/Multiple sclerosis and the immune system: What do we know?

Multiple sclerosis and the immune system: What do we know?


The body’s immune system is a beautiful and complex defense system designed to protect us from infections. In the case of multiple sclerosis and other autoimmune conditions, however, these defenses turn on the body.

In this feature, we investigate the complicated relationship between the immune system and multiple sclerosis (MS), as well as which way the causal relationship may lie.

In a person with MS, the immune system attacks axons — or nerve fibers — in the central nervous system (CNS), which are protected by an insulating layer called myelin.

MS damages these axons in the brain, spinal cord, and optic nerves, which send visual information from the eye to the brain.

The scar tissue that MS causes as a result of its attacks is visible in the brain’s white and gray matter. During an MS attack — also called an exacerbation — different types of immune cells damage or destroy most of the myelin within the targeted area.

Experts regard MS as an autoimmune disease, but the scientific community has not been able to identify any MS-specific antigens, which are proteins that prompt the immune system to attack.

Although much is still unknown, what do we know so far about the immune system and its role in MS?

Similar conditions to MS that are regarded as autoimmune diseases include:

With MS, we know that T cells — which play an important part in the immune system — become activated in the lymph system and then enter the CNS through blood vessels.

They then release chemicals that cause the damage associated with the condition, also activating B cells and other immune system cells to join the immune attack.

What scientists do not understand, however, is what finally knocks the immune system out of balance, allowing the T and B cells to become activated.

Experts consider conditions, such as MS, RA, lupus, type 1 diabetes, and celiac disease, to be examples of autoimmune diseases that are associated with the production of autoantibodies and self-reactive T cells.

However, with psoriasis, inflammatory bowel disease, or ankylosing spondylitis, immunity against these so-called self-antigens is not a feature, even though the immune system is involved.

The question that researchers must tackle in the wake of MS is: what could prevent these self-activating T cells from attacking the CNS?

To find out how to prevent such attacks from T cells, researchers are first attempting to unravel why they attack the CNS in the first place.

There are a few theories for why this occurs, according to the National Institute of Neurological Disorders and Stroke (NINDS).

One theory is that when the immune system is fighting an external invader — such as a virus — that mimics components of the brain, the immune system attacks CNS myelin in its attempts to quash the invader, a process known as molecular mimicry.

Another theory is that the immune system is destroying brain cells because they are unhealthy.

And yet another suggests the immune system simply mistakes normal brain cells for foreign invaders.

There is a blood-brain barrier (BBB) that keeps the brain and spinal cord separate from other substances in the body, including the immune system. However, if there is a breach of this barrier, the brain is then exposed to the immune system.

Experts say that in this case, the immune system may mistake myelin for a foreign invader.

Research has shown that the origins of MS point to both genetic predispositions combined with environmental factors. This is where the link between MS and infectious agents as environmental triggers comes to the fore.

Although many viruses have been found in people with MS, Epstein-Barr virus (EBV) is most consistently linked to the onset of the condition.

EBV is the virus that causes infectious mononucleosis, commonly known as mono, and it is one of the most common viruses in humans worldwide.

In fact, only about 5% of the population have not acquired infection with this virus. Researchers say people who have not contracted EBV are at a lower risk for developing MS than those who have.

Furthermore, people who contracted EBV in early childhood have a significantly lower risk for developing MS than those who did not contract the virus until adolescence or adulthood.

Contracting the virus later in life is typically accompanied by a more exaggerated immune response to EBV. Researchers say the higher MS risk suggests it might be the type of immune response to EBV that could lead to MS, rather than the virus infection itself.

But even this finding is shrouded in mystery for the moment because there is no proof that EBV actually causes MS, and the scientific community does not fully understand the workings behind the increased risk.

Given that MS is regarded as an autoimmune disease, many treatments for it naturally target or indeed harness the immune system.

One such treatment is beta interferon. Interferons are proteins that are naturally produced by the body to change the immune system’s response to invaders.

White blood cells release gamma interferon at the start of an immune response, which encourages inflammation in the tissues being attacked.

On the other hand, beta interferon is released near the end of an immune response, blocking gamma interferon and helping reduce inflammation.

According to the Multiple Sclerosis Trust, beta interferon drugs can reduce the number of MS exacerbations and slow the progression of the disease. Furthermore, when exacerbations do occur, treatment with beta interferon drugs shortens them and reduces severity.

There is also an ongoing stem cell treatment clinical trial from the NINDS, called BEAT-MS. In this experimental trial, researchers are removing immune cells from participants and then infusing some of their own stem cells in an effort to reset their immune system so that it stops attacking the CNS.

With all of the studies in recent years dissecting the role of the microbiome in immunity, MS research has drilled down into the minutiae of gut bacteria.

One research team has looked at samples of blood, spinal fluid, and stool from people with MS, people without MS, and people with other disorders.

They have found that immune cells reacting to specific gut bacteria travel from the gut to the brain during MS exacerbations, potentially protecting the brain and reducing inflammation.

Their study in Science Immunology, which also looked at brain tissue from people who had MS in their life, showed that specific B cells targeted certain strains of gut bacteria linked to MS inflammation.

The team also found that during MS exacerbations — but not during remissions — these B cells traversed the BBB to MS brain lesions, releasing messenger chemicals that aim to reduce inflammation.

The authors note that it is unclear what activates the B cells to travel to the brain on a protective mission, but they say that if they find what activates that process, they could potentially use it to treat MS.

According to lead researcher Dr. Anne-Katrin Pröbstel:

“Apparently, these immune cells migrate from the intestine to the inflammation sites in the central nervous system, where they release an anti-inflammatory messenger substance. That could explain why the illness worsens if these immune cells are removed from the blood with medication.”

While researchers are working to unravel this complicated condition and develop new treatments, there is one bright light that studies have repeatedly pointed to as being beneficial: the sun.

According to the NINDS, studies have shown that people who have higher levels of vitamin D and who spend more time in the sun are less likely to develop the condition.

For those with MS, it also means they are more likely to have a less severe form of the condition and fewer relapses.

We know that sunlight helps human skin make vitamin D, and researchers believe this vitamin helps modulate the immune system to reduce the risk of autoimmunity, including MS.

The research into the causes of MS and potential new treatments continues, as those who live with this condition emphasize its devastating impact on their quality of life.

Responding to interview questions for a BMJ study, one person with secondary progressive MS said that “[i]t’s like living your life with a weight on your back all the time, we can’t do, we can’t plan anything.”

Therefore, the efforts to better understand MS and its mechanisms continue.

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