Why do some vaccines protect us for a lifetime, but threats like tumours and viruses present such an ongoing challenge to our health? The answer lies in our immune system’s memory, and how invading pathogens hack the system.
Our immune cells have memory, just like you’d find in a computer’s memory bank. It’s essentially a living library of past infections and is ready to attack when it detects an infection you’ve had before, destroying the threat before symptoms show. This memory bank lasts a lifetime and is the foundation of how vaccines work.
Unfortunately, some viruses try to bypass your immune cells’ memory bank, like hackers trying to infiltrate a computer system. This is why you can contract the flu, or the common cold, after you’ve had it before.
In a major scientific milestone, our research team at the Frazer Institute has made significant discoveries into how the immune cells’ memory works .
This has completely reshaped our understanding of how the body’s immunity is controlled and could lead to the development of more precise drugs and therapies.
Let me explain…
Not all immune cells are created equal
The immune system has two branches:
- The Innate Immune System features Natural Killer cells that act as the body’s first responders. These cells are critical during the early days of an infection. They patrol tissue like security guards, look for ‘danger patterns’ and attack the threat.
- The Adaptive Immune System is slower to act, but features a highly targeted squad of specialist cells that step in while the first line of defence is holding the fort. The heavy lifters here are the T cells that are trained to hunt down an exact pathogen signature. While it takes these specialist cells a few days to scale up and defeat a new virus, their unique superpower is generating a dedicated, long-term memory pool. This leaves behind a permanent genetic blueprint, ensuring your body is prepared for a future rematch.
Two immune systems are better than one
As viruses evolve, they develop ‘immune evasion’ tactics to trick Natural Killer cells so they can bypass the front line defence system. This is why, through evolution, our bodies developed an Adaptive Immune System, so we have an extra layer of specialist cells waiting right behind the first responders to finish the fight, and maintain a dedicated memory bank to prevent severe disease over a lifetime.
Genes play an important role
To make both first responder and memory specialist cells work efficiently, the body relies on a master switch that is embedded within our DNA. This switch is a single gene called growth factor independence 1 (GFI1).
Scientists have known GFI1 is essential, but for the first time we’ve been able to map the precise molecular mechanics of this single gene.
We found it has a unique and profound importance in both immune systems, which is something that hasn’t been discovered before.
The gene operates as a critical hub for our immunity and regulates both the first-responding Natural Killer cells of the innate system and the long-lived memory T cells of the adaptive system.
Natural Killer cells rely on genes too
Our recent study in Nature Communications looked at how GFI1 was just a critical to Natural Killer cells as memory T cells, even though they are from two completely different parts of the immune system. We found the gene acts as an upstream checkpoint controller, ensuring these first responders have armed themselves appropriately.
When we experimentally removed GFI1, the killer cells failed to mature, resulting in a catastrophic failure of the immune system when challenged by both viral infections and cancer. Without this gene, the cells lose their functional killing capacity, leaving the body vulnerable to tumour spread or viral threats before the rest of the immune system can kick in.
Translating research into clinical practice
By exposing how a single genetic switchboard controls the infrastructure of both first-responding Natural Killer cells and memory-specialist T cells, we have essentially created a blueprint for manipulating the immune system to our advantage.
If we can find a way to dial this genetic response up or down, it opens doors for developing smarter therapies. For example, we might be able to boost GFI1 activity to give T cells the long-term stamina needed to clear chronic viral infections like AIDS, Hepatitis B and C, and chickenpox.
We can also use this knowledge to arm killer cells with the mechanisms to hunt down and destroy cancer cells.
Ultimately, mapping how this single gene spans both evolutionary branches of our defences is a major step towards next-generation vaccines and targeted immunotherapies.
Read the first study published in Nature Communications and the second study published in Nature Immunology.
Dr M. Zeeshan Chaudhry is a Research Fellow at UQ’s Frazer Institute , and is an expert in virus immunology.
