Newly Discovered Micro-Organ Helps Explain How Vaccines And Immunity Work

Immune cells (pink and green) gathering at the subcapsular proliferative loci (SPF), newly discovered components of the lymph node. The surface of the lymph node is in blue. Imogen Moran & Tri Phan/Garvan Institute

A key component of the human immune system has only just been found. Described by its discoverers as a “micro-organ”, it forms a thin layer on the surface of the lymph nodes. The discovery may eventually create pathways to more potent vaccines.

The knowledge that certain diseases do not infect us twice goes back at least 2,400 years and inspired vaccination, but Dr Tri Phan of Australia’s Garvan Institute told IFLScience; “We’ve been focused for such a long time on how to make vaccines work we haven’t cared that much about how the immune system remembers.”

We know that when an infection invades the body, immune system cells produce antibodies until they find those shaped to grip the invaders. Memory B cells retain the appropriate antibody so that, should anything similar be encountered at a later date, they are ready to snuff out the infection before it takes hold. Vaccinations stimulate the production of appropriate memory B cells.

Lasting protection comes from memory B cells' remarkable longevity – they often last decades. To fight new infections, however, they need to generate plasma cells, and this is the part of the process where our knowledge has been lacking.

Phan used two-photon microscopy, a technology that allows scientists to watch cells move in three dimensions inside living things, and saw structures he named subcapsular proliferative foci (SPF) on the surfaces of mouse lymph nodes. Memory B cells, along with some helper cells entered the SPF, Phan reported in Nature Communications, and transformed into infection-fighting plasma cells.

The SPF's surface, shown in purple. Imogen Moran & Tri Phan/Garvan Institute

Phan then looked at lymph nodes removed from cancer patients and confirmed the presence of SPF. He told IFLScience it is likely all mammals, and perhaps other animals, have SPF, but no one has yet checked.

SPF weren’t noticed previously, Phan explained, because they are so thin, making them almost invisible to conventional microscopes. Increasingly widespread availability of two-photon microscopy allowed Phan to observe glowing cells aggregating and transforming within living mice.

“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,” Phan said in a statement.

Not all memory B cells aggregate in the SPF. Others circulate in the body and become exhausted. Phan told IFLScience one way to improve vaccines may be to design them to produce more SPF-located memory B cells, rather than wasting energy elsewhere. This could enhance our capacity to tackle rapid-onset disease.

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

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