News

Written by Dr Carolien van de Sandt

Have you ever wondered why, during the COVID-19 pandemic, the elderly were at greater risk for severe disease, often resulting in hospitalisations, ICU admissions and even death? And why did most children not show any symptoms, despite being infected with the same virus? Then, you’ll find this year’s theme for the International Day of Immunology particularly intriguing: ‘Immunity through the ages’.

The Decade of Healthy Aging

By 2050, around 22% of the world’s population will be over the age of 65. Individuals in this age group are at increased risk for many diseases, including influenza, COVID-19, cancers and autoimmunity and are also more vulnerable to severe disease outcomes. While life expectancy has increased, it does not guarantee a healthy life for everyone, nor that one’s full lifespan is spent in good health. It is therefore not surprising that the United Nations (UN) have declared the 2020s as ‘the Decade of Healthy Aging’.

But what is causing these differences in disease outcomes as people age?

Remembering what you have seen in the past

Immunity is a dynamic process. It evolves and changes throughout life to effectively respond to known and unknown viruses. To understand how this works across the human lifespan, it is important to know that the immune system consists of two parts: the innate immune system and the adaptive immune system.

The innate immune system is the body’s first line of defence against viruses. The innate immune system responds in a very similar way to each virus it encounters, which is why it is also known as the nonspecific immune system. While the innate immune system is great at quickly detecting and responding to viruses, their capacity to eliminating them is rather limited. However, when it does detect an infection, specialised innate immune cells will catch and present the virus to the adaptive immune system, also known as the specialised immune system.

The adaptive immune system consists of killer T cells, helper T cells and B cells which produce antibodies. In contrast to the innate immune system, the adaptive immune system learns to recognise different viruses and trains T cells and B cells to respond to them specifically. Although its initial response is relatively slow, it is more accurate. Its ability to remember a virus allows for a faster and stronger response when the body encounters the same virus again, resulting in milder symptoms.

Mother’s immune system helps protect against infections early in life

When we are born, our immune system has not yet learned how to recognise viruses. Newborns primarily rely on their innate immune system for protection. If they become infected with a virus, their innate immune system may go into overdrive, as their adaptive immune system has not yet kicked in. This exaggerated response can make them much sicker compared to other age groups.

However, newborns receive a gift from their mothers: during pregnancy and breastfeeding, mothers transfer antibodies against viruses they have encountered in the past, through infection or vaccination, to their children. This is why pregnant women are recommended to get vaccinated against certain pathogens, like influenza and pertussis (whooping cough), during pregnancy, enabling them to pass on their antibodies to their unborn child. These maternal antibodies remain in the child’s body for about six months, providing temporary protection against severe disease outcomes until they have had a chance to train their own adaptive immune system through infection or vaccination.

A steep learning curve in children

At school, children learn a lot on a broad number of subjects, one day they want to be a firefighter and the next they want to be a baker or a scientist. Similarly, a young immune system goes through a dynamic learning process during childhood. During childhood, the children get exposed to a great variety of viruses and the immune system needs to learn to recognise and remember each encounter. This is why children cope exceptionally well with both seasonal and pandemic viruses. Whether a child encounters a seasonal influenza virus that circulates every year or a pandemic virus like SARS-CoV-2 in 2020, these viruses are both “new” for the children’s immune system.

We have learned a lot during the pandemic on how the children’s immune system differs from those in adults and elderly. Firstly, our collaborators at MCRI demonstrated that children have a much stronger innate immune response, which helps to rapidly clear the infection. Secondly, we found that children maintain greater flexibility in their B cell and antibody response. While the young immune systems may have had some training through prior exposure to seasonal coronaviruses, their B cells and antibodies were much better in adapting to the pandemic virus compared to those in older individuals. Thirdly, we see something similar happening for killer T cells: both their SARS-CoV-2 and influenza-specific killer T cells get specialised training during the infection but maintain some flexibility, meaning that they can adopt more easily in case the virus changes.

Adults have great memory

Just as adults specialise in a specific career which greatly relies on knowledge acquired in the past, their immune system behaves similarly. The adult immune system has been well trained to identify and eliminate viruses that it has seen in the past, like influenza. Much like swapping to a new profession later in life poses some challenges, it becomes more challenging for the adult immune system to recognise and combat new viruses it has not encountered before, such as SARS-CoV-2. This is why adults often cope well with seasonal viruses like influenza, due to their well-trained immune system, but were more susceptible to contract a (mild) symptomatic infection during the COVID-19 pandemic.

When you retire, the immune system retires with you

As we get older, people retire from work and may adopt a more leisurely lifestyle taking afternoon naps and sometimes becoming forgetful. The same happens to the immune system. It tends to lose its ability to recognise and eliminate viruses it has already encountered and struggles to identify new threats, such as a pandemic virus. This is why the elderly are at higher risk for severe disease outcomes during both seasonal infections and pandemic outbreaks. But it is not just viruses, the older immune system’s ability to recognise cancerous cells declines, which is why many forms of cancer are much more prevalent in the elderly.

Interestingly, the way in which the elderly immune system loses its ability to recognise cancerous cells differs from the mechanism that impact its ability to identify viruses such as influenza. In the case of cancerous cells, the killer T cells become exhausted or “fall asleep”. Recent treatment strategies aim to reawaken those sleeping cells. However, those treatments may not work when it comes to age-related loss to recognise viruses.

In our recent study, we found that  elderly killer T cells with the best memory do not “fall asleep” but are instead replaced by killer T cells with reduced ability to recognise and eliminate virus-infected cells. Our findings suggest that to strengthen the elderly immune response against acute viruses, like influenza and SARS-CoV-2, probably requires a different treatment strategy, tailored to address these distinct immunological challenges.