Abstract
Autoimmune diseases arise when immune tolerance fails, and self-reactive immune responses become sustained against the body’s own tissues. Although these disorders differ in clinical presentation, target organs, and disease course, current evidence suggests that they develop through the interaction of genetic susceptibility, environmental exposure, and immune dysregulation rather than a single causal pathway. This narrative review synthesises biomedical literature on the mechanisms underlying autoimmune disease onset and progression. Genetic variation, particularly within the human leukocyte antigen and major histocompatibility complex region, may increase susceptibility by shaping antigen presentation and immune recognition. Environmental factors, including infection, smoking, hormonal influences, psychological stress, and gut microbiome disturbance, may initiate or amplify autoreactive immunity in susceptible individuals. Mechanisms such as molecular mimicry, dysbiosis, chronic inflammation, cytokine signalling, and regulatory T-cell dysfunction help explain how protective immune responses become pathogenic. Understanding autoimmune disease as a dynamic gene–environment–immune interaction has important implications for risk prediction, biologic therapy, antigen-specific immunotherapy, immune profiling, personalised medicine, and future strategies aimed at restoring immune tolerance.
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