Scientists Have Discovered a Brand New ‘Micro-Organ’ in The Human Immune System: subcapsular proliferative foci


Researchers have identified a brand new ‘micro-organ’ inside the immune system of mice and humans – the first discovery of its kind for decades – and it could put scientists on the path to developing more effective vaccines in the future.

Vaccines are based on centuries of research showing that once the body has encountered a specific type of infection, it’s better able to defend against it next time. And this new research suggests this new micro-organ could be key to how our body ‘remembers’ immunity.

The researchers from the Garvan Institute of Medical Research in Australia spotted thin, flat structures on top of the immune system’s lymph nodes in mice, which they’ve dubbed “subcapsular proliferative foci” (or SPFs for short).

These SPFs appear to work like biological headquarters for planning a counter-attack to infection.

Immune cells gathering at the SPF, with the purple band showing the SPF surface.

These SPFs only appear when the mice immune systems are fighting off infections that have been encountered before.

What’s more, the researchers detected SPFs in human lymph nodes too, suggesting our bodies react in the same way.

“When you’re fighting bacteria that can double in number every 20 to 30 minutes, every moment matters,” says senior researcher Tri Phan. “To put it bluntly, if your immune system takes too long to assemble the tools to fight the infection, you die.”

“This is why vaccines are so important. Vaccination trains the immune system, so that it can make antibodies very rapidly when an infection reappears. Until now we didn’t know how and where this happened.”

Traditional microscopy approaches analyse thin 2D slices of tissue, and the researchers think that’s why SPFs haven’t been spotted before – they themselves are very thin, and they only appear temporarily.

In this case the team made the equivalent of a 3D movie of the immune system in action, which revealed the collection of many different types of immune cell in these SPFs. The researchers describe them as a “one-stop shop” for fighting off remembered infections, and fighting them quickly.

Crucially, the collection of immune cells spotted by the researchers included Memory B type cells – cells which tell the immune system how to fight off a particular infection. Memory B cells then turn into plasma cells to produce antibodies and do the actual work of tackling the threat.

“It was exciting to see the memory B cells being activated and clustering in this new structure that had never been seen before,” says one of the team, Imogen Moran.

“We could see them moving around, interacting with all these other immune cells and turning into plasma cells before our eyes.”

According to the researchers, the positioning of the SPF structures on top of lymph nodes makes them perfectly positioned for fighting off infections – and fast.

They’re strategically placed at points where bacteria would invade, and contain all the ingredients required to keep the infection at bay.

Now we know how the body does it, we might be able to improve vaccine techniques – vaccines currently focus on making memory B cells, but this study suggests the process could be made more efficient by also looking at how they transform into plasma cells through the inner workings of an SPF.

“So this is a structure that’s been there all along, but no one’s actually seen it yet, because they haven’t had the right tools,” says Phan.

“It’s a remarkable reminder that there are still mysteries hidden within the body – even though we scientists have been looking at the body’s tissues through the microscope for over 300 years.”

The research has been published in Nature Communications.

Scientists discover a new human organ – the insterstitium

A newfound organ, the interstitium, resides beneath the top layer of skin, and in tissue layers lining the gut, lungs, blood vessels, and muscles. The organ is a body-wide network of interconnected, fluid-filled compartments supported by a meshwork of strong, flexible proteins.

Using a new way of visualising anatomy, scientists have just discovered a vast new structure in the human body that could be considered an organ in its own right.

The finding, published in the journal Scientific Reports, has important implications for our understanding of how all organs and tissues function, and could reveal previously unknown mechanisms driving diseases such as fibrosis and cancer.

But how could something so significant have gone unnoticed all this time?

It was well known that a layer of tissue lies just below the surface of the skin, and also lines the lungs, the digestive and urinary tracts, and much of the circulatory system. But it was thought this comprised little more than dense, connective tissue.

The new research reveals that it is actually a vast, interconnected system of fluid-filled compartments that extends all over the body.

That contents is extra-cellular, or “interstitial”, fluid. Accordingly, the structure has been dubbed “the interstitium”.

Until now, the interstitium had been hidden in plain sight because the traditional method of preparing microscope slides involves draining away fluid. This had caused the sacs to collapse, leaving only the supportive connective tissue visible.

But recently, researchers led by Neil Theise at New York University in the US began using probe-based confocal laser endomicroscopy, which aims laser light at living tissue and detects reflected fluorescent patterns, providing a different sort of microscopic image. While examining the bile duct of a cancer patient, they found a network of fluid-filled sacks that had never been seen before.

They soon found this network everywhere tissues are distended or compressed as part of normal function — which is quite a lot of the body — and propose that the interstitium may function as a shock absorber.

Its physical structure is certainly quite unusual: the fluid-filled spaces are supported by an extensive lattice of collagen bundles that are lined on only one side by what appear to be a type of stem cell.

These cells may help make collagen, and could aid in wound healing. Similarly, they could contribute to conditions associated with inflammation and ageing.

In addition to cushioning, the interstitium may have another important job. While it was known that interstitial fluid is the major source of lymph fluid, which carries immune cells throughout the body, just how it reaches the lymphatic system was unclear. The new research shows that the interstitium drains directly into the lymph nodes.

The study also shows that cancers, such as melanoma, are able to spread via the interstitium.

“This finding has potential to drive dramatic advances in medicine, including the possibility that the direct sampling of interstitial fluid may become a powerful diagnostic tool,” says Theise.