Science tackles how immunities decline with age

As cases and deaths from the pandemic rise, one trend remains consistent: The virus is deadliest for older adults who are more likely to have existing medical conditions and weakened respiratory systems. Both are major risk factors for becoming severely ill from infection by the novel coronavirus that causes the disease covid-19.

But scientists believe that another factor in the observed heightened risk is probably the general decline in the immune system that happens with age. In medicine, it has long been known that older immune systems struggle to fight off infections.

The ebbing of resistance to infectious disease with age is particularly clear when looking at studies of vaccines. During 2018-2019, for example, the seasonal flu vaccine was effective for roughly 3 of 5 children 17 and younger, according to the Centers for Disease Control and Prevention. The same vaccine was effective for only about 1 of 4 adults 50 and older.

Scientists have rushed to start trials for a vaccine against coronavirus. But even when they succeed in developing an effective one, University of Pennsylvania immunologist Michael Cancro worries that any coronavirus vaccine may be less effective for older adults — just as current vaccines are for other diseases.

“I doubt it’ll be worse, I don’t think it will be any better,” said Cancro, who wrote about age-associated changes in the immune system in the most recent Annual Review of Immunology.

Scientists are working hard to understand how age changes the immune system so that they can better protect seniors against current and future infectious diseases. It’s a timely goal. By 2030, there will be more adults over 60 than children under 10, according to the United Nations. In addition to the current threat of covid-19, influenza poses a serious risk to this age group: Nearly 3 of 4 people who died of flu during the 20182019 season were 65 or older, according to the CDC.

Here’s some information about what researchers know so far.

How do vaccines work? Vaccines stimulate the immune system in much the same way as an actual infection - minus the risk of major, deadly symptoms - because they contain fragments of disease-causing microbes, or pathogens, for the immune system to recognize. A prime example is the seasonal flu shot, made of pieces of the influenza virus. Other vaccines, such as polio, use inactivated or weakened versions of the whole virus or bacterium.

“It’s more or less been: You slice and dice the pathogen, you see what works,” Cancro said.

A successful vaccine will activate two classes of immune cells: B cells and T cells. B cells inactivate pathogens or mark them for killing by coating them with Y-shaped molecules called antibodies. T cells kill infected cells and direct the activity of the rest of the immune system, including B cells.

Those T cells are alerted to potential threats by another immune player called the antigen-presenting cell. It engulfs chunks of the pathogens, chomps them into bits and displays those bits on its surface. Nearby T cells respond to this by dividing rapidly to increase about a thousand-fold; your doctor can feel this by checking for swollen lymph nodes in your neck.

Most of the activated B and T cells will die soon after encountering a microbe or vaccine. But some become memory cells, which can last years or even decades and protect against future infections of the same kind. Memory responses are the hallmark of a successful vaccine, and are especially valuable for those with the least prior exposure to pathogens: children.

How do immune responses change with age?

Older adults struggle to respond to pathogens they haven’t already been exposed to. One example is yellow fever, a virus endemic to sub-Saharan Africa and Latin America. Studies show that older people from other regions, most of whom have never been exposed to the virus before, take longer to produce antibodies in response to yellow fever vaccine and those antibodies tend to be less effective at stopping the virus.

Something similar may happen with a vaccine for coronavirus, Stanford immunologist Jörg Goronzy said. “It will be one of those events where we vaccinate older people for something they’ve never seen before.”