Autoimmunity and Autoimmune Disease

Autoimmunity is an immune response directed against the body's own antigens. When self-reactive antibodies or T cells escape the normal controls of tolerance and cause tissue injury, the result is autoimmune disease, which may be organ-specific or systemic and frequently shows a female predominance.

Definition

Autoimmunity is an adaptive immune response against self-antigens; autoimmune disease is the clinical state in which such self-reactive antibodies or T cells produce tissue injury after central and peripheral tolerance have failed.

Scope

This entry covers the concept of immunological self-tolerance and how its failure leads to autoimmunity, the contributions of genetic, environmental, and immunoregulatory factors, and the distinction between organ-specific and systemic autoimmune disease. It is a mechanistic reference within immunopathology and is not clinical guidance for any specific autoimmune condition.

Core questions

• How does the immune system normally avoid attacking self?
• What causes central and peripheral tolerance to fail?
• Why do genetic and environmental factors interact in autoimmune disease?
• What distinguishes organ-specific from systemic autoimmunity?

Key concepts

• Central tolerance (thymic deletion, AIRE)
• Peripheral tolerance (anergy, regulatory T cells)
• Autoantibodies and autoreactive T cells
• Genetic susceptibility (including HLA associations)
• Environmental triggers and molecular mimicry
• Organ-specific versus systemic autoimmunity
• Female predominance

Key theories

Immunological self-tolerance

Self-reactive lymphocytes are normally controlled by central tolerance (deletion or editing of self-reactive cells during development) and peripheral tolerance (anergy, regulatory T cells, and suppression). Autoimmune disease is understood as a breakdown of these mechanisms allowing self-reactive effectors to persist and cause injury.

Mechanisms

Self-tolerance is maintained centrally, where developing lymphocytes that strongly recognise self-antigen are deleted or edited, and peripherally, where surviving self-reactive cells are held in check by anergy, regulatory T cells, and other suppressive mechanisms. Autoimmunity arises when these checks fail, typically through a combination of genetic susceptibility (notably particular HLA alleles and genes affecting tolerance) and environmental triggers such as infection, which may unmask or mimic self-antigens. The resulting autoantibodies and autoreactive T cells injure tissue through the same effector pathways seen in hypersensitivity: antibody-mediated (Type II), immune-complex (Type III), and T cell-mediated (Type IV) mechanisms. Damage may be confined to one organ or, when antigens are widespread, may be systemic.

Clinical relevance

Autoimmune mechanisms underlie a large group of diseases ranging from organ-specific disorders such as type 1 diabetes and autoimmune thyroiditis to systemic disorders such as systemic lupus erythematosus, and recognising the underlying effector mechanism helps explain their serology and pathology. This entry describes mechanisms for orientation and is not a basis for diagnosis or treatment of any autoimmune disease.

Epidemiology

Autoimmune diseases collectively affect several percent of the population, and many of them show a marked female predominance. Incidence, age of onset, and prevalence differ substantially by specific disease and are covered in the relevant entries.

Evidence & guidelines

The mechanistic framework is synthesised from immunology textbooks and review articles; disease-specific epidemiology, diagnosis, and management are addressed in dedicated clinical entries and external guidelines.

History

The idea that the immune system could attack self, once captured by the phrase horror autotoxicus, gave way during the twentieth century to clear evidence of autoimmune disease, the concept of self-tolerance and its failure, and later the molecular identification of tolerance mechanisms such as thymic deletion and regulatory T cells.

Debates

What triggers loss of tolerance?

The relative contributions of genetic susceptibility, infection, molecular mimicry, hormonal and other environmental factors to the initiation of autoimmunity remain debated and likely differ across diseases, complicating efforts to identify single causes.

Key figures

• Anne Davidson
• Betty Diamond
• George Tsokos

Seminal works

• davidson-diamond-2001

Frequently asked questions

What is the difference between autoimmunity and autoimmune disease?

Autoimmunity is an immune response against self-antigens, which can be present without harm; autoimmune disease is the clinical condition that results when such self-reactive responses actually injure tissue and produce symptoms.

Why are autoimmune diseases more common in women?

Many autoimmune diseases show a female predominance thought to reflect hormonal, genetic (including X-chromosome), and immunoregulatory differences, though the precise reasons remain an active area of study and vary by disease.