Figure 2. Effector mechanisms of anti-AChR Abs.

(A) Ab binding to the AChR activates the complement cascade, resulting in the formation of membrane attack complex (MAC) and localized destruction of the postsynaptic NMJ membrane. This ultimately leads to a simplified, altered morphology of the postsynaptic membrane of the NMJ of MG patients, which lacks the normal deep folds and has a relatively flat surface. (B) Abs cross-link AChR molecules on the NMJ postsynaptic membrane, causing endocytosis of the cross-linked AChR molecules and their degradation (antigenic modulation). This ultimately leads to a reduced number of AChR molecules on the postsynaptic membrane. (C) Ab binding the ACh-binding sites of the AChR causes functional block of the AChR by interfering with binding of ACh released at the NMJ. This results in failure of neuromuscular transmission.