Textbooks have traditionally taught that when it comes to the immune system, the brain and body are separate entities. When exposed to foreign objects such as bacteria or transplant tissue, the body stirs up a torrent of immune activity: white blood cells devour invading pathogens and burst compromised cells; antibodies tag outsiders for destruction. Except, that is, in the brain, where the blood-brain barrier bars both foreign bodies and immune cells from entry. New research, however, uncovered a previously unknown line of communication between our brain and immune system. The report in July in Nature (Scientific American Mind is part of Springer Nature) adds to a fast-growing body of research linking the brain and bodily defenses.
As early as 1921, scientists recognized that the brain is different, immunologically speaking. Tissue grafted into the central nervous system sparks a far less hostile response than tissue grafted to other parts of the body, prompting scientists to consider the brain “immunologically privileged.” Experts have long pointed to the brain's apparent lack of lymphatic drainage as one reason for this privilege. The lymphatic system is our body's third set of vessels, along with arteries and veins. Lymph nodes—stationed periodically along the vessel network—serve as storehouses for immune cells. In most parts of the body, foreign invaders trigger the release of these cells through the vessels into the bloodstream.
The new study discovered that the brain is connected to the lymphatic system after all. Working primarily with mice, senior author and University of Virginia neuroscience professor Jonathan Kipnis and his group identified a hitherto undetected network of lymphatic vessels in the meninges—the membranes that surround the brain and spinal cord—that shuttle fluid and immune cells from the cerebrospinal fluid to the deep cervical lymph nodes in the neck. Kipnis and his colleagues had previously shown that a type of white blood cell called a T cell (shown above) in the meninges is associated with significant influence on cognition and hence were curious about the role of meningeal immunity on brain function. Using neuroimaging on mouse meninges, the team noticed that T cells were present in vessels separate from arteries and veins.
The newly discovered vessels, which were also identified in human samples, could explain the long-standing conundrum of how the immune system manages to contribute to neurological and psychiatric disease. For example, some cases of multiple sclerosis are thought to result from autoimmune activity in response to an infection in the central nervous system and cerebrospinal fluid. “It's early to speculate,” Kipnis says, “but I think that alteration in these vessels may affect disease progression in those neurological disorders with a prominent immune component, such as multiple sclerosis, autism and Alzheimer's disease.”
Some mental illnesses, including depression and schizophrenia, have also been linked with abnormal immune activity and inflammation. Yet scientists have not been able to uncover the underlying mechanism. The new finding suggests a tantalizing target for research and, perhaps one day, drugs. Josep Dalmau, a neurology professor at the University of Pennsylvania who was not involved with the study, agrees that the findings could help explain the initiation, maintenance and perhaps worsening of autoimmune disorders that affect the brain.
In light of the news, the textbooks might need some revising. “It has become increasingly clear that the central nervous system is immune-different rather than immune-privileged,” he says.