6.12 IMMUNO - Myasthenia Gravis

Question 1

Myasthenia Gravis affects what type of muscle only? How does it affect this muscle (where in transmission)? How is this transmisssion decreased?

Answer 1

Weakness of striated muscle.

Impaired neuromuscular transmission.

Antibody specific for ACh receptor => decreased # ACh receptors at neuromuscular jnx.

Question 2

What is the evidence supporting that MG is an autoimmune disease? (in humans)

Answer 2

Antibodies to ACH receptors: in serum, at NMJ.

Plasmapheresis decreases MG severity.

Question 3

What are the 2 common types of antibodies in MG pts? How do antibody levels relate to complement levels? Can pregnant pts. give disease to their baby (why why not)?

Answer 3

Anti-AChR ab = 85-90% of pts.

Anti-AChR negative pts have anti-MuSK (40-50%)

Antibody titer correlates w/ severity: complement levels are inversely related.

Babies of moms with MG may have symptoms: IgG ab are the only ones that cross the placenta.

Question 4

Regarding etiology, what are the genetic factors, how do they vary and correlate with early/ late onset, how are these inherited?

Answer 4

HLA A1, B8, + DR3 (DQ2): early onset, inherited as haplotype (inherited together due to arranged closely on same chrm).

HLA B7 + DR2: late onset (>40)

IL-1B and TNF-a polymorphysms

Question 5

Regarding etiology, what are some exogenous factors for MG?

Answer 5

Bacteria and viruses

Drugs (penicillamine)

Question 6

What are some microorganisms associated with MG, how do they cause this autoimmune disorder?

Answer 6

Microbials: Klebsiella pneumoniae, e. coli, proteus vulgaris, yersina enterocolitica, herpes simplex.

Mechanism: molecular mimicry

Question 7

What is molecular mimicry, how does it happen in MG?

Answer 7

Antigen from virus is processed by APC and presented to CD4+ T-lymphocyte.

If structure of peptide is similar enough to self-peptide (AChR), lymphocyte can react w/ peptides from autologous tissue and induce B-lymphocytes to produce antibodies to ACh receptor.

Question 8

What are the 3 effector mechanisms of anti-AChR antibodies?

Answer 8

1) Complement activation destroys membrane architecture.
2) Cross-linking causes endocytosis of receptors.
3) Antibody binding blocks ACh binding.

Question 9

What is the correlation with the thymus and MG?

Answer 9

Thymus is abnormal in 80-90% of pts:

• Follicular hyperplasia
• Thymoma
• Numerous germinal centers in medulla
• AChR expressing myoid cells
• Mature anti-AChR specific T-cells
• Spontaneous anti-AChR secreting B cells
• Site of activation of B cells???

Question 10

Name a few of the several treatments to decrease the immune response to AChR?

Answer 10

Cholinesterase inhibitors.

Tymectomy (espectially in younger pts)

Plasmapheresis

Corticosteroids

Immunosuppression

Intravenous Ig

Blocking APC presentation

Anti-B cell antibodies

Anti-TNF

TNF-receptor

IL-1R antagonist