Your body goes to great lengths to protect you from the outside world. From your subconscious hinting that jumping a motorcycle over the Grand Canyon might be a bad idea all the way down to killing pathogens before they have a chance to harm you, your health and safety is pretty much a full time job. Occasionally the body gets a bit caught up in fighting the enemy and we get a little collateral damage. Crohn’s Disease is when your gut takes one for the team.
WARNING: Some potentially nauseating pics of the gut after the jump
Crohn’s Disease and Autoimmunity
Crohn’s Disease is an autoimmune disease that is part of a larger group of diseases known collectively as the inflammatory bowel diseases. Before I can talk about Crohn’s specifically its worth just mentioning autoimmunity in general.
Autoimmunity develops when the body confuses its own tissues for foreign invaders and turns the full offensive clout of the immune system onto itself or it’s host. There are many examples of autoimmune diseases including Type 1 Diabetes, Psoriasis and Rheumatoid Arthritis (apparently Narcolepsy is also an autoimmune disease, I smell another post in the making…) but Crohn’s Disease rose to prominence following US President Eisenhower undergoing surgical treatment for the autoimmunity disease in 1956.
Autoimmunity is an example of a failure in a process called ‘tolerance’. The immune system is rigorously tested during its maturation to make sure it is potent enough to kill invaders but also to make sure it only attacks invaders. The body throws up self antigens to see if any immune cells will attack them, if they do the cells are destroyed before they can complete development and begin circulating inside the body. It’s a bit like sniper training. A sniper may be able to shoot a 10 cent piece of a snail shell at 100kms away but if they can’t tell the difference between the enemy and civilians they won’t make a very good sniper and they are kicked out the Army.
For Crohn’s, as with most autoimmune diseases the immune cells that start attacking the body don’t just slip past the bodies testing system to act maliciously, they are somehow inappropriately activated in to self destruction mode. In the case of Crohn’s disease there seems to be no one things that sets it off, rather it is expected to be a combination of environmental factors alongside a level of genetic susceptibility. For example researchers have shown that some, but not all, smokers have a greatly increased risk of developing Crohn’s.
The actual manifests as immune attack of the intestinal lining resulting in loss of the cells and the mucous they produce that protects the colon from stomach acids and other potentially harmful bacteria and viruses. Following induction of the immune system to attack the colon, sufferers can expect all the typical symptoms of irritable bowel disease including abdominal pain, diarrhoea and colitis. In turn colitis, inflammation of the colon, has its own issues including a loss of fecal volume and consistency alongside an increase in frequency. This is probably due to decreased water absorption as the colon is too damaged to operate normally.
I could easily leave it at that but as Thomas pointed out last week we are here to find the interesting things behind the standard responses, and it looks like we can treat Crohn’s using parasitic worms.
This novel idea developed out of our more recent understanding of the immune system and how it sets up to deal with foreign invaders. Most people have heard of B and T cells, the foot soldiers in the continual war between your insides and the outside (but if you haven’t have a look here). Put very simply B cells make antibodies that act as beacons for the immune system to detect and destroy whatever the antibody binds to and T cells act more specifically, targeting individual cells and inducing their death. B cells are better at attacking foreigners outside the cells (such as many bacteria, although many pathogens will invade cells as well) whereas T cells are better at killing cells that have the invader inside (such as viruses).
Whether the body uses B or T cells is a finely controlled process requiring the input of many chemical signals, called cytokines. If B and T cells are the foot soldiers of the immune system then cytokines are the orders they must follow. Typically both T and B cell promoting signals will be present but one will win out and this determines whether B or T cells will be used.
Now I’d like to talk to you about parasitic worms
So how are worms useful? Crohn’s disease is typically caused by inappropriate T cell activation. T cells in the gut attack the intestinal lumen causing all the things I said above but if intestinal worms such as Necator americanus are introduced the immune system has to adapt. As a rule worms, like most life forms, don’t actually want to die so they have to modify their environment to suit them. The best way to do this is for the worm to release ‘immuno-modulators’ that essentially act as signals to the immune system that say ‘move along, nothing to see here’. The result of this is the signal activating the immune system causing Crohn’s is dampened by the concurrent worm infection saying ‘cool it bro’. Eventually the Crohn’s symptoms can disappear! (disclaimer: at a success rate of around 50% of tested patients)
The good news is the worms can be easily controlled with drugs, unlike the T cells. If you try to control the T cells you risk killing all of them off, including those not attacking the gut, causing major issues for the patient.
This kind of approach to dealing with disease, particularly autoimmune disease, represents a major shift in how we view disease and the immune response. The better we understand the immune response the better we can tailor therapies to deal with all the problems that arise within us.
Davidson, S. (2006). Principles & Practice of Medicine. Philadelphia, Churchill Livingstone Elsevier.
Cosnes, J. (2004). “Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice.” Best Pract Res Clin Gastroenterol 18(3): 481-96.
Croese, J., J. O’Neil, et al. (2006). “A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors.” Gut 55(1): 136-7.