Georgetown College. Georgetown University.

The human immune system maintains a precarious balance in the body: while it protects from illness, it can also do great harm. In many cases, the process of fighting off infection can be the very thing that causes the most discomfort.

The immune system’s impact on the body and the way the body fights off infection is of particular interest to Dr. Steven M. Singer, Associate Professor at Georgetown University and Co-Director of Georgetown’s Center for Infectious Diseases. Currently, Singer explores immune system responses by investigating Giardia lamblia, one of the world’s most common parasites.

Currently, Giardia infects an average of 200 million people around the world. The body fights off infection in a variety of ways. Nearly 80 percent of those infected experience only minor, sub-clinical reactions from their body. The other 20 percent experience more significant symptoms, from nausea to severe intestinal problems and diarrhea. Some people experience symptoms for one to two weeks, while others experience them for years. To Singer, identifying the difference between the body’s severe or milder reactions may be crucial in identifying important ways that medical scientists can participate to fight Giardia and to control symptoms. It may also give scientists important insights into several other conditions which impact the intestines, including Crohn’s disease, irritable bowel syndrome, and lactose intolerance.

“The big question is why,” says Singer. “Where does the variation come from? Are there differences in the parasites infecting the human subjects or are the people themselves responding differently?”

The answer is that it’s probably both. Exploring the smaller components of the infection is central to Singer’s investigation. Singer looks at Giardia in a number of areas, including examining specific hormones released by the body, isolating genes produced by the host, and identifying and watching specific cells used by the body to fight infection. Looking at each of these separately allows Singer to examine the way that each component impacts the body, both negatively and positively.

There are many questions to be answered, and they all center around the body’s response to the parasite. “Giardia uses bile as a growth factor,” Singer explains. “You also produce more bile when you’re infected.” The bile may help the Giardia to grow, but it may also promote more severe symptoms. Would controlling for the additional influx of bile help reduce symptoms and fight the infection?

Singer is also looking at the mast cell, a type of cell involved in fighting infections. Key in the body’s response to Giardia, mast cells rush into action at the site of the infection, the intestines, but in the course of battling the parasite, the mast cells may cause specific changes that increase inflammation and irritation, adding to the severity of symptoms experienced. Is there a way to allow the mast cells to do their work while controlling the inflammation and discomfort they cause? Is this response required to fight Giardia?

Singer is working to segregate the immune system’s responses and identify which of the body’s reactions are helpful, harmful, preventable, and/or necessary for the immune system to do its work. The research has many outside implications. Apart from the changes created by the mast cells, Giardia itself seems to actively prevent general inflammation in the intestine. Could Giardia then play a role in fighting Crohn’s disease, a condition characterized by severe intestinal inflammation? Within the body’s reactions to Giardia several connections can be found to lactose intolerance and irritable bowel syndrome, both of which deal with similar issues in the intestines and digestive system.

In Singer’s lab the investigation has just begun and he anticipates that it may take five or six years to fully test out his current theories. In the meantime, while students work in the lab running tests and exploring the different areas of immune response, Singer collaborates with medical facilities in Baltimore, Sweden, and Brazil to collect material and compare data against the research hypotheses, and the results slowly build.

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