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141.
Immune lysis of reconstituted myelin basic protein--lipid vesicles and myelin vesicles 总被引:1,自引:0,他引:1
J M Boggs N Samji M A Moscarello G A Hashim E D Day 《Journal of immunology (Baltimore, Md. : 1950)》1983,130(4):1687-1694
Complement-mediated lysis of reconstituted lipid-myelin basic protein (BP) vesicles and myelin vesicles due to antibody raised against BP and isolated myelin is measured by determination of the amount of a water-soluble spin label, tempocholine chloride, released from the vesicles. The response is shown to be antigen-specific, antibody-dependent, and complement mediated. The relative response to different anti-BP antibody samples is similar to that determined by radioimmunoassay procedures. In contrast to immunoassays with BP in aqueous solution, this method measures immune recognition of the protein in either a synthetic or a natural membranous environment. This is important because this protein has been shown to have a different conformation when bound to lipid bilayers than in aqueous solution and its conformation depends on lipid composition. It is also a more rapid method because no separation of spin label still trapped in the vesicles and that released due to immune lysis is required. In synthetic membranes consisting of sphingomyelin, cholesterol, and an acidic lipid, either phosphatidylglycerol, phosphatidic acid, or phosphatidylserine, the response was greatest when the acidic lipid was phosphatidic acid. The response did not depend significantly on the antigen concentration expressed as molar ratio of BP to sphingomyelin, over the range 0.15:600 to 2:600, although it decreased at molar ratios less than 0.15:600. The antigen density required for immune lysis of vesicles containing this protein antigen is similar to that reported elsewhere for lipid antigens, although the time required for maximal lysis was greater. Both anti-BP and anti-myelin antibodies caused a greater specific complement-mediated response with synthetic vesicles than with myelin vesicles, which may be due to the different lipid and/or protein composition of myelin. Response was also obtained with the myelin vesicles, however, indicating that some determinants of BP can be recognized on the surface of the bilayer in isolated myelin by anti-BP. 相似文献
142.
R H Whitham D N Bourdette G A Hashim R M Herndon R C Ilg A A Vandenbark H Offner 《Journal of immunology (Baltimore, Md. : 1950)》1991,146(1):101-107
Relapsing experimental autoimmune encephalomyelitis (R-EAE) can be induced in SJL/J mice by immunization with spinal cord homogenate and adjuvant. The specific Ag(s) responsible for acute disease and subsequent relapses in this model is unknown. Myelin basic protein (BP), an encephalitogenic peptide of BP (BP 87-99), and proteolipid protein (PLP) can each induce R-EAE in SJL/J mice, and a peptide of PLP (PLP 139-151) has been reported to induce acute EAE. To determine the encephalitogens in cord-immunized mice with R-EAE, the in vitro proliferative responses of lymph node cells (LNC) and central nervous system mononuclear cells to BP, BP peptides, and PLP peptides were examined during acute EAE and during relapses. LNC responded only to PLP peptides 139-151 and 141-151 and did not respond to BP or its peptides during acute or chronic disease. Central nervous system mononuclear cells also preferentially responded to PLP 139-151 and 141-151 during acute and relapsing disease. A PLP 139-151 peptide-specific Th cell line was selected from LNC of cord-immunized donors. Five million peptide-specific line cells transferred severe relapsing demyelinating EAE to naive recipients. We conclude that PLP peptide 139-151 is the major encephalitogen for R-EAE in cord-immunized SJL/J mice. We demonstrate for the first time that Th cells specific for this peptide are sufficient to transfer relapsing demyelinating EAE. The predominance of a PLP immune response rather than a BP response in SJL/J mice suggests that genetic background may determine the predominant myelin Ag response in human demyelinating diseases such as multiple sclerosis. 相似文献
143.
A single amino acid substitution in the sequence of the encephalitogenic determinant for Lewis rats destroyed its ability to induce experimental allergic encephalomyelitis (EAE) but generated a potent immunoregulatory sequence capable of suppressing the development of both clinical and histologic signs of EAE. The EAE-inducing determinant (synthetic peptide S6) H-Ala-Gln-Gly-His-Arg-Pro-Gln-Asp-Glu-Asn-OH (residues 75 to 84) of the bovine MBP induced clinical and histologic signs of EAE when it was administered at doses of 0.5 micrograms or higher. Gly substituted for the C-terminal Asn during the synthesis of peptide S6 generated the homologous sequence designated by peptide S79. Peptide S79 failed to induce either clinical or histologic signs of EAE even when it was administered at dosages up to 1000 times higher than those of S6. Similarly, rats pretreated with a single dose of S79 were not only unresponsive to an encephalitogenic challenge but also were capable of transferring unresponsiveness to syngeneic recipients with viable donor lymphocytes. The induction of unresponsiveness that was abrogated by pretreatment with cyclophosphamide suggests the development of an S79-sensitive lymphocyte subset that regulates MBP-induced EAE in Lewis rats. 相似文献
144.
George A. Hashim 《Neurochemical research》1981,6(6):699-718
Prevention and suppression of experimental allergic encephalomyelitis were demonstrated in rats, guinea pigs, and rabbits immunized with allogeneic, but not with syngeneic lymphocytes from susceptible donors sensitized to myelin basic protein (MBP). Donor lymphnode, splenic, or peripheral blood lymphocytes were effective in inducing a state of unresponsiveness to an encephalitogenic challenge in either of the three species. Unresponsiveness was not obtained in recipients immunized with sensitized allogenic lymphocytes and simulatenously challenged with MBP suggesting that a time lapse between immunization and challenge is necessary for the development of protective immunity. Induced in immunized recipients, unresponsiveness was transferred into normal syngeneic recipients with immunoglobulin-G (IgG) isolated from protected donors before challenge. Furthermore, both immunized and IgG recipients failed to develop cell-mediated immunity after challenge with MBP. The results show that prevention and suppression of EAE was mediated by antibodies which inhibited the development of delayed type hypersensitivity to the challenging antigen. 相似文献
145.
Eugene D. Day George A. Hashim Vincent A. Varitek Jr. Kenneth J. Lazarus Philip Y. Paterson 《Neurochemical research》1981,6(8):913-929
Synthetic peptides with various and overlapping sequences represented by the residue region 65–84 of bovine myelin basic protein (MBP-bov) were tested in sodium sulfate radioimmunoassays for their reactivity with 15 rabbit antisera against MBPs from six different animal species and nine pools of syngeneic Lewis rat anti-MBP antisera. Three of the peptides were labeled with125I and studied by direct binding reactions: (1) the prototype peptide S82 sequence TTHYG-SLPQKAQGHRPQDEG, corresponding to residues 65–84 of bovine MBP except for the C-terminal glycine, which is encephalitogenic in rabbits: (2) S81, which lacks the first three residues of S82 and is nonencephalitogenic in rabbits; and (3) S79, which represents the C-terminal half of S82 and which, because of its C-terminal glycine instead of asparagine, is nonencephalitogenic in Lewis rats. Fourteen of the rabbit anti-MBP antisera were reactive with [125I]S82 (two borderline) including 2 of 3 antisera against human MBP, one against monkey MBP, and one against chicken MBP. The cross-reactions with [125I]S81 were somewhat fewer and less intense. There were no cross-reactions with [125I]S79. None of nine different pools of syngeneic rat MBP antisera cross-reacted with any of the three labeled peptides. With the use of a rabbit anti-MBP-rat antiserum that crossreacted strongly with [125I]S82, 15 additional peptides with overlapping sequences within the residue region 65–84, as well as five MBP preparations from four different species, were tested by equilibrium and nonequilibrium competitive inhibition RIAs. Unlabeled S82 and MBP-bov were completely competitive with [125I]S82 in the equilibrium assays; S81 and three other peptides had low degrees of cross-reactivity; but none of the remaining eight unlabeled peptides or unlabeled MBP preparations of guinea pig, rat, or mouse origin gave any evidence of competitive activity. Nonequilibrium competitive inhibition RIAs, however, did reveal cross-reactivities among several of the peptides as well as guinea pig and rat MBP. It was concluded that the N-terminal half of S82, particularly residues 68–74 (YGSLPQK), must contain an immunodeterminant of amino acid residues which identifies with the corresponding and exposed sequence in intact MBP-bov.This research was supported at Duke University by research grants 833-E-5 from the National Multiple Sclerosis Society and NS-10237 from the National Institutes of Health of the U.S. Public Health Service; at St. Luke's Hospital Center and Columbia University by grant RG1197-A-5 from the National Multiple Sclerosis Society; and at Northwestern University by grant NS-06262 from the National Institutes of Health of the U.S. Public Health Service. 相似文献
146.
G A Hashim H Offner R Y Wang K Shukla E Carvalho W J Morrison A A Vandenbark 《Journal of immunology (Baltimore, Md. : 1950)》1992,149(8):2803-2809
The development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats is mediated by V beta 8.2+ T cells specific for myelin basic protein. One consequence of this biased expression of V beta 8.2 is the spontaneous development of regulatory T cells and antibodies against residues 39-59 of the V beta 8.2 sequence. Moreover, a synthetic V beta 8.2-39-59 peptide could induce protection against and speed recovery from EAE. T cells and antibodies specific for V beta 8.2-39-59 could transfer protection from EAE. Recently, we reported that the protective T cell epitope is subsumed within the V beta 8-44-54 sequence. We now report that protection induced by V beta 8-44-54 lasted at least 102 days and produced "split tolerance," enhancing anti-myelin basic protein antibody titers but reducing anti-myelin basic protein T cell frequency. The shorter V beta 8-44-54 peptide induced a distinct set of antibodies that did not cross-react with the longer V beta 8.2-39-59 peptide, although both specificities could stain V beta 8.2+ T cells and were equally protective against EAE. However, the V beta 8.2-39-59 peptide, but not the V beta 8-44-54 peptide, would appear to represent the natural idiotope: antibodies to V beta 8.2-39-59 that develop spontaneously during EAE could be boosted to higher titers only by the V beta 8.2-39-59, but not by other TCR peptides from the V beta 8.2 sequence, including V beta 8-44-54 that contains the functional T cell epitope. These results suggest that natural processing of the TCR V beta-chain favors the formation of a peptide that resembles the V beta 8.2-39-59 sequence. The B cell epitope present on the V beta 8-44-54 sequence was evident only in the absence of residues 39-43 and 55-59, suggesting that the two peptides possess distinct conformations. However, the V beta 8-44-54 B cell epitope is most likely expressed on the V beta 8.2+ T cells, either as a low affinity determinant on the intact TCR alpha/beta heterodimer or as a cryptic epitope bound in the cleft of surface MHC molecules. 相似文献
147.
Peripheral blood lymphocytes form rosettes in the presence of heterologous etythrocytes. Spontaneous or active rosette formation has been reported to be a measure of circulating and immunologically functional thymus-dependent lymphocytes. The present study utilizes the rosette assay to measure changes in the circulating T cells of guinea pigs sensitized with encephalitogenic myelin basic protein (BP) or with nonencephalitogenic peptide S42 known to induce cellular transformation in experimental allergic encephalomyelitis, a cell-mediated disorder of the central nervous system. The results show a significant depression in the number of active but not in the total number of rosette-forming T lymphocytes from the peripheral blood of antigen-sensitized animals. This reduction, which was not related to the encephalitogenic property of the BP, was readiiy reversible by incubating lymphocytes with the sensitizing antigen but not with histone. Under these conditions, lymphocytes from unsensitized control animals were unresponsive to stimulation by any of the antigens used. The antigenstimulated rosette assay described in this report provides a specific assay for sensitization to basic protein in BP-related demyelinating diseases. 相似文献
148.
Purified lipophilin, a hydrophobic lipoprotein of myelin, induces a cell-mediated demyelinating disease of the central nervous system similar to experimental allergic encephalomyelitis (EAE) induced by the myelin basic protein (MBP). Guinea pigs challenged with lipophilin (emulsified with CFA) developed clinical and histological signs of disease indistinguishable from those developed by animals similarly challenged with MBP. Both lipophilin and MBP induced and elicited delayed-type hypersensitivity in animals challenged with respective antigens. Tryptophan, an essential component of the MBP-determinant for disease in guinea pigs, is required for the encephalitogenicity of lipophilin. 相似文献
149.
Hashim MF Riggins JN Schnetz-Boutaud N Voehler M Stone MP Marnett LJ 《Biochemistry》2004,43(37):11828-11835
The major malondialdehyde-derived adduct in DNA is 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one (M(1)dG). M(1)dG undergoes hydrolytic ring opening in duplex DNA to 9-(2'-deoxy-beta-D-erythro-pentofuranosyl)-N(2)-(3-oxo-1-propenyl)guanine (N(2)OPdG). Template-primers were constructed containing M(1)dG or N(2)OPdG in a (CpG)(4) repeat sequence and replicated with the Klenow fragment of DNA polymerase I (Kf). Incorporation opposite the lesion and replication beyond the adduct sites by Kf was reduced compared to unadducted controls. The amount of bypass to full-length products was significantly greater with the acyclic adduct, N(2)OPdG, than with the cyclic adduct, M(1)dG. Sequence analysis indicated that the fully extended primers contained dC opposite both adducts when replication was conducted with Kf exo(+). In contrast, with Kf exo(-), primers extended past M(1)dG contained T opposite the adduct, but primers extended past N(2)OPdG contained dC opposite the adduct. Single nucleotide incorporation experiments indicated that Kf exo(-) incorporates all four nucleotides opposite M(1)dG or N(2)OPdG. Kf exo(+) removed dA, dG, and T opposite M(1)dG and N(2)OPdG but was much less active when dC was opposite the adduct. NMR studies on duplex DNA indicated that N(2)OPdG hydrogen bonds with dC in the complementary strand. The fact that base pairing can occur for the acyclic adduct may explain why N(2)OPdG is less blocking than M(1)dG. These results support in vivo findings that the ring-closed adduct, M(1)dG, is more mutagenic than the ring-opened adduct, N(2)OPdG. They also provide a detailed picture of in vitro replication in which the outcome is determined primarily by the selectivity of template-primer extension beyond rather than insertion opposite the adducts. 相似文献
150.
Nida Idrees B. Tabassum Elsayed Fathi Abd_Allah Abeer Hashem Robeena Sarah Mohammad Hashim 《Saudi Journal of Biological Sciences》2018,25(7):1365-1368
Water is considered a vital resource because it is necessary for all aspects of human and ecosystem survival. However, due to natural processes and anthropogenic activities, various pollutants have been added to the ground water system. Among these, heavy metals are some of the most serious pollutants. Cd, a toxic heavy metal used in Ni-Cd batteries, the colouration of plastic and various discarded electronic products released into the water system causes serious health issues. The chronic exposure to Cd produces a wide variety of acute and chronic effects in humans. Cd accumulates in the human body, especially in the kidneys, resulting in kidney damage (renal tubular damage), which is a critical health effect. Other effects of Cd exposure are disturbances in calcium metabolism, hypercalciuria and the formation of kidney stones. High exposure to Cd can lead to lung cancer and prostate cancer; hence, poor quality water that may result in Cd toxicity has become a global concern. Thus, the aim of this study is to determine the concentration of Cd in underground water sources in western U.P. regions. Water samples were acidified to 1% with nitric acid and then stored in double-capped polyethylene bottles for further analysis by an atomic absorption spectrophotometer. After comparing the data to the WHO (2011) permissible limit, the study revealed that the concentration of Cd was higher than the regulatory threshold; therefore, the underground water system is seriously affected by Cd toxicity. 相似文献