Autoimmune Disease Basics

Autoimmune disease

Breakdown of self-tolerance resulting in tissue damage caused by autoantibodies and/or autoreactive immune cells

Self-tolerance

The immune system’s ability to recognize self-antigens and avoid attacking host tissues

Prevalence of autoimmune disease

Approximately 5–7% of the population is affected by autoimmune diseases

Sex predisposition in autoimmune disease

Autoimmune diseases occur more frequently in women than in men

Organ-specific autoimmune disease

Autoimmune disease targeting a single organ such as Graves’ disease

Systemic autoimmune disease

Autoimmune disease affecting multiple organ systems such as systemic lupus erythematosus

Human Leukocyte Antigen (HLA)

Human nomenclature for the major histocompatibility complex involved in antigen presentation

Role of HLA in autoimmunity

Certain HLA genotypes increase susceptibility to autoimmune diseases

Major histocompatibility complex (MHC)

Molecules that present peptide antigens to immune cells to initiate immune responses

Genetic susceptibility to autoimmunity

Inheritance of specific HLA alleles increases risk for autoimmune disease development

Release of sequestered antigens

Exposure of normally hidden self-antigens leading to autoimmune activation

Examples of sequestered antigens

Nuclear antigens that are normally hidden from immune surveillance

Molecular mimicry

Foreign antigens resemble self-antigens and trigger an autoimmune response

Common triggers for molecular mimicry

Bacterial or viral infections that share antigenic similarity with self-proteins

Polyclonal B-cell activation

Nonspecific activation of multiple B cells due to immune regulatory defects

Effect of polyclonal B-cell activation

Increased production of autoantibodies

Autoantibodies

Antibodies directed against self-antigens

Autoreactive immune cells

T or B lymphocytes that recognize and attack self-antigens

Environmental contribution to autoimmunity

Infections and environmental exposures may trigger disease in genetically susceptible individuals

Immune regulation failure

Loss of normal control mechanisms that suppress autoreactive lymphocytes

Autoimmune disease heterogeneity

Autoimmune diseases vary in organs affected, antibodies produced, and clinical severity

Clinical relevance of autoimmune mechanisms

Understanding mechanisms aids diagnosis, testing interpretation, and disease management