called granulocytes are filled with noxious chemicals, and chemical messengers like histamines. When the IgE coating the surface of these cells bind to something, the cell explodes - flinging poison and death at anything in the area. Allergens trick your immune system into thinking they're a worm. Your immune system freaks out, and starts flinging hand grenades every time you inhale. As you might imagine, damage and misery result. Up next: what makes your immune system think "worm."