Like so many people (up to 20% of Western society), I have allergies. Tree pollen, grass pollen, cats, dogs, rabbits, carrots, hazelnuts, walnuts, apples, peaches, cherries, and dust mite feces all make me itch, wheeze, and sneeze. So I keep an eye on new developments in allergy research. In this post, I will discuss interesting new insights in why allergies are on the rise, and how we can benefit from researching the co-evolution of parasites and their hosts (us).
Allergy is an inflammation reaction, directed at allergens. Allergens are substances that the immune system in most people recognises as foreign, but not harmful. However, in some people the immune system does not make that distinction and reacts to the allergens. A basic allergic reaction goes as follows: after exposure to the allergen, certain cells (mast cells) release histamine. This protein causes inflammation reactions typical for an allergy: itching, redness, swelling, mucus production, hives or rashes. Consequently, most common allergy medications are anti-histaminica, blocking the action or release of histamine. This, however, does not cure the inappropriate immune response, and the medication, with its side-effects, often needs to be taken for the period of the exposure to the allergen.
A method introduced in the sixties sought to correct the immune response, by desensitizing the immune system (allergy shots, immunotherapy). The patient is exposed to increasing concentrations of allergens, by frequent injections or, nowadays, by sub-lingual administration. This aim is to get the immune system to ignore the allergens. However, the immune system can over-react to increasing exposure to allergens, with the risk of an anaphylactic shock as a result. Desensitising seems to work, but only in a carefully selected group of patients. New developments in this therapy seek to reduce the risk of anaphylactic shock, by manipulating the allergens to reduce their allergenicity but not their immunogenicity.
Some results have been reached in the prophylaxis of allergies by administering '
probiotics' (live bacteria that have a beneficial influence on health) in infants. The most plausible explanation for this is that the intestinal micro flora plays a large role in the maturation of the immune system. There is no evidence that administering probiotics works in older children or adults.
That allergies are prevalent in especially Western society, seems to point to an environmental cause. A link to diet has been investigated, though no convincing evidence has been produced. The hygiene hypothesis, which postulates that increased hygiene deprives the immune system of stimuli that modulate immune response, is still accepted, though not without substantial criticism. Recently, it has been noted that allergies and asthma have not increased in frequency as much in areas, where infections with
helminths (parasitic worms like tape worms, hook worms etc.) are prevalent. Indeed, on a population level, an inverse relationship can be established between infection with helminths and allergy. And now multiple studies point out that variation in the genes that govern resistance to parasitic infection, also influences susceptibility to allergic disorders.
Why are allergic reactions suppressed in people with helminthiasis?
It is possible that the immune system has only a limited capacity for reaction, if it is deployed to fight the parasite infection, it has no resources left to react to allergens. Experimental systems and animal models suggest a different mechanism. Parasites have long been depicted as degenerate ... well... parasites, but it is now increasingly recognised that they are complex, intriguing creatures that have evolved sophisticated mechanisms to thrive in (often multiple) hosts. To achieve this, parasites have to evade the host's immune system, and in some cases even modulate it to their own advantage. As you would expect, in response, the hosts evolve a more effective immune response. But balance is essential, there is the risk of a disproportional immune system that pulls out all stops to harmless antigens as is the case in allergy. The mechanisms by which helminths down-regulate immune response, and therefore allergic reactions, are not yet clear, but human and animal data indicate that regulatory
Tcells (suppressor Tcells) are activated in helminth infected subjects. These Tregs play a significant role in keeping balance (homeostasis) in the immune system. It would be extremely interesting to see whether helminths actively stimulate expansion of Tregs, and how they achieve that. This new development adds up to a prime example of how the study of the evolutionary arms-race between parasites and their hosts can increase understanding of the fine-tuning of our immune system.
Bjorksten B. (2005) Evidence of probiotics in prevention of allergy and asthma. Curr Drug Targets Inflamm Allergy (5):599-604.
Janeway, C.A. et al. (2001) Immunobiology : the immune system in health and disease. Garland Publishing New York.
Maizels, R.M. (2005) Infections and allergy - helminths, hygiene and host immune regulation. Curr Opin immunology 17: 656-661.