1,215 results
Search Results
2. Forthcoming papers.
- Subjects
MEDICAL research ,IMMUNOLOGY ,MICROBIOLOGY ,IMMUNOGLOBULINS ,EPITHELIAL cells ,DENDRITIC cells - Abstract
Presents several research works related to immunology. "Innate mechanisms for Bifidobacterium lactis to activate transient pro-inflammatory host responses in intestinal epithelial cells after the colonization of germfree rats," by Pedro Ruiz, Micha Hoffmann and Silke Szcesny; "Paired immunoglobulin-like receptors and their MHC class I recognition," by Toshiyuki Takai; "Activation of murine dendritic cells and macrophages induced by Salmonella enterica serovar Typhimurium," by Ruwani Sagarika Kalupahana, Pietro Mastroeni and Duncan Maskell.
- Published
- 2005
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- View/download PDF
3. Immune responses in newly developed short-lived SAM mice II. SELECTIVELY IMPAIRED T-HELPER CELL ACTIVITY IN <em>IN VITRO</em> ANTIBODY RESPONSE.
- Author
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Hosokawa, T., Hosono, M., Hanada, K., Aoike, A., Kawai, K., and Takeda, T.
- Subjects
T cells ,LEUCOCYTES ,IMMUNOGLOBULINS ,ANTIGENS ,LYMPHOCYTES ,CELL culture - Abstract
New short-lived strains of mice (SAM-P), which have been developed by Takeda et al. (1981), show a defective antibody response to T dependent (TD) antigen in vitro, as demonstrated in the accompanying paper (see page 419). In the present study, we investigated the cellular site of the defect, using a cell culture system. In this paper, it is demonstrated that T-helper (Th) cell activity for the antibody response to TD antigen is impaired, while other cellular immune responses, e.g. mixed leucocyte reaction, cytotoxic T-lymphocyte response, and delayed-type hypersensitivity reaction, are normal. These results suggest that the defect in T-helper subset is limited in helper function for the antibody response, and that the helper function for the cell-mediated immune responses is intact. These two functions of the T-helper subset are apparently regulated in a different manner. The SAM-P strains of mice may thus serve as an appropriate model for studying functional heterogeneity in T-helper/inducer cell subsets. [ABSTRACT FROM AUTHOR]
- Published
- 1987
4. Complement activation by human IgG antibodies to galactose‐α‐1,3‐galactose.
- Author
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Bernth Jensen, Jens Magnus, Laursen, Nick Stub, Jensen, Rasmus Kjeldsen, Andersen, Gregers Rom, Jensenius, Jens Christian, Sørensen, Uffe B. Skov, and Thiel, Steffen
- Subjects
COMPLEMENT activation ,GALACTOSE ,IMMUNOGLOBULINS ,COMPLEMENT inhibition ,FLOW cytometry ,ESCHERICHIA coli - Abstract
Summary: Some human antibodies may paradoxically inhibit complement activation on bacteria and enhance pathogen survival in humans. This property was also claimed for IgG antibodies reacting with terminal galactose‐α‐1,3‐galactose (Galα3Gal; IgG anti‐αGal), a naturally occurring and abundant antibody in human plasma that targets numerous different pathogens. To reinvestigate these effects, we used IgG anti‐αGal affinity isolated from a pool of normal human IgG and human hypogammaglobulinaemia serum as a complement source. Flow cytometry was performed to examine antibody binding and complement deposition on pig erythrocytes, Escherichia coli O86 and Streptococcus pneumoniae serotype 9V. Specific nanobodies were used to block the effect of single complement factors and to delineate the complement pathways involved. IgG anti‐αGal was capable of activating the classical complement pathway on all the tested target cells. The degree of activation was exponentially related to the density of bound antibody on E. coli O86 and pig erythrocytes, but more linearly on S. pneumoniae 9V. The alternative pathway of complement amplified complement deposition. Deposited C3 fragments covered the activating IgG anti‐αGal, obstructing its detection and highlighting this as a likely general caveat in studies of antibody density and complement deposition. The inherent capacity for complement activation by the purified carbohydrate reactive IgG anti‐αGal was similar to that of normal human IgG. We propose that the previously reported complement inhibition by IgG anti‐αGal relates to suboptimal assay configurations, in contrast to the complement activating property of the antibodies demonstrated in this paper. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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5. Using monoclonal antibodies to investigate molecular immunology: there's more to know!
- Author
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Milling, Simon
- Subjects
MONOCLONAL antibodies ,IMMUNOLOGY ,CELLULAR immunity ,IMMUNOGLOBULINS - Abstract
Summary: The study of cellular and molecular immunology is almost completely dependent on monoclonal antibody technology. Despite the relatively long history of monoclonal antibodies, there is still huge potential for developing novel and transformative uses for this technology. In this issue of Immunology, we present two such papers, one focussing on anti‐complement (C5) antibodies, the other on anti‐CD6‐specific antibodies. Both manuscripts describe novel ways that monoclonal antibodies may be used for scientific and potentially for therapeutic benefit. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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6. <em>In vitro</em> Production of Chicken Globulins and Precipitating Antibody.
- Author
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Patterson, R., Suszko, Irena M., and Pruzansky, J.J.
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IMMUNOGLOBULINS ,IMMUNOLOGY ,SPLEEN ,CHICKENS ,GLOBULINS ,IMMUNOFLUORESCENCE - Abstract
Immunofluorescent and isotope coprecipitation techniques provided methods of studying in vitro production of antibody by chicken spleen cells. In some culture preparations precipitating antibody was produced in sufficient quantity to be measured by quantitative techniques. The in vitro production of globulins by chicken spleen cells has been demonstrated by paper and immunoelectrophoresis of tissue culture medium. The antibody in the globulin produced in the in vitro tissue culture preparations may be shown by an autoradiograph of the immunoelectrophoresis after the addition of antigen trace labelled with radioactive iodine. [ABSTRACT FROM AUTHOR]
- Published
- 1964
7. Increased expression of TACI on NOD B cells results in germinal centre reaction anomalies, enhanced plasma cell differentiation and immunoglobulin production.
- Author
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Banday, Viqar S., Thyagarajan, Radha, Sundström, Mia, and Lejon, Kristina
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B cells ,PLASMA cells ,CELL differentiation ,IMMUNOGLOBULINS ,TYPE 1 diabetes ,CYCLOPHILINS - Abstract
B cells have an important pathogenic role in the development of type 1 diabetes in the non-obese diabetic ( NOD) mouse. We have previously reported that NOD mice display an increased percentage of TACI
high -expressing B cells compared with C57 BL/6 mice and this trait is linked to chromosomes 1 and 8. In this paper the genetic association of the transmembrane activator, calcium modulator and cyclophilin ligand interactor ( TACI) trait was confirmed using double congenic NOD. B6C1/Idd22 mice. TACI ligation by a proliferation-inducing ligand ( APRIL) has been shown to influence plasma cell differentiation, immunoglobulin production and isotype switch. Hence, the functional consequence of the up-regulation of TACI on NOD B cells was analysed both in vitro and in vivo. NOD B cells stimulated with APRIL showed an enhanced plasma cell differentiation and class switch to IgG and IgA compared with B cells from C57 BL/6 mice. Moreover, flow cytometry analyses revealed that germinal centre B cells in NOD failed to down-regulate TACI. Availability of the TACI ligand B-cell activating factor ( BAFF) has been shown to be a limiting factor in the germinal centre reaction. In line with this, upon immunization with 4-hydroxy-3-nitrophenylacetyl hapten-conjugated hen egg lysozyme, NOD mice produced higher titres of low-affinity antibodies compared with C57 BL/6 mice. This observation was supported by the detection of increased levels of BAFF in NOD germinal centres after immunization compared with C57 BL/6 by immunofluorescence. Our results support the hypothesis that increased TACI expression on NOD B cells contributes to the pathogenesis of type 1 diabetes in the NOD mouse. [ABSTRACT FROM AUTHOR]- Published
- 2016
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8. The T-cell response to haptenated insulins II. THE ANTIBODY RESPONSE.
- Author
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Florys, M., Wallace, G.R., Oettel, K., and Chain, B.M.
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T cells ,INSULIN ,IMMUNOGLOBULINS ,LYMPHOCYTES ,GLYCINE ,CELL proliferation - Abstract
As described in an accompanying paper, trinitrophenyl (TNP) modification of pork insulin (PI) at the A1 glycine position allows this molecule to stimulate a proliferative response in H-2
b (B10) mice. We now show that this antigen stimulates low IgG responses in the same strain of mice. Our results show that T-cell help and proliferation may therefore be regulated independently. [ABSTRACT FROM AUTHOR]- Published
- 1989
9. Delineation of two defects responsible for T-cell hyporesponsiveness to concanavalin A in MRL congenic mice.
- Author
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Cameron, R. and Waterfield, J. D.
- Subjects
T cells ,IMMUNOGLOBULINS ,CELL proliferation ,MICE ,GENETICS ,CYTOLOGY - Abstract
MRL-lpr mice and their congenic counterparts MRL- + spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL- + and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL- + mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CRA PEC. The defect could not be explained by a failure of M RL- + or M RL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: (i) the failure of antigen-presenting cells in MRL- + and MRL-lpr to provide the necessary signals to immunocompetent T cells, this defect not being associated with the lpr gene, and (ii) the lpr gene controlled outgrowth of a unique T-cell population that cannot respond in our assay system. [ABSTRACT FROM AUTHOR]
- Published
- 1986
10. Control of human T-colony formation by interleukin-2.
- Author
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Jourdan, M., Commes, T., and Klein, B.
- Subjects
T cells ,LYMPHOCYTES ,INTERLEUKIN-2 ,CHROMATOGRAPHIC analysis ,IMMUNOGLOBULINS ,MONOCLONAL antibodies - Abstract
T-colony formation can be induced in PHA-stimulated peripheral blood mononuclear cells (PBM) from man, but not in PHA-stimulated purified T cells, the latter requiring the presence of factors produced by PHA-stimulated PBM and termed T-colony promoting activity (TCPA). In this paper, we demonstrate that interleukin-2 (IL-2), the growth hormone of T lymphocytes, controls T-colony formation. We show that: (i) IL-2 activity and TCPA produced by PHA-activated PBM are co-purified by gel filtration and chromatography on blue agarose, a procedure which yields a 850-fold IL-2 purification; (ii) recombinant IL-2, produced by genetically manipulated Eseherichia coli, can induce T-colony formation in PHA-stimulated purified T cells; (iii) Monoclonal antibody against the IL-2 receptor (anti-Tac antibody) completely inhibits the T-colony formation in PHA-stimulated PBM when directly added to the culture system. [ABSTRACT FROM AUTHOR]
- Published
- 1985
11. Immunochemical properties of some monoclonal IgE antibodies to 4-hydroxy-3-nitrophenylacetyl (NP).
- Author
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Bose, R., Bundesen, P. G., Holford-Stevens, V., Stefura, W. P., Kelly, K. A., Jeffrey, J. C., Rector, E. S., Fischer, J., Sehon, A. H., and Schwenk, R. J.
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IMMUNOGLOBULIN E ,IMMUNOGLOBULINS ,MONOCLONAL antibodies ,IMMUNOCHEMISTRY ,IMMUNITY ,CELL lines ,CELL culture - Abstract
Several hybridoma cell lines secreting NP-specific, murine IgE antibodies were generated by fusion of P3-X20 (γ,κ) tumour cells with spleen cells from (BALB/c x C57Bl/6)F
1 (CB6F1 ) mice previously immunized with NP-ovalbumin. Four subclones (designated NP-ε-3.57, NP-ε-15,88, NP-ε-91,58 and NP-ε-95,31) were propagated in vivo and milligram quantities of the corresponding IgE antibodies were purified from ascitic fluid by gel filtration, ion exchange chromatography and affinity chromatography. Immunological analyses and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDSPAGE) indicated that NP-ε-15,88, NP-ε-91,58 and NP-ε-95.31 all possessed λ1 (or possibly λ3 ) light chains; and that NP-ε-3,57 possessed λ2 light chains; NP-&elipson;-95,31 also expressed the P3-X20 derived, MOPC-21 κ light chain. Radioallergosorbent test (RAST) titration curves, generated from the interaction of the four monoclonal IgE antibodies with NP-BSA attached to paper discs (NP-BSA-P) were found to be non-overlapping. Measurements of the relative amounts of NP-ε-aminocaproic acid (NP-CAP) and 4-hydro-3-iodo-5-nitrophenylacetyl-ε- aminocaproic acid (NIP-CAP) that were required to inhibit by 50% the binding of the 4 IgE antibodies to NP-BSA-P indicated that these antibodies were all heteroclitic, since their affinity for NIP appeared to be higher than their affinity for NP. These results, in conjunction with other findings reported in the literature, suggested that the V regions of NP-specific IgE antibodies are similar to the V regions of NP-specific IgM and IgG antibodies, produced by the same mouse strains. Finally, in vitro histamine release measurements demonstrated that two of these monoclonal IgE antibodies could mediate antigen induced histamine release from passively sensitized rat peritoneal mast cells. [ABSTRACT FROM AUTHOR]- Published
- 1984
12. Characterization of immunogenic properties of haptenated liposomal model membranes in mice III. SPECIFICITY OF DELAYED-TYPE HYPERSENSITIVITY AND ANTIBODY FORMATION.
- Author
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Van Houte, A. J., Snippe, H., Peulen, Gemma T. M., and Willers, J. M. N.
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BIOLOGICAL membranes ,MICE ,ANIMAL models in research ,DELAYED hypersensitivity ,IMMUNOGLOBULINS ,HAPTENS ,IMMUNOLOGY - Abstract
This paper describes the specificity of delayed-type hypersensitivity (DH) and antibody formation in the mouse to the tripeptide-enlarged hapten, 3-(p-azobenzenearsonate)-N-acetyl-L-tyrosylglycylglycine (A). Hapten A was coupled to phosphatidylethanolamine (PE) and incorporated into liposomal membranes (A PE-liposomes). DH was measured as footpad swelling and antibody formation by the enumeration of direct plaque-forming cells in the spleen. A-PE-liposomes mixed with the cationic, surface-active lipid, dimethyl dioctadecyl ammonium bromide (DDA) induce, on intracutaneous injection in mice, hapten-specific DH without a contribution by the carrier. With other haptenated liposomes it was not possible to induce DH to those haptens, including the closely related hapten 3-(p-azobenzenesulphonate)-N-acetyl-L-tyrosylglycylglycine (S). A-PE- and S-PE-liposomes evoke, after intravenous injection in mice, a humoral response. The antibody formation to A-PE-liposomes was thymus-independent. In this response a considerable cross reaction between haptens A and S was observed. [ABSTRACT FROM AUTHOR]
- Published
- 1981
13. The Immune Response of the Lactating Rat to <em>Nippostrongylus brasiliensis</em>.
- Author
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Connan, R.M.
- Subjects
IMMUNE response ,IMMUNOLOGY ,IMMUNE recognition ,IMMUNOLOGICAL tolerance ,MILK yield ,IMMUNOGLOBULINS - Abstract
It has previously been shown that rats do not expel a primary infection of Nippostronglus brasiliensis during lactation. In the present paper, three aspects of the immune response of the lactating rat to the parasite were examined and compared with the response of non-lactating rats. Protective and reaginic antibodies were present in the circulation of rats first infected during lactation, in titres as high or higher than those in non-lactating controls. The intestinal mast cell response was similar both in timing and magnitude and lactating rats became susceptible to shock with the i.v. injection of antigen. Attention was drawn to the similarity between the response of the lactating rat and that of the neonate to this infection. [ABSTRACT FROM AUTHOR]
- Published
- 1973
14. Grass Pollen Allergens III.--THEIR DIFFERENTIATION FROM THE OTHER POLLEN ANTIGENS BY IMMUNO-ELECTROPHORETIC STUDIES IN RELATION TO SKIN REACTIVITY, ENZYMIC DIGESTIONS, HEAT AND <em>p</em>H STABILITIES.
- Author
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Augustin, Rosa
- Subjects
ORCHARD grass ,POLLEN ,ALLERGENS ,ANTIGEN-antibody reactions ,ANTIGENS ,IMMUNOGLOBULINS ,IMMUNITY - Abstract
Heat and pH stability studies and experiments with organic solvents show that the A-antigens discussed in the preceding paper (Augustin, 1959c) are much more labile than the I-(‘inner ring’) antigens. Breakdown products and/or aggregates are produced which no longer precipitate with antisera to the original extracts, but act as inhibitors. Solutions of pollen allergens, on the other hand, are found to withstand even autoclaving for 15 min. at 20 atm. and vigorous boiling over the naked flame of a bunsen burner. None of the carbohydrates tested has a demonstrable effect on skin reactivity which is, however, destroyed by crystalline pepsin, crystalline trypsin, a crystalline mould protease and a tissue protease (a partially purified extract from rabbit spleen). It follows that the bulk of the allergens—if not all—are proteins. The relation of skin reactivity, immuno-electrophoretic patterns, carbohydrate and protein reactions to the selective destruction of the pollen antigens is investigated. Pollen components prove to have a somewhat wider range of electrophoretic mobilities than serum proteins and are probably as complicated a mixture. The most and least highly negatively charged components are without skin reactivity in allergic subjects. The skin reactive allergens appear to have the mobilities of α- and β-globulins. Not all the hay fever subjects react equally to all the components, and Cocksfoot and Timothy activity patterns vary in different subjects. [ABSTRACT FROM AUTHOR]
- Published
- 1959
15. Sensitive detection of anti‐spike antibodies enables improved understanding of SARS‐CoV‐2 pathogenesis.
- Author
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Milling, Simon
- Subjects
SARS-CoV-2 ,PATHOGENESIS ,IMMUNOGLOBULINS ,VIRUS diseases ,IMMUNE response ,INFECTION - Abstract
Summary: Mass vaccination of the global population against SARS‐CoV‐2 will, we hope, turn the tide against this devastating pandemic. To complement vaccinations, better tools are needed to enable viral infections and immunological protection to be monitored. Accurate tools provide sound data for informed decision‐making at many levels, from personal to governmental. The measurement of viral RNA is currently routinely used to detect active infections, but only gives a positive result during infection and is unable to reveal historic infections. Tests involving a detection of SARS‐CoV‐2‐specific antibodies can reveal prior exposures to virus and can measure anti‐viral immune responses induced after natural infection or after vaccination. They may eventually also be used to predict an individual's likelihood of becoming re‐infected. Here, we report on the development of a sensitive ELISA technique to detect multiple isotypes of antibodies against the spike glycoprotein, in samples of both serum and saliva. This paper provides an important step towards understanding the immune response to SARS‐CoV‐2 and may therefore eventually help us to effectively control it. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
16. Purification, characterization and immunolocalization of porcine surfactant protein D.
- Author
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Soerensen, C. M., Nielsen, O. L., Willis, A., Heegaard, P. M. H., and Holmskov, U.
- Subjects
CELLS ,CONNECTIVE tissues ,IMMUNOGLOBULINS ,CHROMATOGRAPHIC analysis ,GLANDS ,ELECTROPHORESIS - Abstract
Surfactant protein D (SP-D) is a collectin believed to play an important role in innate immunity. SP-D is characterized by having a collagen-like domain and a carbohydrate recognition domain (CRD), which has a specific Ca
2+ -dependent specificity for saccharides and thus the ability to bind complex glycoconjugates on micro-organisms. This paper describes the tissue immunolocalization of porcine SP-D (pSP-D) in normal slaughter pigs using a monoclonal antibody raised against purified pSP-D. Porcine SP-D was purified from porcine bronchoalveolar lavage (BAL) by maltose-agarose and immunoglobulin M affinity chromatography. The purified protein appeared on sodium dodecyl sulphate–polyacrylamide gel electrophoresis as a band of∼53 000 MW in the reduced state and∼138 000 MW in the unreduced state. Porcine SP-D was sensitive to collagenase digestion and N-deglycosylation, which reduced the molecular mass to∼24 000 MW and∼48 000 MW respectively, in the reduced state. N-deglycosylation of the collagen-resistant fragment, reduced the molecular mass to∼21 000 MW showing the presence of an N-glycosylation site located in the CRD. Porcine SP-D bound to solid-phase mannan in a dose and Ca2+ -dependent manner with a saccharide specificity similar to rat and human SP-D. The purified protein was used for the production of a monoclonal anti-pSP-D antibody. The antibody reacted specifically with pSP-D in the reduced and unreduced state when analysed by Western blotting. Immunohistochemical evaluation of normal porcine tissues showed pSP-D immunoreactivity predominantly in Clara cells and serous cells of the bronchial submucosal glands, and to a lesser extent in alveolar type II cells, epithelial cells of the intestinal glands (crypts of Lieberkühn) in the duodenum, jejunum and ileum and serous cells of the dorsolateral lacrimal gland. [ABSTRACT FROM AUTHOR]- Published
- 2005
- Full Text
- View/download PDF
17. Prevalence of salivary anti‐SARS‐CoV‐2 IgG antibodies in vaccinated children.
- Author
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Badano, María Noel, Duarte, Alejandra, Salamone, Gabriela, Sabbione, Florencia, Pereson, Matias, Chuit, Roberto, and Baré, Patricia
- Subjects
IMMUNOGLOBULIN G ,IMMUNOGLOBULINS ,VACCINATION ,VIRAL antibodies ,BOOSTER vaccines - Abstract
Keywords: antibodies; mucosal immunology; vaccination; viral EN antibodies mucosal immunology vaccination viral 384 387 4 06/19/23 20230701 NES 230701 Abbreviations 95% CI 95% confidence intervals BAU/mL binding antibody units per mL GMC geometric mean concentrations Vaccination against COVID-19 has mitigated the impact of SARS-CoV-2 infection, decreasing the probability of progression to severe disease and death in vaccinated people. In this study, we observed a high salivary antibody prevalence (81%), detecting antibodies even in children whose last contact with SARS-CoV-2 antigens had been 270 days before sample collection. Antibody concentrations in binding antibody units (BAU) per mL (BAU/mL) were obtained interpolating the OD 450 nm values of samples into a calibration curve constructed with the provided standard (400 BAU/mL). [Extracted from the article]
- Published
- 2023
- Full Text
- View/download PDF
18. HLA-linked immune suppression in humans.
- Author
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Sasazuki, T., Kikuchi, I., Hirayama, K., Matsushita, S., Ohta, N., and Nishimura, Y.
- Subjects
HLA histocompatibility antigens ,IMMUNOSUPPRESSION ,IMMUNOGLOBULINS ,T cells ,ANTIGENS ,IMMUNE response - Abstract
There is no doubt that HLA-DR molecules are acting as the products of HLA-linked immune response genes (Ir-genes), because (i) HLA-DR molecules are the restriction elements in the interaction between CD4
+ helper T cells and antigen-presenting cells (APC) to respond to many antigens such as streptococcal cell wall antigen (SCW) (Nishimura & Sasazuki, 1983; Sone et al., 1985; Hizayama et al., 1986), schistosomal antigen (Sj) (Hirayama et al., 1987), Mycobacterium leprae antigen (ML) (Kikuchi et al., 1986) and so on; and (ii) anti-HLA-DR monoclonal antibodies completely abolish the immune response to those antigens (Nishimura & Sasazuki, 1983; Sone et al., 1985). However, genetic analysis of the immune response to those antigens in families or populations revealed that responsiveness is recessive and non-responsiveness to those antigens is a dominant genetic trait that is tightly linked to HLA (Sasazuki et al., 1980a, 1983; Watanabe et al., 1988). This is completely opposite to the situation under the Ir-gene control where responsiveness is dominant and non-responsiveness is recessive. In this paper, we report evidence of how we came across the concept of HLA-linked immune suppression genes (Is-genes) besides Ir-genes, and show evidence for the epistatic interaction between HLA-DR and DQ to determine the immune response to several antigens in humans. [ABSTRACT FROM AUTHOR]- Published
- 1989
19. Immunological tolerance then and now: was the Medawar school right?
- Author
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Nossal, G. J. V.
- Subjects
IMMUNOLOGICAL tolerance ,IMMUNOLOGY ,T cells ,IMMUNE response ,B cells ,IMMUNOGLOBULINS ,BONE marrow ,ANTIGENS ,GENETIC mutation - Abstract
As perhaps the staunchest advocates of repertoire purging as the central mechanism of immunological tolerance, we note with satisfaction a spate of recent, elegant papers which suggest an intrathymic clonal abortion model as the explanation for at least some examples of T-cell tolerance. This view agrees with the classical formulation of the Billingham-Brent-Medawar school of tolerance as a specific, central failure of immune responsiveness. Repertoire purging within the B-lymphocyte compartment remains much more controversial. There is no doubt that experimental models exist where the B cell is the reversible target of tolerance induction. The question is, in view of the ease of inducing autoantibody formation both in vivo and in vitro, just how relevant are such clonal anergy mechanisms to authentic self-tolerance? Arguments are presented that there must be two windows of tolerance susceptibility in the ontogeny of the B cell; one while it is maturing in the bone marrow, to prevent autoreactivity of high affinity to important accessible self-antigens; and a second soon after activation of pre-memory cells by exogenous antigen, to prevent fortuitous mutations towards high-affinity anti-self-reactivity establishing a forbidden clone. [ABSTRACT FROM AUTHOR]
- Published
- 1989
20. Recirculation of lymphocyte subsets (CD5+ , CD4+ , CD8+ , T19+ and B cells) through fetal lymph nodes.
- Author
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Kimpton, W. G., Washington, E. A., and Cahill, R. N. P.
- Subjects
PHENOTYPES ,LYMPHOCYTES ,ANTIGENS ,IMMUNOGLOBULINS ,CORD blood ,IMMUNOLOGY - Abstract
The experiments reported in this paper examine the cell-surface phenotype (CD5, CD4, CD8, TI9, MHC class II and sIg) and cell output of lymphocyte subsets circulating through a subcutaneous lymph node in the sheep fetus, in an environment unaffected by foreign antigen and circulating immunoglobulins. CD4
+ lymphocytes were the major T-cell subset in fetal lymph and were clearly enriched in lymph compared with blood, whereas TI9+ , CD8+ and B lymphocytes were not. It seems likely that in the fetus CD4+ lymphocytes are extracted from the blood at a faster rate than are other T-cell subsets and B cells. There was a much higher percentage of CD8+ and T null cells and a lower percentage of MHC class II+ and B cells circulating in the fetal lymph than in adult lymph, while the percentage of TI9+ lymphocytes in fetal blood was twice that in the adult. Although the hourly cell output from an adult prescapular lymph node was far higher than that from a fetal lymph node, the circulation of lymphocytes through fetal lymph nodes was much greater per gram lymph node weight than that through adult lymph nodes. The wholesale recirculation in the fetus of all the major T-cell subsets found in the adult is paradoxical because it is not known what function they serve in the fetus in the absence of antigen and ongoing immune responses, although clearly they are not memory cells. [ABSTRACT FROM AUTHOR]- Published
- 1989
21. T-cell activation: I. EVIDENCE FOR A FUNCTIONAL LINKAGE BETWEEN CLASS I MHC ANTIGENS AND THE TC--TI COMPLEX.
- Author
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Brams, P. and Claesson, M. H.
- Subjects
MHC antibodies ,IMMUNOGLOBULINS ,T-cell receptor genes ,ANTIGENS ,IMMUNITY ,AMINO acids - Abstract
This paper examines the possibility of a functional linkage between class I MHC molecules and the T-cell receptor complex for antigen (T3-Ti). A newly developed anti-CD3 antibody (500A2) was used as an activation signal for EL4 lymphoma cells and allospecific cytotoxic T-cell clones (CTL), and the production of IL-2/IL-2 receptor in EL4 cells and serine esterase in CTL was determined. Anti-CD3 antibody-induced activation of both EL4
+ and CTL cells was enhanced in the presence of immunologically cross-linked and immobilized anti-H-2 (class I) antibody reactive against the H-2 haplotype of the responding T cells. A number of H-2-negative and H-2-positive EL4 subclones were generated and tested for anti-CD3 antibody-induced IL-2/IL-2 receptor production. Although both H-2-positive and -negative subclones expressed CD3 antigen and produced IL-2 after activation with the phorbol ester TPA, only the H-2-positive cell clones produced IL-2 and expressed IL-2 receptor after anti-CD3 antibody induction. Our results are compatible with the existence of a functional linkage between the class I and the CD3 molecules on the surface of T cells. [ABSTRACT FROM AUTHOR]- Published
- 1989
22. Traffic and proliferative responses of recirculating lymphocytes in fetal calves.
- Author
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Hein, W. R., Shelton, J. N., Simpson-Morgan, M. W., and Morris, B.
- Subjects
THORACIC duct ,CALVES ,LYMPHOCYTES ,GESTATIONAL age ,IMMUNOGLOBULINS ,T cells ,IMMUNE system - Abstract
The thoracic duct or efferent prescapular duct was cannulated in four fetal calves aged 121-259 days post-conception. The duration of lymph flow ranged from 2 to 20 days and the mean flow rates sustained over these collection periods varied from 54 to 488 ml/hr. Lymphocyte output ranged from 44 × 10
6 cells/hr in thoracic duct lymph from a 121-day fetus to 3.9 × 108 cells/hr in efferent prescapular lymph from a 259-day fetus. The circulating lymphocyte pool in fetal calves of about 120 and 190 days gestational age was calculated to contain, respectively, 4 × 108 cells and 2 × 1010 cells. The proportion of lymphocytes bearing surface immunoglobulin detected in fetal lymph ranged from 2.1% to 8.7%. Recirculating lymphocytes from fetal calves produced strong proliferative responses when stimulated by T-cell mitogens but responded poorly to B-cell mitogens. Fetal lymphocytes also responded to stimulation by allogeneic cells and stimulated other cells to proliferate during mixed lymphocyte culture. When stimulated with Con A, fetal lymphocytes secreted IL-2 to a degree that was indistinguishable from the secretory behaviour of lymphocytes from adult animals. The results presented in this paper show that chronic lymphatic fistulae can be established successfully in fetal calves to give access to recirculating lymphocytes. This provides a new experimental approach for studying the development of the bovine immune system. [ABSTRACT FROM AUTHOR]- Published
- 1988
23. Variable-region sequence homologies of human <em>K</em>-chains with idiotypic serologic similarities.
- Author
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Kim, H. S. and Deutsch, H. F.
- Subjects
IMMUNOGLOBULINS ,COMPLEMENT (Immunology) ,PROTEINS ,HOMOLOGY (Biology) ,SEROLOGY ,IDIOTYPIC networks - Abstract
An antibody to the V-region of a kI light chain has been used to detect other human sc-chains with similar idiotypic specificitics that appear to be related to complementarity-determining regions (CDR). Four such proteins, three of which react with this antibody, have been sequenced. While the proteins show relatively strong sequence similarities in their CDR2 regions, the relatively high degree of homology in a localized segment of the V-region of A-chains detected by this method was not observed here. [ABSTRACT FROM AUTHOR]
- Published
- 1988
24. Characterization of the Group I and Group II antibody response against PC-KLH in normal and T15 idiotype-suppressed BALB/c mice.
- Author
-
Bruderer, U., Aebersold, R., Blaser, K., and Heusser, C. H.
- Subjects
IMMUNOGLOBULINS ,AMINO acid sequence ,BLOOD plasma ,AMINO acids ,ORGANIC acids ,PROTEIN analysis - Abstract
The memory response of BALB/c mice to phosphocholine-keyhole limpet haemocyanin (PC-KLH) consists of two antibody populations, designated Group I and Group II, that differ in their fine specificity, as determined by hapten inhibition using phosphocholine (PC) and p-nitrophenylphos-phocholine (NPPC). It is known that Group I response is dominated by T15 idiotype-positive antibodies that utilize the VH I heavy-chain gene in combination with V
K 22 light-chain gene. In this paper we show that Group II serum antibodies of BALE/c mice are also highly restricted in their heterogeneity, as determined by N-terminal amino acid sequence analysis. Furthermore, we demonstrate that the Group II response is not affected by neonatally induced T15 suppression, whereas the Group I response in these mice consists of T1 5-negative antibodies. This suggests that the expression of the two antibody populations is regulated independently. Finally, we show that the isotype distributions within a fine specificity are the same in normal and T15-suppressed mice. Interestingly this is true not only for the Group II but also for the Group I antibodies. Because the isolated Group I antibodies from normal mice differ in structure from those of T15-suppressed mice, i.e. different light chains, our data indicate that the isotype distribution of these two populations is associated with their fine specificity in addition to their clonal origin. [ABSTRACT FROM AUTHOR]- Published
- 1988
25. Role of a SER immune suppressor in immune surveillance.
- Author
-
OH, S. K., ROSS, S., WALKER, J., and ZEISEL, S.
- Subjects
IMMUNOSUPPRESSION ,CANCER patients ,BODY fluids ,HAPTOGLOBINS ,IMMUNOGLOBULINS ,B cells - Abstract
A potent immunosuppressor factor, known as SER (suppressive E-receptor factor) has been identified in the body fluids of cancer patients. SER has been proven to be immunochemically analogous to the fetal form of haptoglobin. In this paper, we examine the role of SER immune suppressor in the immune surveillance mechanism of the host, using an affinity-purified SER. As shown in this study, SER, at µg/ml concentrations, inhibits the T-cell proliferation induced with either monoclonal or polyclonal T-cell activators in vitro in human, and also inhibits the primary antibody response to T-dependent antigens in vivo in mice. Likewise, SER also inhibits the immunoglobulin synthesis of human B lymphocytes induced by a B-cell mitogen, pokeweed mitogen, in the presence of a tumour promoter, phorbol myristate acetate (PMA). In contrast to the T-dependent antibody response in vivo in mice or T-dependent mitogen response in vitro in human, SER does not interfere with the T-independent antibody responses to DNP-Ficoll or TNP-LPS in mice. SER also interferes with the natural killer cell function of human peripheral blood mononuclear cells. Although SER inhibits the phagocytic functions of human peripheral neutrophils, it requires at least 10-20 times the concentration of SER present in normal human plasma. Since this concentration of SER is attainable in the sera of solid tumour-bearing patients, highly elevated levels of SER could predispose the patients to microbial infections as well. This study demonstrates that purified SER manifests multi-faceted down-regulatory effects on the defence mechanism of hosts, thereby it could compromise the patients' cell-mediated immunity in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 1988
26. Cross-reactive variable-region associated epitopes of human IgG1λ paraprotein detected by a monoclonal antibody panel.
- Author
-
Walker, L. C., Dhut, S., Gregory, W. M., and Habeshaw, J. A.
- Subjects
IMMUNOLOGY ,MONOCLONAL antibodies ,IMMUNOGLOBULINS ,EPITOPES ,MOLECULAR immunology ,MOLECULAR biology ,LABORATORY mice ,BIOCHEMISTRY - Abstract
This paper describes the production and characterization of a panel of 15 mouse monoclonal antibodies selected for putative activity against V-region related or allotypic determinants of a single IgG1λ paraprotein obtained from a patient with malignant lymphoplasmacytoid lymphoma. The specificity of each reagent for epitopes on the heavy (H) or light (L) chain or for conformational determinants (CD) of the immunogen was determined and the ability of one reagent to compete with another for these sites investigated. The fine specificity of the antibodies was assessed by screening on a large series of normal and paraprotein-containing sera. One monoclonal showed specificity for the Glm(f) allotype. The 14 other reagents identified a minimum of nine different epitopes in the V region of the immunogen, with four antibodies detecting private conformationally determined idiotypic specificities. Eight determinants were V-region markers also expressed on other paraproteins. A total of 30 out of 159 different paraproteins cross-reacted with one or more of the antibodies. Four of the shared epitopes were λ-chain associated, three were H-chain associated and one was a conformational determinant. Homologies of λ chain were identified more frequently among other paraproteins than those of H chain. The relationship between epitope expression and H-chain class of paraprotein was not random. The frequency of expression of cross-reactivities in association with IgG1 proteins was always exceeded by higher frequency of epitope expression in association with other classes of H-chain isotype. The potential therapeutic value of such panels of characterized monoclonal reagents is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1987
27. Characteriztion of rabbit cells by monoclonal and polyclonal antibodies.
- Author
-
Ponsard, D. C., Cinader, B., Chou, C.-T., and Dubiski, S.
- Subjects
MONOCLONAL antibodies ,IMMUNOGLOBULINS ,B cells ,ANTIGENS ,BONE marrow ,LEUCOCYTES ,KILLER cells - Abstract
Reagents for the identification of rabbit cell markers have been developed at a relatively slow rate. In this paper, rabbit cells are being characterized by polyclonal antibodies against a Tall antigen (RTLA), a B-cell antigen (RABELA) and an analogue of murine Ia antigen. A number of monoclonal antibodies, specific for lymphocytes and/or bone marrow and/or polymorphonuclear leucocytes, have been used for the analysis of cells with identifiable membrane antigens. Populations that have cells with two of the above antigens in the membranes were identified. To these ends, complement-mediated cell kill by antisera alone and in mixtures was employed. [ABSTRACT FROM AUTHOR]
- Published
- 1986
28. Anti-I-J alloantisera elicited by immunization of B10.A (3R)(I-Jb) mice with bone marrow-derived macrophages from B10.A (5R)(I-Jk) mice.
- Author
-
Bradley, Linda M., Shiigi, S. M., and Malley, A.
- Subjects
BONE marrow ,IMMUNOGLOBULINS ,MACROPHAGES ,RETICULO-endothelial system ,CONNECTIVE tissue cells ,IMMUNE system - Abstract
In this paper we describe production of alloantisera specific for determinants encoded by I-J gene loci expressed on macrophages. B10.A(3R) (l-J
b ) mice were hyperimmunized with pure populations of macrophages grown in vitro from bone marrow stem cells of congenic B10.A(5R) mice. The antisera contained predominantly IgM antibody that was non-adherent to protein-A-Sepharose with a minor component of IgGI, and IgG2a antibodies that were adherent to protein.A-Sepharose. The protein- A non-adherent antibody completely blocked the in vitro generation of humoral immune responses to sheep erythrocytes by spleen cell from B10.A(5R) mice and from inbred strains that share the I-Jk haplotypes, but did not alter the responses of spleen cells of the I-Jb haplotype. In the presence of complement. both protein-A adherent and protein-A non-adherent antibodies eliminated the capacity of B10.A(5R) spleen cells to generate humoral and proliferative responses, but the functional activity of B10.A(3R) cells was unaffected. These data indicate the I-Jk specificity of the antisera. The capacity of the anti-macrophage antibody to block humoral immune induction was removed by absorption with bone marrow-derived macrophages from B10.A(5R) mice, but not from B10.A(3R) mice. Further, the B10.A(5R) macrophages completely restored the humoral responses of antibody- and complement-treated B10.A(5R) spleen cells, but B10.A(3R) macrophages showed only partial restoration that was consistent with a factor-mediated allogeneic effect. These data demonstrate the specificity of our anti-I-J sera for macrophages and indicate that bone marrow-derived macrophages express surface I-J encoded molecules. [ABSTRACT FROM AUTHOR]- Published
- 1986
29. A new monoclonal antibody (KB61) recognizing a novel antigen which is selectively expressed on a subpopulation of human B lymphocytes.
- Author
-
Pulford, K., Ralfkiaer, E., MacDonald, S. M., Erber, W. N., Falini, B., Gatter, K. G., and Mason, D. Y.
- Subjects
MONOCLONAL antibodies ,IMMUNOGLOBULINS ,MOLECULAR weights ,LYMPHOCYTIC leukemia ,LYMPHOPROLIFERATIVE disorders ,CHRONIC diseases - Abstract
The present paper describes a new monoclonal antibody (K 1361) raised against hairy cell leukaemia cells. Antibody K861 recognizes a molecule of approximately 40,000 molecular weight on human B cells. It reacts with B lymphocytes in the peripheral blood, in primary lymphoid follicles, in the mantle zone of secondary follicles, in interfollicular areas and in splenic marginal zone areas. However, germinal centre lymphoid cells do not express the antigen recognized by antibody KB6I. The antibody shows limited reactivity outside the lymphoid system, i.e. polymorphs, tissue macrophages endothelial cells in the hepatic sinusoids. Antibody K861 discriminates between different types of B- cell malignancies, reacting with the neoplastic cells in hairy cell leukaemia, chronic lymphocytic leukaemia (of B-cell type), prolymphocytic leukaemia and centrocytic lymphoma, but not with acute lymphoblastic leukaemia, germinal centre-derived lymphomas (other than centrocytic), Burkitt's lymphoma and lymphoblastic lymphoma. Antibody KB61 may be of value in the study of B-cell subpopulations and in the differential diagnosis of B-cell neoplasms. [ABSTRACT FROM AUTHOR]
- Published
- 1986
30. Increases in the numbers of immunoglobulin-secreting cells in lymph nodes responding to sperm and other stimuli: possible relationship to immunosuppression.
- Author
-
Hancock, R. J. T., Popham, A. M., Faruki, S., and Dresser, D. W.
- Subjects
IMMUNOGLOBULINS ,LYMPH nodes ,PREGNANCY ,UTERUS ,IMMUNOSUPPRESSION ,SPLEEN ,LABORATORY mice - Abstract
It has been reported that, in early pregnancy in mice, there is an increase in the number of immunoglobulin-secreting cells in the lymph nodes which drain the uterus. This paper describes the results of further investigations provoked by interest in these early changes. Increases in the numbers of immunoglobulin-secreting cells were observed in syngeneically, but scarcely or not at all in allogeneically, mated mice. Increases were not observed in surgically sterilized female mice inseminated by normal males. However, subcutaneous injection of sperm provoked massive increases in the numbers of immunoglobulin-secreting cells in the lymph nodes draining the injection site. The changes were compared with those provoked by the injection of spleen cells and LPS. The results are discussed in relation to (i) the nature of the interactions provoking the increases in the number of immunoglobulin-secreting cells and their possible relationship to immunosuppression, and (ii) the relative immunological unresponsiveness which the female shows to the challenge of inseminated sperm. [ABSTRACT FROM AUTHOR]
- Published
- 1985
31. Cellular bases of the production of and response to interleukin-2 in man: role of autologous rosette-forming T-cell subsets defined with monoclonal antibodies.
- Author
-
Fishbein, Eugenia, Alcocer-Varela, J., and Alarcón-Segovia, D.
- Subjects
T cells ,IMMUNOGLOBULINS ,INTERLEUKIN-2 ,MONOCLONAL antibodies ,LYMPHOCYTES ,INTERLEUKINS ,SCIENTIFIC experimentation - Abstract
In this paper we present experiments that indicate that, in man, most T-celI subpopulations produce interleukin-2 (IL-2), but that the main cell subpopulation which produces it, both upon activation with phytohaemagglutinin or in autologous mixed lymphocyte cultures, is that of autologous rosette-forming (Tar) T4
+ T cells. Conversely, the main IL-2-responding T-cell subpopulation is that composed of T cells depleted of Tar (T-Tar) that are T8+ IL-2 was also found to be more effectively produced by Tar cells that do not bind peanut agglutinin (PNA) than by those that do. The PNA T4+ Tar cells were also found to respond best to interleukin- I (IL-I). [ABSTRACT FROM AUTHOR]- Published
- 1983
32. Studies on the differentiation of T lymphocytes in sheep I. RECOGNITION OF A SHEEP T-LYMPHOCYTE DIFFERENTIATION ANTIGEN BY A MONOCLONAL ANTIBODY T-80.
- Author
-
Miyasaka, M., Heron, I., Dudler, L., Cahill, R.N.P., Forni, L., Knaak, T., and Trnka, Z.
- Subjects
T cells ,CELL differentiation ,ANTIGENS ,MONOCLONAL antibodies ,IMMUNOGLOBULINS ,CELL migration - Abstract
The results presented in this paper demonstrate that a mouse IgM monoclonal antibody (T-80) recognizes an antigen on cells of the T-lymphocyte lineage of sheep. However, this antibody does not identify all T cells, as 10-20% of thymocytes and some peripheral-blood T cells are negative. T-80
- thymocytes reside in the medulla. The majority of cortical thymocytes are T-80+ and classified as dull cells on the basis of antigen density per cell as measured by flow microfluorometry. In contrast, T-80+ cells in the periphery can be categorized into two populations, i.e., dull cells and bright cells. Suggestive evidence was obtained that bright T-80+ cells are fast recirculating T cells, whereas dull ceils are sessile or less easily mobilizable T cells in the periphery. In foetal environment, over 90% of thymocytes and approximately 5% of spleen cells are T-80+ at 54 days of gestation (gestation period = 150 days), which may indicate that T-cell emigration from the thymus commences well before mid-gestation in sheep. [ABSTRACT FROM AUTHOR]- Published
- 1983
33. The role of cellular Fc and C3 receptors on the complement-dependent degradation of stable soluble immunoglobulin aggregates by normal and trypsin-treated peritoneal macrophages.
- Author
-
Daha, M. R. and van Es, L. A.
- Subjects
FC receptors ,CELL receptors ,COMPLEMENT (Immunology) ,IMMUNOGLOBULIN G ,IMMUNOGLOBULINS ,MACROPHAGES ,IMMUNE response ,IMMUNOLOGY - Abstract
The experiments described in this paper were designed to determine the degradation of soluble IgG aggregates (AIgG) bearing C3b by guinea-pig peritoneal macrophages with different numbers of functional C3b receptors. The number of functional Fc receptors for AIgG containing 40 molecules of IgG per aggregate (AIgG40) were kept constant during these experiments. By increasing the concentration of trypsin for the treatment of normal peritoneal macrophages a dose-dependent inactivation of C3b receptors was achieved as determined by the binding of tetrameric [
125 I]-C3b([125 I]-AC3b). Normal peritoneal macrophages bound 148,500 AIgG40 and 60,300 AC3b per cell. Treatment of the macrophages for 15 rain at 37° with incremental amounts of trypsin from 60 to 1000 µg/ml did not affect the binding of AIgG40 to macrophages but caused a dose-related loss of up to 95% of AC3b binding, indicating functional inactivation of C3b receptors. Degradation of trichloroacetic acid non-precipitable protein of [125 I]-AIgG40 by 106 macrophages was 38±6% in medium alone and 60 ±8% in the presence of 10% fresh guinea-pig serum (NGPS) after 60 rain at 37°. The inactivation of 25%, 50%, 72% and 94% of C3b receptors by trypsin did not affect the degradation of AIgG40 in medium alone, but decreased degradation from 69% to 58%, 47%, 32% and 13% of AIgG40 respectively, in the presence of 10% GPS. Macrophages (106 ) in medium alone degraded 40%, 47%, 65% and 68% of AIgG40 beating 0, 5, 10, 16 and 20 C3b molecules per aggregate, indicating a dose-dependent enhancement of degradation by bound C3b; conversely, inactivation of 95% of C3 receptor on the macrophages resulted in 39%, 30%, 12%, 5% and 6% degradation of these AIgG40-C3b, indicating a dose-related inhibition by aggregate-bound C3b in the absence of cellular C3 receptor. These experiments stress the importance of Fc and C3b receptor co-operation and immune complex bound C3b. [ABSTRACT FROM AUTHOR]- Published
- 1982
34. The effect of human IgM rheumatoid factor on renal glomerular immune complex deposition in passive serum sickness in the mouse.
- Author
-
Ford, P.M. and Kosatka, Iva
- Subjects
IMMUNOGLOBULIN M ,IMMUNOGLOBULINS ,RHEUMATOID factor ,IMMUNOGENETICS ,IMMUNE complexes - Abstract
The results of experiments reported in this paper show that intravenously injected human IgM rheumatoid factor binds in vivo to immune complexes previously deposited in mouse glomerulus. Prior injection of human IgM rheumatoid factor does not interfere with glomerular deposition of passively administered immune complexes. Evidence is presented to show that rheumatoid factor once attached to glomerular bound immune complexes is able to act as an immunoabsorbent and to bind further circulating complexes. [ABSTRACT FROM AUTHOR]
- Published
- 1982
35. Potentiation of natural killer cell activity of human lymphocytes <em>in vitro</em>: the participation of interferon in stimulation with <em>Staphylococcus aureus</em> Cowan I bacteria but not with Protein A.
- Author
-
Kasahara, T., Harada, H., Shioiri-Nakano, K., Wakasugi, H., Imai, M., Mayumi, M., Sano, T., and Sugiura, A.
- Subjects
LYMPHOCYTES ,HUMAN beings ,INTERFERONS ,IMMUNOGLOBULINS ,STIMULANTS ,STAPHYLOCOCCUS aureus - Abstract
In the previous paper we reported that human natural killer (NK) cell activity was augmented greatly by preincubation with Staphylococcus aureus Cowan I bacteria (SpA CoI) or its Protein A. We examined here whether the augmentation with these stimulants is ascribable to the direct activation of NK cells or mediated by some soluble factors produced by the stimulants. It was found that a significant amount of interferon (IFN) was produced by the SpA CoI-stimulation but not by the Protein A-stimulation, although the latter usually induced augmentation of NK-cell activity not less than SpA CoI-stimulation. IFN produced by SpA CoI was considered to belong to α-type IFN, because it was stable at pH 2.0 and could be neutralized effectively by anti-IFNα antibody. Kinetics of NK-cell activation by SpA CoI (but not by Protein A) were very similar to those by IFNα. Furthermore, augmentation of NK-cell activity with SpA CoI-stimulated supernatant was inhibited almost completely by diluted anti-IFNα antibody, whereas augmentation with Protein A-stimulated supernatant could not be abolished by the same treatment. It was, therefore, suggested that augmentation of NK-cell activity with SpA CoI might be ascribable in most part to the IFN induced, whereas Protein A can stimulate NK or T cells directly or soluble factors other than IFN might work as well. [ABSTRACT FROM AUTHOR]
- Published
- 1982
36. <em>In vitro</em> responses to the liver antigen F.
- Author
-
Sunshine, G.H., Cyrus, Muriel, and Winchester, Guil
- Subjects
ANTIGENS ,LIVER ,AUTOIMMUNITY ,CELL proliferation ,T cells ,IMMUNOGLOBULINS - Abstract
In this paper we describe the first in vitro response to the liver alloantigen F. The anti-F response serves as a valuable model for autoimmune phenomena since priming appropriate strains of mice (responders) with allogeneic but not syngeneic type F leads to autoantibody production. The in vitro system is based on the proliferation of T cells, from mice primed in vivo with F, when coincubated with splenic adherent cells (SAC) prepulsed with F in vivo. The system displays two important correlates of the in vivo antibody response to F:1.T cells from mice primed with syngeneic F do not proliferate when incubated with SAC prepulsed with syngeneic F and 2. Mice that do not make antibody responses to allo F in vivo (DBA/2) do not show in vitro proliferative responses. These findings indicate that the proliferative assay is a good in vitro model for the F response. [ABSTRACT FROM AUTHOR]
- Published
- 1982
37. Tumour cell-antibody interactions II. <em>IN VITRO</em> STUDIES.
- Author
-
Froese, G., Berczi, I., and Israels, L.G.
- Subjects
CANCER cells ,IMMUNOGLOBULINS ,CELL communication ,IMMUNOGLOBULIN G ,IMMUNE complexes ,IMMUNOTHERAPY - Abstract
The interaction of L5178Y thymic lymphoma cells syngencic to DBA/2 mice and of normal thymocytes with goat IgG antibodies was studied in vitro. Viable turnout and normal cells exerted a rapid, continuous and temperature-dependent destruction of antibody activity. Fractionation studies of culture supernatants from antibody-coated cells revealed that a significant portion of the antibody was completely degraded to amino acids. Tumour cells digested antibody more effectively than did normal lymphocytes. This observed degradation of antibody was most extensive at 37°, significantly less at room temperature (23°) and not detectable at 0°. Undegraded antibody released from antibody-coated cells had also lost its antibody activity to a considerable extent. This was due to the formation of soluble antigen-antibody complexes, which was observed even at 0°. Cells fixed with 10% formalin bound maximum amounts of antibody were incapable of digesting antibody even at 37° and did not release immune complexes. These findings are of relevance to cancer immunodiagnosis and immunotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 1982
38. Human anti-tetanus toxin precipitating and co-precipitating antibodies.
- Author
-
Perdigón, Gabriela, Margni, R. A., Gentile, Teresa, Abatángelo, Carmen, and Dokmetjian, J.
- Subjects
TETANUS ,TOXINS ,IMMUNOGLOBULINS ,SERUM ,ELECTROPHORESIS ,ERYTHROCYTES - Abstract
A comparative study has been made of human precipitating and co-precipitating anti-tetanus toxin antibodies. IgO co-precipitating antibody represented 10% of the total antibodies in the serum and had immunological and biological properties similar to those described for co-precipitating antibodies of other animal species. Human precipitating and co-precipitating anti- bodies had the same electrophoretic mobility and were localized in the same immunoglobulin fraction. By immunoprecipitation it was not possible to find antigenic differences between precipitating and co-precipitating antibodies. Both antibodies were localized in the IgG1 and IgG3 subclasses and neither were in the IgG4 subclass. Only the precipitating antibody can form insoluble complexes with antigen. Precipitating and co-precipitating antibodies agglutinated sensitized sheep red cells, however, only the precipitating antibody agglutinated human red cells. Eight to ten times more co-precipitating antibody was required to obtain a positive reaction in PCA. Precipitating antibody activated the complement system while co-precipitating antibody lacked this capacity. This difference in behaviour could not be attributed to localization of both antibodies in different IgO subclasses. Precipitating and co-precipitating antibodies were cytophilic. Only the former activated phagocytosis and increased clearance of antigen from the blood. These results are not surprising since co-precipitating antibody does not fix complement. Competition between human precipitating and co-precipitating antibodies in opsonization was analysed. In this test competition of both antibodies for the antigen depends on their respective amounts The K= 0.18 diminished to 005 when the ratio of pp:cop. antibody changed from 10:30 to 30:70. The fact that co-precipitating antibody was isolated from the sera of vertebrates other than man indicate that this antibody could possibly play a role in some immune mechanisms. Taking into account that in previous papers we have demonstrated that co-precipitating antibody functions as a molecule with one combining site of high affinity and one of low affinity, we have proposed that this antibody could function univalently and blocks the antigen. This could facilitate chronic parasitic, bacterial and viral infections, tumour growth and other chronic infections. [ABSTRACT FROM AUTHOR]
- Published
- 1982
39. Characterization of immunogenic properties of haptenated liposomal model membranes in mice: IV. INDUCTION OF IgM MEMORY.
- Author
-
Van Houte, A. J., Snippe, H., and Willers, J. M. N.
- Subjects
IMMUNOGENETICS ,LIPOSOMES ,IMMUNITY ,IMMUNOGLOBULINS ,MEMORY ,MICE - Abstract
This paper describes the induction of IgM immune memory to haptenated liposomes in mice. The tripeptide-enlarged haptens 3-(p-azo-benzene-arsonate)-N-acetyi-L-tyrosylglycyiglycine (A) and N-(2,4-dinitrophenyl)-β-alanylglycylglycine (J) were coupled to phosphatidylethanola mine (PE) and the conjugates A-PE and J-PE were incorporated into separate liposomal membranes (monofunctional A-PE-liposomes or J-PE-Liposomes) or into the same liposomal membranes [bifunctional (A,J)PE-liposomes]. The magnitude of the humoral response was measured by the appearance of direct and indirect plaque-forming cells in the spleens of immunized mice. Intracutaneous priming of mice with A-PE-liposomes mixed with the adjuvant dimethyl dioctadecyl ammonium bromide (DDA) and secondary immunization with bifunctional (A.J)-PE-liposomes resulted in enhanced hapten A- and J-specific IgM responses. However, no switch from IgM to IgG antibodies was observed in these mice. The J-specific IgM response was enhanced only when hapten I was incorporated into a bifunctional liposome which also contained A-epitopes. in mice primed with A-PE-liposomes in the absence of DDA, a greatly diminished memory to both hapten A and J was observed. This finding indicates a crucial role for the adjuvant in the induction of memory. J-PE-liposomes and DDA were not able to induce memory to monofunctional J-PE-liposomes or bifunctional (A,J)-PE-liposomes. The possibility that hapten A-specific B lymphocytes were responsible for the induction of memory was excluded by hapten-specific blockade of these cells with a B-cell tolerogen. These data, in addition to the observation that no IgM memory could be induced in congenitally athymic nude mice, suggest that the observed memory can be ascribed to priming of hapten A-specific T lymphocytes. [ABSTRACT FROM AUTHOR]
- Published
- 1981
40. A mechanism of enhancement of immune complex deposition following <em>in situ</em> immune complex formation in the mouse glomerulus.
- Author
-
Ford, P. M. and Ivakosatka
- Subjects
IMMUNOGLOBULINS ,SERUM albumin ,BLOOD proteins ,IMMUNE complexes ,GLOMERULONEPHRITIS ,IMMUNE complex diseases - Abstract
The intravenous injection into mice of small amounts of heat-aggregated bovine serum albumin (BSA) results in deposition of BSA within the glomerulus. Injection of rabbit anti-BSA antibody at a time when all circulating BSA has been cleared results in in situ formation of BSA anti-BSA immune complexes with fixation of mouse C3. Subsequent injection of passively-prepared immune complexes gives much enhanced deposition of immune material when com- pared with mice given immune complexes alone. This paper shows that this is an antigen-specific phenomenon and not a result of non-specific trapping by damaged glomeruli. The implications of these observations on the pathogenesis of immune complex glomerulonephritis are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1981
41. Mechanisms of clonal abortion tolerogenesis II. CLONAL BEHAVIOUR OF IMMATURE B CELLS FOLLOWING EXPOSURE TO ANTI-μ CHAIN ANTIBODY.
- Author
-
Nossal, G. J. V., Pike, Beverley L., and Battye, F. L.
- Subjects
B cells ,IMMUNOGLOBULINS ,LYMPHOCYTES ,CLONING ,LABORATORY mice ,SPLEEN - Abstract
This paper uses B-lymphocyte cloning methods to quantify the effects of anti-μ chain antibody on immature and mature B cells. Nude mouse spleen lymphocytes were incubated with various concentrations of sheep anti-mouse μ chain antibody for times varying from 10 min to 24 h. They were then washed and plated in the agar B-cell colony formation assay. Five to six days later, control B cells had developed into colonies with a plating efficiency of about 5%. B cells from newborn mice pretreated with anti-μ yielded fewer colonies. Remarkably low concentrations sufficed to inhibit subsequent mitogenesis. For example, 3 μg/ml acting for 1 h or 0.1 μg/ml acting for 24 h gave > 50% inhibition. Adult B cells were about thirty-fold more resistant to negative signalling. Immature cells became more profoundly inhibited as anti-μ treatment was prolonged. Anti-Ia or anti-H2 antibodies, in the absence of complement, did not deliver a negative signal. Anti-μ pretreatment also reduced the capacity of immature B cells to form clones of anti-hapten antibody-forming cells in a liquid microculture system where the triggering stimulus was a T-cell independent antigen. Mature 'T-independent' B cells were not inhibited. Populations of hapten-specific B cells prepared by the hapten-gelatin method were investigated in the agar cloning system. Pretreatment of immature cells with anti-μ reduced their capacity to form colonies, this subpopulation of cells behaving like unfractionated B cells. Furthermore, hapten--HGG delivered a negative signal also. Mature hapten-specific cells or unfractionated immature spleen cells formed normal numbers of colonies following hapten HGG treatment. Overall, the studies support the view that anti-μ antibody and hapten--HGG deliver strong negative signals to immature but not mature cells with appropriate receptors. The value of anti-μ as a model, universal tolerogen was supported. Fluorescence-activated cell sorter (FACS) analysis was performed to study the relationships between functional inhibition and Ig receptor modulation. We confirmed that the IgM receptors of immature B cells are more readily modulated by anti-μ antibody than those of mature cells. Furthermore, the receptor regeneration could be partially inhibited amongst immature but not mature B cells. There was not a close quantitative relationship between the degree of modulation and the degree of functional inhibition. The results did not support the view that irreversible receptor modulation as such was the cause of functional inhibition. [ABSTRACT FROM AUTHOR]
- Published
- 1979
42. The elevation of adoptive responses to sheep erythrocytes in protein-deficient mice.
- Author
-
Price, Patricia
- Subjects
ERYTHROCYTES ,PROTEINS ,IMMUNOGLOBULINS ,IMMUNE response ,CELL proliferation ,IMMUNOLOGY - Abstract
Plaque-forming cell responses and antibody titres to sheep red cells (SRC) were elevated in normally-fed irradiated adult mice reconstituted with spleen cells from young mice which had received a 4% albumin diet, compared with those given cells from normally-fed littermates. This was independent of the dose of cells transferred (5 × 10
6 -4 × 107 ), the day of assay (3–10) and the duration of protein-deficiency (1 or 3 weeks). It suggests that the depressed responses produced by protein-deficient (donor) mice reported in earlier papers resulted from an impairment of reticuloendothelial function or a shortage of protein reserves, not directly associated with the spleen. As protein-deficiency (of the donor) accelerated the initiation of the adoptive response and increased the cell yields of the recipients it is considered likely that an enhancement of cell proliferation during the first 3-5 days after transfer was responsible for the elevated responses. [ABSTRACT FROM AUTHOR]- Published
- 1978
43. The immunodepressive effect of Friend virus: III. EFFECTS ON SPLEEN T CELLS.
- Author
-
Dracott, B.N., Wedderburn, Nina, and Doenhoff, M.J.
- Subjects
T cells ,SPLEEN ,FRIEND virus ,IMMUNOGLOBULINS ,PHYTOHEMAGGLUTININS ,B cells - Abstract
Examines various types of T lymphocyte functions in the spleens of mice infected four days previously with Friend virus (FV) in order to analyze its effect on the antibody response. Finding that infection does not reduce the percentage of T lymphocytes in the spleen, nor the ability to respond to phytohemagglutinin (PHA); Results suggesting that FV does not affect spleen T lymphocyte proliferation or helper function; Conclusion that the immune defect resides in the B lymphocytes.
- Published
- 1977
44. Antibody formation in mouse bone marrow.
- Author
-
Benner, R. and Van Oudenaren, A.
- Subjects
IMMUNOGLOBULINS ,BONE marrow ,ESCHERICHIA coli ,ENDOTOXINS ,BACTERIAL antigens ,LYMPHOID tissue ,IMMUNE system ,LABORATORY mice - Abstract
Mouse bone marrow is capable of a distinct plaque-forming cell (PFC) response after i.v. immunization with the thymus-independent antigen E. coli lipopolysaccharide (LPS). Both during the primary and secondary response to i.v. administered LPS the spleen contained the majority of PFC until about 5 days after immunization. In the course of the reaction the number of PFC in the bone marrow rose to a level which surpassed the level in the spleen. This paper deals with the regulating influence of the spleen on the primary and secondary anti-LPS PFC response in the bone marrow. Splenectomy prior to the first injection of 5 μg LPS i.v. initially did not affect the bone marrow PFC response. However, at the 7th day after immunization the PFC response in the bone marrow fell to only 10 per cent of the bone marrow PFC activity in sham-splenectomized mice. In contrast to the primary response no regulating influence of the spleen on the bone marrow PFC activity could be demonstrated during the secondary response. The influence of splenectomy on the appearance of B-memory cells in the bone marrow depended on the priming dose. The appearance of LPS-specific B-memory cells in the bone marrow was not affected by splenectomy at priming doses of LPS as high as 1 and 0.1 μg. On the other hand splenectomy before 0.01 μg LPS i.v. reduced, and splenectomy prior to 0.001 μg LPS i.v. completely prevented the appearance of B-memory cells in the bone marrow. [ABSTRACT FROM AUTHOR]
- Published
- 1977
45. Intracellular modifications induced in mouse submaxillary glands by antibodies directed against saliva.
- Author
-
Weill, J.C. and Goldberg, M.
- Subjects
IMMUNOGLOBULINS ,ANTIGENS ,SALIVARY glands ,SUBMANDIBULAR gland ,SALIVA ,IMMUNOLOGY - Abstract
The purpose of this paper is to investigate whether an antibody directed against the exocrine secretion, saliva, is able to induce a modification in vivo within the specific cells of the submaxillary glands which synthesize this secretion. The salivary antigens synthesized within the glandular acinar cells are secreted into they respective lumen and are not present in the general circulation or in the intercellular spaces of the gland. When heterologous anti-saliva antibodies are injected into mice, they induce marked lesions within the acinar cells of the submaxillary glands. When different antibodies recognizing different salivary components are injected, they ail induce similar modifications; it is not yet possible to distinguish whether different cells are involved in the synthesis of the different salivary components. The lesions described seem specific since other organs studied, such as the pancreas and the stomach, are unaffected. The different possible mechanisms of this cytotoxic effect are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1976
46. Characterization of a T-lymphocyte inhibitor in the serum of tumour-bearing mice.
- Author
-
Levy, Julia C., Smith, Anajane C., Whitney, R. B., McMaster, R., and Kilburn, D. G.
- Subjects
T cells ,IMMUNOGLOBULINS ,CANCER in animals ,MICE as carriers of disease ,LYMPHOCYTES - Abstract
Sera from mice with large tumours from a variety of tissue types and sources have been shown to contain substances capable of suppressing the proliferative response of normal mouse lymphocytes to concanavalin A (Con A), bacterial endotoxin (LPS) and allogeneic cells. The present paper deals with studies on the nature of these inhibitory materials using mainly a methylcholanthreneinduced rhabdomyosarcoma in DBA/2J mice. It was found that a material responsible for inhibition of the Con A response eluted with immunoglobulins on Sephadex G-150 and eluted with monomeric immunoglobulin on Sephadex G-200. The component of tumour-bearer serum responsible for the suppression of the LPS response of normal lymphocytes eluted from Sephadex G-150 with the α and β globulins and albumin (molecular weight < 150,000). The immunoglobulin-containing serum fraction from tumour-bearing animals inhibited the mixed lymphocyte response, Con A response, and specific immune response to purified protein derivative (PPD) in allogeneic cell systems. It also inhibited the in vitro primary response of mouse cells to sheep red blood cells, and, to a lesser extent, the response to a T cell-independent antigen (DNP-dextran). The inhibitory activity continued to elute with monomeric IgG on Sephadex G-200 when columns were run in 1640 medium and adjusted to pH 2.5, indicating that an acid dissociable complex was not responsible for inhibitory activity. Inhibitor activity could be removed by absorption on immunoadsorbents containing goat anti-mouse immunoglobulin, and could be recovered by acid elution from the adsorbent. Inhibitor activity was not removed by immunoadsorption on columns prepared with antisera to chicken immunoglobulin. [ABSTRACT FROM AUTHOR]
- Published
- 1976
47. A Proposition on the Distribution of Antibody Affinities, with Implications for the Mechanism of B-cell Activation.
- Author
-
Taylor, R. B.
- Subjects
ANTIGENS ,IMMUNOGLOBULINS ,B cells ,SERUM ,LYMPHOCYTES ,PLASMA cells - Abstract
For most antisera a linear relationship can be shown between log antigen concentration and the log concentration of antibody required to bind half the available antigen. This paper shows that the slope of this line, s, is related to the distribution of individual antibody clonotypes of different affinity. It is argued that the general form of the distribution approximates to exponential (rather than for example Gaussian) and that this indicates a requirement for some force to be exerted through the antigen-receptor bond in order to activate a B cell. An alternative parameter, A, which gives more weight to high affinity clonotypes, is offered in place of K
0 as a measure of the avidity and biological effectiveness of an antiserum. [ABSTRACT FROM AUTHOR]- Published
- 1975
48. Antigen-binding Small Lymphocytes in the Guinea-pig II. THE IMMUNOLOGICAL RESPONSE TO PURIFIED PROTEIN DERIVATIVE OF MAMMALIAN TUBERCULIN.
- Author
-
Donald, D., King, D. J., and Beck, J. Swanson
- Subjects
ANTIGENS ,IMMUNITY ,IMMUNOGLOBULINS ,LYMPHOCYTES ,IMMUNE system ,GUINEA pigs - Abstract
A mean of 6.9 per cent of small lymphocytes in peripheral blood preparations and between 1.8 and 2.4 per cent of small lymphocytes in lymph node, spleen, bone marrow and thymus preparations from unimmunized guinea-pigs bound
125 I-labelled purified protein derivative of mammalian tuberculin (mammalian PPD). The percentage of these cells fluctuated but did not alter substantially after immunization with BCG or with BCG emulsified with human thyroglobulin (HTg) in Freund's incomplete adjuvant (FIA). Blocking experiments indicated that the binding of125 I-labelled mammalian PPD was specific and there was tentative evidence that the lymphocyte receptors may be IgG. A comparison is drawn between the observed time course of125 I-labelled mammalian PPD- binding small lymphocytes and the response of lymphocytes sensitive to strong histocompatibility antigens, and it is proposed that the propensity of certain anti- gens to induce a delayed hypersensitivity-type response is related to the presence of substantial numbers of antigen-binding cells in unimmunized animals. A noteworthy incidental finding was an unexplained depression in the cellular and humoral responses to mammalian PPD in guinea-pigs that had been immunized with HTg-BCG-FIA emulsion. [ABSTRACT FROM AUTHOR]- Published
- 1974
49. Characterization of a monoclonal antibody that recognizes a lymphocyte surface antigen for the cetacean homologue to CD45R.
- Author
-
De Guise, S., Erickson, K., Blanchard, M., Dimolfetto, L., Lepper, H., Wang, J., Stott, J. L., and Ferrick, D. A.
- Subjects
IMMUNOGLOBULINS ,CD antigens ,LYMPHOCYTES - Abstract
As part of our current efforts to develop assays and reagents to study the immune system of marine mammals, and in view of the effort currently made to develop monoclonal antibodies to cell surface proteins of lymphocyte subsets in different species, the present paper reports on the characterization of a monoclonal antibody against the homologue of CD45R on cetacean lymphocytes. The specificity of this antibody has been characterized on the basis of immunoprecipitation of the antigen it recognized, immunoperoxidase staining on cetacean lymph node and thymus sections, as well as one and two-colour flow cytometric analysis of cetacean peripheral blood mononuclear cells and single-cell suspensions of thymus, lymph node and spleen. Anti-cetacean CD45R (F21.H) immunoprecipitated proteins of 180, 200 and 220×10
3 MW, with the 180×103 MW form being predominantly expressed on T cells and the 220×103 MW form expressed predominantly on B cells and thymocytes. F21.H labelled all B cells and a proportion of T cells on single-cell suspensions of spleen cells. CD45R- killer whale peripheral blood lymphocytes expressed a higher density of CD2 than CD45R+ , a characteristic of memory T cells. Killer whale T lymphocytes also lost the expression of CD45R upon activation with concanavalin A (Con A) and phytohaemagglutinin (PHA). This is the first report of a monoclonal antibody to CD45R in cetaceans, and this antibody is foreseen as a possible valuable diagnostic and research tool to assess immune functions of captive and wild cetaceans as part of the evaluation of their health status. [ABSTRACT FROM AUTHOR]- Published
- 1998
- Full Text
- View/download PDF
50. The high-affinity FcγRI on PMN: regulation of expression and signal transduction.
- Author
-
Hoffmeyer, F., Witte, K., and Schmidt, R. E.
- Subjects
NEUTROPHILS ,CELLULAR signal transduction ,APOPTOSIS ,IMMUNOGLOBULINS ,TYROSINE ,PHOSPHATASES ,CHEMILUMINESCENCE - Abstract
In this paper we report that interferon-γ(IFN-γ) maintains and enhances functional properties of terminally differentiated polymorphonuclear cells (PMN). Such effects are obvious when compared with untreated PMN declining in their functional response. Culture for 18 hr with 100 IU/ml of recombinant IFN-γ resulted in the expression of about 15000 FcγRI per PMN. IFN-γ maintained viability of PMN and prevented reduction of FcγRIIIb caused by apoptosis. No alterations were found in the level of FcγRIIa. Next, functional properties of FcγRI were evaluated. Calcium mobilization was detected in fura-2/acetoxymethylester (AM)-loaded PMN using a spectrophotometer and the respiratory burst was measured as luminol-dependent chemiluminescence. Cross-linking of an F(ab')
2 fragment of monoclonal antibody (mAb) 22.2 to FcγRI gave similar results to those obtained with intact monomeric human immunoglobulin G (mhIgG) when subsequently cross-linked. Moreover, after blocking Fc&gammalRIIa and FcγRIIIb with respective mAb fragments, mhIgG was still effective in triggering a calcium flux demonstrating that second messenger generation was caused by FcγRI engagement. Even though FcγRI expression was lower than that of FeγRIIa, FcγRI induced a higher increase of the respiratory burst. In addition, the protein tyrosine phosphatase CD45 was able to inhibit both ,responses when it was co-cross-linked with CD64, suggesting involvement of tyrosine phosphorylation in early signalling steps. [ABSTRACT FROM AUTHOR]- Published
- 1997
- Full Text
- View/download PDF
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