Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clearance of the neurotropic JHM strain of mouse hepatitis virus from the central nervous system was examined by the transfer of spleen cells from immunized donors. A T cell with the surface phenotype of Thy1.2+ CD4+ CD8- asialo-GM1+ Mac-1- was found to be necessary for viral clearance. The surface phenotype and adherence to nylon wool suggest that these cells are activated helper-inducer T cells. Adoptive transfer to congenic histocompatibility strains demonstrated the necessity for compatibility at the D locus of the major histocompatibility complex. The expression of the CD4 surface marker and the requirement for major histocompatibility complex class I were further studied by the transfer of cells to recipients treated with anti-CD4 or anti-CD8 monoclonal antibodies. Treatment of recipients with either the anti-CD8 or the anti-CD4 antibodies inhibited virus clearance from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system by CD8+ cells that recognize viral antigen in the context of the H-2Db gene product.
 ...
PMID:T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system. 254 13

Infection of the central nervous system by mouse hepatitis virus strain A59, a murine neurotropic coronavirus, induces class I major histocompatibility complex antigens on mouse oligodendrocytes and astrocytes, cells that do not normally express these antigens on their surfaces. This induction, which occurs through soluble factors elaborated by infected glial cells, potentially allows immunocytes to interact with the glial cells and may play a critical role in the pathogenesis of virus-induced, immune-mediated demyelination in the central nervous system.
 ...
PMID:Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes. 301 Apr 60

Using antibodies directed to beta 2-microglobulin (b2-m) and HLADR antigens, the expression of MHC products by normal and abnormal bile ducts in 90 paraffin-embedded biopsies showing various liver diseases, was studied. Normal and abnormal bile ducts constantly expressed b2-m. Increased b2-m expression was found in 17/19 PBC, and 4/7 chronic aggressive hepatitis or cirrhosis of viral etiology with hepatitic bile duct lesions. Normal bile ducts failed to express HLADR antigens. Aberrant HLADR display was found in 24/26 PBC and 10/16 chronic aggressive hepatitis or cirrhosis of viral etiology with hepatitic bile duct lesions. It is concluded that the pattern of the major histocompatibility complex (MHC) display does not discriminate between PBC and hepatitic bile duct lesions. Enhanced expression of class I MHC products at the surface of medium-sized bile ducts in PBC may render these structures more susceptible to lysis by cytotoxic T-cells, whereas its significance in chronic aggressive hepatitis or cirrhosis remains unknown. Aberrant expression of HLADR antigens by abnormal bile ducts in PBC and chronic aggressive hepatitis or cirrhosis of viral etiology is probably induced by gamma-interferon, liberated by intra-epithelial lymphocytes, and may serve to enhance the immune response, either by attracting HLADR-restricted cytotoxic T-cells or by the presentation of non-self antigens at the surface of bile duct epithelium.
 ...
PMID:Expression of MHC products by normal and abnormal bile duct epithelium. 354 67

Murine F9 and PCC4 teratoma cells do not express H-2 major transplantation antigens according to virus-specific T-lymphocyte cytotoxic or serological assays. However, such cells can be infected with and readily replicate many types of viruses (coxsackie B 3, mouse hepatitis, Sindbis, Semliki Forest [SFV], lymphocytic choriomeningitis, Pichinde, vesicular stomatitis, herpes simplex type 1) to the same extent as do murine F12 teratoma cells and mouse embryo fibroblasts, all of which express the H-2 determinants. In contrast, F9 and PCC4 cells are not productively infected with murine cytomegalovirus, whereas F12 and mouse embryo fibroblast cells are. In addition to replicating in H-2-negative murine teratoma cells, SFV replicates in H-2-negative murine lymphoblastoid cells. The ability of SFV to infect cells without H-2 antigens and then to effect viral antigenic expression in the cells' cytoplasm and on their surface with similar kinetics and in equivalent amounts as cells with H-2 antigens indicates that the H-2 receptor is not needed for SFV infection. Daudi cells, which lack HLA antigens, block the replication of SFV. This occurs at some point after receptor binding, as demonstrated by diminished viral mRNA. In addition, a possible membrane defect precludes viral exit in Daudi cells transfected with SFV infectious RNA. These results indicate that a cell's possession of H-2 antigens is not a requirement for SFV infection and that major histocompatibility complex antigens are not specific receptors for this virus.
 ...
PMID:Does the major histocompatibility complex serve as a specific receptor for Semliki Forest virus? 737 8

Cellular immune responses to hepatitis B virus (HBV) play an important role in the resolution of acute infection. They also influence the course of chronic infection and disease but are inadequate to completely clear the infection. Woodchuck hepatitis virus (WHV) infection of the woodchuck can provide a model to study these processes. Lymphocyte responses of woodchucks were assessed by in vitro proliferation and/or interleukin (IL)-2 assays using mitogen (Concanavalin A [ConA]), cytokine (IL-2), superantigen (Staphylococcus aureus enterotoxin B [SEB]), major histocompatibility complex (MHC) allo-antigen (mixed lymphocyte reaction [MLR]), and viral antigens (woodchuck hepatitis virus core antigen [WHcAg] and woodchuck hepatitis virus surface antigen [WHsAg]). ConA-stimulated woodchuck lymphocytes underwent cell division based on cell counting experiments and produced IL-2 as detected using an IL-2-dependent murine cell line but failed to incorporate sufficient tritiated thymidine; however, they did incorporate sufficient tritiated adenosine and deoxyadenosine to permit development of a meaningful proliferation assay. The IL-2 assay was sensitive and specific for detection of woodchuck IL-2 induced by mitogen, superantigen, and MLR, as shown by quantitative titration analysis and anti-body neutralization of ConA-supernatant activity. Cyclosporin A and FK506 specifically inhibited ConA- and SEB-induced IL-2 production by woodchuck lymphocytes. Positive two-way MLRs were detected by IL-2 production and proliferation assay between woodchucks from different geographic regions, thus indicating divergence among MHC molecules; however, occasional negative MLR reactions among indigenous pairs of woodchucks indicated that some woodchucks were mutually immunocompatible to some degree. The radioadenosine proliferation assay was sensitive for detecting peripheral blood lymphocyte responses to WHcAg and WHsAg in adult woodchucks with recently resolved acute infections. The above systems should facilitate the design of adoptive therapy and liver transplantation experiments in the woodchuck, and also enable modeling of immune responses that promote and maintain chronic hepadnavirus infection.
 ...
PMID:In vitro activation of woodchuck lymphocytes measured by radiopurine incorporation and interleukin-2 production: implications for modeling immunity and therapy in hepatitis B virus infection. 754 55

Nonobese diabetic (NOD) mice and beta 2-microglobulin-gene-ablated mice (beta 2M -/-) show impaired presentation of major histocompatibility complex (MHC) class I and self-peptides, structures now recognized as critical for T-cell education to endogenous peptides. The naturally occurring NOD class I presentation abnormality appears to be attributable to, in part, a quantitative defect in the production of Tap-1 mRNA; Tap-1 with Tap-2 normally functions as a transporter for stable self-peptide and class I assembly. This study attempts to reverse NOD and beta 2-M -/- mouse autoreactivity by introduced or reestablished syngeneic class I presentation. Introduction of MHC class I and self-peptides on syngeneic MHC class I-matched cells specifically prevented diabetes in NOD mice and eliminated in vitro class I-directed T-cell autoreactivity in NOD and beta 2M -/- mice. Reestablishment of endogenous class I and self-peptide presentation in NOD mice was achieved with two well-described cures for the NOD mouse, complete Freund's adjuvant and mouse hepatitis virus. Both treatments induced Tap-1 mRNA, reestablished class I presentation of endogenous antigens, and eliminated in vitro and in vivo T-cell autoreactivity of self-peptides in the class I groove. These results substantiate a therapeutic role of self-peptide complexed with class I for T-cell education and suggest that some well-described NOD treatments may work, in part, through reestablishment of tolerance through class I and self-peptide.
 ...
PMID:Elimination of self-peptide major histocompatibility complex class I reactivity in NOD and beta 2-microglobulin-negative mice. 765 37

Neurotropic strains of mouse hepatitis virus (MHV) have been used extensively for the study of viral pathogenesis in the central nervous system (CNS), serving as models for human neurological diseases such as multiple sclerosis (MS). MHV strains A59 and JHMV both cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. In acute disease, CNS damage is most likely the result of lytic infection in neurons and oligodendrocytes, and death can be prevented by the adoptive transfer of Class I-restricted CD8+ T cells. However, in later stages of the disease induced by some MHV strains, virus tends to be restricted to astrocytes in a nonlytic infection, and the immune response appears to contribute to CNS damage. These data lead us to suggest that the astrocyte may play a central role in the neuropathogenesis of MHV infection. Consistent with this possibility, A59 has been reported to induce the expression of Class I molecules of the major histocompatibility complex (MHC) in glial cells following infection in vivo and in vitro. In this communication, we have examined the influence of persistent infection by both A59 and JHMV on MHC Class I expression in primary murine astrocytes. Persistence was characterized by the presence of intracellular viral antigen and mRNA in the absence of detectable infectious virus particles. Under these conditions, JHMV, but not A59, inhibited constitutive expression of the H-2 Kb molecule, with the magnitude of inhibition increasing with postinfection time. A59 was not able to induce Class I during persistence, presumably due to the lack of infectious virus particles. Class I expression was restored by the addition of gamma-interferon (IFN-gamma) to astrocytes persistently infected with either A59 or JHMV. Thus, Class I inhibition is not a permanent consequence of JHMV persistence, and persistence does not interfere with normal signalling pathways for Class I induction.
 ...
PMID:Effect of persistent mouse hepatitis virus infection on MHC class I expression in murine astrocytes. 771 17

Coronavirus-induced acute hepatitis is a complex event and the role of different components of the immune system with regard to defined viral proteins and the course of the infection is not yet clear. We have analysed the cytotoxic T-lymphocyte (CTL) response in mouse hepatitis virus (MHV-A59) infection. Surprisingly, we detected only a very clear virus-specific major histocompatibility complex (MHC) class II-restricted cytotoxicity in mice infected with MHV-A59. We found no evidence of activation of the classical CD8+ MHC class I-restricted CTL. The virus-specific CD4+ CTL derived from two different mouse strains having different MHC haplotypes recognized the same immunodominant epitope. This epitope, comprising the amino acid residues 329-343 of the viral S-glycoprotein, was recognized both at the polyclonal level and by virus-specific CTL clones. Transfer studies using a MHV-A59-specific CD4+ CTL clone showed significant protection against a lethal challenge with MHV-A59, implicating that these CD4+ CTL play a pivotal role in the protection against MHV-A59 infections.
 ...
PMID:Predominance of MHC class II-restricted CD4+ cytotoxic T cells against mouse hepatitis virus A59. 779 24

Induction of immune coagulants has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3)-induced fulminant hepatic necrosis. Previous work from our laboratory has shown that the induction of procoagulant activity (PCA) correlates with the resistance/susceptibility to disease in inbred and recombinant inbred (RI) strains of mice. Macrophages from susceptible, but not resistant, strains of mice expressed increased levels of PCA in response to MHV-3 stimulation. T lymphocytes, however, had a marked regulatory role in the final expression of macrophage PCA. CD3+ CD4+ CD8- lymphocytes from RI H-2 compatible susceptible mice were able to instruct macrophages from susceptible mice to express significantly augmented levels of PCA, whereas CD3+ lymphocytes from RI H-2 compatible MHV-3-immunized resistant mice were able to suppress induction of PCA. In this present study, T-cell lines were derived from draining popliteal lymph nodes from resistant A/J mice, which had been immunized with MHV-3. All T-cell lines showed marked proliferation to MHV-3 and MHV-JHM which was major histocompatibility complex (MHC) restricted. All cell lines were CD3+, four of these were CD4+ and one was CD8+. All of the CD4+ cell lines produced IL-2 and two produced interferon-gamma (IFN-gamma), consistent with the Th1 cytokine profile. One cell line (3E9.1) was able to inhibit the induction of macrophage PCA through production of a soluble factor although cell-to-cell contact could not be excluded. This CD4+ T-cell line conferred protection to infected and susceptible AXB8 mice. These results demonstrate that the existence of a Th1 subpopulation of cells with a regulatory effect on macrophage PCA induction in MHV-3-infected mice contributes to the resistance of the A/J strain of mice to MHV-3 infection.
 ...
PMID:A Th1 cell line (3E9.1) from resistant A/J mice inhibits induction of macrophage procoagulant activity in vitro and protects against MHV-3 mortality in vivo. 783 59

In certain subjects medicinal drugs or toxic agents may induce organ-specific or systemic diseases. The mechanisms of this induction vary according to the type of toxic agent involved. The modification of autoantigens by a toxic agent might be the cause of autoimmune disorders. Thus, certain drugs metabolized by enzymes are known to bind on these enzymes in a covalent manner, thereby making the enzyme immunogenic. The immune reaction thus induced could be responsible for hepatitis. If the modified autoantigen is a molecule, such as the class II molecules of the major histocompatibility complex, which plays an important role in communication between the immune system cells, the autoimmune reaction could result in polyclonal lymphocyte B activation and in a lupus-like autoimmune disease. It is also possible that a drug interferes with one of the element which control the advent of autoreactive T cells and in this way becomes responsible for autoimmune systemic manifestations.
 ...
PMID:[Autoimmunity and toxic agents]. 817 65


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