The immune system exists as a very complex multiorgan system, composed of numerous sub-branches. The process of inflammation itself can be subdivided into: allergic responses; cytotoxic responses involving mast cells, basophils, and the antibody, IgE; antibody-target pathogen complexes, otherwise known as “immune complexes;” and finally, T helper (Th) cells. For the purposes of this blog, we will focus on this last category.
Th cells can be further divided into Th1 and Th2 cells. Th1 cells help to target immune responses to intracellular pathogens and to stimulate chemokines, the latter which attract white blood cells to sites of infection. Chronic stimulation of the Th1 response or its products is associated with specific autoimmune conditions like Rheumatoid Arthritis and Multiple Sclerosis .
Th2 cells on the other hand produce cytokines that are integral in fighting off intestinal parasites and in enhancing antibody-mediated immunity. Unfortunately, that means that chronic stimulation of the Th2 branch or its products can lead to extensive allergies, increasing the likelihood of various respiratory disorders such as asthma, rhinitis, and sinusitis, as well as food and skin allergies.
Although we in first world countries don’t get frequent reminders except for the occasional horror story of bad sushi, intestinal worms have been an age-old human foe, one that often prefers to strike the young ruthlessly and can leave considerable morbidity and mortality in its wake.
Consider the roundworm, Ascaris, that is endemic in many parts of sub-Saharan Africa, Latin America, and Asia and can infest year-round in tropical regions. Because it is a soil-borne parasite, areas with poor sanitation are especially vulnerable.
Because it is so common and so potentially harmful to children in particular, you can imagine any genetic variations arising over time that give an advantage to the Th2 arm of the immune system (or its downstream targets) that is largely responsible for fighting off Ascaris and other helminth infections would be strongly selected for in our evolutionary history.
Why am I so interested in worm infections? Well, I have to admit it’s partly personal. I have a long history of asthma, chronic allergies, ear infections, and sinusitis/rhinitis. So back in November I paid for genotyping through 23andme.com. What I found was extremely interesting to me: It turns out I have both a homozygous variant in my Interleukin-13 (IL13) gene and a heterozygous variant at another point in the same gene, both of which dramatically increase the enzyme’s activity. What that does in effect is ramp up players downstream of the Th2 branch in my body. In essence, my IL13 gene is telling my body I’m besieged by worms! Great if I were a child in sub-Saharan Africa, right? But bad if I’m a woman living in the burbs of America.
Myself aside, I also got to thinking about conditions like autism. Research-wise, immune dysregulation is a huge topic. According to Judy van de Water of the MIND Institute, perhaps up to 60% of children with autism display evidence of immune dysregulation, with roughly equal numbers of kids exhibiting Th1 and Th2 upregulation.
So a couple important question to address in future are: Are these kids inheriting common gene variants, similar to the IL13 variants I myself inherited, that are predisposing them towards immune dysregulation and subsequently increasing autism risk? In addition, what evolutionary factors such as parasites may have strongly selected for the spread of these variants in the human species?
More on this later. To be continued…