Are allergies trying to protect us from ourselves?

I have a love/hate relationship with spring, thanks to the aggravating bouts of hay fever that transform me into a faucet for pretty much the entire season. So I’ll admit I was a little skeptical when my editor at Scientific American asked me last week if I wanted to write about a new paper coming out in Nature suggesting that allergies may actually be a good thing. But always curious, I said sure.

Turns out it’s a fascinating—and pretty convincing—read. It’s dense, but the lead author, Yale immunobiologist Ruslan Medzhikov, was kind to take a good two hours out of his day on Monday to explain some of the gnarlier concepts to me. (Medzhikov is fascinating—you can read more about him in this profile published in Disease Models & Mechanisms.)

Medzhikov’s basic argument is that there is a convincing body of research suggesting that allergies have beneficial effects. They break down the toxic components of bee, snake, scorpion and gila monster venom, for instance, and our allergic reactions to tick saliva prevent the parasites from feeding.

Ultimately, all allergic responses work towards a common goal: avoidance and expulsion, Medzhitov argues. As I explain in my piece,

More generally, hated allergic symptoms keep unhealthy environmental irritants out of the body, Medzhitov posits. “How do you defend against something you inhale that you don’t want? You make mucus. You make a runny nose, you sneeze, you cough, and so forth. Or if it’s on your skin, by inducing itching, you avoid it or you try to remove it by scratching it,” he explains. Likewise, if you’ve ingested something allergenic, your body might react with vomiting. Finally, if a particular place or circumstance ramps up your allergies, you’re likely to avoid it in the future. “The thing about allergies is that as soon as you stop exposure to an allergen, all the symptoms are gone,” he says.

Obviously, Medzhitov’s theory is just a theory, and it involves a lot of speculation (albeit informed speculation by a really smart guy). But some research suggests an association between allergy severity and cancer risk, in that people with more allergy symptoms are less likely to develop certain cancers. (One shouldn’t read too much into this though; some other factor may drive the association. Perhaps people who eat lots of eggs are more likely to have allergies but less likely to have cancer.) But all in all, I think Medzhitov’s idea does make sense and is well-supported, and most of the outside experts I spoke with agreed, though they did raise questions about some of the specifics.

One aspect of the theory that I didn’t mention in my piece is that it could explain a medical mystery: penicillin allergies. Medzhitov argues that in addition to protecting against venoms, vector-borne diseases and environmental irritants, allergies also evolved to protect against a class of toxins called haptens: proteins that bind to extracellular or membrane-bound proteins in the body, rendering them useless and ultimately causing all sorts of problems. As it turns out, in some people, the penicillin molecule undergoes transformation into a hapten. This transformation is very slow and inefficient—very few penicillin markers turn into haptens, which is a good thing because haptenated penicillin could be dangerous—but nevertheless, some people may develop allergic responses to these few haptenated penicillin molecules, and this can result in an allergic hypersensitivity to the drug, Medzhitov posits.

In the case of something like a penicillin allergy, management is fairly simple (though medically inconvenient): avoid penicillin. The problem today is that there may be millions of allergens in the form of environmental pollutants and irritants, and they may simply be unavoidable. This idea could help explain why allergic diseases have become more common in recent decades: We’re exposed to many more pollutants now than we were 50 years ago, and this chemical flurry could be dialing up our innate defense systems to a constant level of 11. An allergy may be protective, but “if it’s taken to an extreme, it is pathological,” Medzhitov says. I wonder, then, if we may have built ourselves a world that will forever make us sick.

Citations:

Palm, N., Rosenstein, R., & Medzhitov, R. (2012). Allergic host defences Nature, 484 (7395), 465-472 DOI: 10.1038/nature11047

Medzhitov, Ruslan (2011). Innovating immunology: an interview with Ruslan Medzhitov Disease Models & Mechanisms, 4 (4), 430-432 DOI: 10.1242/dmm.008151

Akahoshi M, Song CH, Piliponsky AM, Metz M, Guzzetta A, Abrink M, Schlenner SM, Feyerabend TB, Rodewald HR, Pejler G, Tsai M, & Galli SJ (2011). Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice. The Journal of clinical investigation, 121 (10), 4180-91 PMID: 21926462

Wada T, Ishiwata K, Koseki H, Ishikura T, Ugajin T, Ohnuma N, Obata K, Ishikawa R, Yoshikawa S, Mukai K, Kawano Y, Minegishi Y, Yokozeki H, Watanabe N, & Karasuyama H (2010). Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. The Journal of clinical investigation, 120 (8), 2867-75 PMID: 20664169

Sherman, P., Holland, E., & Sherman, J. (2008). Allergies: Their Role in Cancer Prevention The Quarterly Review of Biology, 83 (4), 339-362 DOI: 10.1086/592850

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14 Responses to Are allergies trying to protect us from ourselves?

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  8. Paul Orwin says:

    The article is very interesting – it would be nice if the Nature article were not behind a paywall (seems a little unPLOSsy if you ask me!).
    I have a criticism of your discussion of haptens – I don’t think you have explained this idea very clearly. A hapten is a compound that cannot elicit an immune response by itself, but can become part of a “hapten-carrier complex” that is immunogenic. When this happens, antibodies are made against both the hapten and carrier (and often the strongest antibodies are against the carrier). This is useful in immunology because it allows scientists to make antibodies against small molecules that are not traditional antigens (the classic example is nitrophenol conjugated to an abundant protein, then injected resulting in antibodies against the NP moiety). As I understand from some googling, the penicillin allergy pathway you are referring to is when parts of penicillin bind to proteins in the serum. This creates a hapten carrier complex that is recognized as foreign (I think the rarity of penicillin allergy and the predisposition is based on how rare this event is, because we are not usually able to recognize our serum proteins as foreign in any context). In your article you describe the hapten as binding to proteins and rendering them useless – that may be true but the real issue is producing anti-hapten antibodies (esp. IgE for anaphylaxis).

  9. Thanks, Paul. I’m sure you’re right that I got my description of haptens wrong – Medzhitov only briefly discussed it in his paper and in our interview. Thanks for setting me straight. If you’re curious, the discussion of penicillin In the Nature paper was as follows (hope I don’t get in trouble for posting this excerpt): “Reactivity to noxious xenobiotics presumably explains the existence of drug allergies. For example, penicillin allergy can develop in some people because penicillin can undergo metabolic transformation, result- ing in a reactive product that can form protein adducts23. This property of the reactive form of penicillin is shared with noxious xenobiotics, except that penicillin transformation is very inefficient in most indivi- duals. Free (non-conjugated) penicillin is immunologically inert in non- sensitized people and it is the hapten (conjugated) form of penicillin that seems to be immunogenic. However, once the response to the haptenated form is elicited, a hypersensitivity to free (non-conjugated) penicillin may develop, resulting in penicillin allergy23. Many idiosyncratic drug reactions of allergic aetiology presumably develop by the same mechanism and, more generally, small molecule allergens may elicit allergic reactions because they either have noxious xenobiotic activity (even if that activity is very low), or because they mimic something that has noxious activity. Therefore, although the xenobiotic-elicited response can be intended and protective, unintended allergic responses can develop to xenobiotics that are not intrinsically noxious.”

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  11. I just wanted to thank you for this article. I can relate to being sick almost whole spring because of all the allergies. I am an allergic from about 13-14 years of age and I almost lost all hope. But every time I stumble upon an article like this one, my hopes go up because I always realize how little I do actually know about this stuff. I know just the general, easy-to-find information, but your article opened some new ways of thinking and learning for me. Can you suggest some additional sources apart form the citations you mentioned?

    Again, thank you.

  12. Medicos says:

    Excelent articule, it´s great to see it in that way, becouse we often hate it thinking that it is something bad for us. But the human body has its own mecanism of self-protection.
    So must we reduce the anti alergics drugs in little allergies?

    Thanks for the article, really interesting.

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