For the first time in decades, researchers have a new micro-organ & # 39; in the immune system – and they say it is an important step in understanding how better vaccines can be made.
In a study published this week in Nature Communications, scientists at the Australian Garvan Institute of Medical Research have identified where the immune system & # 39; remembers previous infections and vaccinations & # 39; and where immune cells come together to build a quick response to an infection that the body has seen before.
The structure was only discovered when the researchers had made films of the immune system in action, using advanced high-resolution 3D microscopy in live animals. Packed with immune cells of many species, the structure is strategically positioned to detect infections early, making it a one-stop shop for fighting a & # 39; remembered & # 39; infection – fast.
We have known for thousands of years that people who are exposed to infection are often protected from getting the same infection again – since the plague of Athens in 430 BC, where the survivors of the plague noticed that they had immunity against reinfection. developed. However, major questions remain about how the body can fight back quickly when it encounters an infection to which it has previously been exposed (via a vaccine or by a previous infection).
A new structure that appears when needed
The researchers reveal the existence of thin, flattened structures that extend over the surface of lymph nodes in mice. These dynamic structures are not always present: instead they only appear when they are needed to fight an infection against which the animal has previously been exposed.
Crucially, researchers also saw the structures – which they have called SPFs (or "subcapsular proliferative foci") – within parts of patients' lymph nodes, which suggests that they help combat reinfection in patients. both people and mice.
Using advanced & # 39; two-photon & # 39; In vivo microscopy, the researchers were able to see that different classes of immune cells came together in SPFs. Memory B cells, which contain information about the best way to attack the infection, are clustered there. This also applied to other cell types that function as helpers.
Importantly, the researchers also saw that B memory cells changed into cells that fight infection. This is an important step in the fight against infections, because plasma cells make antibodies to recognize and ward off the intruder and protect the body from disease.
"It was exciting to see that the memory B cells are activated and clustered in this new structure that had never been seen before," says Dr. Imogen Moran, the first author of the new study, by Garvan. "We could see them move, interact with all those other immune cells and turn into plasma cells before our eyes."
A need for speed
A / Prof Tri Phan (who led the study), says that the SPF structures are perfectly placed to fight infections quickly – so they can keep the disease on its way before it gets in its grip.
"When you fight bacteria that can double in number every 20 to 30 minutes, every moment is important – to say bluntly, if your immune system takes too long to collect the resources to fight the infection, you die", says he.
"That's why vaccines are so important: Vaccination trains the immune system so that it can make antibodies very quickly when an infection occurs again." Until now, we did not know how and where this happened.
"Now we have shown that B memory cells in memory rapidly change into large numbers of plasma cells in the SPF.The SPF is in a strategic place where bacteria can re-enter the body and it has collected all the ingredients in one place to – – – so it is remarkably well designed to quickly fight reinfection. "
Hide in clear view
The researchers say that no one had seen the structures before because traditional microscopy approaches look at thin 2D sections of tissue that are chemically fixed & # 39; to provide a snapshot. The SPF is thin and comes and goes: these are both characteristics that make it difficult to detect with a conventional approach.
"Only when we use two photon microscopy, which allows us to look in three dimensions at immune cells that move in a living animal, we could see these SPF structures emerge," says Dr. Moran.
"So this is a structure that has always been there, but nobody has really seen it, because they have not had the right tools, it is a remarkable reminder that mysteries are still hidden in the body – even though we have scientists have been looking at the tissues of the body through the microscope for more than 300 years, "says A / prof Phan.
Hope for better vaccines
A / Prof Phan says the new discovery is an important step to understand how to make better vaccines.
"So far, we have focused on making vaccines that can generate memory B cells," he says. "Our finding of this new structure suggests that we now also have to concentrate on understanding how these B-memory cells are reactivated to make plasma cells so that we can make this process more efficient."
Support for this work
The study was made possible by generous support from the NHMRC, the Garvan Research Foundation and Mr. and Mrs. Peter and Val Duncan.