Worms: Are they good or bad for us?

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.

References

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.

C-sections, allergies, and probiotics

Student guest post by Shylo Wardyn

I recently read the book ‘Good Germs, Bad Germs’ by Jessica Snyder Sachs. I became intrigued by parts of her book that discussed how babies become colonized with bacteria during birth. The most interesting part was the differences between vaginally-delivered and Caesarean-delivered babies. It was not something I had ever thought of before. With my interest piqued, I did a Google scholar search to see what kind of research was being done on this topic. I stumbled upon an article looking at C-sections and risk of childhood allergies, namely asthma. I realized this would be the perfect topic for this assignment!

A little background information:

Asthma is a chronic inflammatory disorder of the airways that affects both children and adults. It is not known why some people develop asthma and others don’t. Rates of asthma have more than doubled from 1980 to 2004 in children <18, but since 2001 have held steady. It is noteworthy to mention that the definition of asthma was altered in 2001, as well (Moorman, et al., 2007). A Caesarean section (C-section) is a surgical procedure in which an incision is made through the mother's abdomen and uterus to deliver one or more babies. While C-sections are traditionally done when a vaginal delivery poses risk to the mother or baby, women can also elect to have a C-section instead of a normal delivery. C-section delivery rates account for 31.8% of all births in the United States; 2007 marked the 11th consecutive year of increase and a record high for the US (Hamilton B.E., 2009). The neonatal period is critical for bacterial colonization of the intestines. Infants delivered vaginally acquire their intestinal flora from their mother's vaginal and fecal flora, generally species of Bacteroides, Lactobaccilus and Bifidobacteria. This intestinal flora colonization is delayed in Caesarean delivered infants; consequently, their gut flora is abnormal for weeks to months. One study found that in Caesarean delivered infants at the age of 6 months, the colonization rate of Bacteroides was half that of infants in the vaginally delivered group (Grölund, 1999). The research: Gut normal flora has a significant impact on the immune system; normal flora strains have been shown to induce the production of IL-10, which has an important regulatory role in the development of the allergic immune response (Kalliomaki & Isolauri, 2003). This is the biological hypothesis behind the proposed association between C-sections and asthma. This issue has been studied, but results are conflicting. I found two meta-analyses that looked at the research to date. Thavagnanam (S. Thavagnanam, 2007) found a 20% increase in the risk of asthma in children who had been delivered by Caesarean. While Bager et al. also found a moderate increase in the risk of asthma after Caesarean, they did not attribute this to the increasing rates of C-sections (Bager, Wohlfahrt, & Westergaard, 2008). They felt that for this to be the case, C-section deliveries should be associated with all allergic outcomes, not just some of them. I felt that they discredited their study by stating this; they still found a biologically plausible and significant association between C-section delivery and asthma. A more recent Norwegian population-based cohort study confirmed a moderate association between C-section and asthma (Tollanes, Moster, Daltveit, & Irgens, 2008). Probiotics and general remarks: While there clearly needs to be more research about the exact role of gut flora in the development of allergies, an interesting area of research is in probiotics. Probiotics are cultures of beneficial bacteria of the normal gut flora. Studies have shown that probiotics administered to pregnant women and their newborns lead to lower rates of development of allergic diseases (including asthma). However, these studies looked at high-risk children; those that had a first degree relative or parent with any allergic disease (Kalliomaki, et al., 2001; Kuitunen, et al., 2009). I couldn't find any randomized placebo-controlled trials with babies delivered by C-section as the group of interest. I think that would be a great study and would answer a lot of questions. While it seems this is still a new area of research, I think the studies speak for themselves. If this information was more widely disseminated, maybe some women would think twice before electing to have a C-section. Maybe in the future, parents will be advised to give their newborns that were delivered by C-section probiotics. Or maybe everyone will be prescribed probiotics after taking broad-spectrum antibiotics....but that is for another blog! Bager, P., Wohlfahrt, J., & Westergaard, T. (2008). Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clin Exp Allergy, 38(4), 634-642. Grölund, M.-M. L., Olli-Pekka; Eerola, Erkki; Kero, Pentti. (1999). Fecal Microflora in Healthy Infants Born by Different Methods of Delivery: Permanent Changes in Intestinal Flora After Cesarean Delivery. Journal of Pediatric Gastroenterology & Nutrition, 28(1), 19-25. Hamilton B.E., J. A. M., S.J. Ventura. (2009). Births: Preliminary Data for 2007. Kalliomaki, M., & Isolauri, E. (2003). Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol, 3(1), 15-20. Kalliomaki, M., Salminen, S., Arvilommi, H., Kero, P., Koskinen, P., & Isolauri, E. (2001). Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet, 357(9262), 1076-1079. Kuitunen, M., Kukkonen, K., Juntunen-Backman, K., Korpela, R., Poussa, T., Tuure, T., et al. (2009). Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol, 123(2), 335-341. Moorman, J. E., Rudd, R. A., Johnson, C. A., King, M., Minor, P., Bailey, C., et al. (2007). National surveillance for asthma--United States, 1980-2004. MMWR Surveill Summ, 56(8), 1-54. S. Thavagnanam, J. F., A. Bromleyz, M. D. Shields and C. R. Cardwell. (2007). A meta-analysis of the association between Caesarean section and childhood asthma. Clinical and Experimental Allergy, 38, 629-633. Tollanes, M. C., Moster, D., Daltveit, A. K., & Irgens, L. M. (2008). Cesarean section and risk of severe childhood asthma: a population-based cohort study. J Pediatr, 153(1), 112-116.

What is the Hygiene Hypothesis?

Guest post by Zainab Khan

In most western countries, germs have become synonymous with the idea of something bad that needs to be killed as quickly as possible. However, people have long been questioning the validity of these ideas; a few decades ago it was hypothesized that not enough exposure to germ can and does cause insufficient development of an individuals immune system. New studies have recently shown that this idea of getting rid of all germs, and keeping children exposure to them at an absolute minimum, may possibly cause more harm then good; over cleanliness is suspected to be one of the main reasons that there is such an increased number in asthma and allergy ridden people in western countries. Also, compared to just a generation or two ago, people today have an increased chance of having/developing allergies. Is this all due to society’s craze over germs?

It is important when talking about allergies to have some working knowledge on what happens when an individual has allergies or an allergic attack. Allergies are an extreme and inappropriate reaction by an individual’s immune system to what typically is a common harmless stimuli found in a normal environment; the body takes something such as hay, food, pollen, etc. and has a hypersensitivity reaction to it. The body ends up activating its white blood cells (these are the cells that defend the body against any foreign bad stimuli), which typically are what help humans ward of virus and bacteria, for example the flu or an infection, which results in an inflammatory response. This inflammatory response manifests itself in different ways: asthma, eczema, hives, runny nose or eyes, coughing etc.

The Hygiene Hypothesis

Over two decades ago, the idea that there is such a thing as too much cleanliness was first proposed by David P. Strachan in his Hygiene Hypothesis. The idea behind this theory is that a lack of early exposure to the types of germs and stimuli that people used to have is the cause of allergies. In developing nations and in earlier time periods families tended to be larger then today. It was uncommon to have just one or two children; the idea behind having more children is that the elder child exposes the younger children to more germs and in turn the children end up having to develop a stronger immune system because the immune system has been fully developed by all the early stimuli [1,2]. This idea of exposure to other children has also held true for children who attend daycare at an early age. Daycare children tend to develop fewer allergies then those who are never in such environments. Research has gone even farther to say that children who are exposed to hepatitis A or the measles are less likely to have certain types of allergies [3].

Arguments against the hygiene hypothesis emerged when statistics were followed about inter city African American children in the United States, who have very high numbers of asthma. A study was done that showed that many of these children had been sensitized to the common allergens found around them; however, they still developed asthma at the same rate as those kids who were not sensitized to the same allergens [4]. Also, it is a scientific fact that some allergies have a genetic component. A child who has two parents with allergies has a 75% chance of also developing allergies. There are genetic links that have been found between certain types of allergic responses which complicates the idea of how much immunity is inherited and how much can be developed [5].

Although the idea of germ exposure has been building momentum within the last few years, the debate and research behind it is certainly not complete. If the hygiene hypothesis is true, this opens up another type of debate on how much and what kinds of bacteria, exposure, and caution should be taken around children. What exactly are the “right” germs, and how many are too many? In a society obsessed with antibacterial hand soaps, disinfectants, and bottled water it is going to be quite a challenge trying to convince people that germs are not all that bad.

Works Cited

1. Am. J. Respir. Crit. Care Med., Volume 164, Number 7, October 2001. The Increase in Asthma Ca Be Ascribed to Cleanliness 1106-1107 Link.

2.Strachan David, Thorax. Family Size, Infection and Atopy: The first Decade of the ‘hygiene hypothesis’ Link.

3. Matricardi Paolo, Rosmini Franceso, Riondino Silvia, Fortini Michele, Ferrigno Luigina, Rapicetta Maria, Sergio Bonini, BMJ 2000;320 Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study 412-417. Link

4. R. Call, T. Smith, E. Morris, M. Chapman, T. Platts-Mills, The Journal of Pediatrics, Volume 121, Issue 6 Risk factors for asthma in inner city children, 862-866. Link

5. Mackay, Rosen, Volume 344, January 2001. Allergy and Allergic Diseases 30-37
Link.