Alberta Innovates- Health Solutions

Recently, researchers postulated that a tiny number of people are immune to AIDS because their ancestors had survived bubonic plague (“The Black Death”), the terrifying disease that scourged Europe up to the 18th century.

Some crucial genetic mechanism that had mutated hundreds of years ago had been passed on through the generations, resulting in immunity to the modern-day plague.

Most of us have no such genetic weaponry. Good health practices and access to medical services help protect most people against deadly viral and bacterial diseases. But for those infected, keeping their immune systems strong with drugs and other therapies is the only way to manage disease and ensure a good quality of life.

Research in immunology, the science devoted to the immune system, has never been more urgent. Advances in understanding how the immune system works could translate into new drugs, treatments, and genetic therapies. University of Calgary Heritage researcher Dr. Julie Deans is delving into one of the most profound levels of the immune system - its signalling system.

The important machinery controlling each of the body's trillions of cells is housed inside the cell's plasma membrane. This inner micro-universe produces all the chemicals needed for cell signalling, the communication between cells. Not only a protective wall, the plasma membrane allows chemicals in and out of the cell.

With advances in technology and in cell research, the plasma membrane's complex make-up is emerging. Much more than a uniform layer, it is imbedded with protein sensors and divided into differentiated areas which allow specific events to occur apart from the rest of the membrane surface. The plasma membrane, it now appears, is key to cell signaling.

Dr. Deans explains, "The proteins on the surface of the cells sense their environment and receive signals that tell the cell what to do: to move, to change its function, to die."She is investigating a specific protein, called CD-20, found in the surface of an immune cell called a B-cell, that controls B-cell activation. B-cells are also known as lymphocytes, part of the immune system involved in long-term, adaptive immunity. If you are infected with measles as a child, you won't get it again as an adult because the immune system recognizes foreign things it has seen before, and adapts.

Tiny cave-like indentations called caveoli, found in most cell membranes, appear to be where some of the important signals are received and transmitted by proteins embedded in the membrane. Lymphocytes have structures similar to caveoli that are also likely to be important in cell signaling. These microdomains have a high density of lipid, and float like lily pads on the lymphocyte surface.

Understanding how CD-20 works eluded Dr. Deans initially. Then she discovered that CD-20 is not like other proteins; it is the first demonstration in a white blood cell of a protein that moves into the microdomains.

Dr. Deans suspects that CD-20 is involved in regulating antibody production, although just what message that CD-20 conveys to the microdomains requires further research. Currently, she is working on a number of related issues, including investigating the mechanisms that make CD-20 move. "If we can find out how it gets to the microdomains, then we might be able to control its movement," says Dr. Deans.

Controlling CD-20 has enormous implications in many disease areas. Autoimmune diseases such as lupus or asthma result when the body's immune system produces antibodies that attack healthy cells. If CD-20 could be regulated to stop making antibodies, new treatments for autoimmune diseases could be devised. Conversely, if CD-20 could be regulated to produce more antibodies in response to tumor cells, scientists could devise new therapies for cancer.

Most recently, a new treatment for non-Hodgkins lymphoma, a cancer of the B-cells in adults, has been developed that involves injections of the antibody to CD-20.

The big question that remains for Dr. Deans, however, is: What is it that's being controlled by CD-20? Her most recent research results show that CD-20 may not be unaccompanied on its signalling trips. Whether the mystery molecule with it is the driver or a passenger remains to be discovered.

Dr. Julie Deans is a Heritage Scholar at the University of Calgary. She also receives support from the Medical Research Council of Canada.