Saving your self from yourself

"Your gut is a complicated place," notes Shannon Turley, an assistant professor of pathology at Harvard Medical School. In addition to processing food three or more times a day, an intestine needs to protect you from being damaged by yourself.

For the food-processing task, your gut carries a small army of bacteria that turn steak and potatoes into tiny molecules your blood and gut can handle. But it also is continually tested with course after course of potentially dangerous molecules that cause a variety of ailments like inflammatory bowel disease. Turley and her colleagues are trying to find out how the gut manages to destroy these toxic molecules without harming "self," normal tissues and organs, or the good bacteria that feed them.

In the process, they have discovered a new solution to this old puzzle, a solution that could lead to a novel way to treat self-attacking or autoimmune diseases. The same research may also shed light on why your body sometimes treats cancer tumors like steak and potatoes, or like normal parts of your body.

"We have found a new pathway that the body uses to establish and maintain tolerance of itself," Turley says. "This finding involves cells not generally thought of as part of the body's immune defense system, but they play an important role in educating that defense system."

When germs enter your body, special cells quickly gobble up some of them, then chop their proteins into tiny pieces known as antigens. These antigen-presenting cells, as they are called, display any harmful molecules on their surfaces, like flags that warn, "this is not self." (When cells are from normal organs, such as the kidney or liver, presenting cells then display "self" flags.)

White blood cells, called T cells, roam the body looking for such flags. These cells make up a powerful self-protecting army, wherein each soldier recognizes only specific "self flags," like those from your gut or liver. When such encounters occur, a T cell continues on patrol without taking action. Non-self flags, on the other hand, trigger to a lethal attack on invading infections.

It's a great system, honed over millions of years of evolution. But it's not as simple as it might sound. In the small intestine, T cells encounter a multitude of different antigens, proteins from many sources. In addition to, say, salmonella bacteria, the gut teems with self-antigens, bacteria who work there, and, perhaps, bits of that chili dog you had for lunch.