An autoantigen is a normal molecule found within the body that the immune system mistakenly identifies as foreign or harmful. These “self” components, typically proteins or protein complexes, should normally be ignored. However, in certain circumstances, the body’s defenses launch an immune response against them.
How the Immune System Recognizes Self
The immune system distinguishes between the body’s own components (“self”) and foreign invaders (“non-self”) like bacteria or viruses. This discrimination involves specialized immune cells, such as T cells and B cells. During their development, these cells undergo a selection process to eliminate those that strongly react to self-molecules.
This process, called immune tolerance, ensures that immune cells capable of attacking the body’s own tissues are either removed or inactivated. For instance, B cells that recognize self-proteins are eliminated in the bone marrow, while T cells undergo a similar selection in the thymus. Cells that pass this inspection then circulate, ready to respond only to genuine threats that carry “non-self” markers or antigens.
The Role of Autoantigens in Autoimmune Diseases
When the immune system fails to maintain self-tolerance, autoantigens become directly involved in autoimmune diseases. The immune system, instead of targeting external pathogens, erroneously attacks the body’s own tissues or organs containing these autoantigens. This misdirected response leads to chronic inflammation and progressive tissue damage.
If an autoantigen is located on cells within a specific organ, the immune attack will target and harm that organ. This sustained assault can impair organ function and manifest as symptoms characteristic of autoimmune conditions.
Common Autoantigens and Their Associated Conditions
Specific autoantigens are linked to distinct autoimmune conditions, illustrating how this misdirected immune response affects different parts of the body. In Type 1 Diabetes, the immune system targets and destroys the insulin-producing beta cells in the pancreas. Proteins within these cells, such as glutamic acid decarboxylase (GAD65) or insulin itself, become autoantigens, leading to an inability to produce insulin and regulate blood sugar.
In Multiple Sclerosis (MS), the immune system mistakenly attacks myelin, the protective sheath surrounding nerve fibers in the brain and spinal cord. Myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) are examples of autoantigens in MS, and their destruction disrupts nerve signal transmission, causing symptoms like muscle weakness and vision problems. Similarly, in Hashimoto’s thyroiditis, autoantibodies target proteins within the thyroid gland, such as thyroid peroxidase (TPO) and thyroglobulin. This attack leads to inflammation and damage to the thyroid, resulting in an underactive thyroid gland.
What Causes Autoantigen Formation
The transformation of a normal “self” molecule into an autoantigen is influenced by a combination of factors. Genetic predisposition plays a role, with certain genes increasing an individual’s susceptibility to autoimmune conditions. Environmental triggers, such as infections or exposure to certain toxins, can also contribute.
One proposed mechanism is molecular mimicry, where a foreign antigen from a pathogen closely resembles a self-antigen. The immune response against the foreign invader then mistakenly cross-reacts with the similar self-molecule, leading to an autoimmune attack. Damage to tissues can also expose formerly hidden self-antigens, making them visible to the immune system and potentially initiating an autoimmune reaction.