摘要:

Recovery from viral infection is a result of very complex interactions between specific and nonspecific immune reactions and the infectious agent. A variety of immune mechanisms are undoubtedly important factors in this event and operate together in overcoming the infectious process. However, despite much available information about these viral defense mechanisms, it has proved remarkably difficult to assign a determinative role in vivo to any single antiviral immunological mechanism in recovery from a single viral disease, particularly since the immune response to the virus itself may frequently contribute to the pathology of the disease. Furthermore, if virus-induced immune responses are also directed against normal host components, this may set the stage for an autoimmune disease. In this context acute measles encephalomyelitis is of interest since in this disease autoimmune reactions against brain antigens have been observed and considered of pathogenetic importance. In this short review, virological and immunological findings of measles virus infections in a rat model in relation to autoimmune reactions will be presented and the mechanisms by which measles virus may alter host reactivity against self-antigens discussed.

ISSN:0300-5526    

DOI:10.1159/000150298

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Studies of myelin basic protein (MBP)-specific T lymphocytes have been extraordinarily informative for several distinct aspects of (neuro) immunology. They indicated for the first time that myelin directed central nervous system (CNS) inflammation is mediated by specific autoaggressive T cells. This provided a conceptual basis for understanding the pathogenesis of anti-myelin autoimmunity in general. We assume at present that human multiple sclerosis (MS) is also caused by myelin-specific autoaggressive T cells, and that these T cells create the inflammatory changes typical for the generation of a mature demyelinating plaque. Large scale demyelination seems, however, not to be caused by purely cellular mechanisms. Second, studies using MBP-specific T-cell lines have critically contributed to elucidating the immune status of the CNS. They showed that the CNS is not completely secluded from the circulating immune cells. Activated, though not resting lymphocytes can pass through the endothelial blood-brain barrier and migrate through the brain tissues. There, in the CNS, some glia components, microglia and astrocytes can be induced by T-cell cytokines to act as efficient antigen-presenting cells. Thus, the CNS is subject to immune surveillance, though to a specialized, adapted variant thereof. Finally, studies using MBP-specific T cells established for the first time the presence of potentially autoaggressive T cells within the normal immune repertoire. This implies counterregulatory regulation required to keep the autoreactive T cells in a safe state of rest. Most recently, the analysis of the intrathymic anti-MBP T-cell repertoire may change our views on the generation of myelin-specific self tolerance. There is now the possibility that this is by no means based on ‘ignorance’ of a sequestered brain autoantigen, but also depends on intrathymic select

ISSN:0300-5526    

DOI:10.1159/000150299

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Human foamy virus (HFV) is a member of the retroviral family of Spumaretrovirinae. In addition to the three retroviral structural genes, gag, pol and env, HFV also contains regulatory sequences, called bel. Foamy viruses have been previously associated with human thyroid disease, notably DeQuervain’s thyroiditis. In indirect immunofluorescence tests we have demonstrated the reactivity of the thyroid glands of 7/7 patients with Graves’ disease and antibodies to HFV gag proteins. No reactivity was observed with antibodies to pol, env and bel proteins. Nine thyroids of patients with struma parenchymatosa, 4 with follicular carcinoma and 2 normal thyroids were negative throughout. From the thyroids of 5 patients with Hashimoto’s disease, 4 were negative and 1 showed a single small focus of anti-gag antibody reactivity. The uniform immunofluorescent staining was restricted to the basal and lateral intercellular areas between the thyroid epithelial cells. Extension of these studies to the retrobulbar tissue of 1 Graves’ disease patient with malignant exophthalmus revealed positive staining with anti-gag antibodies of fibroblasts and fat cells but not eye muscles. Furthermore, we were successful in establishing several T-cell lines derived from the retrobulbar tissue of this patient. They were CD8+ and proliferated, in contrast to peripheral blood cells, upon cocultivation with autologous retroorbital fibroblasts. It remains to be determined whether these observations are of relevance in the pathogenesis of Graves

ISSN:0300-5526    

DOI:10.1159/000150300

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Autoimmune hepatitis is characterized by hypergammaglobulinemia, female predominance, autoantibodies and a good response to immunosuppression, and is based on specific autoantibodies and clinical characteristics. Several subgroups may be distinguished. As in most autoimmune diseases, the etiology is unknown. The asssociation of autoimmune hepatitis with a viral etiology is most prominent in autoimmune hepatitis type 2 which is characterized by liver/kidney microsomal (LKM-1) autoantibodies against cytochrome P-450 II D6. Depending on the geographical origin of the patients, a specific proportion of patients with autoimmune hepatitis type 2 is associated with hepatitis C virus infection. These HCV RNA-positive patients are older, female predominance is not profound, and response to immunosuppression is generally low compared to the HCV-negative patients with autoimmune hepatitis type 2. The genetic background is unclear. HCV sequence analysis revealed that HCV genotype II is prominent in HCV-positive autoimmune hepatitis type 2. HCV mutants with deletions in the HCV envelope region were identified. The relevance of these HCV mutants for the induction of autoimmunity needs to be characterized further. The HCV-negative population of patients with autoimmune hepatitis type 2 seems to have a relation with herpes simplex virus (HSV-1) infection since the B-cell epitope of cytochrome P-450II D6, the major LKM-1 antigen, shares sequence homology with the IE-175 protein of HSV-1. In the HCV-negative population of autoimmune hepatitis type 2, HLA-DR3 and C4-AQ0 alleles are significantly increased.

ISSN:0300-5526    

DOI:10.1159/000150301

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Viral persistence depends on a virus having a non-lytic strategy of replication and the ability to escape immune surveillance. Cells of the immune system (lymphocytes/monocytes/macrophages) and central nervous system (neurons) are most often infected by DNA and RNA viruses that persist. Cytotoxic T lymphocytes (CTL) are the primary host defense that aborts or prevents viral persistence. Viral interaction with these specialized cells and of such infected cells with CTL is explored in this paper.

ISSN:0300-5526    

DOI:10.1159/000150302

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

It has been assumed for many years that liver damage associated with hepatitis B virus (HBV) infection is due to cytolytic immune reactions directed at viral antigens expressed on infected liver cells. Recent studies, however, suggest that in some clinical settings, changes in the HBV genome, possibly selected by immune pressure, can interfere with the export of viral proteins from hepatocytes and lead to direct virus-induced liver damage.

ISSN:0300-5526    

DOI:10.1159/000150303

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Immunopathologic mechanisms leading to liver tissue injury in hepatitis caused by hepatitis A virus (HAV) were studied in an autologous in vitro model. Data show virus-specific killing by liver-infiltrating T lymphocytes in man and support the hypothesis that hepatocellular damage as well as efficient elimination of virus-infected hepatocytes is mediated by HLA-restricted, HAV-specific CD8+ T lymphocytes. Furthermore, experimental results demonstrate that human interferon-γ produced by HAV-specific T cells may act as a key factor in T-cell-promoted clearance of HAV-infected hepatocytes. Besides the well-known hepatotropism, the myelotropic properties of HAV have some important clinical implications. Perturbations of hematopoietic regulation, ranging from transient granulocytopenia to rare cases of bone marrow failure, are associated with HAV infection. In an attempt to elucidate the pathogenetic mechanisms, we could show a direct suppressive effect of HAV on human bone marrow progenitors and a significant progressive decline in these cells in HAV-infected long-term bone marrow cultures

ISSN:0300-5526    

DOI:10.1159/000150304

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In situ hybridization studies have proved that myocardial enterovirus infections are detectable in all stages of acute and chronic enterovirus-induced myocarditis as well as in some patients with end-stage dilated cardiomyopathy, suggesting the possibility of myocardial enterovirus persistence. Possible enterovirus persistence in the human heart is supported by the discovery of enterovirus persistence in different murine models of chronic myocarditis, demonstrating that coxsackievirus B3, typically a cytolytic enterovirus, is capable of evading immunological surveillance in a host-dependent fashion. Progress is currently being made in unraveling the molecular mechanisms of enterovirus persistence, the diversity of host and virus genetics and their impact on the nature and severity of the disease. Apart from providing an etiologic diagnosis, there are therapeutic implications from the in situ demonstration of myocardial enterovirus infection. Evaluation of specific antiviral agents, for example interferons, may lead to the development of new therapeutic strategies capable of providing protection against myocardial enterovirus infection.

ISSN:0300-5526    

DOI:10.1159/000150305

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Neuroinvasiveness, the capacity of virus to enter and progress through the nervous system, may be accomplished by hematogenous or neural routes. We have been interested in defining HSV-1 genes specifically concerned with the neural pathway. In one system (involving HSV strain Ang), we have found that a single amino acid change in glycoprotein D, a viral membrane protein, confers invasiveness upon a noninvasive agent. Preliminary studies of another noninvasive agent, KOS, suggest that at least 2 genes are related to the phenotype. Experiments which establish specificity for the noninvasive phenotype and a discussion of the potential mechanisms involved in the glycoprotein D localization are also discussed.

ISSN:0300-5526    

DOI:10.1159/000150306

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The transmissible agent that causes spongiform encephalopathies such as scrapie, the prion, is believed to be devoid of nucleic acid and identical with PrPSc, a modified form of PrPc. PrPc is a normal host protein encoded by a single copy gene (Prn-p) and is found predominantly on the surface of neurons. PrPSc, in contrast to PrPc, is resistant to protease and accumulates intracellularly. Prusiner proposed that PrPSc, when introduced into a normal host, causes the conversion of PrPc or its precursor into PrPSc (‘protein only’ hypothesis). If indeed PrP is an essential component of the prion, then an animal devoid of the PrP protein should be resistant to scrapie. We generated homozygous PrP ‘knockout’ mice. These Prn-p0/0mice showed no gross abnormalities, and microscopic examination of brain sections of normal and Prn-p0/0 mice revealed no differences. Prn-p0/0, Prn-p+/+and Prn-p0/+mice were inoculated with scrapie agent; the clinical response as well as the prion titer at different time points are being det

ISSN:0300-5526    

DOI:10.1159/000150307

出版商:S. Karger AG    

年代:1993

数据来源: Karger