This brief review is dedicated to the legacy of Prof. Jaroslav Šterzl and his colleagues, who laid the foundation for gnotobiology in the former Czechoslovakia 55 years. Prof. Sterzl became one of the founders of modern Czechoslovak immunology, which was characterized by work on a wide range of problems needing to be solved. While examining the mechanisms of innate immunity, he focused his studies on the induction of antibody production by immunocompetent cells involved in adaptive immune transmission while using the model of pig fetuses and germ-free piglets and characterizing immunoglobulins in the sera of these piglets. Although not fully appreciated to this day, his experimental proof of the hypothesis focused on the common precursor of cell-forming antibodies of different isotypes was later confirmed in experiments at the gene level. Prof. Sterzl's work represented a true milestone in the development of not solely Czechoslovak but also European and global immunology. He collaborated closely with the World Health Organization for many years, serving there as leader of the Reference Laboratory for Factors of Innate Immunity.

• Keywords
• Germ-free model, Gnotobiology, Host-pathogen interaction, Innate immunity, Microbiota,
• MeSH
• Germ-Free Life * MeSH
• Host-Pathogen Interactions * MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Gastrointestinal Microbiome MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The mouse Nramp1 (Bcg) gene on chromosome 1 exerts pleiotropic effects on macrophage function. The gene is known to affect presentation of mycobacteria, and other antigens in vitro, so that macrophages carrying the resistant Bcg allele better support the proliferation of antigen-specific T cells compared with macrophages of the sensitive phenotype. To determine whether the Bcg allele could affect in vivo the antibody response to antigens not related to mycobacterial infections, we tested the primary and secondary responses to sheep red blood cells (SRBC) and glycosylated bovine insulin (G-insulin) in two pairs of Bcg congenic strains: BALB/c (Bcgs) versus BALB/c.CD2 (Bcgr), and B10.A (Bcgs) versus B10Ar (Bcgr), and in C57BL/10ScSn (B10; Bcgs) and A/J (Bcgr) mice. Furthermore, the antigen-specific proliferative responses of T cells primed in vivo by protein antigens were also tested in Bcg congenic mice. We found no significant difference in in vivo antibody response either to SRBC or G-insulin between the Bcgr and Bcgs strains. The magnitude of in vitro antigen-specific proliferation of lymph node cells sensitized in vivo by hen egg lysozyme (HEL) or chicken ovalbumin (OVA) was also similar in Bcgs and Bcgr congenic mice. However, we have documented a higher antigen-presenting capacity of Bcgr macrophages in in vitro antigen-specific proliferation to OVA. Since the macrophages are the only cells in which the Nramp1 gene is expressed, we suggest that the activity of other types of antigen-presenting cells masks the effect of the Bcgr allele on antigen-presentation in vivo.

• MeSH
• Cell Division immunology   MeSH
• Antibody-Producing Cells immunology   MeSH
• Epitopes immunology   MeSH
• Erythrocytes immunology   MeSH
• Glycosylation MeSH
• Mice, Inbred Strains MeSH
• Insulin immunology   MeSH
• Lymph Nodes immunology   MeSH
• Macrophages immunology   MeSH
• Membrane Proteins genetics   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Antigen Presentation MeSH
• Cation Transport Proteins * MeSH
• T-Lymphocytes immunology   MeSH
• Carrier Proteins genetics   MeSH
• Antibody Formation genetics   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Epitopes MeSH
• Insulin MeSH
• Membrane Proteins MeSH
• natural resistance-associated macrophage protein 1 MeSH Browser
• Cation Transport Proteins * MeSH
• Carrier Proteins MeSH

The conditions for induction of memory cells (B-MC) and evocation of the secondary antibody (Ab) response in tissue cultures (TC) were estimated. (1) In vivo primed B-MC cells were isolated 6-150 d after priming and stimulated in TC with different doses of sheep red blood cell (SRBC) antigen. The Ab response has a strict time and dose dependence: only small doses (10(5)) evoke a secondary response, high doses (10(8), 10(9)) a state of immediate tolerance. (2) Antigen added to TC directly with B-MC rescued their Ab production for a long period. Addition of the antigen 1 or 2 d after setting the TC, follows the Ab-response decay, comparable with virgin cells (B-ICC). (3) Primed B-MC stimulated in TC responded preferentially with an IgM secondary response; the same cell suspension adoptively transferred into isologous recipients switched into IgG cells. (4) Virgin, immunocompetent, B-ICC were primarily stimulated in TC with a small dose of antigen (10(5) SRBC); after 7 d of cultivation the cells were transferred into isologous recipients, SCID mice and into TC. In all cases, the secondary response of IgM was determined, 10 times higher than in the primary controls.

• MeSH
• B-Lymphocytes immunology   MeSH
• Immunoglobulin G biosynthesis   MeSH
• Immunoglobulin M biosynthesis   MeSH
• Immunologic Memory * MeSH
• Rabbits MeSH
• Culture Techniques MeSH
• Cells, Cultured MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Spleen metabolism   MeSH
• Antibody Formation * MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Immunoglobulin G MeSH
• Immunoglobulin M MeSH

The mitogenic effects on mouse spleen lymphocytes were determined in a large series of commercially available and laboratory-prepared lipopolysaccharides (LPS) obtained from Escherichia, Salmonella, Serratia and Shigella species; part of these LPS preparations was chemically modified prior to testing. In order to establish whether the degree of mitogenic activity corresponds with other biological effects of these preparations, polyclonal activity, capability to induce specific antibody formation and toxicity were determined for selected LPS's with different mitogenic effects. Some of the detoxication procedures used succeeded in reducing the toxicity of LPS while preserving its high mitogenic activitione of the Fe-detoxified preparations of LPS (from the R-form of Shigella dysenteriae serovar 1) exhibited a medium-degree efficacy in all parameters studied. Generally, there was no correlation between the degree of mitogenic activity and the polyclonal and antibody-inducing activities, but in some instances polyclonal activity did correlate with the antibody-inducing activity.

• MeSH
• Lymphocyte Activation drug effects   MeSH
• Antibody-Producing Cells chemistry   MeSH
• Endotoxins immunology   toxicity   MeSH
• Enterobacteriaceae immunology   MeSH
• Rabbits MeSH
• Lipopolysaccharides immunology   toxicity   MeSH
• Mice MeSH
• Antibodies, Bacterial biosynthesis   MeSH
• Pyrogens biosynthesis   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Endotoxins MeSH
• Lipopolysaccharides MeSH
• Antibodies, Bacterial MeSH
• Pyrogens MeSH

After repeated i.p. immunizations of mice with 10 micrograms of homopolymer poly (HPMA) no antibodies were detected by the ELISA test. Immunization with copolymer P-Acap-Leu-HMDA leads to a weak antibody response, while immunization with a copolymer with some side chains modified with ARS or FITC groups (P-Acap-Leu-HMDA-ARS or P-Acap-Leu-HMDA-FITC) leads to a significant antibody response detectable by PFC, ELISA and haemagglutination tests. Most of these antibodies are aimed against the modifying haptenic group, a smaller amount against side oligopeptide sequences of the carrier. Intensity of the antibody response depends on: 1) the antigen dose--the optimal dose was 10 micrograms: both the higher (100 micrograms) and the lower doses (1 and 0.1 micrograms) induced considerably lower antibody responses; 2) molar mass of the immunizing fractions--fractions of high molar mass induced up to five times higher responses than those of a low molar mass; 3) the bound haptenic group--the ARS-copolymers induced ten times lower response than the FITC-copolymers. We detected no difference between capacities of the H-2a, H-2b and H-2d haplotypes to react with anti-ARS antibodies after immunization with P-Acap-Leu-HMDA-ARS.

• MeSH
• Acrylamides immunology   MeSH
• Pharmaceutical Vehicles immunology   MeSH
• H-2 Antigens genetics   MeSH
• Haptens immunology   MeSH
• Immunization MeSH
• Mice, Inbred Strains immunology   MeSH
• Polymethacrylic Acids immunology   MeSH
• Mice, Inbred C57BL immunology   MeSH
• Mice MeSH
• Antibodies analysis   MeSH
• Antibody Formation MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acrylamides MeSH
• Pharmaceutical Vehicles MeSH
• H-2 Antigens MeSH
• Haptens MeSH
• Polymethacrylic Acids MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Browser
• Antibodies MeSH

Effect of 44 colchicine derivatives on the induction of antibody response in tissue cultures was tested. Lymphatic cells from the spleen of BALB/c mice were cultivated with antigen (sheep red blood cells) and the number of antibody forming cells was determined by the plaque technique. Most compounds with the immunoinhibitory effect are derived from the colchicine formula (I). The effect was increased by introducing ethyl, formyl or methylenedioxide groups. Colchinols exerted very good immunoinhibitory effect resulting by contraction of tropolone ring C into the aromatic one. A complete loss of the effectivity was detected in the case of glucoside of colchicine, colchiceine, isocolchicine, oxycolchicine, allocolchicine and in lumiderivatives of colchicine. No correlations between the immunoinhibitory effect, toxicity and stathmokinetic effect were detected: decrease of cell viability and arrest of mitoses were not observed in cultured lymphocytes within the range of the immunoinhibitory effect. The effect of colchicine derivatives was manifested as the inhibition of lymphocyte blastogenesis, which is probably the result of membrane transport blockade.

• MeSH
• Colchicine metabolism   pharmacology   MeSH
• Cells, Cultured MeSH
• Lymphocytes drug effects   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Antibody Formation drug effects   MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Colchicine MeSH

The immunostimulatory and immunoinhibitory effects of 44 hydroxyanthra- and hydroxynaphthoquinone derivatives in tissue culture were investigated. In the test system used, the final effect, i.e. production of antibodies against sheep red blood cells is a result of cooperation between macrophages, T lymphocytes and B lymphocytes. It was found when testing selected 20 derivatives that methylation, acetylation or substitution of the hydroxy group by the amino group led to the loss of the inhibitory activity and, on the contrary, pronounced immunostimulatory effects could be observed in other derivatives. Naphthoquinones (juglone, lawsone) were more effective as immunoinhibitors than anthraquinones (alizarin, quinizarin) and their derivatives. In both groups of compounds glucosidation results in a substantial increase of the immunoinhibitory effect. The present work is a part of a more extensive study concerning modification of the molecules of various compounds and its relationship with the effect on immunological reactions.

• MeSH
• Adjuvants, Immunologic pharmacology   MeSH
• Anthraquinones pharmacology   MeSH
• Antibody-Producing Cells drug effects   MeSH
• Erythrocytes immunology   MeSH
• Immunosuppressive Agents pharmacology   MeSH
• Cells, Cultured MeSH
• Naphthoquinones pharmacology   MeSH
• Sheep MeSH
• Cell Count MeSH
• Spleen cytology   immunology   MeSH
• Antibody Formation drug effects   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• Anthraquinones MeSH
• Immunosuppressive Agents MeSH
• Naphthoquinones MeSH

Mice (strains Balb/c and A/J) received an intravenous infusion of bilirubin for a 1 d period. The infusion was delivered at various phases of the primary reaction; the degree of the immune response was expressed as the number of antibody-forming cells against sheep erythrocytes. Bilirubin infusion during both the inductive and productive phase of the primary reaction decreased significantly the immune response. We assume that bilirubin influences the differentiation of immunocompetent cells immediately after their contact with the antigen; in addition it acts in the period of the quantitative increase of the number of antibody-producing cells.

• MeSH
• Bilirubin pharmacology   MeSH
• Cell Differentiation MeSH
• Cell Division MeSH
• Antibody-Producing Cells drug effects   MeSH
• Immunosuppressive Agents * MeSH
• Mice, Inbred Strains MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Antibody Formation drug effects   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bilirubin MeSH
• Immunosuppressive Agents * MeSH

• MeSH
• B-Lymphocytes immunology   MeSH
• Clone Cells MeSH
• Time Factors MeSH
• Immunoglobulin G biosynthesis   MeSH
• Immunoglobulin M biosynthesis   MeSH
• Bone Marrow immunology   MeSH
• Mice, Inbred A MeSH
• Mice, Inbred CBA MeSH
• Mice MeSH
• Sheep immunology   MeSH
• Radiation Effects MeSH
• Cobalt Radioisotopes MeSH
• Spleen immunology   MeSH
• T-Lymphocytes immunology   MeSH
• Thymus Gland immunology   MeSH
• Antibody Formation * radiation effects   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Immunoglobulin G MeSH
• Immunoglobulin M MeSH
• Cobalt Radioisotopes MeSH

• MeSH
• Antibody-Producing Cells * MeSH
• Erythrocytes immunology   MeSH
• Hemolytic Plaque Technique MeSH
• Rabbits immunology   MeSH
• Mice immunology   MeSH
• Sheep immunology   MeSH
• Spleen cytology   immunology   MeSH
• Animals MeSH
• Check Tag
• Rabbits immunology   MeSH
• Mice immunology   MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH