How the immune system watches over the brain

Generations of students have learned that the central nervous system has “immune privilege.” This means that — to an extent — the immune system tolerates the presence of foreign proteins, or antigens, and tissue in the brain and spinal cord.

The immune system cannot respond in the usual way to infections, injuries, or tumors in the brain and spinal cord, because the blood-brain barrier prevents immune cells from entering or leaving.

Despite this, scientists know that inflammation plays a pivotal role in many neurological and psychiatric conditions, including Alzheimer’s disease, MS, autism, and schizophrenia.

So the question remains, if there is no exchange of information, how does the immune system respond to and influence the brain in such a broad range of conditions?

A team of scientists led by Washington University School of Medicine in St. Louis, MO, have discovered that immune cells are stationed in the dura mater, which is the tough outer membrane of the brain.

From this vantage point, they monitor the cerebrospinal fluid draining from the brain. If they detect the molecular calling cards of infection, cancer, or injury, they can mount an immune response.

The research appears in the journal Cell.

Immunity and the brain

“Every organ in the body is being surveilled by the immune system,” says senior author Dr. Jonathan Kipnis, Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology.

He explains:

“If there is a tumor, an injury, an infection anywhere in the body, the immune system has to know about it. But people say the exception is the brain; if you have a problem in the brain, the immune system just lets it happen. That never made sense to me. What we have found is that there is indeed immune surveillance of the brain — it is just happening outside the brain.”

In 2015, a study in mice revealed a network of vessels in the dura mater that drains cerebrospinal fluid from the brain into lymph nodes in the neck. Also in 2015, a study led by Dr. Kipnis recorded similar findings in both mice and humans.

Lymph nodes are part of an extensive network of fluid-filled vessels known as the lymphatic system. An accumulation of pathogens in lymph nodes can lead to the initiation of an immune response.

This suggested a more intimate connection between the brain and immune system than previously suspected. However, it remained unclear exactly where and how immune cells surveil the contents of the cerebrospinal fluid as it drains from the brain.

Dr. Kipnis and his colleagues knew that the lymph vessels that carry fluid from the brain run alongside blood-filled cavities, or sinuses, in the dura mater.

Crucially, the walls of these sinuses are more permeable than the blood vessels of the blood-brain barrier.

Following up this clue, the scientists showed in their experiments that small molecules from the brain and immune cells accumulate in the sinuses.

Some of the cells, known as antigen presenting cells, which include dendritic cells, pick up suspicious molecules and present them to other immune cells, called T cells, which patrol the body in the bloodstream.

When they bind to these suspect molecules, the T cells can initiate an immune response.