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Multiple Sclerosis Spectrum Disorders

Autoimmune Demyelinating Disorders of The Brain and Spinal Cord – Overview

Multiple Sclerosis Spectrum Disorders

There are a few diseases of the central nervous system (brain and spinal cord), which are called demyelinating and autoimmune.

Multiple sclerosis is the most well-known one. Much less common are acute disseminated encephalomyelitis and neuromyelitis opticaOptic neuritis and transverse myelitis may occur independently or they might be a part of any of the above mentioned disorders.

Firstly, I would like to set things straight with definitions and terminology.

A few paragraphs below will explain the meaning of the processes occurring in the nervous tissue in these disorders. I will start with a brief description of the immune system.

Immune System Overview

The immune system is meant to protect the body from all sorts of invaders – viruses, bacteria, fungi, and cancer.
This is a well-organized war machine, which consists of numerous members. Unlike the army, there are no generals, no marshals, and no chain of command.  It is a self-regulated system similar to ant or bee colonies.
Every member knows what to do and their actions are regulated by mutual interactions between numerous members of the colony. The immune system is self-regulated by back-feed loops, which allow continuous reassessment of the immune response.
Each member has a very narrow spectrum of skills. Their actions have to be accurate and precise.  Errors will lead to either loss in the war or to damages to civilians and bystanders. “Loss in the war” corresponds to death due to infection. “Civilian injury” is an autoimmune disease.

The very first step in immune system response is the task of spotting the enemy. The intelligence service has to gather some information first. Special cells (macrophages) patrol the body tissues. They sniff, touch, and do some handshaking with the body cells. All suspects are “swallowed” and broken down into pieces. The suspect’s foreign components are displayed on the surface of the macrophages.
The foreign components are called antigens. Antigens are the markers of identity. They are similar to enemy’s uniform. Antigens are large protein or glycoprotein molecules.
Macrophages present these antigens to special lymphocyte cells, which are responsible for the weapon design and manufacturing. This is a constant ongoing process of surveillance.
In autoimmune disease some normal cell components are perceived as foreign.  Once the enemy is identified, the immune system doesn’t care whether the “invader” is real or not. The enemy has to be killed.
The immune system launches a strike.

Let’s review the arsenal.
Similar to conventional war, there are soldiers, guns, and weapons of mass destruction. Soldiers are special cells (T-lymphocytes). The foreigner is approached and killed in close combat. These T-cells are precisely targeted. Special sensing molecules on the cell membrane allow them to attack only specific targets. They don’t miss. No one else suffers until the “mass destruction” stage is reached.
Guns are called antibodies, or the immune globulin. B-cells produce these special proteins (antibodies). Antibodies are fork-shaped proteins. Each particular molecule is capable of attaching to a very specific antigen on the cell membrane. Once it happens, the enemy becomes tagged and is visible to the rest of the immune system.

Targeted attacks are associated with release of numerous chemicals causing local inflammation, which is intended to increase the blood supply and local temperature as well as to attract more “troops”.
The resulting messy environment acts like a weapon of mass destruction. It causes lots of collateral damage to the surrounding tissues.

Autoimmune Disorders

An autoimmune disease occurs when a normal body tissue is destroyed by the immune system as if it is foreign. Why does it happen? It is a simple error. Considering the number of microbes and viruses around, we live for years without even knowing about ongoing fight between them and our body.

We have lots of different tissues in the body. Some of them are actually “foreign” to our immune systems, because they are physically isolated. Brain is one of them. Meanwhile, MS is not a common disease. Yes, autoimmune disease is a simple glitch in the defense system. Nothing is perfect!

Errors in the defense system are often provoked. Some bugs have antigens similar to normal tissue components. An immune response may cause a collateral attack against normal cells. This mechanism is responsible for the rheumatic fever and some cases of Guillain-Barré syndrome.

One more point. We all perceive infections as something bad. It is not the case for the immune system. Periodic infections keep the immune system in the normal working condition. Lack of stimulation from infections puts it in a hyper-vigilant and hyperactive state. This hyperactivity is one of the reasons for autoimmune diseases.

What does “Demyelinating” Mean?

Myelin is a multilayered wrapping material around the nerve fibers. Myelin is simply a cell membrane wrapped around a single nerve fiber multiple times. This wrapping material belongs to the cells named oligodendrocytes. One olygodendrocyte serves myelin to a few neighboring nerve fibers. Myelin is needed for the nerve fiber insulation (to prevent shortcuts) and to help signal conduction along the nerve fiber. The way nerves conduct electricity is very differently from the way a copper wire does. Presence of myelin is essential for a high speed information transmission.

In demyelinating disorders myelin is destroyed in some portion of the brain, the spinal cord, or the optic nerves. In some instances myelin may partially regenerate after the attack is over. Damage is not limited to myelin. Nerve fibers are often damaged as well. Those never regenerate in the central nervous system.

In demyelinating disorders an autoimmune attack may be directed to the myelin-producing cells or maybe not. No one knows what is targeted in multiple sclerosis. In a very similar condition, called Neuromyelitis Optica, the target cells are astrocytes. Astrocytes do not produce myelin. All the damage to the myelin and the nerve fibers in this disease is collateral.

Please note that autoimmune disorders are not the only ones that might destroy the myelin sheath. This set of articles is dedicated only to autoimmune diseases.

Potential Treatments of Autoimmune Disorders in the “Ideal World”

As I mentioned before, the immune system is a perfect war machine. Unfortunately, the modern autoimmune diseases treatment approach is no match. All the treatments for MS spectrum diseases and for the vast majority of all autoimmune diseases are of “mass destruction” type. Treatment effects on the immune system functions are very broad. For example, the whole system shut down for steroids, alteration of T-cells function for interferons, or prevention of leukocytes migration from the blood to the brain for Natalizumab. Newer drugs under development are not much better, since the exact mechanism of MS remains a mystery.

Suppression of immunity is always associated with increased chance of infections, cancers or even other autoimmune disorders. They all lack the most important qualities – specificity and precision.
Basically, we are fighting some camouflaged sniper with a nuclear bomb.

In ideal world, the treatment would be an approach used by the immune system itself. Identify B-cells producing the unwanted antibodies or the line of T-cells attacking normal tissue. Launch an attack on these particular cells. Done! Cured!

Unfortunately we don’t live in the ideal world and this approach is very far from realistic. I don’t want to finish on pessimistic note.
Modern therapies do decrease the number of MS attacks and they may delay significant disability in some forms of MS.

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