Experimental animals are immunized to protein fragments derived from peripheral nerve myelin. Subsequent analysis finds evidence of a T-cell response as well as production of autoantibodies against nonprotein antigens. This leads to segmental demyelination of peripheral nerves in the animals. The experimentally induced condition is most analogous to which of the following?

Question

Experimental animals are immunized to protein fragments derived from peripheral nerve myelin.  Subsequent analysis finds evidence of a T-cell response as well as production of autoantibodies against nonprotein antigens.  This leads to segmental demyelination of peripheral nerves in the animals.  The experimentally induced condition is most analogous to which of the following?

Quizplus · Accepted Answer

11ec160b_39c0_2e9a_9249_856024db8469_MD0001_00 Demyelination of peripheral nerves in response to immune challenge with a myelin-like substance is a pathogenic mechanism similar to Guillain-Barré syndrome (GBS). GBS is thought to be due to molecular mimicry, in which an infectious agent contains a ganglioside-like substance in its lipopolysaccharide layer. Antibodies formed against this substance and activated T-cells cross-react with the ganglioside components of myelin and Schwann cells. Segmental demyelination and an endoneurial inflammatory infiltrate composed of lymphocytes and macrophages are seen on light microscopy. GBS manifests as ascending, symmetric muscle weakness that often occurs after a gastrointestinal (eg, Campylobacter jejuni) or upper respiratory infection. Deep tendon reflexes are decreased or absent (areflexia), and the paralysis may ascend to the cranial nerves (particularly cranial nerve VII). Paralysis of respiratory muscles is fatal without supportive care. (Choice A) Duchenne muscular dystrophy is an X-linked muscular dystrophy that affects boys and is caused by a frameshift mutation of the dystrophin gene. Clinical features include progressive weakness and a waddling gait with onset in childhood. Muscle biopsy shows degeneration of muscle fibers and replacement with fat and connective tissue; peripheral nerves are not involved. (Choice C) Lambert-Eaton syndrome, often seen as a paraneoplastic syndrome in patients with small cell carcinoma of the lung, presents with weakness that improves with muscular repetition. It is caused by autoantibodies that react with the voltage-gated calcium channels on the presynaptic membrane, hampering the release of acetylcholine. The axons are not affected. (Choice D) Beriberi (thiamine deficiency) is characterized by weakness, areflexia, pain, and paresthesias that are worse in the distal lower limbs. Beriberi can cause demyelination of peripheral nerves; however, unlike Guillain-Barré syndrome, no endoneurial inflammation is present. (Choice E) Subacute combined degeneration occurs due to vitamin B₁₂ deficiency and leads to degeneration of dorsal columns and lateral cerebrospinal tracts. Patients develop distal, progressive weakness and ataxia but the symptoms are slowly progressive (unlike GBS, which progresses rapidly). In addition, subacute combined degeneration is associated with spasticity, paresthesia, and a macrocytic anemia. (Choice F) Werdnig-Hoffman syndrome (spinal muscle atrophy type 1) is due to degeneration of the anterior horn cells that is caused by a mutation in the SMN1 gene. Werdnig-Hoffman syndrome causes symmetric progressive weakness, but the weakness is more prominent proximal>distal and typically occurs in childhood. Educational objective: Guillain-Barré syndrome is an acute, demyelinating polyneuropathy thought to be caused by molecular mimicry. Antibodies formed against infectious agents cross-react with myelin and Schwann cells, leading to immune-mediated demyelination. Light microscopy shows segmental demyelination and an endoneurial inflammatory infiltrate composed of lymphocytes and macrophages.

Experimental Animals Are Immunized to Protein Fragments Derived from Peripheral