Demyelination in the central nervous system following a delayed-type hypersensitivity response to bacillus Calmette-Guérin. 1995

M K Matyszak, and V H Perry
University Department of Pharmacology, University of Oxford, U.K.

We describe here a model of delayed-type hypersensitivity response in the CNS directed against a non-CNS antigen. The results presented in this paper show that bacillus Calmette-Guérin sequestrated behind the blood-brain barrier provokes an immune-mediated assault leading to bystander myelin damage. The delayed-type hypersensitivity response was induced by the intracranial injection of heat-killed bacillus Calmette-Guérin followed by subcutaneous immunization two to six weeks later. A single intracranial injection of bacillus Calmette-Guérin resulted in a rapid myelomonocytic response which persisted for approximately two weeks. By four weeks the inflammatory cells were no longer detected. Serum proteins were also excluded from the CNS parenchyma at this time. However, immunohistochemical staining with anti-bacillus Calmette-Guérin antiserum revealed the presence of bacillus Calmette-Guérin debris at the site of the original intracranial injection, indicating that the inflammatory response failed to clear the mycobacterium fully. Following peripheral sensitization with bacillus Calmette-Guérin in complete Freund's adjuvant, a strong delayed-type hypersensitivity response was detected at the site of bacillus Calmette-Guérin deposits in the CNS. An extensive inflammatory lesion was spread over a large area of the dorsal hippocampus. The lesion was composed predominantly of mononuclear phagocytes and T cells. Staining with anti-myelin basic protein antiserum showed bystander myelin damage. Delayed-type hypersensitivity responses were studied over several months and were still detected in the CNS five months after peripheral immunization.

UI MeSH Term Description Entries
D006967 Hypersensitivity Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. Allergy,Allergic Reaction,Allergic Reactions,Allergies,Hypersensitivities,Reaction, Allergic,Reactions, Allergic
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007278 Injections, Spinal Introduction of therapeutic agents into the spinal region using a needle and syringe. Injections, Intraspinal,Injections, Intrathecal,Intraspinal Injections,Intrathecal Injections,Spinal Injections,Injection, Intraspinal,Injection, Intrathecal,Injection, Spinal,Intraspinal Injection,Intrathecal Injection,Spinal Injection
D008297 Male Males
D001812 Blood-Brain Barrier Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue. Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D002490 Central Nervous System The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D003711 Demyelinating Diseases Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. Clinically Isolated CNS Demyelinating Syndrome,Clinically Isolated Syndrome, CNS Demyelinating,Demyelinating Disorders,Demyelination,Demyelinating Disease,Demyelinating Disorder,Demyelinations
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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