Our Immune System Has Evolved in Remarkable Ways, and Shows No Signs of Stopping

The Intricacy of Immunopathology

Comprised of an astonishingly intricate network of cells, molecules, and proteins, the immune system is one of the most complex and pervasive components of the human body. As the body’s primary line of defence, the immune system plays a critical role in protecting us from foreign invaders, including the wide variety of bacteria, viruses, fungi, and parasites that can cause infectious disease. Yet, in its efforts, the immune response can also inadvertently cause the symptoms that we associate with infection.

“The immune system is amazing in its ability to recognize and defend against such a wide range of threats,” says Dr. Gray-Owen, Professor of Molecular Genetics at the University of Toronto.

However, contrary to what many of us believe, Gray-Owens indicates that the symptoms of infectious disease are not always caused by the bacteria or viruses themself. In some cases, the symptoms may instead be caused by the immune system’s response to the invading organism – a process known as immunopathogenesis.

Immune Systems Gone Awry

This is the very essence of Dr. Gray-Owen’s research, who focuses on a family of pathogenic bacteria known as Neisseria that causes meningitis and gonorrhea.

Neisseria meningitidis lives in the throats of humans. In fact, approximately 20% of adults have these bacteria in their throat, and it is completely harmless. Yet, in an instant, if these bacteria were to become invasive and proceed deeper into one’s bloodstream, it could kill an otherwise healthy person within 24 to 48 hours. One can go from cold-like symptoms to dead in a matter of days. Dr. Gray-Owen’s research aims to how to prevent the immune system from over-responding in a manner that can kill us. According to the World Health Organization, approximately one in 10 people who get bacterial meningitis die and 1 in 5 have severe complications.

“This is incredible,” Dr. Gray-Owen remarks, “we don’t understand why this transition from normal resident of the throat to devastating infection happens. We need to understand the trigger.”

Gonorrhea on the other hand lives in the genital tract, beginning in the urethra for men and in the cervix for women. Again, the bacteria itself is not harmful. In fact, they have evolved to keep everything “cool and calm” to avoid detection. But, when the immune system eventually recognizes the infection, it can become quite aggressive. In some cases, it causes scarring in the reproductive tract of women that can lead to chronic pain and/or ectopic pregnancies, and can lead to infertility.

What further puzzles researchers is that, in the case of gonorrhea, people get infected repeatedly, which is not supposed to happen. One’s adaptive immune system is supposed to learn to recognize a foreign entity upon first exposure and then provide immunity In this case, the bacteria have learned to turn off the immune system so that the person does not become immune.

These studies are critical as repeated infection impacts patients and the health care system. Gray-Owens’ research is trying to prevent severe illness in patients and alleviate the pressures on the health care system.

Learning from The Immune System

It’s puzzling, complex cases like these that drive Dr. Gray-Owen’s interest in immunopathology and microbiology. He notes that when beginning his career, “People tried to talk me out of studying infectious diseases because we had antibiotics. This is bonkers to me now that many antibiotics are not useful anymore. Now we need to find new alternatives to antibiotics.”

Through studying Neisseria gonorrhoeae and Neisseria meningitidis, Dr. Gray-Owen marvels at the potential applications that emerge to manipulate the immune system’s response to treat autoimmune diseases, reactivate the immune system against cancers, shut down inflammatory diseases, and cure HIV, to name a few.

Dr. Gray-Owen’s curiosity has led him and his team to understand why the immune response that aims to protect us against gonorrhea promotes sexual transmission of HIV-1, provided strategies to engineer novel vaccines with the potential to broadly protect against bacterial infections, and to develop a new class of more effective antibiotics.

But his work does not stop there. In addition to his research, Dr. Gray-Owen heads the Emerging and Pandemic Infections Consortium (EPIC). The consortium has played a profound role in combatting COVID-19. He aims to keep up this momentum and integrate resources and other experts to combat other, high burden infectious diseases and prevent future pandemics. He is also the Director of the Toronto Combined Containment Level 3 (CL3) unit, a facility that supports the research of infectious biological agents that require high containment infrastructure and operations.

Leveraging Toronto’s Bioinnovation Ecosystem

When discussing Toronto’s health sciences ecosystem, Dr. Gray-Owen did not hold back his appreciation for the city and its leading institutions.

“The University of Toronto is fantastic. As an investigator, it is exciting to experience the vibrant energy for innovation that exists among our community, and to have so many opportunities to work with individuals and agencies that can support our development of new technologies. The highly interconnected research culture helps guide us in the translation of our work, and provides opportunities to develop partnerships with industry and others.”

Indeed, the University of Toronto and its hospital partners provide access to an ecosystem that has helped Dr. Gray-Owen and his team to partner with the National Research Council of Canada, the Gates Foundation and Canadian International Development Agency, Oxford University and Sunnybrook Health Sciences Centre, developing technologies and applications that make use of research, technical expertise and clinical capabilities of these and other parties.

Now that it is established, EPIC aims to provide further opportunities for the research community to work together. It also aims to empower the next generation of trainees so that they can support the development of innovative solutions to combat infectious diseases and bolster Canada’s biomanufacturing sector.

“We have an incredible breadth of expertise in Toronto,” Dr. Gray-Owen says. “It’s just such an exciting place to do work because there’s an expert on everything – lots of discussions take place with several world-leading experts in a room. Yet everyone has humility, and just really wants to help tackle the problem. I’ve found that it has been really gratifying and a privilege to be part of this community.”