The brain is the body’s authority, and it receives protection in accordance with its superior nature. Its cells live longer and are protected within an infamous structure called the blood-brain barrier. For a long time, scientists thought that the brain was completely cut off from the rest of the body – especially its long-awaited immune system, its multicellular immune system and its actions could threaten a ruler caught in fire.Over the past decade, however, scientists have discovered that brain function is not as straightforward as they once thought. They have learned that its defenses have gates and spaces, and that its borders are full of active body cells.
Ample evidence now shows that the brain and the immune system are closely linked. Scientists already knew that the brain has cells that live in cells called microglia; Recent findings draw detailed pictures of their activities and reveal features of other antibodies stored in regions around the brain. Some of these cells originate elsewhere in the body; some are produced locally, in the skull bone. By studying these immune cells and mapping how they interact with the brain, researchers found that they play a vital role in both healthy and diseased brains. Interest in this field has exploded: there were fewer than 2,000 papers per year on this subject in 2010, rising to more than 10,000 per year by 2021, and researchers have found several major results in the last few years.
Scientists no longer regard the brain as a special, closed space. “The whole concept of the immune system is now obsolete,” said KiavashMovahedi, a neurologist at the Free University of Brussels (VUB). Although the brain is still considered unique immunologicallyThis shift in attitude is widespread in the community, says Leonardo Tonelli, chief of the neuroendocrinology and neuroimmunology program at the US National Institute of Mental Health in Bethesda, Maryland. In his experience, almost every neuroscientist who reviews agency proposals is accepting the communication, he says, although many still need to discover new discoveries in neuroimmunology, which have begun to develop basic techniques.The quest for understanding how the brain and the immune system interact has raised questions, says Tony Wyss-Coray, a neurologist at Stanford University in California. “How important is this for normal brain function or disease? That is the hardest question to answer. ”
Special space
More than two decades ago, when neuroscientist Michal Schwartz recently set up his laboratory at the Weizmann Institute of Science in Rehovot, Israel, he could not help but wonder what a popular question could be: could it really be that the brain was completely cut off? in body protection? “It was absolutely amazing that the brain could not tolerate any immune function – everyone thought that if you have immune activation, this is a sign of pathology,” he said. “But it did not make sense to think that such vital tissues, such as the brain, could not support the immune system.”The notion that the brain is no longer functioning in a body that was immune to the disease had its roots in decades earlier. In the 1920’s, Japanese scientist Y. Shirai reported that when tumor cells were implanted in a mouse body, the immune system destroyed them, but when implanted in the brain, they survived – indicating a weak or non-existent immune response. Similar findings followed in the 1940’s.
Many scientists also speculate that the brain did not have the ability to transmit antibodies to the outside and inside of the body – the lymphatic drainage system that exists elsewhere in the body – even though this system was first described in the brain more than two centuries ago. Thus, the common view was that the brain and the immune system live separate lives. The two were thought to clash only under hostile conditions: when immune cells invade, they attack the body’s cells in diseases such as multiple sclerosis.So when, in the late 1990s, Schwartz and her team reported3 that after an acute injury to the central nervous system, two types of immune cells, macrophages and T cells, protected neurons from damage and supported their recovery, many scientists were sceptical. “Everyone told me, you’re absolutely wrong,” Schwartz recalls.Since those early experiments, Schwartz’s team and others have amassed a large body of evidence showing that immune cells do, indeed, have a significant role in the brain, even in the absence of autoimmune disease. Researchers have shown
Examining how bone marrow connects
It is now clear that the edges of the brain are different in terms of the immune system: almost any type of immune system can also be found in the area around the brain. Meninges – a fluid-filled membrane that encloses the brain – are “a wonderful immunological state”, says Movahedi, whose work focuses on macrophages across brain boundaries. “There’s a lot going on there.”Some residents are rare at the border. In 2021, Jonathan Kipnis, a neuroimmunologist at Washington University in St. Louis.In examining how bone marrow connects these cells, Kipnis and colleagues showed8 that, due to damage to the central nervous system or pathogen, signals carried to the cerebrospinal fluid are brought to the bone marrow bone, commanding it to produce and release these. Privacy Protectors’).
His team also discovered a network of snake channels and branches over the brain, and filled with immune cells, forming the lymphatic system of the brain9. These vessels, located on the outer part of the meninges, provide the body cells with a high surface near the brain where they are able to monitor for any signs of infection or injury.
In sickness and health
As evidence builds on cell involvement during brain injury and disease, researchers have been evaluating their function in a healthy brain. “I think the most exciting part of neuroimmunology is that it is related to so many different diseases and conditions as well as general physical science,” said Beth Stevens, a neurologist at Boston Children’s Hospital in Massachusetts.Many groups, including Stevens, have found that microglia are essential for brain development. These cells are involved in neuronal communication, and research suggests that problems with the prognosis may contribute to neurodevelopmental conditions.
Border defective immune cells, too, have been shown to be important for a healthy brain. Kipnis, Schwartz and colleagues, for example, have shown that mice lacking some of these cells indicate problems in learning and social behavior10. Some reported 11 in 2020 that mice that grow out of a certain number of T cells in the brain and throughout the body have dysfunctional microglia. Their microglia struggle to suppress neuronal connections during growth, leading to high levels of synapses and abnormal behavior. The authors suggest that during this critical time, T cells invade the brain and help microglia to mature.
Researchers have been studying how cytokines affect behavior for decades, finding, for example, that cytokines sent by immune cells during an infection can develop ‘sick habits’ such as increased sleep12. They have also shown in animal models that mutations of cytokines – caused by the breakdown of whole bodies or the release of certain cytokine receptors from neurons – can lead to changes in memory, learning, and social behavior13. How cytokines enter the brain and produce their own effects remains a matter of research.Cytokines may also be a link between the immune system and neurodevelopmental conditions such as autism. When Gloria Choi, a neurologist at the Massachusetts Institute of Technology in Cambridge, and her colleagues increased cytokine levels in pregnant mice, they observed brain changes and autism-like behaviors in the offspring14.
Although these theories are impressive, much of the work involved in how immune cells, especially those in the border, work in the brain is just beginning. “We are far from understanding what is happening to the healthy brain,” Kipnis said.
Two-way road
The connection between the immune system and the brain also seems to go in the opposite direction: the brain can direct the immune system.Some of these ideas have been around for decades. In the 1970’s, scientists introduced rats to the immune system when they tasted saccharin, a delicious artificial ingredient, by combining it with an antidepressant drug for a few days15.
In a recent work, Asya Rolls, a neurologist at Technion – Israel Institute of Technology in Haifa, and his team explored the link between emotions, infection and cancer in mice. They reported 16 in 2018 that neurons function in the ventral tegmental region, a region of the brain involved in mood building and motivation, boosting the immune response and, again, slowing tumor growth.Then, in 2021, his team identified neurons in the insular cortex – the part of the brain that plays a key role in processing the body’s emotions and emotions, among other things – that was active during colon cancer, a condition also known as colitis.
Some groups study how the brain regulates the immune system. Choi’s team tracks specific neurons and circuits that regulate the immune response. One day, he hopes to be able to produce a comprehensive map of the interaction between the brain and the immune system, describing cells, circuits and cell messengers that are responsible for communicating in both directions – and linking those with behavioral or physical learning.One of the biggest challenges now is to differentiate which cells are involved in these many functions. To address this, some researchers have been experimenting with the differences between these cells, which are genetically engineered. This revealed a subset of microglia associated with neurodegenerative disease, e.g. Understanding how these microglia work differently from their healthy counterparts will be helpful in improving treatment, Stevens said. They can also be used as indicators to track the progression of the disease or the effectiveness of treatment options, he adds.
Researchers have already begun to apply this information to the immune system in and around the brain. Schwartz’s team, for example, stimulates the immune system in hopes of fighting Alzheimer’s disease. This work has opened up new treatments, especially in neurodegenerative conditions, Schwartz said. “An exciting time in the history of brain research.”
Source journal Reference: Diana Kwon, Guardians of the brain: how a special immune system protects our grey matter, Nature news, 2022, Nature 606, 22-24 (2022), doi: https://doi.org/10.1038/d41586-022-01502-8
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