Woman getting vaccination and flexing biceps – wearing face mask
During the recent Covid-19 pandemic, the rate of serious illness and death was extremely high in the elderly population. Why; Weakened immune system — as we age, we become more vulnerable to infections and vaccination effectiveness falls. Young research suggests we may be able to reverse the trend. By targeting abnormal stem cells using antibodies, a team of Stanford scientists was able to turn back the clock on the immune systems of mice, boosting their responses to viral threats and reducing overall inflammation.
Immune Function and Blood Stem Cells: What’s the Connection?
We have two main types of blood cells: red and white. Red blood cells are mainly responsible for carrying oxygen from the lungs to all the tissues and organs of the body. White blood cells, on the other hand, are key players in the immune system. This includes all the usual big hitters: B-cells that make antibodies, T-lymphocytes that destroy pathogens, macrophages that clean up debris, and so on.
Both red and white blood cells, despite their different functions, come from the same source, called blood stem cells. These are special “progenitor” cells, meaning they can develop into any type of blood cell, either red or white. Their job is to ensure that the body’s supply of blood cells remains replenished at all times. As with most cells in the body, blood cells wear out over time and must be constantly replaced.
When we are young, our bodies do a good job of replenishing our blood cells as needed. But the older we get, the more unstable this process becomes. Not only does production slow, it becomes increasingly unbalanced: stem cells begin to develop a bias, preferentially transforming into certain types of blood cells over others.
This bias comes at the expense of white blood cells, or immune cells, associated with the adaptive branch of our immune system. In particular, B and T cells, which are immune specialists that form very specific responses to each pathogen they encounter. They also have the ability to remember pathogens they have previously encountered, allowing them to strike quickly and accurately in the event of reinfection. It is this memory that provides us with lasting protection against common pathogens.
Instead of replenishing T and B cells, the aging body favors different immune cells, including monocytes, macrophages, and neutrophils. These form a generalized branch of the immune system called innate immunity, which does not discriminate between pathogens and depends on a general response. Think of these cells as your first line of defense — clumsier and brutish, but reliable. These immune cells are also known to cause inflammation as part of their strategy. In short bursts, this is fine, but over extended periods, it can cause damage to surrounding cells and tissues, like a spoiled fruit causing the rest of the bowl to spoil.
Balancing the Scales
This tendency of “exhausted” blood stem cells developing a bias against B and T cells has been observed not only in aged mice but also in humans. Scientists speculate that it weakens the immune system’s respective antibody and T-cell responses, which could explain why older people more prone in respiratory viruses and other similar diseases.
If the immune dysfunction seen in older adults can be traced back to an imbalance in blood cells, then shouldn’t “rebalancing” them rejuvenate the immune system? Easier said than done. Although we know that blood stem cells develop a bias in old age, we still don’t know the exact mechanisms by which this happens, making it difficult to reverse the process.
The team of scientists at the Weissman Lab came up with a neat idea to get around this issue: special antibodies that attach to the imbalanced blood stem cells and destroy them. That way, instead of having to reverse the process entirely, they just get rid of the pesky blood stem cells before they cause any imbalances.
But antibodies require some landmark to help them locate and attach to their intended target—like a lock and key, each antibody has a corresponding receptor on the surface of a cell it’s on. Most importantly, the researchers would have to find receptors on the cell surface that were only present on exhausted blood stem cells that disproportionately develop into innate immune cells. Otherwise, they would risk wiping out all blood stem cells, including normal, balanced ones.
To find potential landmarks to guide their engineered antibodies, the researchers searched large transcriptome databases. They eventually found three promising candidate proteins that were common on the surface of depleted blood stem cells but not on the surface of their normal counterparts.
They then injected their antibodies into older mice to see if they would have the desired effect. Indeed, the treated mice were able to contain the viral infections much more successfully than the older mice that had not received the antibody treatment. The group that received the antibodies also showed a much stronger response to the vaccination. Chronic low-level inflammation was also reduced.
The immune benefits were confirmed at the molecular level, where treated mice had fewer imbalanced blood stem cells. There was also a marked increase in B and T cell production that lasted up to four months after treatment. In short, their immune system was renewed.
Implications
We rely on our immune system every minute of the day. it is always busy at work, protecting us from foreign invaders and threats. Aging weakens the immune system, leaving us vulnerable to infections that we would normally be able to fight off without much trouble. It reaches a point where the flu infection becomes a life-threatening event.
This latest study suggests that we may soon have a way to rejuvenate our immune system, bringing it back to full strength. Although these initial tests were conducted in mice, the researchers are already looking ahead and hoping that the same approach will work in humans. However, it is safe to assume that it will be several years before this treatment option is approved for human use. And even more to make it widely available.
