Search PubMed⌕ Search

Biomedical subjects

H Ambrosius

Publications and source records attributed to H Ambrosius.

At least 91 records · Page 5Linked to original sources

[Biochemistry of antibody production (author's transl)].

A review is given about some biochemical problems in the biosynthesis of immunoglobulins. The following problems are discussed: the specialty of the antibody biosynthesis in comparison to the production of other proteins, antigen binding by lymphocyte receptors, the process of the synthesis of H- and L-chains, the formation of immunoglobulin molecules and their secretion, primary and the secondary immune responses and their regulation, theories of antibodies formation and the problem of the origin of the high number of v genes.

Animals↗

[Effects of dialkyl tin salts on the immune system].

Single intravenous administration of 8 mg/kg of di-n-octyltin dichloride (DOTC) induced in mice a reversible decrease of thymus weight, thymocyte count and antibody titer against sheep red blood cells. After 14 days the values of treated animals were not lower than the values of control groups. The proportion of T and B lymphocytes in spleen and lymph nodes was found unchanged 4--5 days after administration of DOTC. concentrations of DOTC measured in thymus and spleen of treated mice were in the range of concentrations which are toxic for thymocytes and macrophages in vitro. The activity of di-n-alkyltin salts on the thymus of mice was independent of the length of the alkyl chains in the range of 4--8 C atoms.

Animals↗

[Comparative studies of the specificity of idiotypic guinea pig and carp antisera].

The specificity of guinea-pig- and carp-anti-idiotypic antisera were compared by using the radioimmunoassay and the passive hemagglutination inhibition test. Guinea-pigs and carps were immunized with the IgA/k mouse myeloma protein S117 which has binding activity to the hapten N-acetylglucosamine. the resulting antisera were idiotypically specified by absorption and the activity was determined by the binding of the radiolabeled idiotype S117. The binding curves of guinea pig and carp anti-idiotypic antisera are very similar. The idiotype-anti-idiotype reaction could be partially inhibited by the specific hapten N-acetylglucosamine but not by N-acetylgalactosamine. Both antisera, guinea pig and carp, respectively, are different in respect to the immunoglobulin class of anti-idiotypic antibodies which react with the idiotype S117. In the case of the guinea pig antisera the anti-idiotypic antibodies are mainly of the IgG-type whereas the anti-idiotypic antibodies of carp are exclusively of IgM-type. This important difference is discussed.

Animals↗

Anti-idiotypic antibodies of IgM-type produced in carp (Cyprinus carpio L.).

Carp synthesize highly specific anti-idiotypic antibodies of the IgM class. Ant-idiotypic antibodies could be elicited in these animals by a human IgM myeloma protein and were detected in a passive hemagglutination assay. The agglutination was completely inhibited by approximately 0.15 microgram homologous antigen, whereas a 100 000-fold excess of a heterologous IgM myeloma protein of the same L chain type did not produce any inhibition. A possible subgroup specificity of carp anti-idiotypic antisera can be excluded.

Animals↗

[Regulations of IgM immune response. IV. Effect of the hapten: carrier ratio and the nature of the carrier on the intrinsic and functional affinity of carp DNP-antibodies].

Carp anti-DNP antibodies were raised by various DNP-carrier conjugates. Their intrinsic affinity (K0) to monovalent E-DNP-L-lysine and functional affinity (DF) for binding to the multivalent DNP-T4 bacteriophages were determined. The functional affinity of antibodies elicited by T-cell-dependent DMPn-HSA (n = 3, 15, 33) is relatively high (KF):1010-1012 M-1). These KF values increase more than K0 during the immune response. The functional affinity is dependent on the molar KNP: HSA ratio. The mediate coupled DMP15-HSA elicits antibodies with the highest functional affinity. Carps immunized with T-cell-independent DNP-conjugates synthesize antibodies which have similar K0 as the antibodies elicited with DNP-HSA. However, the KF-values are in the range from 107 to 1010 M-1 only. The KF of antibodies raised with DNP-BA are 103-104 fold, those of DNP-S III and DNP-Ficoll elicited are only 4 . 101 to 4,7 . 102 fold higher than their corresponding K0-values. This means that these antibodies are not very effective in binding the multivalent DNP-T4. Specifically purified antibodies have also such low functional affinities. These strong differences in the functional affinity of carp DNP-antibodies elicited by T-cell dependent and independent DNP-conjugates are discussed with regard to stimulation of different B-cell subpopulations.

Animals↗

Studies on the regulation of igm immune response. VII. changes in the affinity of antibodies and cell receptors after immunization with the T-cell independent antigen DNP-Ficoll.

A/J-mice immunized by a single injection with DNP21-Ficoll respond on the humoral level exclusively with IgM antibodies. The intrinsic association constants (K0) of IgM anti-DNP to monovalent hapten E-DNP-L-lysine are within the range of 105-106 M-1 and do not change significantly during the immune response. On the other hand, the functional association constants (KF) of pentameric IgM to multivalent DNP-T4 bacteriophage increase from 1010 M-1 at 3rd day up to 1012 M-1 at 8th day. Subsequently, a decrease of KF to 1011 M-1 can be observed. This rise and fall of the affinity of IgM antibodies of multivalent DNP-conjugate can be detected at the cellular level also by inhibition of plaque formation. The concentration of DNP15-BSA needed for 50% inhibition of plaque formation (I50) decreases from second day to 8 th day by 4 orders, which represents a strong increase of functional affinity. In contrast, the I50 of E-DNP-L-lysine slightly decreases only until day 4 and does not change until day 21. the inhibition of rosette formation by mono- and multivalent ligands was used to study the affinity of lymphocyte receptors. In the course of immunization antigen-binding cells carrying receptors with increasingly higher affinity for multivalent DNP-conjugates occur. These results are discussed with regard to the importance of functional affinity of lymphocyte receptors for the antigen-driven selection of high affinity anti-DNP-cell clones producing IgM antibodies.

Animals↗

[Studies on the control of IgM-antibody synthesis V. Affinity of anti-DNP antibodies in carps immunized with DNP-ficoll (author's transl)].

The dynamics of affinity of anti-DNP antibodies of carps immunized with T cell independent DNP-Ficoll was studied during the immune response. The intrinsic affinity (KO) of antibodies to monovalent epsilon-DNP-lysine is 10(5)--10(6)M-1 and does not change significantly in course of the immunisation. The affinity of tetrameric IgM antibodies to multivalent DNP-T4 conjugate is only 10(2)--10(3)-fold greater than to monovalent hapten, contrary to about 10(6)-fold higher values following immunisation with T cell-dependent antigens. The functional affinity (KF) increases during immune response slightly. KO and KF or antibodies are dependent on antigen dose. High antigen doses elicite antibodies with higher affinity.

Animals↗

[Studies of the antibody heterogeneity in carp (Cyprinus carpio L.). I. Electrophoretic and isoelectric spectra of anti-DNP-antibodies].

Carp IgM as well as carp anti-DNP-antibodies migrate electrophoretically very well as a diffuse band into polyacrylamide gel of large pore size. The isoelectric spectra of the carp anti-DNP-antibodies are heterogeneous and show bands in the pI-range of 4.0 to 6.4. The activity of focused anti-DNP-antibodies could be demonstrated in the pI range between 5.4 to 6.4 even in high antibody dilutions. The investigated structural heterogeneity of the anti-DNP-antibodies of carp is a further proof for the phylogenetically early onset of a large antibody heterogeneity of lower vertebrates.

Animals↗

[Immunological studies after the cryosurgical treatment of urologic tumors].

It is stated that a general final evidence is not yet possible from the existing results of immunological investigations and it may be possible only when taking into consideration the extensive furthering controls mentioned. On the basis of the therefore further existing uncertainty in the evaluation of the immunological valency of the cryotherapy, which is expressed also in literature, the originally optimistic suggestions concerning an increased immune response to the cryotherapy must be judged critically. Even when the clininically favourable courses after cryotherapy, above all in the treatment of the penis carcinoma, may be impressible--a cryospecific immune reaction was not to be proved by the test systems at our disposal.

Cell Migration Inhibition↗

[Structural and immunochemical studies of carp (Cyprinus carpio L.) immunoglobulin. V. Tryptic fragments of carp (Cyprinus carpio L.) immunoglobulin M].

Carp IgM, isolated from normal serum is more sensitive to trypsinization compared to a human myeloma protein IgMGo. Under the same conditions (treatment with trypsin at 56 degrees C for 30 min) carp IgM was degraded to small, mostly dialysable peptides to a larger extent than IgMGo. In both cases the fragmentation resulted in immunoelectrophoretically pure Fab mu and Fc mu fragments. The Fab mu fragments of human IgM (yield: 20% of used IgM material) had a molecular weight of 54,000, the Fc mu fragments (yield: 30%) were a heterogenous mixture as far as molecular sizes concerned with values of about 300,000. For the corresponding fragments of carp IgM we could analyze a molecular weight of about 43,000 for Fab mu (yield: 8%) and for Fc mu (yield 10%) three fractions of 160,000, 130,000 and 90,000. The reductive subunits of Fc mu fragments showed different molecular weights: 39,000 for IgMGo and 45,000 for carp IgM. The anti-fragment antisera prepared in rabbits were monospecific as demonstrated by immunodiffusion.

Animals↗

[Comparative investigations of quantitative determination of cell-mediated immunity by skin test, macrophage migration inhibition test, and lymphocyte transformation test in guinea pigs (author's transl)].

Following an intradermal immunization of guinea pigs with bovine gamma globulin (BGG) and/or human serum albumin (HSA) emulsified in complete Freund's adjuvant we studied the cell-mediated immune response and its manipulation by 6-mercaptopurine. Three accepted correlates of cell-mediated immunity (CMI) have been used for the estimation of the immune reaction: - Intracutaneous test (IT) - Macrophage migration inhibition test (MMIT) - Lymphocyte transformation test (LTT). Comparative studies of quantitative determinations of CMI showed a correlation of the results of the in vitro test systems (MMIT and LTT) with the state of delayed hypersensitivity of the experimental animals, estimated by the IT in vivo. The cell-mediated immune response against BGG was much higher than that against HSA. This could be shown by all three test systems. We detected an immunosuppressive influence of 6-mercaptopurine on the CMI of guinea pigs, due to the dose and the mode of application. Thereby the in vitro test systems detected quantitative differences and indicated already a partial success of the immunosuppressive therapy, whereas the IT allowed a qualitative estimation only.

Animals↗

[6-(2,4-Dinitrophenyl)-mercaptopurine, a stronger immunosuppressive drug than 6-mercaptopurine to primary humoral T-cell dependent immune response in mice].

The suppressive effect of 6-(2,4-Dinitrophenyl)-mercatopurine (DNP-MP) and 6-mercaptopurine (MP) was investigated on the early primary immune response of mice against the T-cell dependent antigens DNP49-bovine gamma globuline (BGG), sheep red blood cells (SRBC) or FITC8-BCG and the T-cell independent DNP22-Ficoll. The number of IgM antibody forming cells (AbFC) to the hapten determinants and to the SRBCs per 10(6) spleen cells was determined. DNP-MP reduced the number of AbFCs after the immunisation with the T cell dependent antigens always stronger than the MP, independently of the antigen type by which the mice had been immunised. The Anti-DNP22-Ficoll immune response was suppressed equally by both immunosuppressive drugs. DNP-MP is not a specific immunosuppressive drug for the anti-DNP-B-lymphocytes. Helper T-cells and macrophages are discussed as target cells for the stronger unspecific action of DNP-MP.

Animals↗

[Structural and immunochemical studies on carp (Cyprinus carpio L.) immunoglobulins. IV. In vitro reassociation of carp immunoglobulin].

Mildly reduced high molecular immunoglobulin and antibody of carp with tetrameric structure, carbohydrate content of 6 to 7% and absence of J-chain can reassociate to native molecules. The disulphide bonds between subunits and polypeptide chains are sensitive and can be completly splitted by treatment with only 1 mM DTE. One half of the immunoglobulins retained their high molecular structure as expression of strong non-covalent bonds between subunits of the tetrameric molecule. The other half of immunoglobulins dissociate into HL-halfmolecules. We suppose that carps possess 2 "typs of immunoglobulins" which differ in the tendency to aggregate to high molecular immunoglobulins.

Animals↗

[Manipulations of immune reactions by antigen-immunosuppressive agent-conjugates. VI. Antigen specific binding of 6-mercaptopurine-protein conjugates by lymphocytes].

The immunologic specificity of 6-mercaptopurin-protein conjugates has been determined by rosette inhibition test using antigen-stimulated lymphocytes and antigen-coated sheep erythrocytes. The specific binding of antigen-immunosuppressive agent-conjugated onto immunocompetent cells is as strong as the binding of the native antigen. The increasing aggregation of the conjugates in consequence of the higher coupling ratio and the thus increased multivalence of the antigen may compensate the effect of antigen determinant loss.

Animals↗

[Detection of cell-mediated immunity against protein antigen by the macrophage adherence inhibition test (author's transl)].

The macrophage adherence inhibition test is a suitable assay for detection of cell-mediated immunity against bovine gamma globulin (BGG) in guinea pigs. The test was performed with peritoneal cells (PC) in hemocytometer chambers. 10 mg/ml BGG were added as antigen. The washing step was performed with a burette. An average standard deviation of 5% was obtained with this washing method. Day-to -day-investigations in individual animals show differences with respect to the degree of cell-mediated immunity against BGG. Supernatants of sensitized spleen cells or lymph node cells produce adherence inhibition in PC of nonimmunized guinea pigs too.

Animals↗

Checking of carcinoma patients with the leukocyte migration technique (LMT) under agarose.

Leukocyte migration tests under agarose (Clausen technique) were performed in 28 patients tentatively diagnosed as having any malignancy with the use of a 3 M KCl-extract panel prepared from bronchogenic, gastric, colonic, renal, and mammary carcinoma, corresponding normal tissues, carcinoembryonic antigen (CEA), and human encephalitogenic protein (HEP). 17 out of 22 proven carcinoma patients showed sensitization by reaction with optimal concentrated KCl-extract of cancer from the same organ type as their own tumor. In some cases positive reactions could be observed also with normal tissue antigen (NTA) of tumor organ type (7/22) or with an additional carcinoma extract of organ type differing from patients own primary tumor (8/22). Gastrointestinal carcinomas, especially, showed sensitization to CEA (7/12) contrary to nongastrointestinal carcinomas (1/10). With HEP no positive reactivity could be found (0/10). With the use of tumor antigen panel (5 antigens) only few positive reactions (MI less than 0.80 or greater than 1.20) could be observed in 6 patients with nonmalignant diseases (1/30 tests) and 8 healthy blood donors (1/40 tests). A widespread individual screening program using tissue antigens for patients suspected of malignancies could give a pattern of reactivities and improve the recognition of cell-mediated sensitization against tumor tissues.

Aged↗