摘要:

Epidemiology is frequently neglected in the study of uveitis. Little is known on the incidence and prevalence of this disease. This review presents data on the subject from the literature and from the uveitis clinic at Rotterdam.The distribution of uveitis varies in different parts of the world and these differences might be attributed to geographic, alimentary or genetic factors. The discovery of associations of certain types of uveitis and HLA antigen subclasses provided at least part of an explanation for racial and genetic factors. These associations are dealt with in more detail.

ISSN:0271-3683    

DOI:10.3109/02713689208999505

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Posterior uveitis is thought to be a T-cell mediated disease since active foci of inflammation, identified in eyes enucleated for the complications of intraocular inflammation, are found to be predominantly composed of CD4+ T-cells. Few B-cells and little immunoglobulin are found suggesting that antibody and immune complex deposition do not play a major role in perpetuating the inflammatory process. As ocular biopsy is not a feasible method for monitoring disease activity and response to treatment, parameters of T-cell activation and retinal damage have been studied in the peripheral blood. These have included antibody and T-cell sensitisation to retinal S-antigen, serum soluble IL-2 receptors and IL-2 receptors on activated T-cells. None of these parameters, however, have been found to be useful in the monitoring of ocular disease activity alone or in the prediction of disease relapse.

ISSN:0271-3683    

DOI:10.3109/02713689208999506

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Molecular genetic techniques are being widely applied to the study of autoimmune diseases. Major advances have been made in diabetes, rheumatoid arthritis and coeliac disease. Work on experimental models of autoimmune uveitis suggests that similar advances will follow in this field. The application of molecular genetics to the study of immunology has lead to great advances in our understanding of the anatomy of antigen recognition. This work has lead to the identification of some of the structural determinants of antigen binding by MHC molecules and is helping to explain some MHC-disease associations. More recently, molecular studies of the T cell receptor have characterized patterns of T cell receptor expression in humans and have lead to the identification of regions of the T cell receptor critical for antigen recognition. These techniques will hopefully provide insights into the nature of autoimmunity and permit the identification of targets for disease specific immunotherapies. This review describes attempts to corelate MHC structure and function in the context of autoimmunity and discusses some of the strategies for analyzing T cell receptor usage in autoimmune disease.

ISSN:0271-3683    

DOI:10.3109/02713689208999507

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The blood-retinal barrier (BRB) is believed to play an important part in the pathogenesis of experimental autoimmune uveoretinitis (EAU). Central to the disease process is the recruitment of inflammatory cells from the circulation, a mechanism that is controlled in part by the BRB. As the disease progresses the BRB becomes disrupted first to small and then to large molecular weight tracers. In these two respects EAU shares many similarities with experimental autoimmune encephalomyelitis (EAE) in which there is dysfunction of the blood-brain barrier (BBB). In EAU, however, the differential roles played by the two barrier sites that comprise the BRB are not clear although some evidence would suggest that it is the retinal endothelium that is initially involved. BRB breakdown in EAU has been found to occur concomitantly with lymphocyte infiltration by mechanisms that remain to be elucidated.

ISSN:0271-3683    

DOI:10.3109/02713689208999508

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Experimental autoimmune uveoretinitis (EAU) is a useful model of human posterior uveitis and as such, permits the analysis of strategies for immuno-intervention. Modulation of the autoimmune response may be attempted at the stages of induction of EAU, during homing of autoreactive lymphocytes to the target organ, the retina, or during the effector stage of the disease. This paper presents a brief overview of current immuno-therapeutic modalities and assesses the usefulness for extrapolation to human disease.

ISSN:0271-3683    

DOI:10.3109/02713689208999509

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The normal aqueous humor contains a variety of soluble immunosuppressive factors, including transforming growth factor-beta, alpha-melanocyte stimulating hormone, and vasoactive intestinal peptide. These factors are largely the secretory products of parenchymal cells of the iris and ciliary body. TGFβhas recently been shown to alter the functional capacity of intraocular antigen presenting cells, such that they are capable of inducing Anterior Chamber Associated Immune Deviation (ACAID). This deviant systemic immune response is characterized by an impaired capacity to mount an effective cell-mediated immune attack directed at antigens that are placed in, or arise within, the eye. A second property of immunosuppressive factors in aqueous humor is to suppress directly the expression of delayed hypersensitivity in the anterior chamber. In fact, even when the intraocular microenvironment is disturbed by local instillation of gamma-interferon, making it possible for limited expression of cell-mediated immunity in the eye, the microenvironment of the anterior chamber remains profoundly immunosuppressive. In this latter instance, prostaglandins replace TGFβas the major molecular mediators of suppression in the aqueous humor. In the aggregate, factors present in the normal (or perturbed) intraocular microenvironment have the capacity to modify both the afferent and efferent limbs of the systemic immune response, and this accounts for the longstanding observation that the anterior chamber is an immunologically privileged site. Since evidence suggests that the eye can mobilizemore than onemolecular mechanism in its effort to limit the sightdestroying potential of immunogenic inflammation, we believe that elucidation of intraocular cytokines and factors that create and maintain an immunosuppressive microenvironment will contribute to a better understanding of the pathogenesis of the acute and chronic uveitides, especially those of autoimune and infectious etiology.

ISSN:0271-3683    

DOI:10.3109/02713689208999510

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The recognition event between self-antigen, the MHC and the T cell receptor has become the target for potential immunotherapy of T cell mediated autoimmune disease. For this approach to succeed in uveoretinitis, uniformity in T cell receptor usage, restricted MHC usage and limited epitope recognition by individuals would be required. In this study we have shown that despite clonal heterogeneity of response to multideterminate retinal extract antigens, proliferation to the antigens tested was restricted by the IA MHC class II molecule. Different patterns of reactivity to retinal antigens in the presence of various protease inhibitors was observed. Natural processing of IRBP appears to be complex, requiring a number of enzymes to generate immunogenic fragments, in contrast, for S-antigen, plasmin alone may suffice. The RPE cells which are potential processors and presenters of retinal antigens produce PGE2and may act as suppressors of ocular inflammation.

ISSN:0271-3683    

DOI:10.3109/02713689208999511

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Retinal s-antigen (SAg) and interphotoreceptor retinol-binding protein (IRBP) induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are good models for studying the mechanisms involved in autoimmune diseases. Many immunogenetically active epitopes have been identified in these proteins but immunodominance of one or more epitopes in vivo, has not yet been established. In this paper we present and discuss some experiments that led to the discovery of a dominant“tolerogenic”epitope in SAg. We also demonstrate the presence of cross reactive epitopes in the two potent retinal antigens, SAg and IRBP and finally introduce early data on a unique anti S2.4.C5 idiotypic (Id) monoclonal antibody (MAb) which appears to be a site non associated antibody that binds not only to S2.4.C5 but also to SAg.

ISSN:0271-3683    

DOI:10.3109/02713689208999512

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Several observations in the characterization of EAU are examined. First, sequences of heterologous S-Ag (bovine S-Ag in LEW rats) which induce strongin vitroT cell proliferative responses are dissociated from sequences which induce EAU. Strongin vitroresponses were detected only to nonself peptide homologues. Second, T cells specific for self-sequences of S-Ag are unresponsivein vitro.Third, TCR Vβ8 gene usage is associated with pathogenic T cells. Vβ8.2 bearing hybridomas from a pathogenic line exhibited enhanced reactivity to pathogenic self-peptides, but were unresponsive unless presented Ag on nonirradiated, splenic APC. We propose that these findings reflect self, nonself discrimination of the epitopes on heterologous autoantigen, and examine the hypothesis that TCR containing Vβ8 have enhanced avidity for MHC complexed with autologous sequences, but that these Vβ8 autoreactive T cells appear unresponsivein vitrodue to mechanisms of self-tolerance involving superantigen/coligand participation.

ISSN:0271-3683    

DOI:10.3109/02713689208999513

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

In the pathogenesis of most experimental autoimmune diseases T lymphocytes play a crucial role in the initiation, whereas macrophages are essential in the effector phase. This review deals with several methods to elucidate the exact role macrophages play in different stages of autoimmune models in the rat. By using monoclonal antibodies an inventory has been made on the different macrophage subsets that are present in the infiltrates of the affected tissues. That macrophages play a decisive role in provoking the clinical signs has been shown by several macrophage elimination studies. The severe tissue damage caused by macrophages is brought about by the release of inflammatory mediators. Especially interference with the production or action of these products could provide new therapeutical means.

ISSN:0271-3683    

DOI:10.3109/02713689208999514

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor