Primary demyelination as a nonspecific consequence of a cell-mediated immune reaction.
Primary demyelination occurs in a variety of human and experimental diseases known to be associated with the presence of inflammatory cells. However, the mechanism of demyelination remains unclear. The possibility that myelin can be damaged as a nonspecific consequence of a specific delayed type of hypersensitivity reaction directed at nonnervous tissue antigens was investigated. Guinea pigs were sensitized to tuberculin with Freund's complete adjuvant, and were challenged in the central and peripheral nervous system either with live or killed sonicated tubercle bacilli, Old Tuberculin, or tuberculin purified protein derivative (PPD). Local inflammatory reactions were invariably produced and primary demyelination was a constant feature of the lesions. The morphological picture was rather similar to that observed in human neurotuberculosis and early tuberculoid leprosy, and in experimental allergic encephalomyelitis and distemper encephalitis in animals. The infiltrates consisted predominantly of mononuclear cells with some polymorphonuclear cells as well. Vesicular disruption of the myelin sheath in the immediate vicinity of the inflammatory cells and stripping of the myelin lamellae by the histiocytes without axonal damage were the leading features of the lesion. The results indicate that cell-mediated immune reactions to a variety of nonbrain antigens could be responsible for a component of the demyelination seen in some inflammatory demyelinating conditions, and suggest that this system may serve as a useful model for studying the immunopathology of demyelinating disease.
D000818:Animals; D001921:Brain / Q000473:pathology; D003391:Cranial Nerves / Q000473:pathology; D003711:Demyelinating Diseases; D006168:Guinea Pigs; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009474:Neurons / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D012584:Sciatic Nerve / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D014374:Tuberculin Test; D014390:Tuberculosis, Meningeal / Q000276:immunology*