Multiple sclerosis (MS) is an autoimmune disease characterized by the destruction of the protective myelin sheath that covers nerve cells in the central nervous system (CNS). But what exactly is an autoimmune disease? “Autoimmune” is made of two words: “auto-,” derived from Ancient Greek meaning “self,” and “immune,” which means “protected from disease.” “Autoimmune” refers to an immune response against oneself. Therefore, an autoimmune disease occurs when the body’s immune system attacks its own tissues.
The type of autoimmune disease a person develops will depend on the tissue their immune system attacks. For example, type 1 diabetes involves the autoimmune destruction of cells in the pancreas, whereas rheumatoid arthritis involves the destruction of cells in the joint tissue. There are also different types of autoimmune diseases that attack a wider variety of cells and tissues in the body, such as systemic lupus erythematosus.
Different types of cells in the immune system recognize pathogens (disease-causing organisms) and foreign material in different ways. Once the immune system recognizes an invading substance, it can orchestrate an attack to remove it. The immune system needs to know the difference between “self” material — the body’s own cells and tissues — and “foreign” material in order to prevent autoimmune diseases from developing. This is referred to as immune tolerance, meaning the immune system is aware and tolerant of the body’s own cells and tissues and therefore does not attack them. Autoimmunity occurs when immune tolerance is lost. When this happens, the immune system can no longer tell the difference between some self and foreign materials. This is when problems can arise.
In MS, the immune system is responsible for the demyelination — the removal of the protective myelin sheath — of the nerve cells in the CNS. This affects how the neurons in the brain, optic nerves, and spinal cord function and communicate with each other.
But how does the autoimmune response against the CNS work? Many studies have been performed involving humans and animals to determine the immune system’s role in MS. In particular, the animal model for MS — known as experimental autoimmune encephalomyelitis (EAE) — has clarified many of the functions for immune cells in the development of MS. This is also known as the “pathogenesis” of MS, referring to what causes a disease to develop.
While the pathogenesis of MS is still not completely understood, there are some key players in the immune system that contribute to autoimmune destruction of the CNS, which fall under the categories of lymphocytes and macrophages.
Lymphocytes are important cells in the immune system, responsible for its specific response when confronted with an invading substance. Lymphocytes are capable of forming immune memory. This memory means the body’s immune response can become specific and therefore quite strong. Lymphocytes recognize specific pieces of foreign or disease-causing material known as antigens.
There are two main types of lymphocytes: B cells and T cells. These cells also have multiple subtypes.
B cells can play a role in MS by releasing antibodies that react against your own body’s molecules, also known as autoantibodies. These autoantibodies can destroy the body’s tissues and activate other types of immune cells. B cells can also act as antigen-presenting cells (APCs), which are cells that introduce the material to your immune system. These APCs present self-molecules — components of an organism's body — to T cells, thus causing them to activate. B cells are known to be involved in the pathology of MS, as demonstrated by the fact that B-cell-depleting therapies help improve disease outcomes.
There are two main types of T cells: CD8-positive (CD8+) T cells — also called cytotoxic T cells and killer T cells — and CD4-positive (CD4+) T cells, also known as helper T cells. CD8+ T cells directly kill other cells that present antigens they recognize. CD4+ T cells help in organizing how other cells respond in the immune system.
CD4+ T cells and CD8+ T cells are both thought to play a role in the pathogenesis of MS. Both cell types have been found in lesions from individuals with MS. Additionally, activated myelin-reactive CD4+ T cells — T cells directed against the myelin sheath — have been found in the cerebrospinal fluid of people with MS.
There’s a subtype of CD4+ T cells known as regulatory T cells. These cells help dampen the immune response by directly inactivating cells or releasing anti-inflammatory substances. Regulatory T cells are also known to play a role in the pathogenesis of MS. In particular, the dysfunction of T regulatory cells is associated with the disease. Researchers have found that regulatory T cells may not work correctly in MS.
Macrophages are another kind of immune cell. Whereas lymphocytes recognize pathogens through antigen-specific receptors, macrophages identify invading material through receptors that pick out patterns. These patterns are known as pathogen-associated molecular patterns (PAMPs).
Macrophages cannot form immune memory the way lymphocytes can, but they do help direct the immune response by releasing inflammatory mediators, known as cytokines. Macrophages are thought to play a role in MS because they have been found in demyelinating lesions.
The immune system is an incredible organ system. While it is essential for our protection from infection, it also has the potential to cause autoimmune disease. By understanding how the immune system works, one can learn more about MS, what causes it, and how it is treated.
Moreover, as scientists learn more about the immune system and how to control it, they will be able to develop more effective treatments for MS. Some of the current treatments for MS already target the immune system by regulating different types of cells and inflammatory mediators.
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