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Research searches to uncover mysteries of adaptive immune system

Ongoing research into the capacity of the immune system to adapt and fight disease is uncovering exciting new possibilities. 

“Adaptive immunity is amazing – there are myriad different microorganisms out there and the immune system can specifically recognize and respond to every one of those.” says Dr. Stefan Keller, a pathobiologist in the Ontario Veterinary College at the University of Guelph. His current research, with Natural Sciences and Engineering Research Council of Canada funding, focuses on adaptive immunity, the factors that influence its composition and dynamics in health and disease as well as possible impacts on diagnosing disease.

Dr. Stefan Keller, Ontario Veterinary College, University of GuelphFor an individual to mount an immune response, it must first recognize that an invader is present, explains Keller and this is done using highly variable receptors. The most well-known type of these receptors is antibodies or immunoglobulins.

“If you haven’t encountered a certain microorganism, you might have antibodies that recognize it but they won’t be present in very high levels,” says Keller. “If you stimulate the immune system before it encounters the microorganism, the immune system can mount a response much more quickly and efficiently when it does encounter the pathogen -- essentially it is the principle of vaccination.”

Each individual responds differently to pathogens
However, individuals respond differently to exposure to pathogens, he adds. “For example, if we are both vaccinated for the flu you might respond to it differently than I would. Your ability to defend yourself is dependent on the repertoire of receptors that you have available.”

The immune system randomly generates millions and millions of different receptors, explains Keller, so each individual ends up with a certain repertoire.

Keller is investigating the molecular basis for this response, examining how these receptor repertoires are shaped, including the influence of genetic background and environment.

“The dog provides a perfect model for this work because it allows us to take genetic variability out of play while working with individuals that are exposed to the same antigenic environment as humans,” explains Keller. “If two humans react to an immunogenic stimulus differently, we don’t know if that is because of environmental or genetic factors. However, if there are differences in the immune response of two dogs with the same genetic background it is probably because dog one has been exposed to different immune stimuli than dog two.”

“I’m not looking at the actual receptor, I’m looking at the building plan of the receptor, its DNA coding,” he adds. “Think of the building plan as a long word of a few hundred letters from a four-letter alphabet,” says Keller. “If I know the word that codes for a receptor recognizing a given virus, I can use that information in a reverse fashion. I can look at the receptor repertoire and infer if this dog has seen this virus in the past. The infectious organism may be long gone in samples, but I can look at the immune response retroactively and establish correlations between immune stimuli and receptors.”

Can this information be used to diagnose disease and predict outcome?
In addition to elucidating basic mechanisms, Keller is investigating how he can use this information in diagnosing disease. Can he find specific hallmarks, signatures of repertoires, which allow him to identify the cause of the disease or predict outcome?

He hopes the data generated will provide a basis for further preventative or therapeutic strategies and to generate novel methods to diagnose disease in animals. 

There are a lot of situations where the immune system comes into play, he adds. “Adaptive immunity can prevent infectious diseases or cancer but it can also be the cause of disease as in autoimmune disorders. Investigating the factors that influence the fate of an immune response will help to better understand and control diseases.”