Paper I
Question
Mechanisms of autoimmune disease
Answer
Mechanisms of autoimmune disease — breakdown of self-tolerance allowing the immune system to attack the body’s own tissues:
- Failure of central/peripheral tolerance — defective clonal deletion of self-reactive T/B cells, or failure of peripheral control mechanisms (anergy, Treg suppression).
- Molecular mimicry — structural similarity between a microbial antigen and a self-antigen leads to cross-reactive immune responses against self-tissue following infection (e.g., rheumatic fever).
- Release of sequestered (hidden) self-antigens — antigens normally hidden from the immune system are released into circulation following trauma/infection, triggering a response.
- Polyclonal B-cell activation — certain infections/superantigens non-specifically activate B cells, including autoreactive clones.
- Genetic susceptibility — association with particular HLA alleles and immune-regulatory gene polymorphisms.
- Defective regulatory T-cell function — reduced Treg number/function fails to suppress autoreactive effector lymphocytes.
- Epitope spreading — an initially restricted response against one self-epitope broadens over time.
- Environmental/hormonal factors — infection, UV light, and drugs can precipitate disease in genetically susceptible individuals; female preponderance suggests hormonal influence.