Multiple sclerosis (MS) is a complex neurological disease where the immune system plays a central and destructive role. At its core, MS is considered an autoimmune disorder, meaning the body’s immune defenses mistakenly identify parts of the central nervous system (CNS) as foreign and attack them. Specifically, the immune system targets myelin, the protective sheath that surrounds nerve fibers in the brain and spinal cord. Myelin acts like insulation on electrical wires, allowing nerve signals to travel quickly and efficiently. When myelin is damaged or destroyed, nerve signals slow down or fail to transmit properly, leading to the wide range of symptoms seen in MS.
The immune system’s role in MS involves several types of immune cells and molecules that contribute to inflammation and tissue damage. One of the key players are T cells, a type of white blood cell that normally helps defend the body against infections. In MS, certain T cells become autoreactive, meaning they mistakenly recognize myelin or the cells that produce it (oligodendrocytes) as threats. These autoreactive T cells cross the blood-brain barrier, a protective shield that normally keeps harmful substances out of the CNS, and enter the brain and spinal cord. Once inside, they trigger an inflammatory cascade that recruits other immune cells, such as B cells and myeloid cells, amplifying the attack on myelin.
Myeloid cells, including microglia (the resident immune cells of the CNS) and macrophages, play a crucial role in this neuroinflammatory process. These cells become activated in response to the immune attack and contribute to tissue damage by releasing inflammatory molecules and enzymes that degrade myelin and harm nerve cells. Recent research has identified specific receptors on these myeloid cells, such as SLAMF5, which regulate their activation state. Blocking such receptors can reduce inflammation and slow disease progression, highlighting the importance of myeloid cells in MS pathology.
B cells, another type of immune cell, also contribute to MS by producing antibodies that target myelin components and by presenting antigens that activate T cells. The presence of these immune cells and antibodies in the CNS leads to the formation of lesions or plaques, areas of demyelination and scarring that disrupt normal nerve function.
The immune attack in MS not only damages myelin but also affects the oligodendrocytes responsible for producing and maintaining it. This impairs the natural repair process known as remyelination. While the body can sometimes repair myelin damage, in MS this repair is often incomplete or fails over time, leading to chronic disability.
The immune system’s involvement in MS is dynamic and complex. It varies between individuals and over the course of the disease. In the most common form of MS, relapsing-remitting MS, immune attacks occur in episodes or relapses, followed by periods of remission where symptoms improve. Over time, the immune system may cause more continuous damage, leading to progressive forms of MS.
Because the immune system drives the damage in MS, many treatments focus on modulating or suppressing immune activity. Some therapies aim to reduce the number or activity of autoreactive T and B cells, while others target specific molecules involved in immune cell activation and migration into the CNS. Experimental approaches include resetting the immune system by wiping out the existing immune cells and regenerating them from stem cells, hoping to create a new immune system that no longer attacks myelin.
In summary, the immune system in MS acts as both the initiator and perpetuator of damage to the nervous system. Autoreactive immune cells breach the CNS, attack myelin and oligodendrocytes, and create a chronic inflammatory environment that impairs nerve function and repair. Understanding the precise roles of different immune cells and molecules continues to guide the development of therapies aimed at halting or reversing the disease process.
