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Why do we have allergies? (mosaicscience.com)
97 points by Hooke on April 7, 2015 | hide | past | favorite | 57 comments


> Suddenly the misery of allergies took on a new look. Allergies weren’t the body going haywire; they were the body’s strategy for getting rid of the allergens.

Well of course. I'm just a layman when it comes to allergies, but I thought it was well understood that allergies were the body's inflammatory reaction to an allergen, i.e., an attempt to eliminate (or otherwise neutralize) the allergen. The problem is that, according to the conventional wisdom, the body's reaction to allergen is mistaken. Presumably the body is attempting to target and eliminate something that is actually harmful, but it winds up responding to something harmless, or by triggering a response so severe that it does more harm than good. That's, broadly speaking, the difference between an allergen and a pathogen/poison. A poison/pathogen will actually harm you if it is not eliminated. An allergen will not (or, at least, not in proportion to the severity of the reaction. But I don't see why the observation above has anything to say about the real question, which is why does the body sometimes mistakes one for the other, and freaks out in the presence of harmless substances?


It's not an inflammatory response, it's an immune response. The inflammation is simply a side effect of the immune system swinging into action.


I have theorized that allergies, such as cat allergies, may, in some cases, be your body's way of warning you that there are Big Cats in the vicinity and you should GTFO.


This is not how Type I hypersensitivity works. Epitope recognition is powered by a biological RNG (somatic hypermutation) and evolves at runtime via the process of somatic / V(D)J chain recombination. Your body learns to be allergic, perhaps due to a bad ashy vent (you got sick that one spring), under-stimulation (play outside!), or just plain bad luck. Unfortunately for all of us, the immune system has no concept of the innocuous nature of harmless antigens. It will continue to pick up bad habits until the day we die. But thankfully it also keeps the trillions of cells, leaky programming, our own broken and errant self, and other uninvited guests that would just as soon eat us at bay (bacteria, viruses, cancer, fungi, nematodes, ...).


Did you just say that allergies are never genetic?


No. I described at a high level just one of the mechanisms of adaptive immunity--one of the most incredible biological systems in my opinion. (Runtime metaheuristics search!) These are complex pathways that involve many genes.

If the system isn't working you probably won't live very long. And while there may be certain functional alleles that may increase odds of an initial false positive stimulation, by in large the entire class of failure known as "allergic reactions" is simply a result of how the system itself works. You don't really need to invoke genetic differences to see how it fails. This is why the hygiene hypothesis is so strong.

There are actually four major categories of hypersensitivity that involve different cell populations and signalling pathways (eg. why poison ivy allergy is different from pine allergy).

If you're interested, the Wikipedia articles aren't a bad read. I also recommend Janeway's Immunobiology as a great intro to the entire subject.


Are "autoimmune disorders" another label for a class of failures of this search and respond system?


Loudly sneezing, blurring your vision, and ruining your sense of smell are really not conducive to surviving an encounter with a big cat.

I mean, you might piss it off if you sneeze on it, I guess. Yay?


It's an environmental allergy, not an emergency one. If you notice you feel like crap in a certain place (because cats like to lurk there), and subsequently avoid it, that's a win.

Not that I necessarily believe that's a good explanation for allergies, but it's plausible enough to think about.


Costs vs benefits.


When plants are stressed by bruising from machines, poor storage after harvest, poor soil, or various pesticide/fungicide exposures, they produce defensive toxins, for examples chitinase and solanine. These various chemicals trigger reactions when humans consume the plants. There's a credible argument that the increased "intensity" of modern agriculture has resulted in stressed plants dominating the modern food supply. This is very easy to see if you buy fresh potatoes. The ones that have been cut up a bit by the harvester often smell weird, taste bad, and can even be a bit green with solanine production. You'll find it's typically much harder to get good potatoes in March and April as the ones on sale have been in cold storage a long time and are stressed.

I think peanuts as a crop have suffered from very intensive industrialization more than other crops. Also, I have read that the storage facilities have problems with mold growth. Many peanut butters test positive for mold toxins.

With many of these food allergies where people wonder why it seems to be a modern phenomenon can probably be linked to the degradation of the industrialized food supply.

Furthermore, the ongoing stress of slightly toxin loaded food primes the immune system to over-reactivatity. Things like pollen allergies are aggravated.


Under this proposal, would the prediction be that someone who has a "peanut butter allergy" could eat peanut butter made under special conditions (cleanroomesque greenhouse environment, lots of TLC to the plants, and with screening to ensure that no molds were impacting the final product) without having the reaction?


I spent my early childhood in a third world country, and I never heard of anybody having an allergy. It was one of the surprising things I learned about when I moved to the first world.


In my case it seems I only got what seems to be allergies when I moved to the city some 5 years ago. In my rural area I don't remember ever sneeazing so much as if I was gonna die.


The structure of this article makes it difficult to read. It's a news article written as a story; endless lead-up and back story where there should have been thesis and defense of that thesis. Or at least summary and then summary with more detail and then full details.


Billy was just a regular ol' schmuck in Anytown, USA who wouldn't read anything technical unless there was a human element in the story that he could relate to.

Not sure if there's a name for that literary mechanism, but pretty much every NYT article and every other TED talk starts out with that kind of human element. A thesis and a technical defense of the thesis is what journal submissions do... other mediums find their engagement through the human struggle (eg the immigrant who escaped the crumbling soviet university system and became the nobel-slighted yale academic with a promising rogue theory).


> “You’re sneezing to protect yourself. The fact that you don’t like the sneezing, that’s tough luck,” he said, with a slight shrug. “Evolution doesn’t care how you feel.”

Well, as somebody that has allergic asthma, I've had episodes so severe that I thought I was going to die and I ended up in ER about 3 times. Then due to a 1 year treatment with Symbicort, my asthma is now in control and I haven't had episodes or felt the need for treatment in years. However asthma can always come back and it is something you leave with.

Allergic asthma is also correlated with heart problems, like for example I suffer from supraventricular tachycardia from time to time and treatment for one has a negative impact on the other - broncho-dilators or corticosteroids are known to produce tachycardia episodes as side-effects.

Therefore I have a hard time not thinking about my asthma as being a disease and the only reason I can have a normal life right now is due to modern medication that wasn't available 15 years ago.


Is the cleanliness theory completely discounted now? It's not mentioned in the article. The idea is that there are so few pathogens in the environment during childhood so the immune system can't tune itself. So then it reacts out of proportion to some trigger substances which then form the basis of the allergy.


This study supports what you are mentioning: http://www.health.harvard.edu/blog/children-eat-peanuts-earl...

However, I'm not sure it would be called a cleanliness theory..


It's called the hygiene hypothesis:

http://en.wikipedia.org/wiki/Hygiene_hypothesis


Seems like a misnomer then, eating allergies wouldn't be considered hygiene related, would they?

Even pollen isn't really hygiene related.


When did it get discounted? I thought there was a reasonable amount of evidence supporting it (at least the last pop-science TV show I watched on the subject suggested that).


Interesting, and it makes sense. To summarize:

1964 theory: Allergies are caused by a misfiring reaction to generally harmless compounds that have a similar structure to proteins presented by parasitic worms.

Medzhitov's theory: Allergies are caused by the body mounting an intense immune response to compounds that are actually harmful and need to be eliminated.

..or so the article says. I don't know how true that is.

What I find much more probable is that the answer is somewhere in between. It's ridiculous to suggest that ALL allergens must look like worm proteins to the body. Why just worms? Why have such a specific restriction?

However, I also don't agree entirely with Medzhitov. In order for his theory (as presented in the article) to be correct, he has to prove that every single allergen is actually harmful. How does this explain food allergies? Why do peanuts harm one person but not another? It's possible, but it's a big task to prove.

So while I don't agree entirely with him, I think his theory is very close. I believe it more probable that some allergens are actually harmful, but that there are also harmless ones that are interpreted as harmful by the body and thus elicit an allergic response.

The biggest question to answer is why different people have different reactions to allergens. We're all exposed to pollen, after all. But.. what if there's an (unknown) compound that looks like pollen to the body, but is actually harmful? It would rightfully train the immune system to react to a specific molecular signature to eliminate the threat, but simultaneously train it to wrongfully respond to a harmless element.

No idea! I look forward to seeing the outcome of his research.


Oh! rediscovering basic science: allergies are violent reactions to toxins!

My physic teachers used to say science is not about why but about how.

Why is religion, how is science.


So, is there a compound in say, peanuts, that "rips apart cells"? I can see the logic as applied to bee venom (though bee stings might in themselves be enough of an incentive to leave the area) but not so much the many other seemingly harmless allergens.


I think the article is implying that heightened defenses equals heightened false positives. Peanuts would be a false positive to something else that is actually harmful.

So if you have an allergy to peanuts it means your body is primed to defend against something in which peanuts are only a side effect. The author implies that if you have allergies, you have better defenses against other things.


Peanuts are a new world plant which is probably why it's a more common food allergy.

It'd be interesting if people of indigenous decent from south america are less likely to have peanut allergies.


What I always puzzled over was the following: if our main goal in life is, in fact, to survive/live (and insure the existence of our species through procreation), why would our body, in the case of an allergenic reaction, mount a defense mechanism that could kill us? If your body swelled up to the extent of restricting your ability to breath, why wouldn't your body recognize this as a threat to your existence and counteract the measure? Even if your system made a mistake reacting to the allergen, wouldn't the act of killing itself (your body) trigger another prioritized reaction to take measures to save itself?


Why would the body include congenital defects of any kind? Bugs and duplication errors that didn't produce useful results. One mutation or genetic development might lead your body to be predisposed to overreact to otherwise harmless allergens; a similar mutation might ramp up your immune system so that you're less vulnerable to fatal diseases.

Don't anthropomorphize evolution; it has no intent, and does not actively "select" beneficial traits. Over time, whatever traits happened to propagate will propagate. Some of those will be beneficial; others just didn't happen to kill people.

Notice that there's no widespread anaphylactic-level allergy to, for instance, water, or some standard component of atmosphere. But an allergy to peanuts does not systematically kill everyone who has it before they can reproduce.


I'm not referring to evolution or defects here unless you're implying that it is a defect that our body would willingly choke itself to death in reaction to an allergen (I agree that it's probably a defect that we react to the allergen in the first place)


Exactly that. Your body has a defect that causes it to choke itself to death in certain circumstances.

And thanks to the evolution, if not for science, the defect might be eliminated in a few generations. Or not - perhaps this is an optimal variant of immune the immune system. That is - 90% of organisms will have an excellent immunity, but it will go haywire in 10% of cases, whereas an alternative would be a system with 99% organisms having just an average immune system, but 1% being haywired.

Finally, evolution has no "target" or "goal" really. Some features will be broken, and some will be useless. Some may serve a purpose that's beyond our understanding or extremely complex.


> if our main goal in life is, in fact, to survive/live (and insure the existence of our species through procreation), why would our body, in the case of an allergenic reaction, mount a defense mechanism that could kill us?

Because our bodies are the product of selection over random variation, not perfectly crafted designs for survival. So we end up with systems that, while some are surprisingly simple and elegant, are often complex, convoluted, and despite working well and correctly most of the time in normal cases (and even often in many extreme ones) still can have very bad failure modes.


We have so many built-in mechanism designed to keep us alive that I find it strange a counter measure to extreme inflammation would be excluded. Pain sensors, fear, adrenaline, etc.


Inflammation is itself a countermeasure. It's the same principle as boiling water before you drink it or cooking meat before you eat it. How many countermeasures do you provide for the countermeasures?


It's a question of risk vs reward.

Your body has an extremely complicated and mostly successful system of defence. If a pathogen enters the body and is not attacked, it may easily kill you, for this reason pathogens, once identified, are always attacked. There is a system that is responsible for identifying threats(lymphocyte), some times this messes up and identifies the wrong thing as a threat. This is easier than you might think because your body makes antibodies(attack living stuff like bacteria but quasi stuff like viruses) and antitoxins(attacks toxins), when the body sees a foreign substance in the blood, it only takes one lymphocyte is misread it as a threat, and boom all-of-sudden your body fights like the devil to kill/remove/subdue that thing.

Backing down the response would alleviate some allergy problems, but it would also cause the body to perhaps miss some actually-bad things in your system. It'll be hard to change this, and problem inadvisable, as the system has been tuned over millions of years. The best course of action is probably treating symptoms, or finding targeted and intelligent ways to trick the system into handling these corner cases better.


Let's say someone punches you in the nose and breaks it. It'll hurt. You'll bleed out a bit, eyes water, and you're throbbing pain. Let's further say that someone then proceeds to choke you with their bare hands. Your immediate instinct, even though your nose is in a world of hurt, would be to try to escape because breathing is prioritized higher than a bloody, throbbing nose.

While I am no pathogen expert, I can't imagine many things (if anything) more dire to the human body then oxygen deprivation. To the extent that if you're intentionally holding your breath, you'll pass out and your body will involuntarily start breathing again to keep you alive.

That said, maybe the body does view internal (pathogen/poisons) attacks more critical to preserving life then oxygen. Anyone know?


If you look at it from the perspective of the entire species instead of an individual, it makes sense. Reproduce with the strongest genes possible. So if the body sees that this particular individual doesn't handle certain substances well, it terminates the line and avoids spreading that particular weakness in the species.


This sort of makes sense but now we're supposing that the individual, subconsciously, puts it's species ahead of itself. Is this the wide belief or is it that each person fights to keep themselves alive (again, subconsciously, as I believe some people will consciously sacrifice themselves for the greater good).


> This sort of makes sense but now we're supposing that the individual, subconsciously, puts it's species ahead of itself.

Not at all. The individuals (and the genes) don't need to have any goals or any notion of autonomy. It could just be that genes come about randomly, and the ones that are most successful at existing in the future will be the ones that cause a small portion of individuals to die when doing so increases the odds of survival of the rest of the individuals.


Perhaps "what doesn't kill you only makes you stronger" applies here. The mechanisms that kill some small percentage of people might increase the survivability of the vast majority of people.


One could ask the same of obesity. The simple answer is that the conditions of life we face day to day now are different from those to which our bodies evolved for.


Evolution isn't intentional. That which does not kill you gets passed on to the next generation.

"Your body" doesn't have anything like the ability to analyze good or bad. Some mysterious emergent phenomena in your brain does, but the overall mechanisms we reused from other species don't.


Allergies are awful. Throughout my twenties I "suffered" what I thought was chronic fatigue syndrome, only to discover later this year it was actually just an Allium allergy (Onions, Garlic etc). I'd estimate that this was at least a 50% drop in my overall productivity during what could have been some of my most productive years. If anyone is suffering from allergies I highly suggest experimenting with your diet.


How did you find out that you had this allergy? Do the standard tests pick it out?


The standard tests didn't get it. I actually discovered it when I just totally gave up (at this point I'd been to doctor for numerous blood tests - especially for mono). I cook a lot, and have always eaten fairly well. I just got tired of it... so I ate a lot of terrible food for a month, mostly fried, and I felt awesome. Then i started to get fat. So, i started cooking again. The first meal was beef stew. I ate it, then felt terrible. So I eliminated everything in it, and reintroduced them one-by-one to my diet. The onions were obvious, garlic less so.


> The fact that you don’t like the sneezing, that’s tough luck

I had a teacher in high school who would call out any student who suppressed a sneeze. He used to say "It's one of the best natural highs you can get! Don't fight it, just cover your mouth!"

I tend to agree, but they do get annoying when they are incessant.


For some reason, reading all this makes me feel like I am having an allergic reaction. I wonder if there are some psychosomatic triggers as well. Not saying it's all that, or anything, but worrying about it seems to make it worse.


Allergies are really weird things. They run from the mild, like a slight itch some people get when they eat peaches, to deadly.

I have a neighbor who's daughter is basically deadly allergic to just about everything anybody would consider normal. It's so bad that they struggle combining foods she can eat to get her complete nutrition...it's so bad that she's gone to the hospital with respiratory issues from accidentally coming in contact with somebody who had come in contact with one of her allergy triggers...

Her mother fought (and lost) a campaign to keep eggs out of school meals because they're one of the guaranteed-to-kill-her-daughter triggers. I had no idea how many foods have egg in them, but it appears to be just about all of them.

So you sit down and think about this, there is no way evolution could have possibly produced a person who's immune response to fairly normal environmental factors would be to send her into immediate shock, stop her breathing and kill her...it's just not possible, unless she's a random mutation, her entire genetic line would have been killed off the first time they encountered a wild grass or tried to eat a wild egg or whatever of the other couple dozen triggers she has. (I'm not ruling out that there may be some genetic predisposition to a wildly out of control immune system). So my conclusion is that it either has to be environmental (which genetics could make her predisposed to some combination of genes and environment that's gotten her here) or behavioral, the clean house theory (which I suppose also ends up being environmental in a way).

I think it's also possible, knowing her mother, that once she found out she was allergic to one thing, helicopter parenting stepped in and her exposure to other normative immune triggers was stopped, perhaps making things worse.

This year her mother finally started taking her to some kind exposure therapy where she's training her system to be able to handle eggs. Apparently so far successfully. So my guess is that she probably just needed to grow up getting dirty and eating all kinds of stuff to train her system.

Another story, my wife and I were out at he seashore some time ago for vacation. Of course we ate a bunch of seafood there, something my wife grew up with (growing up in South Korea) and I didn't (growing up a normal picky American). One night, her eyes and mouth swelled up and we determined she must have an allergy to something she ate (she has no other allergies we know of). When we got back we took her to an allergy specialist and they did a whole bunch of tests and she came back with some kind of alarmingly high measure in some blood test. They told her to stop eating some class of foods and a bunch of other stuff and to start carrying around an Epinephrine injector.

The thing is, that was it. They had no information at all for why she was suddenly "deathly" allergic to food she'd literally been eating weekly for her entire life (whatever the measure was in her blood, it was so high they sent it off to another senior specialist for further comments since they had never seen it that high in their office...an allergy specialist clinic).

They also had no information later on why, when she ate the same foods they warned her against (she's stubborn) she had absolutely zero reaction and continues to have no reaction to this day. The whole testing process looked reasonably scientific, with the grid of pin pricks and before and after blood draws and tables full of numbers from this or that blood factor. But in the end it seemed like the specialists knew no more about the subject than either of us, and we didn't know anything at all!

Very little has done more to shake my belief in modern medicine than the series of interactions with her doctors.


I am definately no expert, but reading abouy allergic load is fascinating. I think the general idea is you have a pitcher of allergies, when it gets full you see a reaction. So while in many cases you may never see a response, with enough allergies in play, you might have a more severe reaction to an item than normal if you are overloaded, this doesnt only apply to food and or pollens, but also potentially airborne chemicals (i mean we probably are pumping a variety of new things in the atmosphere i would guess) i find allergies and why we have them fascinating(i Am also allergic to tons of stuff, but hardly notice a reaction except to peanuts and other nuts. Out of 80 items i wasnt allergic to lobster, chicken,and bananas, random i know). I also wonder if your allergic load is high, you might show a reaction for something that you normally dont have a reaction to in a skin test... i would love to experiment.... hahahaha


There is also the possibility of cross-reactive allergies, where something that normally does not cause any issues will cause problems if you've already exposed to something else.

For example, during birch season (pollen and such) apples can cause allergy reactions.


Why aren't the people who work in restaurants concerned about food allergies? It's not so much that they could kill a diner as that they could get sued. :-/

"We'd both like the chef's choice please. But no tuna for her, she's allergic to tuna."

"No substitutions!"

"But she's allergic to tuna!"

"NO SUBSTITUTIONS!"

"Tuna could kill her. Anaphilaptic shock would lead her trachea to swell shut so she would suffocate."

"NO! SUBSTITUTIONS!"

"Ok look I'll just trade some of my sushi for her tuna."

My concern though was that her allergy might be so bad that just having a little tuna juice on her plate, or for her other sushi to be cut on the same chopping board or with the same knife as the sushi could kill her.

At least my father explained to me how to do a tracheotomy with a pocketknife and a ball-point pen.

Much less than a single peanut can kill someone, yet I see peanuts served at restaurants all the time.


I don't understand what the problem was here. If you're allergic to tuna, don't order a dish that contains tuna. Substitutions to accommodate an allergy are nice but are certainly not required.

As for peanuts, restaurants serve them because they're delicious and most of their customers enjoy them. We shouldn't take this away from people just because some people are allergic. If you're allergic to peanuts, you should avoid ordering dishes that contain peanuts, not somehow expect all restaurants to avoid serving them in the first place.

There are legitimate complaints here. Some restaurants simply don't take this stuff seriously, and either don't take precautions against contamination or just outright ignore allergy-related requests. But expecting them to go beyond keeping allergens out of dishes that aren't supposed to contain them is odd.


English restaurants have to by law know about a range of allergens and to provide that information to anyone who asks.

http://www.bbc.co.uk/news/health-30395142

> "We'd both like the chef's choice please. But no tuna for her, she's allergic to tuna."

> "No substitutions!"

They're probably doing the right thing there. You've said that she risks death if she eats tuna. That then becomes the most important thing to them. Keeping the "no tuna" part of your order correct through the various parts of the kitchen is tricky. It's worth it if an error means a bit of grumbling; it's not worth it if an error means a noisy visable death and ambo call out and press coverage.


> Why aren't the people who work in restaurants concerned about food allergies?

IME, they tend to be. If you let them know about them, they will let you know if various menu items contain the thing that is the subject of the allergy.

That doesn't mean that they will always modify menu items (especially things like "chef's choice") to account for them. And, while its nice if they would, I don't see why one should be surprised that they don't -- expecting people to order something they aren't allergic to from the menu doesn't seem unreasonable.


If you're allergic to tuna, you shouldn't eat at a sushi restaurant.


That was the very first time in her entire life she had eaten sushi.

She was depending on me to ensure she wasn't killed by her supper.


> My concern though was that her allergy might be so bad that just having a little tuna juice on her plate, or for her other sushi to be cut on the same chopping board or with the same knife as the sushi could kill her.

I think that would be their concern, too. If they gave you a meal and didn't add the tuna, how can they ensure that every station, utensil, and dish hasn't touched something contaminated by tuna? They probably can't.




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