Immune 4


Type IIB Hypersensitivity: Myasthenia Gravis

Myasthenia gravis is an autoimmune disease caused by inhibitory (antagonistic) autoantibodies that bind and block the acetylcholine receptor (AChR), causing muscular weakness and fatigue. The AChR is found at postsinaptic membranes of neuromuscular junctions and binds acetylcholine released from a nerve ending, transiently opening a calcium channel. The signal is terminated by acetylcholine esterase, an enzyme located in the basal lamina between the nerve ending and the postsynaptic membrane. As in mothers with Graves disease, transplacental passage of IgG autoantibodies from mothers with myasthenia gravis can cause transient neonatal myasthenia gravis. Anti-AChR autoantibodies cause disease by down-regulating expression of the receptor and by complement-mediated lysis of the cells bearing the AChR. Intermolecular cross-linking of AChR by the autoantibodies may lead to antigenic modulation.

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