Allergies of the first kind---type I hypersensitivity explained in context

If you have kids you have probably been exposed to the idea that more kids have food allergies these days. Well, the data seem to bear this out. There are several hypotheses about why this is so, but not a lot of data. Rather than engage in speculation, I'd like to wade back into the dangerous waters of real science and tell you a little about allergies. Perhaps after you've read my grossly oversimplified explication, you'll come up with your own science-based hypothesis to explain increased childhood food allergies.

First, let's talk about what isn't going on. The Huffington Post, always a target-rich environment for woo-hunters, has a writer named Sloan Barnett. She is about as well-informed about health issues as Bill O'Reilly is about anger management. Two of her recent posts address child health, and both display a stunning level of ignorance. Her fetishization of "green" bears no relation to actual research on childhood health.

An example of her ignorance?

But what really stopped me in my tracks was that children with food allergies are two to four times as likely to have related conditions such as asthma or other allergies. And guess whose very own children have nut allergies AND asthma....

Um, yeah, Sloane. That's because food allergies, asthma, and related conditions are, er, related! Asthma, allergy, and atopy are all a type of immune dysfunction known generally as type I hypersensitivity. Its determinants are partly genetic, partly environmental.

Despite many studies, no one knows why this [increase in allergy] is happening. Here's what I know. My third child, who was raised in a non-toxic home, eating only organic formula and food, recently tested allergy free. Look, I can't be certain that our new lifestyle is the reason this baby is allergy free, but it sure does make you think.

Actually, one of the most popular theories in scientific circles is the "hygiene hypothesis" which roughly states that our cleaner and more sterile environment exposes our kids to allergens later. If they had been exposed earlier, their immune systems may have developed a tolerance for common allergens. This hypothesis is based on observational studies that kids raised with pets, on farms and other "dirty" places have lower rates of environmental allergies.

Still, we don't know why we have an increase in childhood allergies, and clearly, neither does Sloane. Her evidence is based on what she's heard and her own experiences, which is worth bubkes.

Alright, let's get to a little actual science.

A common question from parents after seeing a child's first allergic reaction is, "he's had it before and it never bothered him. Why now?" When you understand how allergies work, the answer will be clearer.

An allergy is a disorder of the immune system. It involves what's known as a "type I (immediate) hypersensitivity reaction". This reaction looks familiar to those with allergies: hives, wheezing, runny nose. Oh, and anaphylactic shock and death. But hopefully not.

The part of the immune system that goes awry during allergic reactions appears to have evolved to fight parasites. Most of the same cells and antibody types are involved both in fighting parasitic infections and in causing allergy, and this machinery is located in areas where parasites can invade---the skin, lungs, gut, etc.

This is how it works (and for another branch of the immune system, feel free to look at this...about halfway down the page). One quick fact---the immune system has both "generalist" and "specialist" branches. Some parts of the immune system will attack anything vaguely "not you". Other parts react only to specific invaders, and in the case of allergies, otherwise harmless substances are treated as invaders.

For an allergic reaction, you first need an allergen. Let's take peanuts. Let's say my kid eats some peanuts for the first time. She will not have an allergic reaction. Why not?

Because her body won't recognize the peanuts yet. The nasty symptoms of an allergic reaction are caused by a type of cell called a "mast cell"---when a mast cell attaches to an allergen, it releases granules full of fun things like histamine, which cause swelling and leaking of blood vessels, itching, hives, and difficulty breathing. But for a mast cell to "degranulate", it has to be coated with antibodies that recognize the allergen. And that can't happen until your immune system learns about the allergen.

Here's how we learn about a brand new allergen (sticking with the example of peanuts). Some of the proteins from the peanuts get picked up by an immune cell (dendritic cell) in the gut that's hanging out looking for new, nifty invaders. This protein gets taken in and processed, then presented on the surface of this patrol cell. A T-cell comes along and happens to (randomly) be able to recognize this protein (now called an allergen). Other bits of peanut protein are picked up by B-lymphocytes, who chop them up and put the pieces up like a sign on their membranes. The T-cell gets very excited and produce a number of chemicals that tell B-cells to make lots of IgE, a type of antibody.

This IgE, which is produced specifically against this peanut allergen, attaches itself to mast cells. The B-cells that make this anti-peanut IgE are specific for the particular peanut protein. That's all they do. They cannot recognize, say, tree pollen. The anti-peanut IgE-covered mast cells then hang out waiting for the next dose of peanuts, and when they are exposed to them again, all hell breaks loose.

The point here is that when you are exposed to peanuts for the first time (or any allergen for that matter), your mast cells don't yet have a clue. They aren't covered with anti-peanut IgE and you cannot mount an allergic response.

So why don't your body's immune cells just react to everything? Why don't they, for instance, attack their neighbors? Well, sometimes they do, leading to auto-immune diseases such as multiple sclerosis and lupus. But early in development, when your immune system is young, it works a bit differently. If, for example, a B-cell or T-cell happens to recognize something that's part of you, say cell in the thyroid gland, instead of gearing up for a reaction, it shuts down. Your body learns to "tolerate" itself. This is another reason that some people hold to the hygiene hypothesis. Since we isolate our kids from so many foods, molds, dirts, dusts, and other nasties, perhaps our kids never learn to tolerate them.

Or perhaps not. Either way, Sloane's hypothesis, that our kids are exposed to all sorts of "toxins", doesn't seem to hold with science. In fact, isolating kids from the real, messy world may have the opposite of the intended effect.

Hey, we certainly don't know enough yet to recommend either putting your kid in a bubble or rolling them around in dirt. But that's the point---this is something we can study. We don't need bad science writers spreading fear of...well, of what I'm not sure. But I'm sure if it sounds vaguely scary, the Huffington Post will make something up.


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lol Ive been meaning to blog on this. Sooooo many allergy stories since I moved to Oklahoma. NEVER had allergies until I moved to here. Even Arnie has allergies for Petes sake.

Oklahoma, where the wind comes sweeping down the plains... full off ceder pollen and rag weed.

*head desk*

Link between feeding an infant before his/her digestive system is fully developed and allergies later in life?

I still find allergies a little bit inexplicable, I was raised on a farm, I have no allergies that I am aware of, my brother who was raised right alongside me has a list of food allergies as long at his flaky red arm. I'm sure we'll come up with the answer soon, but for now there just doesn't seem to be enough evidence out there to support a theory.

I know ASCIA here in Australia have been pushing for more research on the sterile environment = more allergies front. Their latest infant feeding guide goes so far as to suggest introducing allergens early, in a very cautious hedging manner. I think its the right approach, I just wish we could get some evidence.

By CaladanGuard (not verified) on 02 Nov 2008 #permalink

This is a great post, PalMD. I'd really like to hear you discuss inhaled steroids as maintenance therapy in asthma -- a topic in which Dr. Isis has an intelelctual interest. I worked for a good bit of time to convince patients to put down their daily Albuterol or even Serevent in favor of a daily steroid or steroid/beta 2 combo. My experience was that as soon as some people hear the word "steroid" they completely lose their junk. Now, there is clearly a difference between long-term oral prednisone and inhaled Advair or Symbicort, but for some patients their only experience has been with an oral steroid during an exacerbation and they remember the experience less than fondly. Granted, Dr. Isis is aware of the potential for oral fungal infections and what-not, but she thinks this relatively small risk (and relatively easily treated) is probably preferable to airway inflammation.

Now, luckily Dr. Isis could always bat her eyelashes and get most patients on board, but how do you talk to the patient who has a knee-jerk reaction to inhaled steroids?

Any chance you'll do a follow-up on immune reactions to foods normally called "intolerances?" These reactions tend to take longer to appear and are not histamine-related -- that is, there isn't immediate swelling, but GI trouble, neurological problems, and/or fertility issues.

As a person with allergies, pretty well controlled, but still problematic when the trees have their hypersexual love in twice a year, I'm interested in the subject.

Question one: The 'hygiene hypothesis' makes a lot of sense. A friend who did her anthropology research in a very fragrant third-world country noted that the kids there don't seem to get allergies. They are dirty, smelly, malnourished and uneducated kids who are often shot through with parasites. But they don't have allergies.

Given that the hygiene hypothesis has been around for so long why aren't there more answers? Seems to my uneducated eyes that answering that question would be a clear breakthrough in understanding our immune defense systems. Is there anyone working on the question?

Question two: In various scientific and pseudo-scientific literature there is the idea that if you tend to develop an allergic reaction to something that if you eat this substance and gradually increase the dose you body can acclimate to it.

I vaguely remember reading about some lab animals that were prone, genetically engineered?, to have arthritis. according to the story they were fed a diet with an increasing amount of cartilage and their arthritis was, in time, moderated. Might have been a scientific study, might have been a guy torturing animals in his back yard. Is there anything to the idea that the body can be reacquainted with substances through the digestive tract and stop seeing them as allergens?

It makes some sense I guess seeing as that you wouldn't go very far if you became allergic to and stayed allergic too what you depended on for sustenance. The sensitization mechanism you outline has to have some moderator that allows the immune system avoid learning new, or even to unlearn, allergens.

It makes some sense to me that this mechanism would be mostly, or most active, in the digestive tract. Where you need to be able to interact with, consume and extract energy from, foreign tissues without having your immune system explode.

I was actually thinking about adding a section on desensitization therapy but ran out of gas. I'll perhaps explain it in more detail in the future, but the idea behind allergy shots is to tone down your immune response.

You can also be desensitized to necessary drugs. If you are unfortunate enough, for example, to be allergic to penicillin and contract syphilis, you will likely be told to undergo penicillin desenitization, where gradually increasing doses of pen are given in a controlled setting.

This topic is interesting.

I had all the 'advantages' of the 'hygiene hypothesis': breast fed, raised on a small farm, cats and dogs in the house, an older sibling.

I'm not aware of any allergies (except poison ivy). I had all the regular childhood diseases (born 1950), but very mild doses.

Good post. It isnt just allergies and asthma that are involved in the hygiene hypothesis, but heart disease, diabetes, hypertension, obesity, essentially all of the diseases of modern civilization. All of them are rare to non-existent in the rural undeveloped world.

My own hypothesis is that the differential effects of living in the rural undeveloped world and the developed world derive from the loss of ammonia oxidizing bacteria living on the external skin which metabolize the ammonia in sweat into NO and nitrite and so set the basal NO level. When a region becomes developed, there is abundant clean water which is used for bathing. The ammonia oxidizing bacteria are slow growing (doubling time ~8 hours), so it is easy to wash them off faster than they can proliferate.

Intestinal parasites cause the release of NO from iNOS and are being experimented with as a treatment for Crohns disease and IBD (trials have shown excellent results).

NO is one of the major regulators of the immune system, with NO inhibiting NFkB, the major transcription factor regulating inflammation. Low NO increases the sensitivity of mast cells to degranulation. NO is also what regulates mitochondria biogenesis (I think that is the main pathway for low NO causing heart disease, diabetes, and obesity, but they are all related). NO also regulates angiogenesis, bone density, steroid synthesis, and lots of pathways in development.

There is some thought that peanut allergies may be due to peanut allergens in peanut oil used topically. Allergens from the gut are usually from foods, allergens on the skin are usually from non-foods. Avoiding food-nut oils in cosmetic products might be a good idea. They might be ok the first few times, until you become sensitized to them, then it is too late.


I don't run into too many problems talking people into inhaled corticosteroids. I do go over with them the fact that the side effect profile is quite good (aside from the mostly-preventable thrush, which my wife just got over!).

As you said, batting the eyelashes (or whatever kind of connection you can make with a patient) goes a long, long way to convincing people to doing what they need to.

ERV, my sympathies. Ceder pollen is vicious. The second ceder season in Austin when the car regularly had an eight of an inch of yellow dust covering it in every morning really sucked. Ceder fever is no fun at all.

Allergies are a fascinating and frustrating topic... I like to blame my own asthma and allergies on growing up in a cigarette-contaminated environment (my father smoked 1+ pack/day all through my childhood), but have absolutely no data to support that. I didn't grow up in a manically-cleaned, sanitized environment, either, and lived in all kinds of environments from semi-rural to big-city when I was a kid.

By liveparadox (not verified) on 03 Nov 2008 #permalink

I second the request for more on "intolerance." I have a personal interest in IgG reactions.

I developed most of my allergies in my 20s. My mast cells must be slow learners.

Has anybody looked at correlations between decreasing infant and child mortality (from "unknown causes") and allergies? It seems plausible to me at least (disclosure: not anything like an expert) that more people with the genetic determinants are living longer, and perhaps the genetic components are becoming more common in the developed world's population.

By Interrobang (not verified) on 04 Nov 2008 #permalink

Charles Richet won the 1913 Nobel Prize for his anaphylaxis research.....
"Charles Richet and Paul Portier were able to isolate the toxin and tried to vaccinate dogs in the hope of obtaining protection, or "prophylaxis," against the toxin. They were horrified to find that subsequent very small doses of the toxin unexpectedly resulted in a new dramatic illness that involved the rapid onset of breathing difficulty and resulted in death within 30 minutes. Richet and Portier termed this "anaphylaxis" or "against protection." They rightly concluded that the immune system first becomes sensitized to the allergen over several weeks and upon re-exposure to the same allergen may result in a severe reaction."

The researched continued with Betty J. Hargis, Saul Malkiel and Leon S. Kind in the 50's-60's.
Here's one of many........
The Journal of Immunology, 1970, 104: 942-949.
Production of Hypersensitivity in the Neonatal Mouse

More of what I've found............

Erm, Rita, I'm not sure what to make of your post... it seems fairly sensible, but then at the end you link to of all places. What the hell?

Julius, i did a bit of a WTF as well. She mentions some distant historical research which is somewhat interesting, then randomly pulls a It's hard to take anything that precedes such a link seriously.

Rita, I am sorry but you have invoked Scopie's Law:
"In any discussion involving science or medicine, citing as a credible source loses you the argument immediately ...and gets you laughed out of the room."


Maybe Rita is invoking Poe, since it was thrown in at the end?

No, I don't think she was invoking Poe. She was not going for a parody... especially with throwing in 38 and 90 year old studies like they had any significance.

By the way, she seems to imply she found them on, which is consistent with the papers found there. Scudamore loves stinking old papers. It is often surprising that he has one that is less than a quarter century old, most are often a century or two old.