Autoimmunity is the process by which the immune system mounts a response against the body’s own tissues, recognizing self‑antigens as foreign and leading to inflammation and tissue damage.
Mechanisms and causes
Under normal conditions, immune cells are educated to distinguish self from non‑self through mechanisms called central and peripheral tolerance. Central tolerance eliminates autoreactive lymphocytes during development in the thymus and bone marrow, while peripheral tolerance uses regulatory T cells, anergy and deletion to suppress stray responses in the periphery. Autoimmunity arises when these mechanisms fail or are overridden. Genetic factors, particularly certain major histocompatibility complex alleles, predispose individuals to specific autoimmune diseases. Environmental triggers such as infections, toxins and tissue injury can promote autoimmunity through molecular mimicry, bystander activation or release of sequestered antigens. Hormonal influences help explain why many autoimmune diseases are more common in women. The result is activation of autoreactive T cells and B cells that produce autoantibodies and cytotoxic responses. Epitope spreading can broaden the response over time, and chronic inflammation perpetuates tissue destruction.
Examples and clinical significance
Autoimmune diseases encompass a wide range of organ‑specific and systemic disorders. In type 1 diabetes, T cells attack pancreatic β cells, leading to insulin deficiency. Multiple sclerosis results from autoreactive immune responses against myelin in the central nervous system, causing neurological deficits. Systemic lupus erythematosus involves autoantibodies directed against nuclear components such as DNA and histones, producing multi‑organ inflammation including skin, joints, kidneys and nervous system. Rheumatoid arthritis features chronic inflammation of synovial joints due to autoantibodies and pro‑inflammatory cytokines, leading to pain and joint destruction. Autoimmune thyroid diseases include Graves’ disease, where stimulating antibodies activate the thyrotropin receptor, and Hashimoto’s thyroiditis, characterized by lymphocytic infiltration and destruction of thyroid tissue. Therapies for autoimmune diseases aim to suppress immune activation using corticosteroids, disease‑modifying drugs or biologics targeting cytokines and co‑stimulatory molecules. Understanding autoimmunity has also led to targeted immune tolerance therapies and improved antigen‑specific diagnostic tests.
Autoimmunity reflects a breakdown of the immune system’s self‑recognition safeguards and manifests as diverse chronic diseases. Identifying the factors that precipitate autoimmunity and developing targeted therapies remain central challenges in immunology.
Related Terms: Self tolerance, Autoimmune disease, Autoantibody, Regulatory T cell, Immune tolerance