For decades, immunologists have believed that the human brain is “immune privileged”, meaning that it can tolerate the introduction of antigens because to a large extent it is anatomically separated from the immune system by something known as the “blood-brain barrier”. However, recent research suggests that the brain may not be as isolated as once believed, and in fact may be the site of an on-going evolutionary battle waged between microbes and the immune system.
For instance, one study, published in 2015, examined the circulation of lymph in the brains of mice and found a previously unknown network of lymphatic vessels in the outer layers of the brain, known as the meninges, which shuttle fluid and immune cells from the cerebrospinal fluid to a group of lymph nodes in the neck – the deep cervical lymph nodes.
Jonathan Kipnis and his group at the University of Virginia went on to show that T-cells in the meninges were linked with how sociable mice were with other mice. The researchers would even manipulate the cognitive behaviour of mice through a single molecule, known as interferon gamma, which is normally produced by the immune system in response to bacteria, viruses or parasites. Blocking the molecule in mice using genetic modification made the regions of the brain hyperactive, causing the mice to be less social, whilst restoring the molecule caused brain functioning to revert to a normal state, with normal, social interactions being the result.
“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,” explained Kipnis. “And now, not only are we showing that they are closely interacting, but some of our behaviour traits might have evolved because of our immune response to pathogens.”
The research is part of a wider body of work into an emerging field known as neuroimmunology, which has generated a revision in our views of how the immune system and the central nervous system interact. It is now understood that immune cells can cross the blood-brain barrier and infiltrate the brain tissue where they can interact with a network of deeper brain structures.
The work may eventually help to explain the link between the immune system and certain neurodegenerative diseases, such as multiple sclerosis, Alzheimer’s, Parkinson’s, depression and schizophrenia. Chronic, low-grade inflammation is thought to hasten or even prompt the progression of these conditions, which suggests that development in immunology could play a critical role in future treatments for some of the most intractable neurodegenerative disorders of today.