Intelligent Defense: The Brain-Immune System Connection By David Webster and Aubree Kozie

Up until recently, it was a popular belief among the medical community that the body’s lymphatic system and the brain functioned totally separately, “The brain is thought to be what is called immune-privileged. It has a different immune system from the rest of the body”, says Dr. Daniel Reich, senior investigator at the National Institute of Neurological Disorders and Stroke (Hamilton, 2017). It was thought that the immune system would not interact with the central nervous system unless something had gone terribly wrong. This is due to the fact that the relationship between the two bodily systems were only studied in terms of disease up until recently. For instance, multiple sclerosis (MS) is caused by T-cells which pass through the selective border of the blood-brain barrier (BBB), enter the central nervous system (CNS), and degrade the myelin sheath which covers neural cells.

But recently, new research with human cadavers shows the brain and lymphatic system may have something in common “there are lymph vessels in the head, which I had learned in medical school didn’t exist,” Reich continued to explain. Lymphatic vessels have been confirmed on the surface of the brain, which make it likely that the lymphatic system communicates and interacts with the brain (Hamilton, 2017). Over the past two decades, empirical research has demonstrated that the entire immune system is intricately involved with the CNS. The immune system plays important roles in cognition, injury repair, neurodegenerative disease, and sensory systems. Microglia, specialized cells which are responsible for clearing cellular debris and pruning dead neurons from nervous tissue through the process of phagocytosis (cell eating) appear throughout the brain and spinal cord, including the white and gray matter. Other immune cells, including T cells, monocytes, and mast cells, reside in the brain and spinal cord’s outer membranes, known as the meninges, and circulate in cerebrospinal fluid (Keener, 2016). 

Advancing research continues to demonstrate the extensive network of communication between the central nervous system and the immune system. 

Not only does the lymphatic system actually permeate the CNS, but the autonomic (involuntary and unconscious) nervous system actually branches into the lymphatic system throughout the body. Some immune cells even have receptors for neuropeptides and neurotransmitters, the chemicals which neurons use to communicate. Activation of these neural communication receptors via chemicals sent from the brain alters the function of the immune system, directing it about cell proliferation, chemotaxis (the movement of cells toward areas of disease or injury) and other specific immune responses. Additionally, it has been demonstrated that lesions in the brain and stressors can alter immune function, which we will discuss further. When the body is injured or threatened with disease, it appears that cytokines (immune signalling cells) produced in the periphery of the body induce the expression of CNS cytokines, produced by macrophages and microglial cells in the brain. These centrally generated cytokines diffuse throughout the functional tissues of the brain, directing specific brain areas to organise the nervous and immune systems to respond to infection, fever, neuroendocrine activation and/or illness behaviour (Dantzer, & Wollman, 2003). All of this makes it abundantly clear that the immune system and central nervous system are far more interrelated than was thought. 

Holistic Interaction

This interaction between the immune system and brain which continues to be studied reveals the ways in which the brain not only affects the health of the body, but that the health of the body can affect the health of the brain. 

This is to say that a healthy immune system contributes to a robust nervous system, and that a well-toned nervous system helps to secure a fit brain. However, this is not to oversimplify the interaction of the two, in the words of Honathan Kipnis, a researcher from the university of Virginia, “Saying the immune system is always good for the brain, it’s wrong; saying it’s always bad for the brain, it’s wrong. It depends on the conditions” (Keener, 2016). It is apparent that the holistic interaction between these two complicated systems is quite complex itself. 

One way in which the immune system supports brain health is by repairing tissue after damage caused an event such as a TBI or stroke or even infection. Macrophages, immune cells which produce transforming growth factor-beta (TGFβ), which promotes wound healing and interleukin 10 (IL-10) which dispels inflammation accumulated in brain tissues when injured. However, when macrophages go awry, they are known to damage neurons by secreting cytokines, proteases, or reactive oxygen species.

Another example of the complex way in which the CNS and immune system support each other is the microglia which not only clear away dead tissue and toxins but also serve to reinforce the Blood Brain Barrier. Microglia fill in spaces left by astrocytes killed or damaged during injury. The barrier serves to make sure that unwanted immune cells do not flood the brain’s functional tissue, where they can begin to cause harm via neurotoxic proteins (Keener, 2016). The immune system not only prevents toxins from reaching the brain tissues, it also provides the pathway via which toxins in the brain are removed. Sleep studies reveal that the brain appears to flush out waste and toxins from the tissues during sleep, protecting the health of the brain. Scientists are beginning to believe that these waste products and toxins may find their exit from the brain via the lymphatic system (Hamilton, 2017). However, in cases in which toxins are removed or allowed to accumulate, inflammation and disease follow. 

Degenerative Disease

Research which explores how the immune system interacts with the brain shows promise for the study of chronic degenerative diseases like Parkinson’s and Alzheimer’s. 

It has been theorized that these diseases are a result of a build-up of toxic waste products in the brain, and that the lymphatic vessels play a protective role by removing these waste products (Hamilton 2017). Monocytes in blood vessels also help protect the brain by clearing amyloid-β deposits (associated with Alzheimer’s Disease) within veins (Keener, 2016). Once again, this interaction is complex and not always straightforward, as research also shows that inflammation can send the brain’s immune cells into damaging hyperdrive, causing microglia to become overactive, excessive pruning neural connections and causing neural damage which is linked to neurodegenerative diseases including dementia. But these same microglial cells which can cause inflammation and have the potential for destruction, when regenerated after damage, come back in full force, actually boosting learning and memory in the process (RMIT University, 2020). 

Functional Support

Not only does the immune system help to clear toxic build-up that contributes to neurological disease, it also serves to activate and support normal and healthy cognitive function. 

For instance, chronic psychological stress can induce proinflammatory signals (we will discuss this more in detail) in the brain which inhibits one of the proteins which support learning and memory, called brain-derived neurotrophic factor (BDNF). T-cells which produce cytokine interleukin-4 (IL-4), protect against the deleterious effects of these proinflammatory signals, providing for the secure production and release of BDNF, thereby supporting cognitive processes. If these t-cells are not present or are too few in numbers, unchecked proinflammatory factors secreted by macrophages in times of stress will prevent effective learning and memory formation. 

Mast cells may also play a role in supporting brain function on a daily basis. They have been located not only in the meninges, but also in the perivascular spaces of brain structures including the thalamus, hypothalamus, and amygdala. Mast cells also serve the important role of secreting the neurotransmitter serotonin into the memory structure of the brain, the hippocampus, where that serotonin is needed for neurogenesis (the birth of new neurons), and where it supports learning and memory in addition to helping to regulate anxiety. This evidence makes it clear that the immune system not only serves to address injury and disease in the brain, but also serves important roles in the support and maintenance of its day-to-day function.

Like microglia we discussed earlier, mast cells can be a catch-22 for wellness at times in that they have been known to respond to excess stress by releasing a growth factor which increases blood-vessel permeability, and disease susceptibility. This complicated love-hate relationship between CNS and the immune system is moderated by an important element of wellness: psychological stress (RMIT University, 2020).

Stress Management

It would hardly be a complete discussion of human immunity without exploring the effects of stress on the brain and immune function. The function of the immune system is moderated by inflammation, and inflammation is directly related to stress. 

75–90 percent of human disease is related to the activation of stress systems. Stress causes a release of stress hormones including cortisol and adrenaline. Prolonged stress over long periods of time causes chronic activation of the stress response and in the process inordinate levels of stress hormone are released into the body. This not only disrupts the stress-response further, making an individual more prone to chronic hyperarousal, but it also causes inflammation in tissues where excess stress-hormone begins to accumulate. Inflammation is typically the body’s reaction to injury or disease, but when inflammation becomes excessive, it ceases to heal and actually begins to do harm, much like the presence of excess immune cells. Chronic inflammation of this kind is linked to chronic disease including heart disease, cancer, Alzheimer’s, Parkinson’s and MS, even depression (Liu,Wang, & Jiang, 2017). 

The brain’s ability to cope with stress exerts an effect on the immune response and either serve to contribute to or prevent disease. 

Psychiatric disorders also come into play as conditions such as anxiety, depression, bipolar, etc. tend to elevate levels of stress and arousal of the nervous system. Research demonstrates that stress not only contributes to features of depression, but also contributes to changes in immune response. In fact, stress triggers inflammation and emotional and cognitive alterations that play a critical role in the onset, maintenance, and recurrence of depression. Thus, it becomes apparent how psychological stress mediates the brain-immune system relationship in complicated ways (Maydych, 2019). 


Research has made it abundantly clear that the CNS and immune system not only communicate but in fact interact and rely on each other in intricate and complex ways. It is clear that maintaining a strong immune system is vital to supporting not only brain function, but also preventing disease. By the same token, maintaining optimal brain health and proper stress management are also clearly essential to toning and aiding the immune system, and preventing any of its complex cells from becoming too numerous, or their functions going awry. Together, these two systems interact in a holistic way to keep one well throughout the lifetime. Thus it is essential not only to view this iteration through a holistic framework, but also to treat it via a holistic method or practice such as yoga, which not only supports brain health and immune function, but which serves to bolster the whole body system, for an intelligent defense against injury or disease. 


Hamilton, J. (2017). Brain’s Link To Immune System Might Help Explain Alzheimer’s. National Public Radio.

Keener, A. B. (2016). Immune System Maintain Brain Health. The Scientist.

RMIT University. (2020). How the brain’s immune system could be harnessed to improve memory. Science Direct.

Liu, Y. Z., Wang, Y. X., & Jiang, C. L. (2017). Inflammation: the common pathway of stress-related diseases. Frontiers in human neuroscience, 11, 316.

Maydych, V. (2019). The interplay between stress, inflammation, and emotional attention: relevance for depression. Frontiers in neuroscience, 13.

Dantzer, R., & Wollman, E. E. (2003). Relationships between the brain and the immune system. Journal de la Societe de biologie, 197(2), 81-88.

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