Fewer killer T cells, which are also less efficient and weaker reinforcements:
During World Immunisation Week, we look at revelations about how the body responds to influenza over time – and new research reveals why older people are at higher risk of severe influenza infection.
KEY FINDINGS:
> Older people are at higher risk of severe influenza infections because their killer T cells that normally play an important role in stopping the infection are now in lower numbers and less efficient. We gradually lose our most optimal killer T cells, and their backup cells are also of reduced quality, new research has revealed.
Protecting us from severe disease caused by viruses such as influenza is the busy work of killer T cells, part of our immune system. These cells can remember viruses they have eliminated, which allows them to respond faster – and more strongly – when reinfected with the same virus.
In older people, killer T cells targeting the influenza virus are less effective versus those in younger people. There is a growing body of evidence to explain why this difference occurs.
Researchers observed how the killer T cell populations of a group of adults and older people changed over time (7-12 years). In particular they wanted to find out if they could detect the same Killer T cells across multiple time points.
Commenting on the findings was the University of Melbourne’s Dr Carolien van de Sandt, senior research fellow in the Kedzierska Laboratory:
“The highly functional killer T cells in adults are long lived; we were able to detect the same cell at multiple time points in the same donor. This is good news as it means our body has good defences against influenza for at least 10 years in our adult years.”
“However the highly functional killer T cells in adults gradually declined over time. We discovered that adults have a high functioning killer T cells ‘in reserve’ which can take over once the initial highly functional cell populations decrease.”
In older people, it was a different picture.
“Once the highly functional populations start to decrease they eventually disappear, the void is filled by less functional killer T cells. As these less functional cells diminish, similarly low-functioning cells replace them, leading to a progressive decline in immune effectiveness.
“We now have a better understanding of why older people are at higher risk of severe influenza infections. Their killer T cells that normally play an important role in stopping infection are now in lower numbers and less efficient. Our most recent study shows their backup cells are also of reduced quality.”
Dr van de Sandt says in light of these findings, it is especially important for older people to get vaccinated at the start of the flu season, to boost other parts of their immune system, helping to protect them against circulating flu viruses.
Read more of Dr van de Sandt’s work here:
University of Melbourne Dr Carolien van de Sandt, a Senior Research Fellow and early-career researcher at the Doherty Institute, is a 2023 Victorian Young Tall Poppy Award recipient. Dr van de Sandt was recognised for her work in virology and immunity.
New approaches to induce protective immunity needed?
Current influenza vaccines are designed to generate antibody responses which bind to the outside of the virus and form a shield to prevent the virus from infecting your cells. However, these antibodies are directed against parts of the virus that can change from year to year. Leading to an almost annual update of the vaccine, to make sure it still matches with viruses circulating in the upcoming influenza season.
Although current influenza vaccines are immensely important in preventing severe disease, particularly in high-risk populations including older people, the vaccine gives the best protection if the vaccine components are well matched with the circulating influenza viruses.
Dr van de Sandt believes that further improvements to the vaccine can be made. New approaches, for example the mRNA vaccines used during the COVID-19 pandemic, can also boost the bodies killer T cells. Killer T cells recognise parts of the influenza virus that are less likely to change, which means that they can provide a second layer of protection against severe disease.
“If vaccines that boost the killer T cells become available, our research indicates that they probably work best earlier in life, when we still have these highly functional killer T cells.”
“However, it will be important to investigate whether these novel vaccines will also induce highly functional killer T cells that can be maintained into old age.”
Dr van de Sandt considers the possibility that just boosting these cells will not be sufficient.
“We may need an additional vaccine component to specifically boost their longevity.”
Dr van der Sandt is available to present on these topics:
- Influenza
- Ageing immunity
- Pandemic risk/preparedness
- Vaccination
Follow Dr van de Sandt on Twitter: @CvandeSandt, BlueSky: @cvandesandt.bsky.social and LinkedIn: linkedin.com/in/carolienvandesandt