摘要:

A secondary immune response in the rabbit eye can be provoked by intravenous injection of the antigen, previously injected intravitreally. The inflammation process consists of iris hyperemia, pericorneal redness and cellular and proteinous exudates in the anterior chamber and vitreous.The influence of vitrectomy combined with lensectomy or preceded by extracapsular lens extraction on the character of the secondary immune response has been studied in the rabbit eye.Both eyes of adult rabbits were injected intravitreally with human serum albumin. Five to ten weeks later, when the primary inflammation process had vanished, the vitreous and the lens were removed from the right eye in one group of animals. In a second group of rabbits, an extracapsular lens extraction was performed upon both eyes, later followed by vitrectomy of the right eye. Four weeks later all animals received an intravenous booster injection with human serum albumin.The eyes which still contained the vitreous developed a secondary inflammation consisting predominantly of cells and fibrin clots in the anterior chamber however without flare. On the contrary, the eyes which underwent vitrectomy developed a flare in the anterior chamber with only a few cells detectable. Analysis of cells and protein in the anterior chamber and histological evaluation supported the clinically observed differences between both eyes.These results suggest that the persistence of the vitreous is associated with the reactivation of a secondary immune response. Vitrectomy combined with lensectomy or preceded by extracapsular lens extraction leads to increased passive transfer of proteinous material through the vessels.

ISSN:0271-3683    

DOI:10.3109/02713689008999431

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Co-culture of rat retinal pigment epithelial (RPE) cells or retinal capillary endothelial (EC) cells with T lymphocytes from immunised syngeneic rats indicated that RPE cells but not EC could process retinal S-antigen and induce antigen specific T cell activation. Activation of lymphocytes by EC however was also antigen independent, and may be due to T cell (CD2) endothelial cell (LFA-3) ligand interactions which are functional on EC but not RPE.

ISSN:0271-3683    

DOI:10.3109/02713689008999432

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Experimental autoimmune uveoretinitis (EAU), induced in (LEW X BN) F1 rats by immunization with S antigen (S-Ag) is T cell and antibody (ab) mediated and anti-S-Ag IgE ab have been involved in the occurrence of ocular lesions. (LEW X BN) F1 rats repeatedly injected with HgCl2develop an autoimmune disease characterized by numerous auto-ab and a high increase of serum IgE level. We hypothesize that large amounts of non anti-S-Ag IgE induced by HgCl2would compete with anti-S-Ag induced by S-Ag immunization so as to prevent EAU to occur. Indeed (LEW X BN) F1 rats immunized with S-Ag 7 days after the first HgCl2injection are strongly protected against EAU. The putative role of the different mercury-induced autoimmune phenomena in the protection against EAU are discussed.

ISSN:0271-3683    

DOI:10.3109/02713689008999433

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Several experimental models of autoimmune diseases have been studied which often mimic the human situation. Autoreactive T cells that emerge either spontaneously or after immunization have been identified in several stiuations. The main lesson from these models is that these autoreactive T cells are negatively controlled in the normal situation and that a defect either inherited or acquired in this regulatory circuit is responsible for autoimmunity.

ISSN:0271-3683    

DOI:10.3109/02713689008999434

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Elucidation of the amino acid sequences of retinal S-antigens from several species has allowed the fine dissection of T cell and antibody epitopes using synthetic peptides. S-antigen, isolated from retinal rod photoreceptor cells, elicits experimental autoimmune uveoretinitis (EAU), a predominantly CD4+ T-cell mediated autoimmune disease of the retina and uveal tract of the eye and pineal gland. Three uveitogenic T cell lines, R9, R17 and R208, prepared against native bovine S-antigen, human S-antigen and cyanogen bromide peptide CB123, respectively, were used to identify the T cell recognition sites responsible for uveitogenic and proliferative responses. T cell epitopes were found to be clustered into 6 regions, some of which were species-specific. The two synthetic peptides known to actively induce EAU, residues 286–297 and 303–314 of bovine S-antigen, were unable to induce significant proliferative responses in any of the three T cell lines. However, both of these sites were adjacent to synthetic peptides, residues 273–292 and 317–328, respectively, which were unable to actively induce EAU, but elicited proliferative responses from the T cell lines. We also report the presence of a new pathogenic site, also associated with an adjacent proliferative site, together in residues 343–362 of bovine S-Ag. Our results indicate that spatially separate and distinct T cell epitopes are present in S-antigen which are responsible for the active induction of EAU, lymphocyte proliferation, and adoptive transfer of EAU.

ISSN:0271-3683    

DOI:10.3109/02713689008999435

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

S-antigen is a highly pathogenic retinal autoantigen for the induction of experimental autoimmune uveitis (EAU). EAU is predominately a T cell mediated autoimmune disease of the uveal tract and retina of the eye and the pinealocytes of the pineal gland. Using synthetic peptides it has been possible to identify several B cell and T cell epitopes in the molecule. In addition, synthetic peptides derived from proteins of diverse origin with amino acid sequence homology to pathogenic regions of S-antigen induce an EAU which is indistinguishable from the disease induced by native S-antigen. These studies aid in the understanding of immune mechanisms in EAU and provide a basis for the pathogenesis of uveitis in humans.

ISSN:0271-3683    

DOI:10.3109/02713689008999436

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

S-antigen has been considered a specific protein of photoreactive cells by immunohistochemical criteria. It was observed in the retina and pineal gland of all examined vertebrates as well as in photoreceptors of invertebrates, but not currently in other organs. However, contrary to pineal cells of poikilotherms and birds which are true or modified photoreceptors, mammalian pinealocytes are not photosensitive. Recent experiments demonstrated that S-antigen-like proteins are present in low amount in many other cells in the body. These proteins are characterized by the same migration pattern (the same molecular weight) as retinal S-antigen in SDS-electrophoresis and by their immuno-reactivity with a panel of monoclonal and polyclonal antibodies to S-antigen. These cells are not photosensitive, but are controlled byβadrenergic, G-protein mediated adenylate cyclase system, a transduction system that shares many structural and functional homologies with visual transduction. S-antigen (arrestin) plays a regulatory role in phototransduction in rods by desensitizing rhodopsin. In the mammalian pineal and in other cells or tissues, S-antigen, or a family of structurally related proteins, could similarly be involved in the regulation of chemical signal transduction. Whether any systemic pathology is associated with uveoretinitis and pinealitis after S-antigen immunization deserves further investigations.

ISSN:0271-3683    

DOI:10.3109/02713689008999437

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

An EAU model has been developed in the mouse using the retinal soluble antigen (SAg), and the interphotoreceptor retinoid-binding protein (IRBP). Immunogenetic studies indicate that sensitivity to disease is H-2 dependent, but some data suggest that non-MHC genes may also contribute to the regulation of EAU. IRBP was a more potent uveitogen than SAg. Ability to mount lymphocyte and antibody responses was exhibited both by EAU-susceptible and by EAU-resistant strains, and could not be used as a predictive parameter. Dependence of disease induction on variables of immunization was studied in B10.A mice (I-Ak) immunized with IRBP. Use ofBordetella pertussisas additional adjuvant was a prerequisite for successful disease induction. Use of purified pertussis toxin (PTX), rather than a suspension of pertussis bacteria, allowed reduction of the immunization protocol to a single dose of IRBP in CFA. Severity and incidence of disease, as well as its clinical course, were directly affected by the dose of antigen and PTX, and could be controlled by varying their respective doses. A spectrum of disease, from hyperacute to chronic, could be obtained. The chronic type of EAU tended to relapse, with lesions reappearing after a brief period of essential quiescence. The special advantages of the murine EAU model for the study of ocular autoimmunity are discussed.

ISSN:0271-3683    

DOI:10.3109/02713689008999438

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The immune response to antigens within the anterior chamber is deviant (anterior chamber associated immune deviation - ACAID) in that delayed hypersensitivity is deficient, whereas other immune effector modalities are intact. Experimental evidence indicates that the eye itself is critical to the induction of ACAID. We have examined the antigen processing and presenting potential of cells within the anterior segment of the eye, and have analyzed the potential immunoregulatory properties of these cells, their secretory products, and the aqueous humor itself. Evidence indicates that bone marrowderived cells within the stroma of the iris and ciliary body inhibit antigen-driven T lymphocyte activation, although they themselves lack the capacity to present antigens to T lymphocytes. The mechanism is in part through secretion of immunosuppressive cytokines. Since aqueous humor contains similar cytokines, it is inferred that these molecules are constitutively secreted. We have determined that a major inhibitory molecule within normal aqueous humor is transforming growth factor-beta (TGFB), which inhibits antigen processing and presentation, and suppresses both T lymphocyte activation and certain aspects of non-specific inflammation. These effects also turn out to be properties of normal aqueous humor. These findings support the hypothesis that local features of the eye modify intraocular antigens such that an ACAID-inducing signal is produced. Experimental evidence suggests that these same properties may play a major role in suppressing efferent immune responses in the eye.

ISSN:0271-3683    

DOI:10.3109/02713689008999439

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Experimental autoimmune uveoretinitis (EAU) induced by retinal antigens is a CD4+ (Th) lymphocyte mediated disease. Generation of autoreactive CD4+ cells requires the processing and presentation of autoantigen by antigen presenting cells (APC) in combination with MHC Class II antigen. Efficient presentation of antigen to T cells has also been shown to depend on accessory molecules of adhesion such as intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1).Aberrant expression of Class II antigens by local tissue cells has been suggested as a possible mechanism in autoimmune processes. Several ocular cells express Class II antigens during inflammation, while other cells such as Muller cells inhibit antigen presentation in vitro. We have also shown that retinal pigment epithelial cells (constitutively) and endothelial cells (after induction) express ICAM-1 and that CD4+ lymphocyte adhesion to these cells is inhibited by antibodies to ICAM-1. Accessory molecules may therefore be important, not only in local presentation of antigen but in recruitment of circulating autoreactive cells to the eye since these cells represent the site of the blood-retinal barrier. Regulation of the local immune response in the eye therefore, may occur at several levels.

ISSN:0271-3683    

DOI:10.3109/02713689008999440

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor