Studying the complications
In 1982, while he was working as a resident in internal medicine, AHFMR Senior Scholar Dr. Chris Mody cared for the first AIDS patient in Calgary. "In those days, AIDS was very mysterious and very scary. We didn't even know it was a viral disease. Caring for this patient was a profound experience that marked an important point in my career. It got me thinking: Why is it that some people are infected with certain microbes and others are not?"
The question led Dr. Mody to study the defence mechanisms of hosts such as humans-how to manipulate these defences to our advantage, and how to restore them to full functionality when they are defective. His research team investigates the immunological response to infections in patients whose immune systems are weakened, such as those with cystic fibrosis and AIDS. One of the hallmarks of HIV infection is that it leaves people vulnerable to opportunistic infections from other viruses, as well as bacteria and fungi.
At the University of Calgary, Dr. Mody studies a particular fungus called Cryptococcus neoformans. It usually does not cause disease in healthy people, but it often causes meningitis and pneumonia in AIDS patients. Dr. Mody has begun to explore how the immune system protects against organisms that can cause disease. It turns out that different types of white blood cells use different mechanisms. The T cells, for example, use a protein called granulysin to kill pathogens; the NK cells use one called perforin. "The interesting thing about this is that both kinds of cells have access to both killing proteins, yet each kind chooses to deploy only one," says Dr. Mody. "The natural follow-up to this observation is: Can we exploit the other mechanism when the first one is exhausted?"
Dr. Mody's team found that the mechanism that triggers T cells to make granulysin is defective in patients who are infected with HIV. "We are trying to figure out whether we can overcome this defect and restore the response of the T cells. And if we can get them to make granulysin, we will have to determine whether that protein is effective. This could be the key to improving the immune response of people with AIDS."
Quick Facts
HIV is a retrovirus. This type of virus spreads by inserting itself into a host's cells and taking over the cells' self-reproduction mechanism to make copies of itself.