Shocking new role found for the immune system: Controlling social interaction

July 13, 2016
A hyperactive brain. A matching .gif depicting a normal brain is available upon request. Credit: Anita Impagliazzo / UVA School of Medicine

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 great implications for neurological conditions such as autism-spectrum disorders and schizophrenia.

"The brain and the adaptive immune system were thought to be isolated from each other, and any 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 to pathogens," explained Jonathan Kipnis, PhD, chairman 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.

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 , 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."

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Researchers discuss the shocking finding that the immune system can control social behavior. The discovery could have enormous implications for conditions such autism-spectrum disorders and schizophrenia. Credit: Harry Moxley / UVA School of Medicine

"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, PhD, 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; instead, 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 .

"Immune molecules are actually defining how the brain is functioning. So, what is the overall impact of the 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."

Kipnis and his team worked closely with UVA's Department of Pharmacology and the group of Vladimir Litvak, PhD, 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 , an important cytokine secreted by T lymphocytes, in promoting social 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."

Explore further: Surprising contributor to Rett syndrome identified

More information: Anthony J. Filiano et al, Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour, Nature (2016). DOI: 10.1038/nature18626

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3.5 / 5 (2) Jul 13, 2016
This makes sense from an evolutionary perspective as those whose immune system is stressed are more likely to be developing or fighting a virus. From a group perspective, the individual is less likely to infect other people and from an individual's perspective it is important not to risk acquiring any other type of pathogen when one is already fighting off an infection.
5 / 5 (1) Jul 14, 2016
lol, "you people make me sick" is more than just a figure of speech
Jul 17, 2016
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not rated yet Jul 18, 2016
Obviously you guys haven't read my book, Exocrinology The Science of Love! Basically, the human immune system is a pheromone recognition system, ours and our environments both internal and external. Chemicals are exchanged in love, chemical signatures which are unique to the individual with 735 components, one of which, sebaleic acid is unique in all nature found nowhere else but upon human skin, therefore marking us as human beings. The stereochemistry is pheromonal, just like butterfly pheromones.
Emotions are pheromone emission or reception devices. Crying emotional tears differs chemically from irritant induced tears. The proteins dissolved in tears of sadness and joy vary and look like pheromone receptor proteins. Those high ion concentrations facilitate pheromone receptor protein function, which is sequestration of ions to be released on pheromone contact to alter the potential difference across a nearby reversed membrane.
not rated yet Jul 18, 2016
The immune system is adaptive, and so should our brains, which is to say, our thoughts.

We should avoid things which will cause harm; however, exposure is necessary to learn.

But the completion of this process is knowledge. If brain is subordinate to this process, then shouldn't logic and reason be taught to children instead of prejudice and superstition? And what role could children play in educating us precisely where our thoughts are miscalibrated?
not rated yet Jul 18, 2016
"Controls social interaction" is a bit strong.

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