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- Wold, Agnes E, 1955, et al.
(författare)
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Difference between bacterial and food antigens in mucosal immunogenicity.
- 1989
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Ingår i: Infection and immunity. - 0019-9567. ; 57:9, s. 2666-73
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Tidskriftsartikel (refereegranskat)abstract
- The mucosa-associated lymphoid tissue may deviate from its systemic counterpart in being able to discriminate between microbial and nonmicrobial antigens. To study this, the systemic and mucosal antibody responses to bacterial and food antigens were followed in parallel in female rats during two pregnancies and lactation periods. Germfree rats were monocolonized with an Escherichia coli O6K13H1 strain, and their diet was switched to pellets containing large amounts of ovalbumin and beta-lactoglobulin. Antibodies against O6 lipopolysaccharide already appeared in serum and bile 1 week after colonization, and those against type 1 fimbriae appeared a few weeks later. Serum immunoglobulin G antibodies against the E. coli enzyme beta-galactosidase were found in moderate titers in all rats after 16 weeks of exposure. In contrast, few rats had detectable antibody levels against the dietary proteins ovalbumin and beta-lactoglobulin in serum or bile even after 16 weeks of exposure. In the milk, antibodies against E. coli beta-galactosidase and type 1 fimbriae reached the highest titers, while moderate titers were found against the food antigens and against O6 lipopolysaccharide. The difference in immune reactivity against bacterial versus dietary antigens was not likely due to insufficient amounts of the latter reaching lymphoid tissue, since (i) uptake studies indicated that ovalbumin was more efficiently taken up than endotoxin and (ii) the same difference in antigenicity between ovalbumin and E. coli was seen after immunization directly into Peyer's patches. We therefore suggest that a prerequisite for a strong mucosal antibody response is that the antigen be encountered by the gut-associated lymphoid tissue within microorganisms capable of stimulating antigen presentation.
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- Hedin, Anders, 1952-
(författare)
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Monoclonal antibodies against carcinoembryonic antigen and their use in tumor diagnosis
- 1982
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A new CEA-related substance, (CEAlow) was isolated from liver metastases of colorectal cancer. Purified CEAlow was homogeneous by several physico-chemical criteria. It had an apparent molecular weight of 125,000. 2/9 monkey anti-CEA sera gave a spur with CEA over CEAlow in immunodiffusion. Analysis of peptide relatedness showed that CEAlow was more closely related to CEA than two other purified CEA related antigens, nonspecific cross-reacting antigen (NCA) and biliary glycoprotein I (BGPI). Since CEAlow appeared to lack unique determinants, we tentatively conclude that it is a naturally occuring fragment of CEA.Of seven monoclonal antibodies (mabs) produced against CEA, all reacted with CEAlow, 5 reacted strongly with NCA-2 (a highly cross-reactive meconium antigen) while 2 mabs were only weakly reactive, 2 were reactive with NCA and 1 gave a weak reaction with BGPI. Five different epitopes present in the peptide moiety of CEA were recoonized by these mabs. Affinity constants of 1.2-7.4x108M-T were obtained. Two mabs bound to >2 epitopes on CEA indicating regions of homology in CEA.Three mabs were used for tumor immunolocalization of CEA, containing human tumor cells (LS174T, Detroit 562 and HT29) grafted in nude mice. Excellent tumor localization was obtained with one radiolabelled antibody. A second antibody gave an intermediary degree of tumor localization while a third mab was not enriched in the tumor. Normal mouse IgG did not localize in the tumor. Similarly anti-CEA mab did not bind to grafts of a non-CEA producing sarcoma. By y-scintigraphy, the first antibocty gave a definite spot corresponding to the tumor.Two mabs were used as reagents in a two site monoclonal enzyme immunoassay (MEIA) for CEA. Both were nonreactive with NCA and BGPI. One mab was strongly reactive with NCA-2 while the other was only weakly reactive with this antigen. Interestingly, in the MEIA, all normal CEA-related antigens, including NCA-2, and normal tissue extracts were nonreactive. Sera from healthy individuals gave values <5 ug CEA/1 with this MEIA and with a RIA tested in parallel. However, the CEA values in patients with nonmalignant liver disease and ulcerative colitis were significantly lower in the MEIA than in the RIA. No difference in CEA values between the two assays was seen in patients with colon-, lung-, pancreas and breast carcinoma. We conclude that this MEIA has an increased specificity for carcinoma than conventional immunoassays against CEA.
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| 7. |
- Ohlin, Mats, et al.
(författare)
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The effect of leucyl-leucine methyl ester on proliferation and Ig secretion of EBV-transformed B lymphocytes.
- 1989
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Ingår i: Immunology. - 0019-2805. ; 66:4, s. 485-490
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Tidskriftsartikel (refereegranskat)abstract
- The selective cytotoxicity of the lysosomotropic methyl esters of leucine or its lysosomal condensation product leucyl-leucine has been used to investigate the effect of cytolytic cells on the clonal outgrowth, cellular proliferation and antibody secretion of Epstein-Barr virus (EBV)-transformed human B cells. Large granular lymphocytes (LGL), monocytes, and a subset of T cells (CD8/CD11+) were permanently eliminated by the ester treatment. These lysosome-rich cells severely inhibit the clonal outgrowth of EBV-infected B cells, as determined by Poisson distribution calculations. Furthermore, leucyl-leucine methyl ester-treated and EBV-infected lymphocytes showed a significant increase in proliferative capability as well as immunoglobulin (Ig) production (three to 11 times) compared to non-treated but similarly infected lymphocytes. Since the effect of leucyl-leucine methyl ester treatment was also detectable in low-density (100 B cells/well) cultures, the suppression was unlikely to be exerted by EBV-specific T-cell clones, but pointed rather to the natural killer (NK) cells as effectors.
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| 8. |
- Paulie, Staffan, 1951-
(författare)
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Immunological analysis of the human tumor cell surface : characterization of polypeptides associated with urinary bladder carcinoma
- 1985
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tumors express antigens characteristic of their malignant phenotype, a fact that has become exploited for the diagnosis of certain types of cancer. As these tumor-associated antigens (TAA) may also provide Information on the molecular mechanisms of tumorogenesls as well as constituting the basis for immunotherapeutlc approaches, much Interest has been focused on the Identification and characterization of TAAs.In the present study we have Investigated the cell surface of human urinary bladder carcinomas (TCC) for the presence of TAAs. Three different approaches were used: 1) lectins of various sugar specificities were employed for the Isolation and comparison of the glycoprotein patterns of different normal and malignant cells, 2) mouse monoclonal antibodies were raised against Intact TCC cells and a large number of hybridomas were searched for tumor-related reactivity, 3) antibody producing B cell cultures from TCC- patients were established by Infection with Epstein Barr virus (EBV).Totally six distinct antigens of protein or glycoprotein nature have 1n this way been Identified as being more or less restricted to TCC cells. Five of these were Identified with mouse monoclonal antibodies and have been subjected to serological analysis against a large number of normal and malignant cell types derived from cell cultures or from fresh tissue Isolates. Although showing a high degree of specificity with both cell lines and tissue the TCC-restr1cted expression was generally more pronounced in the histological samples. Thus, two antigens (plOO and the pl90, pl70 complex) were found on almost all TCC specimens but not on any other cell type tested Including normal uroepithel1um. A third antigen (p92, p23) showed a similar distributional pattern but was to some extent also found on certain normal cells. With the antibody S2C6 an interesting antigenic relationship between TCC tumors and B lymphocytes was revealed. In addition to being selectively expressed by TCC cells the S2C6 antigen (p50) appeared to represent a novel B cell marker of high restriction within the hematopoietic system. Although found on both normal and malignant B cells antigen expression was highly Increased 1n rapidly proliferating B cell cultures suggesting that expression may be growth related. Two other antigens, gp115 Identified by Its affinity for leukoagglutinln and the pl40, p85 complex defined by a mouse monoclonal antibody, have been less well established in terms of tissue type distribution but the available data suggest a close TCC-assoc1at1on also of these molecules.With hopes of finding antibody reactivities reflecting the humoral antitumor response of TCC-patients, a series of EBV-transformed B cell cultures were also established. Although no tumor-related antibodies were found 1n this Initial study the observation that B cell cultures producing antibodies to a variety of cellular antigens could be Isolated from most patients confirms that the method may be of value for the delineation of the Immune response to tumors.In conclusion, the present study has led to the Identification and preliminary characterization of several antigenic components associated with urinary bladder cancer. The restricted distribution of these molecules make them interesting as markers of this disease and their potential use for clinical applications as well as possible Implications 1n tumorogenesis 1s discussed.
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- Telemo, E., et al.
(författare)
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Maternal dietary antigens and the immune response in the offspring of the guinea-pig
- 1987
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Ingår i: Immunology. - 0019-2805. ; 62:1, s. 35-38
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Tidskriftsartikel (refereegranskat)abstract
- Guinea-pig dams and their litters were raised on either a cow's milk protein-containing diet (MCD) or a milk-free diet (MFD). At 8 weeks of age all litters were challenged i.p. with 50 μg milk whey-protein concentrate (v67) and 100 mg A1(OH)3 in saline. The immune response was estimated 2 weeks later as the serum IgG antibody titres against V67, β-lactoglobulin (β-LG) and α-lactalbumin (α-LA) using enzyme-linked immunosorbent assay (ELISA) and the tracheal Schulze-Dale response to these antigens. Feeding milk protein antigen to dams from birth and during pregnancy induces antigen-specific hyporesponsiveness (tolerance) in their offspring, despite no direct contact between the offspring and the milk proteins. Tolerance seems to be induced by the antigen itself since withdrawal of the MCD 10 days before delivery reduced tolerance in the offspring. No tolerance was produced in the offspring of dams fed the antigen from 3 months of age (adult). β-LG appears to be a major antigen in milk whey while α-LA is a minor one since there was almost no antibody or tracheal response to α-LA in any of the animals tested. The results indicate that maternal antigen experience and antigens present during pregnancy are important for the subsequent immune response to these antigens in offspring.
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