New approaches to human immunology in health and disease

Some of the deep complexities of our immune system, once seen as a "black box" in medicine, have been demystified, but we need new approaches to reveal all its mysteries, says renowned Stanford University immunologist Professor Mark Davis.

Delivering the Wolfson Memorial Lecture on 2 November 2014, Davis said researchers have lifted the lid on the immune system in the past 50 years, but discoveries in basic immunology have led to few improvements in human health. New strategies are needed to understand immunity and apply these findings to human health.

Science and Technology Minister Naledi Pandor, South African Medical Research Council (MRC) President Glenda Gray and guests attended the lecture delivered at the Institute of Infectious Disease and Molecular Medicine's (IDM) tenth anniversary celebrations.

The limits of mouse models

Davis said mouse models have been "very limited" and "uninformative". "Most of the strategies we use in mice will never work in humans. You cannot slice and dice people and no one works in blood in mice as there is no technology devoted to this."

Instead Davis, the director of Stanford University's Institute for Immunity, Transplantation and Infection, advocates a systems approach where his team works with human blood samples to see particular immune responses.

He said it is vital to understand the metrics of health in a functioning human immune system "as we have not had a way of measuring how robust any given individual system is". For example, he said, "Why do some people who receive flu vaccine stay healthy while others get the flu?" His approach is not hypothesis driven but a board strategy where his team first "search" the immune system and then wait to see what is revealed.

Revisiting memory cells

In a seminal study, Davis and his team waded through blood-bank blood from adult donors and newborn babies and "surprisingly" found anti-HIV memory cells in people who were HIV negative, and antibodies for bird flu in people who had never had bird flu. This casts doubt on previously held dogma that the body builds a memory of a pathogen or bug and develops an enhanced ability to fight the bug once it has been exposed to it or to components of it in a vaccine.

In the study, newborn's blood showed no signs of this enhanced memory, which could explain why young children are more vulnerable to infectious diseases. He does not know where the memory cells in adults come from but speculates that the infections with low virulence bugs trigger the immune system to develop responses to other related bugs it has never seen before. He says the process of developing memory cells probably starts around the age of 10.

Davis highly recommends setting up a central facility with high-throughput assay equipment '“ which immunologists, vaccinologists and even cardiologists and oncologists could use.

"The immune system is an undiscovered link between almost all branches of medicine as almost every disease involves inflammation and this is part of the immune system. There are a lot of immunological sequela in diseases that we don't even know about because specialists in these diseases do not look at the immune system," he said.

Celebrating a pathbreaking institute

Opening the event, Vice-Chancellor Dr Max Price described the IDM as a "pathbreaker" for having taken molecular medicine and creating a niche for it by linking it to infectious diseases. Although the IDM is not only about infectious disease, this focus has been a "secret to its success" '“ making it a partner of choice for institutes and funders worldwide.

He said the IDM has attracted top researchers and funding which enables it to do a volume and quality of research that outstrips anything achieved before in developing countries. "The bar has been raised through the 10-year IDM history for the country and for the Global South."

Gray congratulated former IDM director Professor Greg Hussey and director of UCT's Desmond Tutu HIV Foundation Professor Robin Wood on each receiving a 2014 MRC platinum lifetime achievement award. She said the MRC wanted to fund big science, big ideas, improve the health of the nation and was committed to building research infrastructure in South Africa.

"Our aim is to ensure that we fund and execute health science that will hopefully change the lives of South Africans." She said UCT had the lion's share of MRC funded extra-mural units which put "a lot of pressure on [the Faculty of Health Sciences) to deliver high-impact research".

"We are committed to spending more money in the extra-mural space ... and hope that UCT will collaborate with other historically disadvantaged universities to grow them in the way it has [grown]."

Earlier Faculty of Health Sciences Dean Professor Wim de Villiers said that in 2014/2015, UCT was ranked 48 of all "clinical, pre-clinical and health" universities globally in the Times Higher Education World University Rankings. "Research and internationalisation are strong influencers of ranking, so the IDM plays a significant role in UCT's international recognition."

Story by Adele Baleta. Photo by Je'nine May.