Zusammenfassung
Hintergrund
Komponenten des Schleimhautimmunsystems (MALT) für die Intakterhaltung der Augenoberfläche befinden sich neben der Tränendrüse auch in der Konjunktiva (als CALT) und den ableitenden Tränenwegen (als LDALT). Ihr struktureller und funktioneller Zusammenhang ist allerdings noch ungeklärt.
Material und Methode
Es wurden normale Gewebe der Konjunktiva, der ableitenden Tränenwege und der Tränendrüse mittels Betrachtung von Aufhellungspräparaten, Histologie, Immunhistologie sowie Raster- und Transmissionselektronenmikroskopie untersucht.
Ergebnisse
Ein typisches diffuses lymphatisches Gewebe aus Effektorzellen des Immunsystems unter einem Epithel, das den IgA-Transporter SC enthält, liegt nicht isoliert in der Konjunktiva und den ableitenden Tränenwegen vor. Es verläuft anatomisch kontinuierlich vom periazinösen Bindegewebe der Tränendrüse entlang ihrer Ausführungsgänge in die Konjunktiva und setzt sich in den ableitenden Tränenwegen bis zur Nase fort. B-Lymphozyten wurden fast ausschließlich in Lymphfollikeln gefunden, die einer der Mehrzahl der Präparate seitengleich auftraten. Die Topographie von CALT korrespondiert mit der Position der Kornea bei geschlossenem Auge.
Schlussfolgerung
Das schleimhautassoziierte lymphatische Gewebe von Tränendrüse, Konjunktiva und ableitenden Tränenwegen bildet eine anatomische und funktionelle Einheit zur Immunprotektion der Augenoberfläche. Daher ist es als „Eye-Associated Lymphoid Tissue“ (EALT) in das Schleimhautimmunsystem des Körpers einzuordnen. EALT kann über Lymphfollikel Antigene der Augenoberfläche erkennen und über die regulierte Rezirkulation lymphatischer Zellen andere Organe sowie die Augenoberfläche einschließlich der Tränendrüse mit spezifischen Effektorzellen versorgen.
Abstract
Introduction
Components of the mucosal immune system (MALT) have been identified in the conjunctiva (as CALT) and the lacrimal drainage system (as LDALT). Their structural and functional relation with the established immune protection by the lacrimal gland is unclear.
Material and methods
Macroscopically normal and complete tissues of the conjunctiva, lacrimal drainage system and lacrimal gland from human body donors were investigated by analysis of translucent whole mounts, and using histology, immunohistology as well as scanning and transmission electron microscopy.
Results
A typical diffuse lymphoid tissue, composed of effector cells of the immune system (T-lymphocytes and IgA producing plasma cells) under an epithelium that contains the IgA transporter SC, is not isolated in the conjunctiva and lacrimal drainage system. It is anatomically continuous from the lacrimal gland along its excretory ducts into the conjunctiva and from there via the lacrimal canaliculi into the lacrimal drainage system. Lymphoid follicles occur in a majority (about 60%) and with bilateral symmetry. The topography of CALT corresponds to the position of the cornea in the closed eye.
Conclusion
These results show that the MALT of the lacrimal gland, conjunctiva and lacrimal drainage system constitute an anatomical and functional unit for immune protection of the ocular surface. Therefore it should be integrated as an “eye-associated lymphoid tissue” (EALT) into the MALT system of the body. EALT can detect ocular surface antigens by the lymphoid follicles and can supply other organs and the ocular surface including the lacrimal gland with specific effector cells via the regulated recirculation of lymphoid cells.
Literatur
Allansmith MR, Greiner JV, Baird RS (1978) Number of inflammatory cells in the normal conjunctiva. Am J Ophthalmol 86:250–259
Allansmith MR, Hahn GS, Simon MA (1976) Tissue, tear, and serum IgE concentrations in vernal conjunctivitis. Am J Ophthalmol 81:506–511
Augustin AJ, Spitznas M, Kaviani N et al. (1995) Oxidative reactions in the tear fluid of patients suffering from dry eyes. Graefes Arch Clin Exp Ophthalmol 233:694–698
Axelrod AJ, Chandler JW (1979) Morphologic characteristics of conjunctival lymphoid tissue in the rabbit. In: Silverstein AM, Connor GR (eds) Proceedings of the Second International Symposium on the Immunology and Immunopathology of the Eye. Masson Publishing, New York, pp 292–301
Barton K, Monroy DC, Nava A, Pflugfelder SC (1997) Inflammatory cytokines in the tears of patients with ocular rosacea. Ophthalmology 104:1868–1874
Baudouin C, Haouat N, Brignole F et al. (1992) Immunopathological findings in conjunctival cells using immunofluorescence staining of impression cytology specimens. Br J Ophthalmol 76:545–549
Belfort R Jr, Mendes NF (1979) T- and B-lymphocytes in the human conjunctiva and lacrimal gland. In: Silverstein AM, O’Connor RG (eds) Immunology and immunopathology of the eye. Masson Publishing, New York, pp 287–291
Bhan AK, Fujikawa LS, Foster CS (1982) T-cell subsets and Langerhans cells in normal and diseased conjunctiva. Am J Ophthalmol 94:205–212
Bialasiewicz AA, Barthelmess S, Lang GK et al. (1984) Zur Abklärung infektiöser, entzündlicher äußerer Augenerkrankungen. Klin Monatsbl Augenheilkd 185:174–176
Bienenstock J, McDermott M, Befus D, O’Neill M (1978) A common mucosal immunologic system involving the bronchus, breast and bowel. Adv Exp Med Biol 107:53–59
Brandtzaeg P (1998) Development and basic mechanisms of human gut immunity. Nutr Rev 56:S5–18
Brandtzaeg P, Berstad AE, Farstad IN et al. (1997) Mucosal immunity-a major adaptive defence mechanism. Behring Inst Mitt 98:1–23
Brandtzaeg P, Farstad IN (1999) The human mucosal B-cell system. In: Ogra PL, Mestecky J, Lamm ME et al. (eds) Handbook of mucosal immunology, 2nd edn. Academic Press, San Diego
Brewitt H (1997) Das „trockene Auge“. Z Allg Med 73:729–735
Brewitt H (2000) Das Trockene Auge. Was war? Was ist? Was wird? Z Prakt Augenheilkd 21:52–58
Brewitt H, Zierhut M (2001) Physiologie des Tränenfilms. In: Brewitt H, Zierhut M (Hrsg) Trockenes Auge. Kaden, Heidelberg, S 33–41
Butcher EC, Picker LJ (1996) Lymphocyte homing and homeostasis. Science 272:60–66
Cohen EJ, Allansmith MR (1981) Fixation techniques for secretory component in human lacrimal gland and conjunctiva. Am J Ophthalmol 91:789–793
Collins FM (1978) Cellular antimicrobial immunity. CRC Crit Rev Microbiol 7:27–91
Cornes JS (1965) Number, size, and distribution of Peyer’s patches in the human small intestine. Part I: the development of Peyer’s Patches. Part II: The effect of age on Peyer’s Patches. Clin Exp Immunol 6:225–233
Cross WD, Lay LF Jr, Walt JG, Kozma CM (2002) Clinical and economic implications of topical cyclosporin A for the treatment of dry eye. Manag Care Interface 15:44–49
Doane MG (1985) Tear spreading, turnover and drainage. In: Holly FJ (ed), Proc 1. Int Tear Film Symposium, Lubbock, Texas, pp 652–661
Dua HS, Donoso LA, Laibson PR (1994) Conjunctival instillation of retinal antigens induces tolerance. Ocular Immunol Inflamm 2:29–36
Dua HS, Gomes JA, Jindal VK et al. (1994) Mucosa specific lymphocytes in the human conjunctiva, corneoscleral limbus and lacrimal gland. Curr Eye Res 13:87–93
Dursun D, Wang M, Monroy D et al. (2002) Experimentally induced dry eye produces ocular surface inflammation and epithelial disease. Adv Exp Med Biol 506:647–655
Franklin RM, Kenyon KR, Tomasi TB Jr (1973) Immunohistologic studies of human lacrimal gland: localization of immunoglobulins, secretory component and lactoferrin. J Immunol 110:984–992
Franklin RM, Remus LE (1984) Conjunctival-associated lymphoid tissue: evidence for a role in the secretory immune system. Invest Ophthalmol Vis Sci 25:181–187
Fujishima H, Saito I, Takeuchi T et al. (1997) Characterization of cytokine mRNA transcripts in conjunctival cells in patients with allergic conjunctivitis. Invest Ophthalmol Vis Sci 38:1350–1357
Gillette TE, Greiner JV, Allansmith MR (1981) Immunohistochemical localization of human tear lysozyme. Arch Ophthalmol 99:298–300
Haynes RJ, Tighe PJ, Dua HS (1999) Antimicrobial defensin peptides of the human ocular surface. Br J Ophthalmol 83:737–741
Hazlett LD (2002) Pathogenic mechanisms of P. aeruginosa keratitis: a review of the role of T cells, Langerhans cells, PMN, and cytokines. DNA Cell Biol 21:383–390
Hingorani M, Metz D, Lightman SL (1997) Characterisation of the normal conjunctival leukocyte population. Exp Eye Res 64:905–912
Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580
Jones DT, Monroy D, Ji Z et al. (1994) Sjogren’s syndrome: cytokine and Epstein-Barr viral gene expression within the conjunctival epithelium. Invest Ophthalmol Vis Sci 35:3493–3504
Karnovsky MJ (1965) A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J Cell Biol 27:137–138
Kessing SV (1968) Mucous gland system of the conjunctiva. A quantitative normal anatomical study. Acta Ophthalmol Copenh [Suppl] 95:1–133
Knop E (2001) Konzept eines Augen-assoziierten lymphatischen Gewebes als funktionelle Einheit zur Immunabwehr der Augenoberfläche. Habilitationsschrift, Medizinische Hochschule Hannover
Knop E, Claus P, Knop N (2003) Eye-Associated Lymphoid Tissue (EALT): RT-PCR verifies the presence of mRNA for IgA and its transporter (secretory component) in the normal human conjunctiva. Invest Ophthalmol Vis Sci 44:S3801
Knop E, Knop N (1996) Flachpräparation des Konjunktivalsackes: eine Methode zur topografischen und mikroskopischen Untersuchung seiner Bestandteile. Verh Anat Ges [Anat Anz Suppl 178] 92:262
Knop E, Knop N (1996) MALT tissue of the conjunctiva and nasolacrimal system in the rabbit and human. Vis Res 36:60
Knop E, Knop N (1997) The mucosa associated lymphoid tissue of the human conjunctiva consists of three components: solitary follicles, crypt associated MALT and a lymphoid layer. Invest Ophthalmol Vis Sci 38:125
Knop E, Knop N (1998) Die menschliche Konjunktiva enthält mukosa-assoziiertes lymphatisches Gewebe vom organisierten und diffusen Typ. Verh Anat Ges [Anat Anz Suppl] 180:70
Knop E, Knop N (2000) The human lacrimal drainage system contains lymphoid tissue and is a component of the secretory immune system. Verh Anat Ges [Anat Anz Suppl 182] 95:44
Knop E, Knop N (2001) Lacrimal drainage associated lymphoid tissue (LDALT): a part of the human mucosal immune system. Invest Ophthalmol Vis Sci 42:566–574
Knop E, Knop N (2002) Human lacrimal drainage-associated lymphoid tissue (LDALT) belongs to the common mucosal immune system. Adv Exp Med Biol 506:861–866
Knop N, Knop E (1996) Mucosa-assoziiertes lymphatisches Gewebe in Konjunktiva und nasolacrimalem System des Kaninchens. Ophthalmologe 93:62
Knop N, Knop E (1996) The lacrimal sac in the rabbit and human is associated with MALT. Vis Res 36:195
Knop N, Knop E (1997) The MALT tissue of the ocular surface is continued inside the lacrimal sac in the rabbit and human. Invest Ophthalmol Vis Sci 38:126
Knop N, Knop E (1998) Mukosa-assoziiertes lymphatisches Gewebe im Tränensack von Mensch und Kaninchen. Verh Anat Ges [Anat Anz Suppl] 93:132
Knop N, Knop E (2000) Conjunctiva-associated lymphoid tissue in the human eye. Invest Ophthalmol Vis Sci 41:1270–1279
Kraehenbuhl JP, Neutra MR (1992) Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev 72:853–879
Kunert KS, Tisdale AS, Stern ME et al. (2000) Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Arch Ophthalmol 118:1489–1496
MacDonald TT, Bajaj-Elliott M, Pender SL (1999) T cells orchestrate intestinal mucosal shape and integrity. Immunol Today 20:505–510
McGhee JR, Lamm ME, Strober W (1999) Mucosal immune responses. an overview. In: Ogra PL, Mestecky J, Lamm ME et al. (eds) Handbook of mucosal immunology, 2nd edn. Academic Press, San Diego, pp 485–506
Mestecky J, McGhee JR, Michalek SM et al. (1978). Concept of the local and common mucosal immune response. Adv Exp Med Biol 107:185–192
Metz DP, Hingorani M, Calder VL et al. (1997) T-cell cytokines in chronic allergic eye disease. J Allergy Clin Immunol 100:817–824
Nava A, Barton K, Monroy DC, Pflugfelder SC (1997) The effects of age, gender, and fluid dynamics on the concentration of tear film epidermal growth factor. Cornea 16:430–438
Osterlind G (1944) An investigation into the presence of lymphatic tissue in the human conjunctiva, and its biological and clinical importance. Acta Ophthalmol Copenh [Suppl] 23:1–79
Paulsen FP, Paulsen JI, Thale AB et al. (2002) Organized mucosa-associated lymphoid tissue in human naso-lacrimal ducts. Adv Exp Med Biol 506:873–876
Paulsen FP, Paulsen JI, Thale AB, Tillmann BN (2000) Mucosa-associated lymphoid tissue in human efferent tear ducts. Virchows Arch 437:185–189
Pearlman E, Lass JH, Bardenstein DS et al. (1995) Interleukin 4 and T helper type 2 cells are required for development of experimental onchocercal keratitis (river blindness). J Exp Med 182:931–940
Perra MT, Serra A, Sirigu P, Turno F (1995) A histochemical and immunohistochemical study of certain defense mechanisms in the human lacrimal sac epithelium. Arch Histol Cytol 58:517–522
Pflugfelder SC, Jones D, Ji Z et al. (1999) Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjogren’s syndrome keratoconjunctivitis sicca. Curr Eye Res 19:201–211
Pflugfelder SC, Solomon A, Stern ME (2000) The diagnosis and management of dry eye: a twenty-five-year review. Cornea 19:644–649
Pleyer U (2001) Immunologie des Tränenfilms. In: Brewitt H, Zierhut M (Hrsg) Trockenes Auge. Kaden Verlag, Heidelberg, S 49–56
Pleyer U, Baatz H (1997) Antibacterial protection of the ocular surface. Ophthalmologica 211 [Suppl 1]:2–8
Pleyer U, Dannowski H, Volk HD, Ritter T (2001) Corneal allograft rejection: current understanding. I. Immunobiology and basic mechanisms. Ophthalmologica 215:254–262
Ruprecht KW, Bialasiewicz AA (1987) Bakterielle Konjunktivitis. Fortschr Ophthalmol 84:55–64
Sacks EH, Jakobiec FA, Wieczorek R et al. (1989) Immunophenotypic analysis of the inflammatory infiltrate in ocular cicatricial pemphigoid. Further evidence for a T cell- mediated disease. Ophthalmology 96:236–243
Sacks EH, Wieczorek R, Jakobiec FA, Knowles DM (1986) Lymphocytic subpopulations in the normal human conjunctiva. A monoclonal antibody study. Ophthalmology 93:1276–1283
Sall K, Stevenson OD, Mundorf TK, Reis BL (2000) Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology 107:631–639
Sullivan DA (1999) Ocular mucosal immunity. In: Ogra PL, Mestecky J, Lamm ME et al. (eds) Handbook of mucosal immunology, 2nd edn. Academic Press, San Diego, pp 1241–1281
Tang Q, Chen W, Hendricks RL (1997) Proinflammatory functions of IL-2 in herpes simplex virus corneal infection. J Immunol 158:1275–1283
Thale A, Paulsen F, Kohla G et al. (2001) The efferent lacrimal ducts of the human. Morphological and biochemical studies. Ophthalmologe 98:67–73
Tiffany JM, Bron AJ (1978) Role of tears in maintaining corneal integrity. Trans Ophthalmol Soc UK 98:335–338
Virchow H (1910) Mikroskopische Anatomie der äusseren Augenhaut und des Lidapparates. In: Saemisch T (Hrsg) Graefe-Saemisch Handbuch der gesamten Augenheilkunde, Band 1, 1. Abteilung, Kapitel II, 2. Aufl. W. Engelmann, Leipzig, S 431
Westermann J, Engelhardt B, Hoffmann JC (2001) Migration of T cells in vivo: molecular mechanisms and clinical implications. Ann Intern Med 135:279–295
Westermann J, Pabst R (1996) How organ-specific is the migration of „naive“ and „memory“ T cells? Immunol Today 17:278–282
Wieczorek R, Jakobiec FA, Sacks EH, Knowles DM (1988) The immunoarchitecture of the normal human lacrimal gland. Relevancy for understanding pathologic conditions. Ophthalmology 95:100–109
Wotherspoon AC, Hardman L, Isaacson PG (1994) Mucosa-associated lymphoid tissue (MALT) in the human conjunctiva. J Pathol 174:33–37
Zierhut M, Stiemer R (1997) Physiological protective mechanisms of the eye. Klin Monatsbl Augenheilkd 211:1–11
Zuckerman BD (1966) Conjunctival pigmentation due to cosmetics. Am J Ophthalmol 62:672–676 (abst)
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Die Untersuchungen dieser Arbeitsgruppe über das Schleimhautimmunsystem der Augenoberfläche wurden mit dem Sicca-Preis 2000 and 2002 der „Arbeitsgruppe Trockenes Auge“ des BVA ausgezeichnet.
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Knop, E., Knop, N. Augen-assoziiertes lymphatisches Gewebe (EALT) durchzieht die Augenoberfläche kontinuierlich von der Tränendrüse bis in die ableitenden Tränenwege. Ophthalmologe 100, 929–942 (2003). https://doi.org/10.1007/s00347-003-0936-6
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DOI: https://doi.org/10.1007/s00347-003-0936-6