Zusammenfassung
Nach einer Übersicht der immunologischen Reaktionen, die zur Antikörperbildung führen, werden deren krankhafte Nebenerscheinungen—die verschiedenen Überempfindlichkeitszustände und die Autoimmunkrankheiten—besprochen. Im Rahmen dieser Betrachtungen wird die Pathogenese der granulomatösen und nichtgranulomatösen Uveitis erörtert sowie Möglichkeiten, durch immunologische Untersuchungsmethoden eine Ätiologie-Diagnose zu stellen. Bei den eigenen Untersuchungen wird von der Auffassung ausgegangen, daß das entzündliche Infiltrat im Uveagewebe und die aus ihm stammenden Exsudatzellen in der Vorderkammer Antikörper gegen das ursächliche Antigen enthalten. Zur Bestimmung der zellgebundenen Antikörper wurde die indirekte Technik der fluoreszierenden Antikörper angewandt. Bisher konnte keine sichere spezifische Fluoreszenz festgestellt werden. Daneben wurden die Zellmorphologie im gefärbten Zellpräparat, die Eiweißbestandteile im Kammerwasser und freie Antikörper mit der Präzipitationstechnik in Agar-gel untersucht. Im Tierexperiment wurde eine allergische Entzündung der Uvea durch intravitreale Eiweißinjektion bei Tieren mit einer verzögerten Überempfindlichkeit verursacht. Bei den histologischen Untersuchungen mit Hilfe der Technik der fluoreszierenden Antikörper wurde festgestellt, daß im Infiltrat der Chorioidea und des Ciliarkörpers zahlreiche antikörperhaltige Zellen zu finden waren. Solche Zellen konnten nicht auf den histologischen Schnitten in der Vorderkammer gefunden werden, auch nicht im Zellsediment des Vorderkammerpunktats. Es wird daraus gefolgert, daß die entzündliche Reaktion im vorderen Abschnitt der Uvea eine unspezifische Begleiterscheinung der in dem hinteren Abschnitt der Uvea, in der Umgebung des intravitrealen Antigendepots sich abspielenden spezifischen allergischen Entzündung sein könnte.
Summary
After a review of the immunological responses giving rise to antibody formation, the author mentions the various possibilities of their clinical manifestations: such as allergy and auto-immune disease. From this point of view the aetiology of granulomatous and nongranulomatous uveitis has been discussed as well as the possibilities of a diagnosis based on the knowledge thereof. The author's investigations were based on the principle that the inflammatory cells in the uveal tissue, as well as those spreading from it into the anterior chamber would contain antibodies against the original antigen. In order to demonstrate the cellbound antibodies the technique of fluorescent antibodies was employed. However no specific fluorescent reaction has so far been encountered. Cytology and electrophoreses were performed on the aqueous fluid. Direct antibodies were searched for by way of the agarprecipitation technique of OUCHTERLONY. An allergic inflammation of the uvea was experimentally induced by intravitreous injection of the same antigen, in rabbits with a delayed type of hypersensitivity to human gammaglobulin. The histological examination of these eyes using the fluorescent antibodies technique established the existence of many cells containing specific antibodies in the infiltrations of the choroid and ciliary body. No specific fluorescence could be found in those cells situated next to the iris in the anterior chamber. There was no fluorescence in the cells obtained by puncture of the anterior chamber, at the culmination of the inflammatory process. The author comes to the conclusion, that the inflammation of the anterior uvea is possibly a non-specific process, due to a specific allergic inflammation, induced in the choroid and ciliary body by the vitreal antigen injection.
Résumé
Une revue des processus immunologiques généraux est suivie d'une discussion des états de hypersensibilité et des maladies autoimmunes en tant que produits nuisibles de l'activité, au fond utile, de l'appareil immunologique. L'immunogénèse de l'uvéite, granulomateuse et nongranulomateuse, est située dans le cadre de ces observations. La description des réactions cellulaires qui aboutissent à la formation des anticorps, est suivie d'un essai de définir les traits caractéristiques et les causes possibles des maladies autoimmunes. Les possibilités restreintes des différentes réactions sérologiques en tant que moyens d'éclaircir l'étiologie d'une uvéite sont discutées ensuite. Les recherches, dont les résultats sont rapportés ci-dessous, sont basées sur la conception, que les cellules qui constituent l'infiltration de l'uvée ainsi que les cellules dans la chambre antérieure, qui probablement en proviennent, produisent et contiennent des anticorps contre l'antigène qui a été la cause du procès inflammatoire. En même temps les cellules dans le sédiment de l'humeur aqueuse furent examinées après coloration d'après Pappenheim. Les protéines dans l'humeur aqueuse furent étudiées par une méthode quantitative et par électrophorèse. Aussi la technique de double diffusion en agar gel d'après Ouchterlony a été essayée pour chercher des anticorps libres dirigés contre le tissu uvéal, les protéines du cristallin et des antigènes toxoplasmatiques. Dans des expériences avec des lapins sensibilisés à la gammaglobuline humaine une uvéite allergique a été provoquée par injection intravitréenne de gammaglobuline. L'examen histologique de ces yeux par la technique des anticorps fluorescents a prouvé l'existence de nombreuses cellules, contenant des anticorps spécifiques dans les infiltrats de la choroide et du corps ciliaire. Dans la chambre antérieure, près de l'iris, des cellules fluorescentes n'ont pas pu être constatées. Le même résultat négatif fut obtenu à l'examen des cellules dans l'humeur aqueuse prélevées par ponction camérulaire au point culminant de l'inflammation. L'auteur en tire la conclusion que la réaction inflammatoire du segment anterieur est peut-être un processus non spécifique, accompagnant l'inflammation allergique spécifique, provoquée dans la choroide et le corps ciliaire par l'injection intravitréenne de l'antigène.
Article PDF
Literatur
ALEXANDER, MUDD, HAUROWITZ, zit. nach MACKAY J. & BURNET F., ed. Ch. Thomas Autoimmune disease. (1962).
ARONSON, S. B. Hypersensitivity reactions in the uveal tract caused by uveal antigen-antibody reactions. In A. E. MAUMENEE & A. M. SILVERSTEIN (eds.) “Immunopathology of uveitis” (1964).
— HOGAN, M. T. & P, ZWEIGART. Homoimmune Uveitis in the Guinea Pig. I. General concepts of auto- and homoimmunity, methods and manifestations.Arch. Ophthal. 69:105–109 (1963). II. Clinical manifestations of the disease.Arch. Ophthal. 69,203–207 (1963). III. Histopathologic manifestations of the disease.Arch. Ophthal. 69,209–219 (1963). V. The effect of adrenal corticosteroid.Arch. Ophthal. 69,379–388 (1963).
— SCHNELLMANN, O. C. & E. A. JAMAMATO. Uveal auto-antibody in ocular disease.J. Amer. med. Ass. 196,225–228 (1966).
ASHTON, N. Allergic factors in the etiology of uveitis. Trans. XVII. Int. Congr. Ophthal. 2,214 (1955).
AUGUSTIN, R., CONNOLLY & G. M. LLOYD. Atopic reagins as a prototype of cytophilic antibodies. Protides 11th. Colloq. (1963).
BERENS, C., S. ROTHBARD, & D. M. AANGEVINE. Cultural studies on patients with uveitis and other eye diseases.Amer. J. Ophthal. 25,295–301 (1942).
BILLINGHAM, R. E., L. BREUT, & P. B. MEDAWAR. Actively acquired tolerance of foreign cells.Nature, Lond. 172,1055 (1953).
BLODI, F. G. Hypersensitivity reactions in the uveal tract due to sympathetic uveitis. In A. E. MAUMENNE & A. M. SILVERSTEIN, (eds.), “Immunopathology of uveitis” (1964).
BLOOM. Conference on cellbound antibodies of the Nat. Acad. of Sciences May 1963. Ed. by BERNARD AMOS & HILARY KOPROWSKI,124–125 (1963).
BÖKE, W. & B. DIECKHUES. Passiver Transfer der Tuberkulinempfindlichkeit auf das Auge im Tierversuch.v. Graefes Arch. Ophthal. 166,494–508 (1963).
BOYDEN, ST. Cytophilic antibody. Conference on cellbound antibodies of the Nat. Acad. of Sciences May 1963. Ed. by B. AMOS & H. KOPROWSKI (1963).
— The Adsorption of proteins on erythrocytes treated with Tannic Acid and subsequent haemagglutination by antiprotein sera.J. exp. Med. 93,107–120 (1951).
BREYERE, E. J. & L. B. WILLIAMS. Antigens associated with a tumour virus: Rejection of Isogenic skin grafts from leucemic mice.Science 146,1055 (1964).
BROCKHURST, W. F. Pharmacological mediators of hypersensitivity reactions. In P. G. M. Gell & R. R. A. COOMBS (eds.) “Clinical aspects of immunology”,360–385 (1963).
BURNET, F. M. Enzyme, antigen and virus. Cambridge University Press (1956).
— A modification of JERNES theory of antibody production using the concept of clonal selection.Aust. J. exp. Biol. med. Sci. 20,67–68 (1957).
— The clonal selection theory of acquired immunity. Vanderbilt University Press, Nashville (1959).
COCHRANE, CH. La technique des anticorps fluorescents. Applications à la microbiologie et au phénomène d'Arthurs.Ann. Inst. Pasteur 99,329–350 (1960).
COLES, R. S. Allergy of the ueea. In FREDERICK H. THEODORE & ABRAHAM SCHLOSSMAN. (eds.) “Ocular allergy” (1958).
COLLINS, R. C.. Experimental studies on sympathetic ophthalmia.Amer. J. Ophthal. 32,1687 (1949).
— Further experimental studies on sympathetic ophthalmia.idem 36,150 (1953).
O'CONNOR G. R. Antitoxoplasma precipitins in aqueous humour.Arch. Ophthal. 57,52–57 (1957).
COONS, A. & M. H. KAPLAN. Localisation of antigen in tissue cells II.J. exp. Med. 91,1–15 (1950).
COONS, A. H., E. H. LEDUC & J. M. CONNOLLY. Studies on antibody production. I. A method for the histochemical demonstration of specific antibody and its application to a study of the hyperimmune rabbit.J. exp. Med. 102,49 (1955).
— Antibodies and antigens labelled with fluorescein.Schweiz. Z. Path. 22,693–699 (1959).
CROWLE, A. J. Delayed hypersensitivity in health and disease. (1962).
DAVID, J. S., S. AL-ASKARI, H. S. LAWRENCE, & L. THOMAS.J. Immunol. 93,264–282 (1964).
DUKE-ELDER, ST. System of Ophhtalmology. Vol II:169–175 (1961).
ELSCHNIGG, A. Studien zur sympathischen Ophthalmie. II. Die antigene Wirkung des Augenpigments.v. Graefes Arch. Ophthal. 76,509 (1910).
EHRENFELD, E. N., K. GERY, & A. DAVIES. Specific antibodies in heart disease.Lancet I:1138 (1961).
FAVOUR zit. nach. A. J. CROWLE (1962) “Delayed hypersensitivity in health and disease”, p.33.
FERNANDO, A. N. Immunological studies with J131 labelled antigen in experimental uveitis.Arch. Ophthal. 63,515–539 (1960).
FRANÇOIS, J. & M. RABAEY. Microelectrophoresis in agar of normal and pathological aqueous humor.Arch. Ophthal. 63,836–849 (1960).
FRENKEL, J. K. Pathogenesis of toxoplasmosis with a consideration of cyst rupture in besnoitia infection. Toxoplasmosis Symposium Nov. 1960. Ed. by A. E. MAUMENEE. The Williams & Williams Comp.:799–825 (1960).
FRIEDENWALD, J. S. Notes on the allergy theory of sympathetic ophthalmia.Amer. J. Ophthal. 17,1008–1018 (1934).
FREUND, J. The effect of paraffin oil and mycobacteria on antibody formation and sensitization.Amer. J. clin. Path. 21,645 (1951).
FUCHS, A. (1920) zit. nach ST. DUKE—ELDER. System of Ophthal. Vol. II. Anatomy of the visual System.169–175.
GELL, P. G. H. & B. BENACERAFF. Delayed hypersensitivity to simple protein antigens. In W. H. TALIAFERRO & J. H. HUMPHREY, (eds.) “Advances in Immunology” Vol. I:319–345 (1961).
GOLDMAN, M. Staining toxoplasma gondii with fluorescein labelled antibody.J. exp. Med. 105,549–573 (1957).
— Staining toxoplasma gondii with fluorescein labelled antibody.Amer. J. clin. Path. 35,541 (1962).
GOLDMANN, H. & R. WITMER. Antikörper im Kammerwasser.Ophthalmologica (Basel) 127,323–329 (1954).
GOODNER, E. K. Experimental lens-induced uveitis in rabbits. in: A. F. MAUMENEE & A. M. SILVERSTEIN (eds.) Immunopathology of Uveitis,233–239 (1964).
GRABAR, P. Anticorps et “Globulines transporteurs”. Protides of the biological fluids. 11. Colloq. Brughes. (1963).
GRASSMANN, W. & K. HANNIG. Ein quantitatives Verfahren zur Analyse der Serumproteine durch Papierelektrophorese.Z. physiol. Chemie 290,1 (1952).
HACKETT, E. & AL. THOMSON. Anti-lens antibody in human sera.Lancet Sept.663–666 (1964).
HAMILTON, L. D. Metabolic stability of RNA and DNA in human leucemic leucocytes; the function of lymphocytes. From “The leucemias, etiology, pathophysiology and treatment”. New York, Academic Press (1957).
HIJMANS, DONIACH, ROITT & HOLBOROW Serological overlap between lupus erythematodes, Rheumatoid Arthritis u. M. Hashimoto.Brit. med. J. 909–914 (1961).
HOGAN, M. J. Similarities of ocular, joint and other tissues: anatomic and histochemical observations. In A. E. MAUMENEE & A. M. SILVERSTEIN (eds.) “Immunopathology of uveitis”, (1964).
— & L. E. ZIMMERMAN. Ophthalmic pathology. W. B. Saunders Comp., Philadelphia (1962).
JERNE, N. K. The natural-selection theory of antibody-formation.Proc. nat. Acad. Sci. (Wash.) 41,849–857 (1955).
JERNE, N. K., NORDIC, A. & C. HENRY. The agar plaque technique for recognizing antibody producing cells. In conference on cellbound antibodies of the Nat. Acad. of Sciences. Ed. by BERNARD AMOS & HILARY KOPROWSKI (1963).
KELLY et al. (1960) zit. nach P. G. H. GELL & B. BENACERAFF in TALIAFERRO, W. H. & J. H. HUMPHREY (eds.) “Advances in Immunology” (1961) Vol. 1, p.319–345.
LAWRENCE, H. S. “Transfer Factor”: A mechanism of tissue dammage in delayed hypersensitivity. In A. E. MAUMENEE & A. M. SILVERSTEIN (eds.) Immunopathology of uveitis.
V. LOGHEM, J. J. Beschouwingen over Auto-immunziekten.Ned. T. Geneesk. 1613–1622 (1965).
LUNTZ, M. H. Auto-immune response to lens- and Uveae protein.S. Afr. med. J. 38,130–133 (1964).
MAGARIv. Graefes Arch. Ophthal. 159,257 (1956) Zit. n. sr. DUKE-ELDER: System of Ophthal., Vol. II,169–175.
MAISEL, H. Immunopathologic specificity of lens antigens.Amer. J. Ophthal. 55,1208–1215 (1963).
MARSHALL et al. Method for fluorescein-iso-thiocyanate labelling.Proc. Soc. exp. Biol. (N.Y.) 98,898–900 (1958).
NAIRN R. C. (ed.) Fluorescein protein tracing. (1962).
NOZAKI MICHO et al. Eye and kidney tissue reactions to heterologous anti-uveal antibodies.Amer. J. Ophthal. 447–453 (1964).
OFFRET, G. & H. SARAUX. Etude bactériologique de l'humeur aqueuse humaine. Technique et résultats.Arch. Ophtal. 15,573 et705 (1955).
—— Infection focale et Uvéite; foyers streptococciques.Docum. Ophthal. XIV,247–263 (1960).
OUCHTERLONY, Ö. Antigen-Antibody reactions in gels.Acta path. microbiol. scand. 26,507–515 (1949).
PAPPENHEIMER, A. M., SCHARFF, M. & J. W. UHR. Delayed hypersensitivity and its possible relation to antibody formation. In J. H. SHAFFER, G. A. LOGRIPPO, M. W. CHASE (eds.) Mechanism of hypersensitivity (1959).
PAULING, L. A theory of the structure and process of formation of antibodies.J. Amer. chem. Soc. 62,2643 (1940).
PERKINS, E. S. & R. M. WOOD. Autoimmunity in uveitis.Brit. J. Ophthal. 48,61–69 (1964).
POTTER (1963) zit. nach v. EIPSTEIN W. (1964): New information on the structure of gammaglobuline in relation to studies of rheumatoid arthritis. In A. E. MAUMENEE & A. M. SILVERSTEIN (eds.) “Immunopathology of Uveitis”.
RAFFAEL & STOERK zit. nach A. J. CROWLE (1962) “Delayed hypersensitivity in health and disease.” p. 30.
REMKY, H. Etiological diagnosis of endogenous uveitis. In H. REMKY (ed.) International Ophthalmology Clinics: The uveal tract and its endogenous inflammations789–822 (1965).
REMKY, H. Auto-anticorps, facteurs iridogènes de l'iritis?Bull. Soc. franç. Ophtal.: 401–412 (1965).
RILEY, J. F. The mast cells. Ed. Livingstone Edinburgh (1959).
SAINTE-MARIE, G.J. Histochem. Cytochem. 10,250–256 (1962).
SAINTE-MARIE, G. & C. P. LEBLAND. Thymus-cell population dynamics. In R. A. GOOD & A. E. GABRIELSEN (eds.) “The thymus in immunology”,207–224 (1964).
SALZMANN (1912) zit. nach ST. DUKE-ELDER. System of Ophthal. Vol. II. Anatomy of the visual System:169–175.
SEDAN, J. & P. GUILLOT. Uvéites médicamenteuses.Bull. Soc. franç. Ophtal. 11,145 (1955).
SILVERSTEIN, A. M. Allergie reaction of the eye. In P. G. H. GELL & R. R. A. COOMBS (eds.) “Clinical aspects of immunology”,555–571 (1963).
SILVERSTEIN, A. M. Ectopic antibody formation in the eye. Pathologic implications. In “A. E. MAUMENEE & A. M. SILVERSTEIN (eds.) “Immunopathology of uveitis” (1964).
— & L. E. ZIMMERMANN. Immunogenic endophthalmitis produced in the guinea pig by different pathogenetic mechanisms.Amer. J. Ophthal. 48,435–465 (1959).
STAVITSKY, A. B. The origine of antibodies. In A. E. MAUMENEE & A.M. SILVERSTEIN (eds.) “Immunopathology of uveitis”, (1964).
WITEBSKY, E. & F. MILGROM. The nature of autosensitization with particular reference to the eye. In A. E. MAUMENEE & A. M. SILVERSTEIN (eds.) “Immunopathology of uveitis”, (1964).
WOLKOWICZ, M. J., J. W. HALLET. & I. H. LEOPOLD. Studies on antibody production in the rabbit eye. I. Antibody formation in vitro after intraocular injection of typhoid bacilli.Amer. J. Ophthal. 50,126 (1960).
WUNDERLY, CH., R. STEIGER & H. R. BÖHRINGER. Neue mehrfache Untersuchungen am gleichen Kammerwasser menschlicher Augen.Experientia (Basel) 10,432–433 (1954).
WITMER, R. Local antibody-formation in the iris of the second eye.Docum. ophthal. XVI,271–276 (1962).
— Klinik der Uveitis, Labordiagnostik.Ophthalmologica (Basel) 149,390–404 (1965)
WOODS, A. C. The influence of hypersensitivity on endegenous uveal diseases.Amer. J. Ophthal. 30,257 (1947).
WOODS, A. C. Pathogenesis of granulomatous uveitis, p.7–21. Pathogenesis of nongranulomatous uveitis, p.31 In: Endogenous Uveitis (1956).
Author information
Authors and Affiliations
Additional information
Die Arbeit wurde durch ein Stipendium der “H. J. Flieringa-Stiftung” unterstützt. Besonderer Dank gebührt Dr. Houtsmuller für seine wertvolle leitende Mitwirkung bei der Durchführung der Laboratoriumsuntersuchungen.
Rights and permissions
About this article
Cite this article
Riaskoff, S. Zur Immunogenese und Immunodiagnostik der Endogenen Uveitis. Doc Ophthalmol 24, 68–112 (1968). https://doi.org/10.1007/BF02550948
Issue Date:
DOI: https://doi.org/10.1007/BF02550948