An encephalitogenic event provokes inflammation of the brain, a condition known as encephalitis. The term is most frequently applied to autoimmune scenarios where the body’s immune system incorrectly targets components of the central nervous system (CNS). In these cases, defensive mechanisms that normally protect against foreign invaders are redirected against the body’s own tissues. This misdirected immune attack involves a complex sequence of cellular interactions that can lead to inflammation and damage within the brain.
The Encephalitogenic Immune Response
The encephalitogenic immune response begins with sensitization, which occurs in peripheral lymphoid organs like the spleen or lymph nodes. Here, immune cells called antigen-presenting cells (APCs) encounter a substance they identify as a threat. These APCs process the substance and present fragments of it to other immune cells, specifically a type of T-lymphocyte known as a helper T-cell. This initial activation sets the stage for the subsequent inflammatory cascade.
Once activated, naïve T-cells differentiate into specific subtypes, with T-helper 1 (Th1) and T-helper 17 (Th17) cells being prominent actors in this process. These differentiated T-cells multiply and circulate throughout the body. For an attack on the CNS to occur, they must be able to cross the blood-brain barrier (BBB), a selective border of endothelial cells that protects the brain.
Activated Th1 and Th17 cells produce signaling molecules called cytokines, which increase the permeability of the blood-brain barrier. This allows the T-cells, along with other immune cells like monocytes, to pass through this layer and enter the brain parenchyma. Once inside the CNS, these T-cells can be reactivated if they encounter their target antigen presented by local APCs, such as microglia, the brain’s resident immune cells.
This reactivation unleashes an inflammatory response within the brain. The T-cells release more cytokines that recruit additional immune cells to the site, amplifying the attack. This inflammation can damage neural tissues, particularly the myelin sheath that insulates nerve fibers. The destruction of myelin disrupts nerve signal transmission, leading to the neurological symptoms characteristic of encephalitogenic disorders.
Primary Encephalitogenic Molecules
The molecules that trigger this autoimmune cascade are proteins native to the central nervous system. These proteins are normally shielded from the immune system, but if this seclusion is breached, they can be mistaken for foreign invaders. The most studied of these molecules are proteins within the myelin sheath, the layer that insulates nerve axons. Examples include Myelin Basic Protein (MBP), Proteolipid Protein (PLP), and Myelin Oligodendrocyte Glycoprotein (MOG).
These proteins help maintain the myelin sheath’s stability. MOG, for instance, is located on the outermost surface of the myelin sheath and is a primary target in some autoimmune conditions. MBP is important for the compaction of the myelin layers. Normally, the immune system develops a tolerance to these self-proteins, but an encephalitogenic response occurs when this tolerance breaks down.
A breakdown in tolerance can be initiated through molecular mimicry. This occurs when a foreign agent, like a virus or bacterium, has a protein component that structurally resembles one of the body’s own proteins, such as MOG or MBP. The immune system then creates antibodies and T-cells that target the foreign protein to eliminate the pathogen.
Due to the structural similarity, these same immune cells and antibodies may incorrectly recognize the self-protein in the CNS as a threat. The immune system then crosses the blood-brain barrier and begins to damage the myelin sheath, initiating an autoimmune disease. This process tricks the body’s defenses into attacking its own nervous system.
Associated Central Nervous System Diseases
An encephalitogenic immune response is linked to several diseases of the central nervous system. The most recognized is Multiple Sclerosis (MS), a chronic and progressive autoimmune disorder. In MS, the persistent immune attack on myelin leads to recurrent inflammation, demyelination, and the formation of scar tissue, or plaques, in the brain and spinal cord. The symptoms of MS vary widely depending on which areas of the CNS are affected.
A related condition is Acute Disseminated Encephalomyelitis (ADEM). Unlike the chronic nature of MS, ADEM is an acute, monophasic illness, meaning it occurs as a single event. It often develops weeks after a viral or bacterial infection, particularly in children. This timing suggests that molecular mimicry is a primary driver, where the immune response to an infection inadvertently attacks the CNS.
While both conditions involve an attack on myelin, their clinical courses differ. ADEM presents with a rapid onset of widespread neurological symptoms, including fever, headache, and altered consciousness. Many individuals with ADEM experience a significant recovery. MS is characterized by a long-term pattern of relapse and remission or steady progression, reflecting a persistent autoimmune process.
Experimental Models of Encephalitis
To investigate these diseases and test potential treatments, scientists use animal models. The most common model for studying autoimmune brain inflammation is Experimental Autoimmune Encephalomyelitis (EAE). This condition is induced in laboratory animals, like mice, by immunizing them with specific encephalitogenic molecules from the CNS.
Researchers can inject animals with proteins like MOG or MBP, mixed with an adjuvant to stimulate a strong immune reaction. This injection prompts the animal’s immune system to develop T-cells and antibodies that target these myelin proteins. The resulting inflammation closely mimics what is observed in human diseases like MS.
The EAE model allows for the detailed study of the disease process in a controlled environment. Scientists can track T-cell activation, migration into the brain, and the resulting demyelination and neurological symptoms, which can manifest as progressive paralysis. Using this model, researchers identify which immune cells and molecules are involved in the damage and evaluate new therapeutic strategies designed to suppress this autoimmune response.