Wednesday, November 21, 2018

Newly identified structure in lymph nodes was 'hiding in plain sight'

In a study published this week in Nature Communications, scientists at Australia's Garvan Institute of
Medical Research have identified where the immune system 'remembers' past infections and vaccinations—and where immune cells gather to mount a rapid response against an infection the body has seen before. The structure was only discovered when the researchers 'made movies' of the immune system in action, using sophisticated high resolution 3-D microscopy in living animals. Jam-packed with immune cells of many kinds, the structure is strategically positioned to detect infection early, making it a one-stop shop for fighting a 'remembered' infection—fast.
We have known for millennia that people exposed to an infection are often protected from getting the same infection again—ever since the Plague of Athens in 430 BC, where plague survivors were noted to have developed immunity against reinfection. Yet, major questions remain about how the body can fight back fast when it encounters an infection that it has been previously exposed to (through a vaccine or through an earlier infection).The researchers reveal the existence of thin, flattened structures extending over the surface of lymph nodes in mice. These dynamic structures are not always present: instead, they appear only when needed to fight an infection against which the animal has previously been exposed.
Crucially, researchers also saw the structures—which they have named SPFs (or 'subcapsular proliferative foci') - inside sections of lymph nodes from patients, suggesting that they help fight reinfection in people as well as in mice.
Using sophisticated 'two-photon' in vivo microscopy, the researchers could see that several classes of immune cells gathered together in SPFs. Memory B cells, which carry information about how best to attack the infection, clustered there. So did other cell types that act as helpers.
Importantly, the researchers could also see that memory B cells were changing into infection-fighting plasma cells. This is a key step in the fight against infection, because plasma cells make antibodies to recognise and fend off the invader and protect the body from disease.
"It was exciting to see the memory B cells being activated and clustering in this new structure that had never been seen before," says Garvan's Dr. Imogen Moran, the first author on the new study. "We could see them moving around, interacting with all these other immune cells and turning into plasma cells before our eyes."