Student guest post by Shylo Wardyn
"Of all the parasites I've had over the years, these worms are among the... hell, they are the best".
Was Fry from the animated show 'Futurama' right in his assessment of worms being good for him? Did he know something about parasitic worm infections that I was unaware of? Well, in the show, his parasites were doing remarkable things for his body, but does this translate to real life at all? Some people think so. Altman reviews the idea that over evolutionary time, our ancestors were infected with all sorts of parasites and this led to an interaction between the worm gene products and the immune system. These interactions led to modulation of dendritic cells and establishment of T-cell networks. It has been hypothesized that in an environment without these interactions, as is the case for most people living in "Westernized" countries, there is a loss of the 'fine tuning' of the adaptive immune system.
In another review, Jackson et al. discuss how this mechanism could have co-evolved. It is generally believed that the T helper cell type 2 (Th2) evolved to counter infections with parasitic worms. These cells are activated in response to parasitic worm infection, which leads to a large regulatory T cell response. Our response to worms seems to involve an immune response that is less inflammatory than our response to microbes, and it also takes much longer to reach the peak of effectiveness. This is due in large part to an initial systemic suppression of innate and adaptive immunity in the host. This is likely caused by regulatory CD4+ and CD25+ T cells producing suppressive cytokines or other suppressor T cell subsets. Anti-inflammatory responses are also caused by alternatively activated macrophages. These macrophages secrete anti-inflammatory cytokines and express genes whose functions relate to wound healing and repair. Therefore, being infected with parasitic worms leads to a down-regulation of proinflammatory responses, while allowing mechanisms for wound repair and a controlled development of the Th2 response. This Th2 and T regulatory response is beneficial for both the worm and the host. For us, the regulated Th2 response is less costly than the generation of a strong immune response, which often can be detrimental to our own cells. For the parasites, they are able to survive the initial immune response and therefore reproduce, while later parasites would not be able to survive the developed immune response.
The overall thought is that since parasitic worm infections are ubiquitous in mammals and have been since mammals first evolved, there would be a positive selective pressure for those individuals whose immune systems respond well to worm infections. Our immune systems may have been selected to anticipate a chronic exposure to Th2 and T regulator inducing pathogens. Since our ancestors were chronically infected by worms, their immune systems would have developed to work well in this context, while not necessarily working as well in the absence of worms. This scenario may explain why in some cases the immune system goes haywire in populations that are free from parasitic worms.
So is there any strong evidence linking parasites with populations free from allergies and autoimmune diseases? There have been many ecological studies which show an inverse correlation between the parasite load and allergy level for a particular region. Does this prove anything? Not really, the data is simply correlative. There have been other studies showing that treatment of worm infections is accompanied by an increase in skin test reactivity to allergens and IgE antibody levels. It appears that in the absence of worms, the immune system overreacts to allergens to which it normally wouldn't mount a response in the presence of worms. This gives us a better idea about the link between parasitic worms and immune responses. While the evidence is still shaky, it is biologically plausible that the lack of worms in our environment has led to the massive increase in the amount of immune related diseases, such as asthma, multiple sclerosis, type 1 diabetes, and general allergies. However, the immune system is incredibly complex, as are those diseases, and I've barely scratched the surface of it for this topic. So while it seems being infected with worms may prevent immune system diseases, I doubt anyone would trade their asthma for a tapeworm. It does make for an interesting hypothesis (and Futurama episode) though and should be researched more thoroughly.
Altmann D. M. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases. Immunology, 126(1); 1-2.
Jackson J. J., Friberg I.M., Little S. and Bradley J. E. (2008). Review series on helminths, immune modulation and the hygienehypothesis: Immunity against helminths and immunological phenomena in modern human populations: coevolutionary legacies? Immunology, 126(1); 18-27.
Weiss S.T. (2000). Parasites and asthma/allergy: What is the relationship? Journal of Allergy and Clinical Immunology, 105(2); 205-210.
There's a more general principle involved. A response (immune, whatever) is a response to information, which is a ratio of energetic inputs. That ratio, and the gain associated, must be tuned to a certain range -- it can be a very large range, but there will always be a falloff below and above it.
If your context changes so that the denominator becomes very small, you will explode the response to small variations in the numerator -- at least until you retune to have the proper gain.
So an immune response has to measure the ratio of an acute signal to a background signal. If that background signal approaches zero, your response to 'noise' will explode, and you'll cease being able to extract the real information. Immune dysfunction is inevitable.
The principle applies to light adaptation, sound adaptation -- pretty much any information processing.
An interesting article, though I think for some people, worms would be considered a step up. In particular, I recall anepisonde of NPR's Radiolab in which they discussed hookworms as a potential treatment for Crohn's disease.
Hard to create controlled medical tests, given the rules surrounding medical testing with human subjects. (Not that the rules are necessarily bad, just that they make some kinds of treatments, such as worms for autoimmune disease and bacteriophage treatments for bacterial infections, harder to get approved.)
So people would rather face a life suffering asthma, or MS,or any of these immunological diseases for aesthetic reasons. If tapeworms, or in the recent discussion about hookworms, were not so ugly, would people allow themselves to be treated? People are funny.
"So while it seems being infected with worms may prevent immune system diseases, I doubt anyone would trade their asthma for a tapeworm."
There's a Radiolab podcast describing a guy who did exactly that. Went all the way to West Africa to try to pick up a case of hookworm.
The same guy in the podcasts referred to above is now helping lots of other people get infected with worms - hookworms and whip worms, very different from tapeworm. http://autoimmunetherapies.com/ I find it fascinating as many of my family members are suffering different types of autoimmune diseases.
This post ignores the possibility of symbiosis. A parasite doesn't want to harm its host unnecessarily. It can happen that a parasite does something useful for the host, and there can be selection pressure on the parasite to favour that. If that parasite is ubiquitous in the host population then the host may lose the capability that the parasite is now supplying. Admittedly that doesn't seem to be the case here, and there is no evidence for it. However it is a part of a more general issue. It is a mistake to think of humans as being innately perfect, with disease being some correctable deviation from that perfection.
Could it be that we are just not exposed to a large enough variety of natural materials anymore? Our indoor, clean lifestyles keep us away from so much, but expose us to chemicals we know very little about. Some allergies can be reduced by eating honey or consuming small amounts of some specific pollens which cause allergies.
I want nothing to do with any of those worms...it would be my luck that they would leave my gut to go live in the liver ductwork! Really enjoying your posts, hope this is not too far off base or a problem.
Urm...does it have to be tapeworm OR asthma? Can't we choose a less disgusting (and sizable) worm? Something more petite and more easily (forcefully) ignored? That tapeworm can also cause distended belly at the same time one is actually suffering some malnutrition because it is taking up too much of the food load.
Let's search for that perfect SMALL worm to trade for asthma, MS, etc. Something that doesn't grow potentially to 10s of feet in length and distend the belly (body image does matter!). At the same time we don't want a nice, petite little worm that "tickles" as it, ahem, occasionally exits the body on its own recognisance (it's best if it leaves exclusively all packaged with the stool, know what I mean?).
That lost post at number 8 was definitely funny! I would prefer we just simply clean our homes and offices less. Let the exposure rate to our environment increase.
Possibly stop the vaccinating as well. Let our bodies fight naturally. I would be okay to do a double blind study on the influenza virus vaccine just to see how effective it truly is.
Didn't our ancestors actually eat a lot less meat? Didn't they eat more non-genetically modified grains? Wasn't the obesity and diabetes rates lower as well?
For now, I will pass on the worm.
@ Sajman; hmm thats an interesting idea?
Are you one of those people who like genki genki? if so let me know, id love to have you in my anus anytime. Its very healthy to have worms in your anus. Even live worms from the garden as they clear your insides quite well. Downside you have to shit them out. Very common in Japan these days.