Myasthenia gravis: the neuromuscular junction
- Lesion
Antibodies against acetylcholine receptors weaken the muscles of the eyes, face and limbs; weakness worsens with use and improves with rest.
What it is
Myasthenia gravis is an autoimmune disease in which antibodies reduce the number of functional acetylcholine receptors at the neuromuscular junction. Most patients have IgG antibodies to the receptor itself, which block it, cross-link and internalize it, and fix complement that destroys the postsynaptic folds. Others have antibodies to MuSK or LRP4. The thymus is involved: thymic hyperplasia with germinal centres in many young patients, and thymoma in about one in ten. Weakness fluctuates and worsens with repetitive use, affecting extraocular, bulbar, facial and proximal limb muscles; respiratory crisis is the gravest risk.
Structure
- End plate: simplified postsynaptic membrane with fewer, shallower folds and widened synaptic cleft (electron microscopy).
- IgG and complement (membrane attack complex) deposited on the postsynaptic membrane.
- Muscle biopsy is usually near normal; type II atrophy or scattered lymphocytes (lymphorrhages) may be seen.
- Thymus: lymphoid follicles with germinal centres in the medulla, or a thymoma.
Step by step
- Loss of tolerance in the thymus generates T cells and B cells against the acetylcholine receptor.
- IgG antibodies bind the receptor on the postsynaptic membrane.
- Antibodies cross-link and internalize receptors, block acetylcholine binding and activate complement.
- Complement destroys the postsynaptic folds, cutting receptor number further.
- Each nerve impulse releases less effective transmission; with repeated firing, more junctions fail and the muscle weakens.
Clinical notes
- Ptosis and double vision that worsen by evening, improve with rest or an ice pack on the eyelid.
- Myasthenic crisis (respiratory failure) can follow infection, surgery or certain drugs and needs intensive care.
- All patients get chest imaging to look for thymoma.
In the lab
- Serum anti-AChR antibodies; anti-MuSK if negative.
- Repetitive nerve stimulation: decrement; single-fibre EMG: increased jitter.
Test yourself
Think of the answer, then tap the question to see it.
What is the target of the antibodies in most cases of myasthenia gravis?
The nicotinic acetylcholine receptor on the postsynaptic muscle membrane.
Which thymic lesions are linked to myasthenia gravis?
Thymic follicular hyperplasia and thymoma.
How does repetitive nerve stimulation respond in MG?
With a decrement: falling amplitude of successive muscle responses.
Which hypersensitivity type is myasthenia gravis?
Type II, antibody-mediated against a cell-surface receptor.
Elsewhere in DurgiPedia
- Type II hypersensitivity (antibody against cells)
- Autoantibodies: the table to know
- Thymus: where T cells learn
- Neuromuscular junction: motor end plate and acetylcholine receptors
- The neuromuscular junction
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Myasthenia gravis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Myasthenia Gravis | MG | MedlinePlus (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.