Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We define the initiation of elicited delayed-type hypersensitivity (DTH) as a series of processes leading to local extravascular recruitment of effector T cells. Responses thus have two sequential phases: 1) 2-h peaking initiation required for subsequent recruitment of T cells, and 2) the late classical 24-h component mediated by the recruited T cells. We analyzed DTH initiation to protein Ags induced by intradermal immunization without adjuvants. Ag-spceific initiating cells are present by 1 day in spleen and lymph nodes. Their phenotypes, determined by depletion of cell transfers by mAb and complement, are CD5(+), CD19(+), CD22(+), B220(+), Thy1(+), and Mac1(+), suggesting that they are B-1 B cells. DTH initiation is absent in micro MT B cell and xid B-1 cell deficient mice, is impaired in mice unable to secrete IgM, and is reconstituted with 1 day immune serum, suggesting that early B-1 cell-derived IgM is responsible. Study of complement C5a receptor-deficient mice, anti-C5 mAb neutralization, or mast cell deficiency suggests that DTH initiation depends on complement and mast cells. ELISPOT assay confirmed production of Ag-specific IgM Abs at days 1 and 4 in wild-type mice, but not in B-1 cell-deficient xid mice. We conclude that rapidly activated B-1 cells produce specific IgM Abs which, after local secondary skin challenge, form Ag-Ab complexes that activate complement to generate C5a. This stimulates C5a receptors on mast cells to release vasoactive substances, leading to endothelial activation for the 2-h DTH-initiating response, allowing local recruitment of DTH-effector T cells.
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PMID:B-1 B cells mediate required early T cell recruitment to elicit protein-induced delayed-type hypersensitivity. 1463 39

To prevent injury to host tissues, complement activation is regulated by a number of plasma and membrane-associated proteins, most of which limit C3 and C5 activation. An influx of circulating C3 from a syngeneic host into donor kidneys deficient in Crry (a membrane protein that reduces C3 convertase activity) causes spontaneous complement activation, primarily in the tubulointerstitum, leading to renal failure. To determine the roles of the C3a and C5a anaphylatoxins in tubulointerstitial inflammation and fibrosis, kidneys from Crry-/-C3-/- mice were transplanted into hosts lacking the C3a and/or C5a receptor. While unrestricted complement activation in the tubules was not affected by receptor status in the transplant recipient, C3a receptor deficiency in the recipients led to significantly reduced renal leukocyte infiltration and the extent of tubulointerstitial inflammation and fibrosis, all of which led to preserved renal function. The absence of C5a receptors in recipients was not only inconsequential, but the protective effect of C3a receptor deficiency was also eliminated, suggesting distinct roles of C3a and C5a receptor signaling in this model. There was significant infiltration of the tubulointerstitum with 7/4+F4/80+CD11b+ myelomonocytic cells and Thy1.2+ T cells along injured tubules, and interstitial collagen I and III deposition, all of which were C3a receptor dependent. Thus, blockade of C3a receptor signaling is a possible treatment to reduce renal inflammation and preserve renal function associated with complement activation.
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PMID:Distinct roles for C3a and C5a in complement-induced tubulointerstitial injury. 2167 37