Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental allergic encephalomyelitis is characterized by invasion of lymphocytes and macrophages into the central nervous system resulting in inflammation, edema, and demyelination. Sera from Lewis rats from 7-95 days after immunization with purified guinea pig CNS myelin were examined with respect to their ability to opsonize myelin. This was correlated with the appearance of antibody components and the relative amounts of antibody to myelin basic protein (MBP) and proteolipid protein (PLP). Sera from rats 10-95 days after immunization preincubated with purified myelin induced phagocytosis of myelin by cultured macrophages with the resulting production of cholesterol ester. This opsonization activity as measured by the percentage of cholesterol esterified reached a peak at 26-27 days after immunization but remained significantly elevated up to 95 days post-immunization compared to the activity of serum from the Freund's adjuvant-injected controls. Immunoblots of the sera revealed a gradual increase in antibody activity against myelin components. ELISA assays for MBP and PLP antibody showed a similar pattern. Antibody to galactocerebroside (GC) was not detected by immunostains nor by the ELISA assay. Areas of demyelination were observed histologically by luxol-fast blue stained spinal cords up to 60 days post-immunization. These results indicate that antibodies to myelin protein when given access to myelin through or within the blood brain barrier could initiate or enhance the phagocytic response by peripheral or resident macrophages.
 ...
PMID:Induction of anti-myelin antibodies in EAE and their possible role in demyelination. 178 38

The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination.
 ...
PMID:The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection. 226 Jun 33

Clinical, histologic, and ultrastructural characteristics of acute experimental allergic encephalomyelitis (EAE) induced by sensitization with a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 139-151 HCLGKWLGHPDKF were studied in SJL/J mice. Groups of mice were immunized with 20, 50, or 100 nmol of the peptide and were killed from seven to 28 days after sensitization or when they were moribund. Beginning on Day 9, the mice showed signs of EAE and the disease progressed rapidly to paralysis. Central nervous system (CNS) inflammation, edema, gliosis, and demyelination were found in all mice killed between Days 10 and 28 and white matter lesion areas correlated with clinical score at the time the mice were killed. Peripheral nerve roots and the cauda equina did not have lesions. Within the range studied, the severity of clinical or histologic disease was the same regardless of the PLP peptide dose. Two of ten mice immunized with 100 nmol and none of 14 mice given smaller doses of a synthetic peptide of mouse myelin basic protein (MBP) showed clinical EAE. These mice had small numbers of CNS lesions that were indistinguishable from those in PLP peptide-sensitized mice. These findings demonstrate that immunization of SJL/J mice with PLP peptide 139-151 produces a disease with the clinical and morphologic features of CNS tissue-, whole PLP-, whole MBP-, and MBP peptide-induced acute EAE. Thus, PLP is a major encephalitogen and immune reactions to epitopes of different myelin proteins may induce identical patterns of injury in the CNS.
 ...
PMID:Acute experimental allergic encephalomyelitis in SJL/J mice induced by a synthetic peptide of myelin proteolipid protein. 227 4

T-cell clones have been isolated from SJL/J mice after immunization with myelin proteolipid protein (PLP). The cloned cells responded strongly to PLP stimulation in vitro as well as to the synthetic PLP-related peptide 139-151. The response to PLP is Ia mediated, since it was inhibited by monoclonal antibodies to the matched I-As haplotype, but not with antibodies to other I-A haplotypes. Phenotypic analysis using immunofluorescence demonstrated the following characteristics of the clones: Thy-1+, CD4+, CD5+ and CD8-. Injection of 10-30 million PLP-activated cells from one clone induced severe experimental allergic encephalomyelitis in five mice, both clinically and histologically. This represents to our knowledge the first report of PLP-specific encephalitogenic cloned T cells.
 ...
PMID:The development and characterization of encephalitogenic cloned T cells specific for myelin proteolipid protein. 229 82

Intravenous administration of neuroantigen-coupled syngeneic splenocytes is an efficient regimen for Ag-specific regulation of relapsing experimental autoimmune encephalomyelitis (R-EAE) at the effector level of the disease process. Treatment of SJL/J mice with splenocytes coupled with mouse spinal cord homogenate (MSCH) or myelin proteolipid protein after immunization with mouse spinal cord homogenate in CFA, but before the onset of clinical signs specifically inhibited the expression of neuroantigen-specific delayed-type hypersensitivity responses and significantly suppressed the onset, severity, and the duration of clinical and histologic signs of R-EAE. In contrast, the clinical course of R-EAE was not affected by tolerization with myelin basic protein-coupled splenocytes, indicating that proteolipid protein-specific responses play the major role in active MSCH-induced R-EAE. To ensure a physical and temporal separation between the inductive and effector stages of the disease process, we also examined the effects of neuroantigen-coupled splenocytes on adoptive R-EAE. Treatment of recipient mice with MSCH-coupled splenocytes up to 6 days after the transfer of MBP-primed lymph node cells induced a dose-dependent, profound, and long-lasting inhibition of clinical and histologic signs of adoptive R-EAE. The demonstration that splenocytes coupled with a heterogeneous mixture of neuroantigens (i.e., MSCH) can inhibit established immune responses suggests that this methodology has potential for regulating ongoing immune responses associated with autoimmune disorders or chronic graft rejection in which the specific (auto)Ag has yet to be identified.
 ...
PMID:Regulation of the effector stages of experimental autoimmune encephalomyelitis via neuroantigen-specific tolerance induction. 235 69

A chronic experimental allergic encephalomyelitis (EAE) was produced in Hartley guinea pigs with bovine white matter proteolipid protein (PLP), in which the levels of myelin basic protein (MBP) and galactocerebroside (GC) were less than 0.014% and 0.13%, respectively, by our method of purification. Cells of an MBP-specific T-cell line did not proliferate in the presence of 100 micrograms of PLP and antigen-presenting cells. Eleven animals were sensitized with 250 micrograms of PLP in Freund's complete adjuvant. Three guinea pigs developed paraplegia about 45 days after sensitization. Histological examination of the three animals revealed marked demyelinating lesions in the spinal cord, particularly in the dorsal columns and subpial regions of the lateral and anterior columns. Another guinea pig without apparent clinical symptoms had demyelinating plaques in the dorsal columns of the spinal cord and periventricular white matter of the brain. Antibodies to PLP were highly elevated in the animals with demyelinating plaques but antibodies to MBP and GC were not elevated in the serum samples. Skin response to PLP was positive in sensitized animals, but was not related to the clinical state. Since none of four strain 13 guinea pigs developed chronic EAE, it seems to be strain specific. These results suggest that PLP is encephalitogenic and produces demyelination in the central nervous system without contamination by MBP or GC in Hartley guinea pigs.
 ...
PMID:Chronic experimental allergic encephalomyelitis in guinea pigs induced by proteolipid protein. 240 37

Following intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV), susceptible mouse strains develop a chronic demyelinating disease characterized by mononuclear cell-rich infiltrates in the central nervous system. Current evidence strongly supports an immune-mediated basis for myelin breakdown, with an effector role proposed for TMEV-specific, major histocompatibility class II-restricted delayed-type hypersensitivity, which temporally correlates with disease onset and remains chronically elevated in susceptible mice. This study examined the fine specificity of class II-restricted T cell responses in TMEV-infected mice to better define the relevant virus-encoded T cell determinant(s) responsible for triggering the demyelinating process, and to determine if class II-restricted neuroantigen-specific autoimmune responses could be detected in mice with TMEV-induced demyelination. The data clearly show that T cell responses in TMEV-infected mice are directed against determinants shared by closely related TMEV strains and are cross-reactive with related picornaviruses, such as encephalomyocarditis virus. In contrast, class II-restricted autoimmune responses against syngeneic mouse spinal cord homogenate and the two major protein components of myelin, myelin basic protein and proteolipid protein, are not demonstrable in susceptible SJL/J mice undergoing chronic TMEV-induced demyelinating disease, but are readily seen in SJL/J mice displaying chronic, relapsing experimental allergic encephalomyelitis. Cross-reactivity (or lack thereof), as determined by functional T cell analyses, was found to correlate with the extent of exact amino acid homology between the TMEV capsid proteins, the two neuroantigens, and related picornaviruses. The data thus do not support a major role for autoimmune responses against myelin proteins in TMEV-induced demyelinating disease, but are consistent with our previously proposed hypothesis that TMEV-specific T cell responses constitute a major effector mechanism of myelin breakdown.
 ...
PMID:Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. I. Cross-specificity among TMEV substrains and related picornaviruses, but not myelin proteins. 243 27

T cells were directly cloned from autopsied MS brain plaque tissue and reactivity was measured with the major encephalitogenic neuroantigens, myelin basic protein (MBP), and proteolipid protein (PLP). Control clones were simultaneously derived from the blood. The proportion of T4+ and T8+ T cell clones from the brain tissue differed from that of peripheral blood T cell clones derived at the same time, suggesting that the clones were not derived from the peripheral blood. None of 57 brain-derived T cell clones proliferated to either MBP or PLP, although they responded well to PHA and IL 2. An additional 235 clones derived from the cerebrospinal fluid and 126 clones from the peripheral blood of other subjects with multiple sclerosis also did not proliferate to MBP or PLP. In contrast, five of nine T4+ clones from the CSF of a subject with postinfectious encephalomyelitis exhibited low but clear reactivity to human MBP, supporting the possible role of MBP as the target antigen in this disease. These studies, the first to clone T cells directly from MS plaque tissue, suggest that the lack of consistent T cell reactivity to MBP or PLP in the peripheral blood of MS patients does not appear to be secondary to the sequestration of a large number of these cells in the brain.
 ...
PMID:Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis. 243 52

The geographic distribution of multiple sclerosis (MS) may relate to the age of initial exposure and degree of sensitization to common viruses or bacteria which have proteins with epitopes (antigenic determinants) which are homologous with potentially encephalitogenic peptides in central myelin proteins, such as basic protein and proteolipid protein. Comparable homologies may exist for the as-yet-undefined nonencephalitogenic myelin antigen(s) which evoke demyelinating factors (probably complement-fixing antibodies). Many of these homologous epitopes occur in microorganisms that also possess adjuvant activity for evoking not only the sensitized T-cells but also the antibodies that cross-react with the target antigens in central myelin. If sufficient sensitization to myelin basic protein or proteolipid protein occurs, especially in infections of young adults, the individual develops acute disseminated encephalomyelitis, exactly comparable to ordinary acute experimental allergic encephalomyelitis (EAE). If very young children are infected, however, practically complete resistance develops, and neither acute disseminated encephalomyelitis nor MS follows. In between these two extremes, especially in slightly older children in whom insufficient sensitization occurs to induce acute disseminated encephalomyelitis, the individual may become resistant to acute disseminated encephalomyelitis, but susceptible to chronic relapsing or progressive disseminated encephalomyelitis, otherwise generally recognized as MS. This is exactly comparable to a recently described variant of chronic EAE in which demyelinating antibodies and large subpial plaques of demyelination occur. The similarity of this form of chronic EAE or chronic disseminated encephalomyelitis to one form of MS is emphasized.
 ...
PMID:The multiple causes of multiple sclerosis: the importance of age of infections in childhood. 276 88

Relapsing experimental allergic encephalomyelitis (R-EAE) in SJL/J mice was examined in relation to the development of neuroantigen-specific T cell proliferative (Tprlf) and delayed-type hypersensitivity (DTH) responses. R-EAE was induced by injecting syngeneic mouse spinal cord homogenate in CFA on days 0 and 7 over the shaved flanks of female SJL/J mice. Mice primed in this manner exhibited significant Tprlf and DTH responses specific for both major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP). A time course comparison between the induction of R-EAE and the development of neuroantigen-specific cell-mediated immune (CMI) responses (Tprlf and DTH) revealed that the MBP- and PLP-specific Tprlf and DTH responses peaked prior to the onset of initial clinical symptoms and the DTH responses remained at significant levels throughout the relapsing course of the disease. Monoclonal antibodies were used to determine whether in vivo inhibition of class II-restricted Tprlf and DTH responses correlated with inhibition of R-EAE. In vivo administration of a total of 100 micrograms anti-L3T4 antibody, but not anti-Lyt-2 antibody, resulted in delayed onset and reduced severity of clinical signs of R-EAE concomitant with significantly reduced levels of MBP- and PLP-specific Tprlf and DTH responses. Treatment with a total of 300 micrograms of purified anti-L3T4 resulted in total abrogation of R-EAE induction and neuroantigen-specific CMI. Thus, clinical signs of R-EAE were found to correlate with the activity of neuroantigen-specific, class II-restricted T cells.
 ...
PMID:Monoclonal antibody-induced inhibition of relapsing EAE in SJL/J mice correlates with inhibition of neuroantigen-specific cell-mediated immune responses. 244 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>