Immunity; can be driven by neurons (Introduction)

by David Turell @, Wednesday, September 06, 2017, 23:42 (2636 days ago) @ David Turell

Newly discovered neurons drive immune responses much faster than vaccinations:

https://medicalxpress.com/news/2017-09-scientists-adrenaline-immune.html

"Scientists at the Champalimaud Centre for the Unknown and the Instituto de Medicina Molecular, in Lisbon, Portugal, have discovered that neurons located at mucosal tissues can immediately detect an infection in the organism, promptly producing a substance that acts as an "adrenaline rush" for immune cells. Under the effect of this signal, immune cells rapidly become poised to fight the infection and repair the damage caused to surrounding tissues.

***

"In 2016, Henrique Veiga-Fernandes and his colleagues (then at the Institute for Molecular Medicine, in Lisbon) published, also in Nature, a study where they showed that glial cells in the gut can stimulate a type of immune cells, called ILC3, to produce substances against bacterial infections.

"These immune cells that are being studied by Veiga-Fernandes - collectively called "innate lymphoid cells", or ILC -, are also very special. We are born with them; they are not produced in response to an immunization, for instance through vaccination. "ILCs were discovered very recently, in 2010, but they are very ancient in evolutionary terms. Even lampreys have them!", says Veiga-Fernandes. Lampreys belong to a very old animal lineage.

"There are several types of these innate lymphocytes (white cells). In their 2016 study, the team had analyzed the behavior of ILC3s in the gut - and their "dialog" with their glial cell neighbours. In the new study, also led by Veiga-Fernandes, they focused on another type of innate lymphoid cells: ILC2s.

***

"The study brings "two big novelties", says Veiga-Fernandes. The first, he explains, "is that neurons define the immune cells' function. Nobody could have imagined that the nervous system coordinates, commands and controls the immune response throughout the whole organism." Second, he adds, "it's one of the fastest and most powerful immune reactions we have ever seen". Comparatively, the newly discovered neuronal stimulus induces an immune response in a few minutes, while the immune response following vaccination typically takes several weeks to mount.

"How did the scientists discover this neuro-immune "tandem"? "What happened was that we observed, in high-resolution microphotographs of the lungs and gut of mice, that ILC2s were placed along the axons of neurons residing in these mucosa, a bit like pearls on a string", replies Veiga-Fernandes. "So we asked ourselves if these two distinct tissues could productively 'talk' to each other."

"To test this hypothesis, the team started by analyzing the whole genome of a series of immune cells - ILC1s, ILC2s, ILC3s, T-cells, etc. -, "searching for genes that code molecules that may act as receivers of neuronal signals", says Veiga-Fernandes. They found that only ILC2s possessed a defined "receptor" (membrane molecules that act as antennae) for nervous signals.

"Notably, the authors discovered that ILC2s have receptors to a neuronal messenger called neuromedin U (NMU). Since neurons are the only cells that produce abundant levels of NMU, this indicated that only neurons could be sending this signal to ILC2s.

"Later, they used a rodent parasite, Nippostrongylus brasiliensis (a sort of hookworm) to infect "normal" control mice and mutant mice whose ILC2s had been stripped of their NMU receptors. In the first group of animals, the innate immune cells immediately triggered a response to neutralize the parasite and repair damaged tissue. In the second group, the mice were unable to fight the infection and the damage caused by the parasite - including the internal bleeding of the lungs due to N. brasiliensis.

"The researchers also showed that neurons are able to detect the products secreted by parasites that infect the organism - and that, when this happens, they rapidly produce NMU. In turn, NMU acts vigorously on ILC2s, thus generating a protective response in a few minutes.


"Could these results be extrapolated to humans? "Maybe. In humans, ILC2s also have NMU receptors", replies Veiga-Fernandes. "But we are still very far from understanding how we could safely use this neuro-immunological 'bomb'; for now, we are at the fundamental research level", he adds."

Comment: This complex immune mechanism allows for rapid response to infection by organisms previously not known by the host animal. Shows purposeful design of the immune system.


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