Shocking New Role Found for the Immune System: Controlling Social Interactions

In a startling discovery that raises fundamental questions about human behavior, researchers at the University of Virginia School of Medicine have determined that the immune system directly affects – and even controls – creatures’ social behavior, such as their desire to interact with others.

So could immune system problems contribute to an inability to have normal social interactions? The answer appears to be yes, and that finding could have significant implications for neurological diseases such as autism-spectrum disorders and schizophrenia.

“The brain and the adaptive immune system were thought to be isolated from each other, and any immune activity in the brain was perceived as sign of a pathology. And now, not only are we showing that they are closely interacting, but some of our behavior traits might have evolved because of our immune response to pathogens,” explained Jonathan Kipnis, chair of UVA’s Department of Neuroscience. “It’s crazy, but maybe we are just multicellular battlefields for two ancient forces: pathogens and the immune system. Part of our personality may actually be dictated by the immune system.”

Evolutionary Forces at Work

It was only last year that Kipnis, the director of UVA’s Center for Brain Immunology and Glia, and his team discovered that meningeal vessels directly link the brain with the lymphatic system. That overturned decades of textbook teaching that the brain was “immune privileged,” lacking a direct connection to the immune system. The discovery opened the door for entirely new ways of thinking about how the brain and the immune system interact.

Normal brain activity, left, and a hyper-connected brain. (Images by Anita Impagliazzo, UVA Health System)

The follow-up finding is equally illuminating, shedding light on both the workings of the brain and on evolution itself. The relationship between people and pathogens, the researchers suggest, could have directly affected the development of our social behavior, allowing us to engage in the social interactions necessary for the survival of the species while developing ways for our immune systems to protect us from the diseases that accompany those interactions. Social behavior is, of course, in the interest of pathogens, as it allows them to spread.

The UVA researchers have shown that a specific immune molecule, interferon gamma, seems to be critical for social behavior and that a variety of creatures, such as flies, zebrafish, mice and rats, activate interferon gamma responses when they are social. Normally, this molecule is produced by the immune system in response to bacteria, viruses or parasites. Blocking the molecule in mice using genetic modification made regions of the brain hyperactive, causing the mice to become less social. Restoring the molecule restored the brain connectivity and behavior to normal. In a paper outlining their findings, the researchers note the immune molecule plays a “profound role in maintaining proper social function.”

“It’s extremely critical for an organism to be social for the survival of the species. It’s important for foraging, sexual reproduction, gathering, hunting,” said Anthony J. Filiano, Hartwell postdoctoral fellow in the Kipnis lab and lead author of the study. “So the hypothesis is that when organisms come together, you have a higher propensity to spread infection. So you need to be social, but [in doing so] you have a higher chance of spreading pathogens. The idea is that interferon gamma, in evolution, has been used as a more efficient way to both boost social behavior while boosting an anti-pathogen response.”

Understanding the Implications

The researchers note that a malfunctioning immune system may be responsible for “social deficits in numerous neurological and psychiatric disorders.” But exactly what this might mean for autism and other specific conditions requires further investigation. It is unlikely that any one molecule will be responsible for disease or the key to a cure. The researchers believe that the causes are likely to be much more complex. But the discovery that the immune system – and possibly germs, by extension – can control our interactions raises many exciting avenues for scientists to explore, both in terms of battling neurological disorders and understanding human behavior.

Postdoctoral researcher Anthony J. Filiano, left, and Jonathan Kipnis, chairman of UVA’s Department of Neuroscience. (Photo by Sanjay Suchak, University Communications)

“Immune molecules are actually defining how the brain is functioning. So, what is the overall impact of the immune system on our brain development and function?” Kipnis said. “I think the philosophical aspects of this work are very interesting, but it also has potentially very important clinical implications.”

Findings Published

Kipnis and his team worked closely with UVA’s Department of Pharmacology and with Vladimir Litvak’s research group at the University of Massachusetts Medical School. Litvak’s team developed a computational approach to investigate the complex dialogue between immune signaling and brain function in health and disease.

“Using this approach we predicted a role for interferon gamma, an important cytokine secreted by T lymphocytes, in promoting social brain functions,” Litvak said. “Our findings contribute to a deeper understanding of social dysfunction in neurological disorders, such as autism and schizophrenia, and may open new avenues for therapeutic approaches.”

The findings have been published online by the prestigious journal Nature. The article was written by Filiano, Yang Xu, Nicholas J. Tustison, Rachel L. Marsh, Wendy Baker, Igor Smirnov, Christopher C. Overall, Sachin P. Gadani, Stephen D. Turner, Zhiping Weng, Sayeda Najamussahar Peerzade, Hao Chen, Kevin S. Lee, Michael M. Scott, Mark P. Beenhakker, Litvak and Kipnis.

This work was supported by the National Institutes of Health (grants No. AG034113, NS081026 and T32-AI007496) and the Hartwell Foundation.

ORIGINAL: News UVA
Josh Barney, jdb9a@virginia.edu
July 13, 2016 

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The discovery was made possible by the work of Antoine Louveau, a postdoctoral fellow in Kipnis’ lab. The vessels were detected after Louveau developed a method to mount a mouse’s meninges — the membranes covering the brain — on a single slide so that they could be examined as a whole. After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. “Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris,” Kipnis noted. Harris is an assistant professor of neuroscience and a member of the Center for Brain Immunology and Glia. Kipnis also saluted the “phenomenal” surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.

Engineers are designing, building mechanical ray

ORIGINAL: Science Daily

ScienceDaily (July 26, 2012) — Batoid rays, such as stingrays and manta rays, are among nature's most elegant swimmers. They are fast, highly maneuverable, graceful, energy-efficient, can cruise, bird-like, for long distances in the deep, open ocean, and rest on the sea bottom.

The mantabot doing a tight left turn. (Credit: Image courtesy of University of Virginia)

"They are wonderful examples of optimal engineering by nature," said Hilary Bart-Smith, an associate professor of mechanical and aerospace engineering in the University of Virginia's School of Engineering and Applied Science.

Bart-Smith and her colleagues at three other universities are trying to emulate the seemingly effortless but powerful swimming motions of rays by engineering their own ray-like machine modeled on nature.

They are designing an "autonomous underwater vehicle" that someday may surpass what nature has provided as a model. The vehicle has potential commercial and military applications, and could be used for undersea exploration and scientific research.

Sometimes called "bio-mimicry" -- the attempt to copy nature -- Bart-Smith calls her work "bio-inspired."

"We are studying a creature to understand how it is able to swim so beautifully, and we are hoping to improve upon it," she said. "We are learning from nature, but we also are innovating; trying to move beyond emulation."

Bart-Smith's team, which includes researchers at U.Va., Princeton University, the University of California-Los Angeles and West Chester University, are modeling their mechanical ray on the cow-nosed ray, a species common to the western Atlantic and Chesapeake Bay.

The team members, who are experts in marine biology, biomechanics, structures, hydrodynamics and control systems, have created a prototype molded directly from a real cow-nosed ray. By studying the motions of living rays in the field and the laboratory and through dissection, this prototype attempts to replicate the near-silent flaps of the wing-like pectoral fins of a ray, to swim forward, turn, accelerate, glide and maintain position.

"Biology has solved the problem of locomotion with these animals, so we have to understand the mechanisms if we are going to not only copy how the animal swims, but possibly even to improve upon it," Bart-Smith said.

Her team is trying to achieve optimal silent propulsion with a minimum input of energy.

The mechanical ray is remotely controlled by researchers via computer commands. The plastic body of the vehicle contains electronics and a battery, while the flexible silicone wings contain rods and cables that expand and retract and change shape to facilitate what is essentially underwater flight.

Bart-Smith's ultimate goal is to engineer a vehicle that would operate autonomously, and could be deployed for long periods of time to collect undersea data for scientists, or as a surveillance tool for the military. It also could be scaled up, or down, to serve as a platform carrying various payloads, such as environmental monitoring instruments. For example, it possibly could be used for pollution monitoring, such as tracking the locations of underwater oil spills.

And because the vehicle looks and behaves like a common sea creature, it likely would operate in the sea without affecting natural creatures or their habitats.