The immune system's foot soldiers
Dr. Robin Yates studies the cells that make up the front-line defense of the body's immune response.
Story by Julie Sedivy/Illustration by Dwight Allott
Our bodies are equipped with hungry immune cells called macrophages, so named by combining the Greek roots for the words "large" (makros) and "eat" (phagein). Much of the time, these cells play a routine housekeeping role by removing dead cells and debris. They engulf these bits of matter and break it down within the cell. However, these quiet custodial macrophages become more warrior-like when they encounter potentially harmful bacteria. Dr. Robin Yates studies the various ways in which macrophages act as an important line of defense against infection.
When macrophages surround foreign matter, the area inside the cells that contains the engulfed particle forms a type of sac, called a phagosome. Dr. Yates describes the phagosome as the "ground zero" for the body's immune response, with all subsequent responses depending on the chemistry inside this sac. In order to destroy bacteria, the contents of the phagosome, which initially contains just the fluid and matter from outside of the cell, needs to become a hostile killing zone within a matter of minutes to hours. When the right chemical responses are initiated, the acidity level inside the sac increases, and the cell produces such toxic substances as hydrogen peroxide.
Some bacteria , for example, those that cause tuberculosis, are able to prevent the phagosome from becoming toxic. The bacteria can then thrive and multiply in the phagosome, which begins an infection that can ultimately lead to tuberculosis. Although there have been many explanations of how this may occur, scientists currently do not know how the bacteria do this. Some researchers study this bacterium's properties by subjecting it to various conditions and substances. Instead, Dr. Yates turns his attention to the bacteria's natural habitat within the phagosome. He hopes that, by shedding light on this complex and delicate system, he will help scientists understand some of the mechanisms that lie at the very heart of immunity.
Dr. Yates has developed an innovative set of techniques that allow him to monitor how the phagosome changes once bacteria are detected. Armed with these new techniques, he aims to understand how the macrophage, which he describes as a jack of all trades, fulfills its many roles. For example, in addition to mopping up debris and killing bacteria, macrophages play a role in making other immune cells aware of the presence of the bacteria, which trigger a broad inflammatory response. In order to do this, the macrophage needs to preserve enough of the bacterial proteins that the other immune cells can recognize them as invaders and launch the appropriate attack against the bacteria. This means that the normal process of breaking down proteins, as happens during the routine housekeeping function of the macrophage cells, needs to be controlled when bacteria are detected.
Dr. Yates's study of the "ground zero" of immunity has the potential to affect several areas of health. For example, understanding the intricate chemistry inside the multipurpose macrophage cell could lead to the development of more targeted and efficient vaccines. It could also lead to better treatments for autoimmune disorders, in which immune cells trigger an overly aggressive immune response that targets the body's own cells, believing them to be foreign invaders.
Dr. Yates, who is a trained veterinarian, credits his background with giving him a framework for thinking about the fundamentals of the immune system. Because vets need to become comfortable with treating many different types of animals, they are used to thinking broadly about the very roots of diseases, which can manifest in different ways across species. Since its inception, the University of Calgary's Faculty of Veterinary Medicine has been closely integrated with the Faculty of Medicine in recognition of the unique contribution that veterinary expertise can make to basic medical research. For Dr. Yates, who is affiliated with both faculties, this integration has been conducive to his study of the miniature environments in which our bodies' first battles with bacteria take place.