Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelium lining the posterior corneal surface performs physiologic pump functions essential to corneal clarity and integrity. A hallmark of keratitis, anterior ocular inflammation, and corneal allograft rejection is leukocyte adherence to the corneal endothelium (CE) forming keratitic precipitates. To elucidate mechanisms governing cornea-leukocyte interactions, cultured human CE cells and intact corneas were examined for expression of intercellular adhesion molecule-1 (ICAM-1), which binds the lymphocyte function-associated antigen-1 (LFA-1) on all leukocytes and enhances delayed-type hypersensitivity mediated by class II major histocompatibility complex antigens. Immunohistochemistry on culture CE cells using monoclonal anti-ICAM-1 antibody yield positive staining that increased after exposure to interleukin-1-beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (gamma-IFN). Standard leukocyte adherence assays demonstrated ICAM-1-mediated CE-neutrophil binding, which was specifically blocked by antibody to ICAM-1 or antibodies to LFA-1 on neutrophils. In whole human corneas, gamma-IFN increased CE and stromal keratocyte ICAM-1 immunoreactivity and enhanced CE-neutrophil adherence. As in CE cell cultures, antibody to ICAM-1 effectively blocked neutrophil binding to the CE cells of whole corneas. These results are the first to demonstrate ICAM-1 in ocular tissue. They indicate that CE cells express functional ICAM-1, which may be modulated by inflammatory cytokines, ICAM-1 provides mechanisms for keratitic precipitate formation, regulation of corneal leukocyte trafficking and the generation of immune responses that may be crucial to allograft rejection.
 ...
PMID:Intercellular adhesion molecule-1 in human corneal endothelium. Modulation and function. 170 51

Immunohistochemical techniques were used to study expression of HSV-1 antigen, induction of class I and II major histocompatibility complex (MHC) antigens, and infiltration of L3T4+ and Lyt2+ cells were analyzed during the acute phase of herpetic keratitis. The results were as follows: 1) HSV-1 antigens were detectable in the corneal epithelium at 2 days post infection (p.i.), then localized in the stroma after 5 days p.i.. 2) Class I MHC antigens (H-2d) were evenly expressed in all layers of infected as well as uninfected corneas. On the other hand, class II MHC antigens (Iad) were induced in the superficial corneal stroma 2 days p.i., then gradually spread in the entire corneal stroma with increased intensity. 3) L3T4+ (helper/inducer) cells penetrated the stroma at 2 days p.i.. These cells infiltrated the central stroma at 5 days p.i.. Lyt2+ (suppressor/killer) cells were first seen in the corneal stroma as late as at 5 days p.i.. These results imply that L3T4+ cells play a role in the early immunological events concerning class II MHC antigens and viral antigens, both concomitantly expressed in the corneal stroma.
 ...
PMID:[Expression of major histocompatibility complex antigens, and kinetics of infiltrated lymphocytes in murine herpetic keratitis]. 839 Dec 5

The IgG2a(b) heavy chain allopeptide determinant gamma2a(b) 436-451 (Kabat numbering) presented by the major histocompatibility complex (MHC) class II molecule I-Ad is recognized by T cells which cross-react with a corneal self antigen and with the UL6 protein of the herpes simplex virus which induce autoimmune keratitis, and is the target of Th1 clones that suppress IgG2a(b) production in vivo. In the gamma2a(b) peptide/l-Ad complex, tyrosine438 is the first primary anchor (P1) and residues 440-445 encompass the T cell receptor contact residues. Amino-terminal elongation of gamma2a(b) 437-451 by a single residue (P-2) augmented the I-Ad binding capacity 10-fold and the antigenicity 55-195-fold. This was a function of the peptide main chain, since non-conservative substitutions were accepted. The gamma2a(b) peptide also bound HLA-DR1, and amino-terminal extension by a single aromatic amino acid at P-3 augmented binding 15-fold. The interaction between HLA-DR1 and P-3 specifically required an aromatic peptide side chain, and computer simulations indicated that the aromatic ring at P-3 engaged conserved HLA-DR1 phenylalanine residues at the edge of the peptide binding groove. Thus, these data demonstrate that residues amino terminal to P1 may substantially increase peptide affinity for MHC class II by main chain-dependent as well as side chain-dependent interactions, and imply that the HLA-DR1 motif should be extended to include an aromatic amino acid at P-3.
 ...
PMID:N-terminal elongation of a peptide determinant beyond the first primary anchor improves binding to H-2 I-Ad and HLA-DR1 by backbone-dependent and aromatic side chain-dependent interactions, respectively. 993

Peptide epitopes derived from immunoglobulin variable regions represent tumour-specific antigens on B-cell neoplasms and can be recognized by syngeneic, major histocompatibility complex (MHC) class II-restricted T cells. Immunoglobulin peptide/MHC class II complexes may also be involved in autoimmunity and CD4+ T-cell-mediated B-cell regulation. Thus, the IgG2a(b) H-chain allopeptide gamma2a(b) 435-451 presented on I-Ad mimics the epitope implicated in herpes simplex virus-induced autoimmune stromal keratitis and is the target of T helper 1 (Th1) clones that suppress IgG2a(b) production in vivo. We here report that spleen and thymus cells constitutively present the autologous gamma2a(b) epitope to a gamma2a(b) 435-451/I-A(d) reactive T-cell hybridoma as a function of the animal housing conditions (specific pathogen-free or not) and the serum levels of IgG2a(b). Constitutive presentation in the spleen was predominantly performed by dendritic cells. Whereas spleen cells poorly presented native IgG2a(b) to a gamma2a(b) 435-451/I-A(d) reactive T-cell hybridoma, IgG2a(b) in the form of immune complexes were presented > 200-fold more efficiently owing to internalization via low-affinity FcgammaR on macrophages. The antigenicity could also be improved by homotypic aggregation and by targeting IgG2a(b) to complement receptors on the A20 B-cell lymphoma. Mice without detectable IgG2a(b)-containing immune complexes typically exhibited minimal constitutive presentation. Nevertheless, native IgG2a(b) can sensitize antigen-presenting cells in vivo, as mice that were devoid of immune complexes and carried an IgG2a(b)-producing tumour did present constitutively, even at physiological IgG2a(b) serum levels. Whereas the amounts of IgG released from most B-cell lymphomas may be too low to allow spontaneous priming of tumour-specific MHC class II-restricted T cells, administration of tumour immunoglobulin in aggregated form might improve the efficacy of idiotype vaccination.
 ...
PMID:Native IgG2a(b) is barely antigenic to major histocompatibility complex class II-restricted T cells owing to inefficient internalization by professional antigen-presenting cells. 1079 98

Diabetes Mellitus (DM) is a serious medical problem that causes long-term systemic complications and considerable associated morbidity. DM can cause retinopathy (DRP), maculopathy, cataract, optic neuropathy, defects of eye muscles. DM is a risk factor for acute infectious conjunctivitis, bacterial keratitis, herpes virus infections and endophtalmitis. Elevated blood glucose induces structural, physiological and hormonal changes which affect retinal capillaries. DRP is recognized by loss of pericyte function and capillary occlusions together leading to breakdown of blood-retinal barrier, edematous changes and proliferation of vessels and fibrous tissue. Depending on stage of DRP, there are different preferable therapeutic approaches applied. In the case of ETDRS, in the area of leakage focal treatment should be performed, while panretinal photocoagulation is applied towards ischemic areas or beginning proliferations. Vitreal haemorrhage followed by fibroproliferative changes or tractional retinal detachment is treated by vitrectomy alone or in combination with ILM peeling. In pathogenesis of DRP, Insulin Growth Factor (IGF-1) can play an important role in production of VEGF (Vascular Endothelial Growth Factor). Hypoxia can up-regulate VEGF expression levels leading to pathologic ocular neovascularisation. An application of intravitreal corticosteroid treatment modulates vascular permeability by suppressing the production of VEGF, reducing both extracellular matrix metalloproteinase activity and basic fibroblast growth factor, decreasing major histocompatibility complex 2 Ag expression levels, and inhibiting activity of inflammatory cells. Clinical effects of treatment using intravitreal corticosteroids are evaluated by reduction of macular thickness and visual improvement. Intravitreal use of Anti-VEGF drugs, Pegaptanib, Ranibizumab and Bevacizumab can modify vasoproliferation, trigger macular edema, and, therefore, influence a prognosis for visual loss.
 ...
PMID:Eye disorders in diabetes: potential drug targets. 1853 2