Our immune system protects us from all sorts of bacterial and viral invaders, but sometimes it does its job too well. When the immune system becomes overactive, it can cause serious damage to otherwise healthy cells.
The result can be diseases such as diabetes mellitus, rheumatoid arthritis, lupus erythematosus and a host of others. The mechanisms which cause these diseases are not well known, but researchers at Trinity College and the Royal College of Surgeons are trying to find answers by learning more about the biochemistry of the body's immune cells.
The Health Research Board project is studying the T cells, a central element of our immune defences, explained Prof Dermot Kelleher, a professor of medicine at Trinity. He leads the work which also involves Dr Yuri Volkov, of Trinity and formerly of the Institute for Immunology in Moscow, and Dr Aideen Long, of the Department of Biochemistry at the Royal College of Surgeons.
"The research is on the subject of T cells which are the critical cells of the immune system," Prof Kelleher explained. His group is looking in particular at the biochemical changes in these lymphocytes or white blood cells which allow them to migrate through the body and penetrate tissues to get to the site of infections and disease.
Their work is published in the current issue of the Journal of Immunology. They describe the alterations which take place, changing the cell from a roughly spherical shape to one which includes a "tail", which allow the cell to move.
"A molecule called FLA-1 is the trigger for these cells to change their shape completely and to begin to migrate," he said.
In response to the trigger, two enzymes are expressed by the cells which alters their "skeleton", causing the tail to form. These enzymes then begin to form and reform in a pattern along the tail. "This is almost a caterpillar-track effect," he said, and this propels the cell forward.
"What we are seeing is the molecules concentrating on a single spot like a necklace." They then shuttle down through the tail. "The process of movement has been seen before but not a demonstration of the internal dynamics," said Prof Kelleher.
They are also studying substances at the head of the migrating T cell. This allows the cell to push between and past cells without causing excessive damage.
The value of their work lies in the potential to devise strategies to interfere or moderate the T cell immune response and so reduce the risk of autoimmune disease. Many of these diseases are characterised by an uncontrolled influx of lymphocytes to the affected area. Once the immune process is initiated, it causes a cascade of reactions which can lead to tissue damage.
The aim, he said, would be to discover a way to interfere with the T cell biochemistry as a way to slow down the influx of lymphocytes. One method might be to disturb the expression of the enzymes which allow migration.