1. Nobody knows why your nose is runny.

Or, rather, we know why your nose is running, but we don't know whether that drip does anything useful, or whether it's just an annoying side effect of the underlying immune response. And, right now, scientists tend to think that the runny nose — along with most of the nasty symptoms that, taken together, we call an allergy — really are just side effects.

It works like this: A grain of ragweed pollen gets into your nose, lodges in the mucous membrane and dissolves there, exposing pollen proteins to sensitive tissues. The proteins get picked up by dendritic cells. These are sort of the beat cops of your immune system. They patrol around, looking for shady characters, which they cuff and collar and take in for fingerprinting. Dendritic cells are part of a family of cells called antigen presenting cells, said Mitchell Grayson, associate professor at the Medical College of Wisconsin. They take all sorts of foreign invading antigens — in this case, pollen proteins — to the lymph nodes to present those antigens to T cells. If your T cells happen to have the "right" (or, you might say, "wrong") receptor that fits the ragweed pollen protein, then you will eventually have an allergic response. Eventually. First, though, the T cells have to send a message to their cousins, the B cells, to make a particular type of antibody called Immunoglobulin E, or IgE.

IgE is the stuff that causes allergies and it only exists in mammals. Fish, for instance, can't have an allergy the same way that people do. This IgE travels around your body and latches itself onto mast cells, fat dumplings stuffed with granules of histamine, and other chemical compounds. The next time your body encounters ragweed pollen protein, that protein no longer gets picked up by dendritic cells, which only focus on things the body doesn't recognize. Now, your body recognizes the pollen protein. In fact, it's made a bunch of IgE designed to match. And as soon as the IgE links up with the proteins, it triggers the mast cells to dump out their contents. What follows are the symptoms we're all familiar with. Histamine and those other chemicals in the mast cells are the stuff that cause inflammation in your mucus membranes — and all the itchiness, drippiness, congestion, and sneezing that goes along with it.

People have speculated that these symptoms might be the body's way of trying to force foreign invaders to leave. Something is trying to sneak in your nasal passages, and it won't get far if everything in your nose is running out. But that doesn't totally make sense. You body shouldn't have an immune response to ragweed pollen, in the first place, said Alkis Togias, branch chief of the Allergy, Asthma, and Airway Biology Branch of the National Institute of Allergy and Infectious Diseases. Pollen isn't dangerous. There's no reason to force it out. So nobody is really sure why pollen triggers the creation of IgE. And nobody is really sure why the IgE response process ends in a runny nose.

2. The first time you encounter an allergen is a freebie

Remember how I said it takes a little while for the T cells to get in touch with the B cells and for the B cells to start making IgE? Grayson said that process can take four-to-six weeks. And it's a completely silent process. You have no idea it's happening. That means, the first time you encounter an allergen, you won't think you're allergic to it. In fact, if you've just moved to a new place, with new types of plant pollen that your body hasn't come into contact with before, you might go through your first spring with no sign that anything is amiss. It's only a year later, after your immune system has been primed with lots of IgE, that the allergy will make itself apparent.

3. There are reasons to doubt the hygiene hypothesis

There are more people today allergic to more things than in the past. In fact, in the United States, 50% of the population is now allergic to at least one thing. Over the years, scientists have collected a lot of correlational data showing a relationship between higher rates of allergies and autoimmune disorders and the sort of cleaner, less-crowded living we've come to know and lover in developed countries. Those correlations have led to an idea that you have probably heard a lot about — the hygiene hypothesis. The basic idea is that your immune systems needs to be primed, early in life, with exposure to lots of different microbes — bacteria, viruses, parasites, etc. If that doesn't happen, the the regulatory cells that keep your immune system functioning properly as an adult never learn how to do their jobs right and so your immune system goes haywire — for instance, putting a lot of effort into tracking down and fighting completely harmless pollen. In other words: Too much hygiene in childhood equals more allergies later.

There are a lot of reasons why the hygiene hypothesis makes sense. But there are also pretty good reasons to suspect that it's not the only thing responsible for that increase in allergies and autoimmune disorders. For example, there's the other 50% of Americans who aren't allergic to anything, but who, when scientists compare them to the allergic, don't seem to have had particularly less hygienic childhoods. Another confounding factor is asthma. Asthma is basically just the lung equivalent of the IgE and histamine-caused inflammation that happens in nasal mucus membranes. It's an expression of the allergic response, but it doesn't seem to fit the hygiene hypothesis pattern. As a whole, asthma prevalence is on the decline in western countries, among both children and adults, and those countries haven't gotten any dirtier lately. Nor have family sizes increased. At the same time, asthma rates are rising among specific populations — like African Americans in the US who live in poverty. But the factors that would predict that according to the hygiene hypothesis — i.e., changes in living conditions that would reduce early childhood microbial exposures — haven't happened there either.

Scientists think the hygiene hypothesis is definitely on to something. But it's not the end-all-and-be-all that explains everything. There's still a lot more to learn.

4. Seasonal allergies are highly responsive to the placebo effect.

"Placebos work really well for allergies," Mitchell Grayson said. "The placebo effect is around 20-to-40 percent." That's an astonishingly high placebo success rate and it makes it really difficult to be sure that the stuff we give people to treat their allergies is actually, you know, treating their allergies. It also calls into question what "treating your allergies" really means. If a placebo works and makes people feel better, maybe that's okay. For instance, there have been studies that showed people taking Claritin experiencing a 46 percent improvement in symptoms, while people taking a placebo saw their symptoms improve by 35 percent. That's not much of a difference. So why take the actual drug?

Alkis Togias had a couple reasons. First, the high placebo success rate really only applies to the sort of drippy nose, runny eye allergies that, relatively speaking, aren't a huge medical issue. Asthma doesn't have that high of a placebo effect in play. And it wouldn't be advisable to use sugar pills to, say, fight off a case an anaphylactic shock. He speculates that the high placebo rate for nasal allergies is due to a couple of factors. First, there's the fact that describing nasal allergy symptoms is a subjective process. Nobody is measuring quantity of snot flowing out of people's noses. Instead, they're asking people how they feel. And that can really screw up data.

Second, he said, the FDA prefers to do allergy studies that start after the subjects are already experiencing allergy symptoms. If you started before the symptoms kicked in, you wouldn't know how many of your subjects were symptom-free because of the drugs and how many just didn't get allergies that year. On the downside, it also means that the studies are highly affected by regression to the mean. If you take a bunch of people at the height of allergy season, they're probably going to get better — even if you don't do anything at all — simply because seasonal allergies peak, and then get better. That's just how they work.

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