Which autoimmune mechanism characterizes myasthenia gravis?

• A. Autoantibodies against acetylcholine receptors at the neuromuscular junction
• B. Demyelination of CNS white matter
• C. Degeneration of substantia nigra
• D. Autoimmune attack on myelin in peripheral nerves

Answer: (A)

Myasthenia gravis is an autoimmune attack on the neuromuscular junction, where antibodies target the acetylcholine receptors on the postsynaptic membrane. These antibodies block acetylcholine binding, cause receptor cross-linking and internalization, and activate complement to damage the postsynaptic folds. The result is a reduced number of functional receptors and a diminished end-plate potential, so motor impulses fail to produce a reliable muscle contraction after repeated use. Clinically this leads to fatigable weakness that worsens with activity and improves with rest, commonly presenting with ptosis and diplopia. The thymus often shows abnormalities (hyperplasia or thymoma) linked to autoantibody production. While some patients may have antibodies to other NMJ proteins like MuSK, the classic mechanism is autoantibody-mediated disruption of acetylcholine receptors at the neuromuscular junction. This is distinct from conditions involving central nervous system demyelination, degeneration of the substantia nigra, or autoimmune attack on peripheral myelin, which involve different targets and paths of disease.