Newly found 'micro-organ' is immune response 'headquarters'

We know that our bodies learn how to mount efficient defenses to disease and infection after exposure to such health hazards. In short, our bodies "learn" to identify the culprits and how to destroy them. Where is that "memory" activated and the response mounted?

Due to advances in clinical research technology that have led to the development of some very sophisticated devices, scientists can now learn more about the human body, and how it works at the micro level.

Much still remains unknown about our body's mechanisms, and surprising discoveries just keep piling up.

For instance, innovative techniques have allowed researchers to learn, earlier this year, that the interstitium — which had been defined as "support tissue" — actually functions as an organ, and it is more important to our health than we had believed.

Now, scientists from the Garvan Institute of Medical Research in Darlinghurst, Australia, have finally been able to ascertain where it is that our bodies "remember" previous exposure to pathogens — through infection or vaccination — and where they start to "strategize" and assemble an appropriate immune response.

In a paper now published in the journal Nature Communications, the researchers explain that they have discovered a kind of "micro-organ" that forms within lymph nodes and acts as the "headquarters" of the immune response.

A tiny dynamic 'organ' drives immunity

The scientists used sensitive 3-D microscopy — a state-of-the-art technique allowing them to follow changes taking place at microscopic level — in mice.

When they did this, they noticed peculiar structures that form over the surface of lymph nodes when the system is exposed to an infection that it has already encountered before.

The scientists found these structures — which they named "subcapsular proliferative foci" (SPF) — not just in mice, but also in sections of lymph nodes collected from human patients.

When looking closer at the SPFs, the scientists saw that different types of immune cells clustered in these structures — most prominently memory B cells, which carry information regarding how to fight pathogens that the body has already encountered.

Also in the SPFs, memory B cells converted into plasma cells, whose role it is to defend the system against infection. Plasma cells generate antibodies, which recognize pathogens and aim to destroy them.

"It was exciting to see the memory B cells being activated and clustering in this new structure that had never been seen before," says study first author Dr. Imogen Moran.

"We could see them moving around, interacting with all these other immune cells and turning into plasma cells before our eyes," she explains enthusiastically.

A 'remarkably well engineered' structure

Importantly, the SPFs are strategically positioned so that they can mount a quick response against infection. This, the researchers explain, is key when it comes to the likelihood of success against pathogens.

"When you're fighting bacteria that can double in number every 20 to 30 minutes, every moment matters. To put it bluntly, if your immune system takes too long to assemble the tools to fight the infection, you die," says study co-author Tri Phan.

He adds that vaccines are key in teaching the immune system to respond efficiently. "Vaccination," he explains, "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. Now, we've shown that memory B cells rapidly turn into large numbers of plasma cells in the SPF."

"The SPF is located strategically where bacteria would re-enter the body and it has all the ingredients assembled in one place to make antibodies — so it's remarkably well engineered to fight reinfection fast."

Tri Phan

The only reason why scientists had been unable to uncover the existence of these key immune formations before is, simply, because they are so tiny and so dynamic.

It was only with the development of two-photon microscopy — the technique used in the recent study — that researchers finally had the possibility to dive deeper and learn more.

Dr. Moran says, "It was only when we did two-photon microscopy — which lets us look in three dimensions at immune cells moving in a living animal — that we were able to see these SPF structures forming."

"So," states Phan, "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. It's a remarkable reminder that there are still mysteries hidden within the body."