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Immunological Responses in the Eyelid and Orbit

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Immunological Responses in the Eyelid and Orbit Eye (1988) 2, 15&-163 Immunological Responses in the Eyelid and Orbit R. VANDER GAAG Amsterdam, The Netherlands Summary Immunological responses in the eyelid and the orbit are reviewed: (1) A local immune response is dependent on the presence of lymphoid tissue in an organ. Lymphoid tissue is found in the conjunctival fornices and in the lacrimal gland but not in the orbit. The eyelids also have lymphatic drainage into the local lymph nodes. A local immune response is found in the palpebral conjunctiva and in the lacrimal gland, measureable both as immunoglobulin or specific antibody levels in tears or as immunoglobulin producing cells within the tissue. No local immunity has been demonstrated in the orbit. (2) The other type of immune response found in the eyelids, the lacrimal gland and the orbit is the involvement of these tissues in systemic diseases. Systemic diseases with an immunological basis, which affect the above mentioned tissues are: atopic diseases of the skin, autoimmune diseases, immunodeficiency diseases and lymphoproliferative diseases. (3) Finally, it is possible that the extraocular muscles and the lacrimal gland have tissue specific antigens and therefore may be target tissues for organ specific auto­ immune processes. The initiation of an immune response to an observed due to overreaction or misrouting infectious agent depends on the presence of (hypersensitivity), lack or breakdown of tol­ lymphoid tissue at the site of infection. Both erance to one's own antigens (autoimmunity) the conjunctiva and the lacrimal gland contain or breakdown III T-cell control the necessary lymphoid elements for the ini­ (autoimmunity). tiation of an immune response. 1,2 The foreign The involvement of the eyelids, the lacrimal agent must first be picked up by an antigen gland and the orbit in beneficial and path­ presenting cell and its antigens processed and ological immune responses is presented. presented to a T lymphocyte. The T lympho­ cytes are cytotoxic, destroying the foreign (1) Local Immune Response in Eyelids and agent directly, or possess helper or suppressor Lacrimal Gland potential. B lymphocytes can also recognise The eyelids and the lacrimal gland participate the antigen and if an appropriate T cell signal in two types of immune response: the innate is also received the B cell will transform into a and the adaptive immunity. Apart from the plasma cell which produces antibody [for mechanical removal of foreign particles by details see Roitt et a[3]. Until now it has been blinking, the skin of the eyelids and the con­ impossible to detect lymphoid tissue or lym­ junctiva are an effectivebarrier to most infec­ phatic drainage to a lymph node in the orbit. tious agents ' and the lacrimal gland The immune system is meant to protect the participates in this system by producing host but sometimes harmful reactions are also lysozyme and lactoferrin in tears. The resis- Correspondence to: Dr. R. van der Gaag, PhD. Department of Ophthalmo-Immunology, The Netherlands Ophthalmic Research Institute, PO Box 12141, 1100 AC Amsterdam, The Netherlands, IMMUNOLOGICAL RESPONSES IN THE EYELID AND ORBIT 159 tance conferred by the innate immune system than their conventionally reared sibs.11 When is not improved by repeated infection. In the these germ free rats were subsequently adaptive immune response repeated infection exposed for 4 weeks to a conventional confers resistance and the principle role is environment, the number of plasma cells in played by the lymphocytes. The palpebral their lacrimal gland was indistinguishable conjunctiva and the lacrimal gland are con­ from that in conventionally raised rats. In sidered part of the mucosa associated lym­ humans, Damato et al.12 have shown a tre­ phoid tissue.4 This secretory immune system mendous heterogeneity in the presence of serves as the principle line of defence against lymphocytes within the lacrimal gland. In 29 antigenic challenge at mucosal surfaces. The out of 99 lacrimal gland autopsy specimens protective function is mediated primarily (age range 7 to 93 years) no lymphocyte infiltr­ through secretory IgA (sIgA), which is the ates were found at all. predominant antibody in external secretions. The local immune response of the lacrimal (2) Systemic Immunological Diseases gland and the palpebral conjunctiva is mea­ Affecting the Eyelids, the Lacrimal Gland surable as immunoglobulin levels in tears or as and the Orbit p\;lque forming cells in the tissues itself. In The eyelids are involved in allergic and auto­ patients with herpes simplex keratitis, anti­ immune reactions which affect the skin: acute herpes simplex virus (HSV) antibodies were and chronic allergic conjunctivitis and detected in tears.5•6 The production of these blepharitis, vernal conjunctivitis, atopic antibodies was shown to be local since they eczema, pemphigus, pemphigoid, vitiligo, were found only during the active phase of the psoriasis, Stevens-Johnson syndrome, con­ infection, they were of sigA type which is not tact dermatitis and hereditary angioneurotic present in serum, they were not found in the oedema. These diseases are discussed in detail tears of seropositive healthy controls without elsewhere (White and Wright). ocular disease and leakage of other serum Other systemic immunological diseases proteins (albumin, transferrin or measles anti­ which affect the eyelids, the lacrimal gland body) was not observed. Other examples of and/or the orbit: are lymphoproliferative local production of immunoglobulins are diseases, Wegener's granulomatosus, sar­ found in patients with contact lens giant coidosis and myasthenia gravis. papillary conjunctivitis, where elevated levels Diseases such as Graves' ophthalmopathy of IgE and IgG were found in tears in com­ and Sjogren's syndrome are certainly part of parison with both normal controls and contact systemic autoimmune diseases but possibly lens wearers without symptoms. 7 Patients also have an organ specific component and with vernal conjunctivitis were found to have will therefore be presented separately. elevated IgG levels in their tears, the antibody was shown to be specific for rye grass or LymphoproliJerative diseases ragweed.8 Lymphoid proliferations comprise 10 to 15 Attempts to induce local immunity in per cent of all space fillinglesions of the orbit. experimental animals by antigen instillation Histopathologically the differentiation into the conjunctival sac were only successful between some benign and malignant lesions when high doses of antigen and frequent may present a problem. The use of immu­ application were employed or when lower nological techniques to determine cell surface doses were used in presensitised recipients.9 .10 markers has therefore become indispens­ Both humoral and cellular immunity were able.13.14,15 From our study it appeared that found, and a response was also observed in patients in the fourth or fifth decade of life the regional lymph node. with a history of pain, oedema, epiphora, The presence of lymphocytes in the inter­ double vision and ptosis, with a mass localised stitium of the lacrimal gland is probably the in the anterior part of the orbit, are more result of antigenic stimulation, since rats likely to have a benign lymphoproliferative which have been reared germfree have 5 to 8 process. A biopsy should always be taken and fold less plasma cells in their lacrimal glands submitted for cytological analysis of imprint 160 R. VAN DER GAAG smears, routine histology and immuno­ sensitising agents have been found as yet. The histochemistry to determine the monoclonal development of lymphomas in the orbit is dif­ or polyclonal nature of the lymphocytes ficult to explain in the absence of systemic involved. Cell membrane marker analysis disease but could be attributed to the malig­ with monoclonal antibodies permits classifica­ nant mutation and subsequent uncontrolled tion into T and B cells. T cells can be sub­ growth of one lymphocyte involved in an divided into helper cells and suppressor cells. inflammatory process. Most orbital lymphomas are however, of B cell origin and these may be classified on the Myasthenia gravis basis of the type of immunoglobulin light Myasthenia gravis (MG) is a systemic disease, chain which they carry on their cell mem­ which may affect the ocular muscles first, brane. Polyclonal proliferations are charac­ resulting in diplopa and ptosis. Anti-acetyl­ terised by the presence of T cells and two choline (ACh)-receptor antibody is impli­ types of light chains on the B cells in the cated in this diseasel8 and has been shown to 9 tumour. be pathogenic in mice.1 Deposition of IgG In our patients with non Hodgkin lym­ and complement on the post-synaptic folds of phoma (NHL) of the orbit, systemic disease the muscle results in increased ACh-receptor appeared to be rare. J akobiecl6 associates well turnover and blockage of ACh binding. differentiated monoclonal lesions with a GarJepp et af20 suggest that restricted favourable prognosis and cytological irreg­ ocular-MG and generalised -MG have dif­ ularities with systemic spread. ferent pathogenetic mechanisms. In It remains puzzling however, that isolated ocular-MG anti-ACh receptor antibodies benign and malignant lymphoproliferative were found less frequently but anti-thyroid lesions are found in a tissue devoid of lym­ antibodies were more common than in phoid tissue and lymphatic drainage. Experi­ generalised-MG, furthermore female pre­ mentally, both the occurrence of pseudo­ dominance was not seen in ocular-MG. lymphomas and the lack of local immune Wegener's granulomatosus response in the orbit have been described by Wegener's granulomatosus is a necrotIsmg Liu et al17 in the following experiments. BCG vasculitis of the arteries and veins. Half of the or Ovalbumin (0 A) were bound to Sepharose affected patients have ocular involvement, beads to immobilise the antigen. These beads the orbit being the site of predilection. 21.22 The were then injected into the right, respectively disease is thought to be immunologically left, orbit of guinea pigs which had been mediated, by a cellular reaction, but no ini­ systemically immunised with BCG 4 weeks tiating agent is known.
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