The body’s immune system has the unique ability to evolve over one’s lifespan by developing a “memory” for pathogens it encounters so a person can be protected upon a repeated, secondary infection. This is the basis for protection conferred by vaccinations. Understanding how protective immunity works and is maintained throughout the lifespan is the focus of two researchers in the UA’s Department of Immunobiology: Dr. Michael Kuhns and Dr. Janko Nikolich-Zugich.
Nikolich came to the UA to pursue his passion for research on aging and its effect on the immune system. He is a professor and immunobiology department head, and he is a co-director of the UA Center on Aging.
“[The] UA gave me twice as much as I hoped for, in both immunology and aging,” Nikolich said. “Also, I am able to mentor undergraduates and it is more rewarding than I imagined.”
Inspiration for Kuhns’ research came from his early days of taking apart and rejoining equipment at home.
“Our research is largely reverse engineering,” said Kuhns, an assistant professor in the immunobiology department. “If you know how a machine works, you can build a better one.”
Kuhns hopes to engineer new therapeutic methods by picking apart the body.
“The ultimate goal is to figure out how evolution has designed the immune system’s molecular machinery to see if we can build new ones that will redirect T-cells so we can get them to do what we want them to do,” he said.
Kuhns explained his research by defining the big picture: The immune system is full of mobile cells. Their job is to survey the tissue and determine how they should respond to it. Kuhns and his team study CD4 T-cells, that function to coordinate the immune response.
Kuhns carries out his research by mutating a protein to see how it performs. The team tries to infer how that mutated region would function normally.
“It is basically a test to see how the puzzle pieces come together to make a picture,” he said.
Kuhns’ research at the UA since 2010 has led him to multiple discoveries about the immune system.
“For one, we found what we call a mechanical switch to explain how information gets from the outside to the inside of a cell,” Kuhns said. “It involves some kind of conformational change.”
The big idea is to understand how the pieces fit together to make the molecular machinery function.
Kuhns also collaborates with Nikolich-Zugich. Their team studies the impact of aging on T-cells.
“Aging affects CD8 T-cells differently than it affects CD4 T-cells. The rules change and that may have to do with the environment in your body,” Kuhns said.
Nikolich explained the relevance of studying aging effects on the immune system.
“We study the most compelling human condition imaginable,” he said. “Everyone is going to age.”
There are more than 500 million people in the world over the age of 65, and research on aging will increase health spans globally. Infectious diseases are one of the top-10 killers in the older adult population.
“With aging there is also increased inflammation in the body that makes all chronic diseases—cancer, diabetes, Alzheimer’s, etc.—worse,” Nikolich said. “Using mechanisms discovered by researchers like Dr. Kuhns and myself will help us improve defense against infection and control unwanted inflammation in aging.”
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