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Biomedical subjects

I Nakashima

Publications and source records attributed to I Nakashima.

At least 253 records · Page 14Linked to original sources
PubMed1982

Differential effector functions of central and peripheral compartments of immune response system: characterization of immune responses in the spleen and mesenteric lymph nodes to directly injected sheep red blood cells.

When sheep red blood cells (SRBC) were injected intraperitoneally (i.p.), intravenously (i.v.), or into the Peyer's patches, definite plaque-forming cell (PFC) and rosette-forming cell (RFC) responses were induced in the spleen but not in the mesenteric lymph nodes (MLN). When SRBC were injected directly into the spleen or MLN, stronger PFC and RFC responses were induced in the spleen or MLN, respectively, than when injected i.p. or i.v. PFC response induced in MLN by injecting SRBC into MLN with or without the polysaccharide of Klebsiella pneumoniae type 1 Kasuya strain (CPS-K) as an immunological adjuvant was weaker than that induced in the spleen by injecting the antigen into the spleen. Direct PFC (PFC of IgM type) and RFC responses induced in the spleen by injecting SRBC into MLN were rather stronger than those induced in the spleen by injecting the antigen into the spleen. In contrast, no significant responses were induced in MLN by injecting SRBC into the spleen, and no definite indirect PFC (PFC of IgG type) response was induced in the spleen by injecting the antigen into MLN. The levels of whole immunological memory as well as isolated B- or T-cell memory in the spleen and MLN of mice injected with SRBC directly into the spleen or MLN were determined by using an in vitro assay system. Definite amounts of either B- or T-cell memory were detected in the spleen of mice injected with SRBC directly into the spleen of MLN. Smaller amounts of memory were detected in MLN injected with SRBC directly into the spleen. Moreover, the amounts of whole memory detected in MLN were much less than compared with those of isolated T- and B-cell memories in MLN. Further experiments showed that in vitro expression of the memories preserved in MLN required supplement of glass non-adherent cells from normal spleen. Based on these results, we discussed the possible differential and collaborative functions of the central (spleen) and peripheral (MLN) immune response systems in antibody responses.

Animals↗
PubMed1982

Adjuvant action of bacterial lipopolysaccharide in induction of delayed-type hypersensitivity to protein antigens. II. Relationships of intensity of the action to that of other immunological activities.

Various kinds of lipopolysaccharides (LPS) isolated from different bacterial strains exhibited more or less an adjuvant action in induction of delayed-type footpad response to ovalbumin (OA) in mice when antigen was injected subcutaneously together with LPS. There was a wide diversity in strength of the adjuvant action of LPS, and the action of the 03 antigen isolated from the culture supernatant fluid of Klebsiella was the most potent of eleven kinds of LPS tested. Besides this substance, LPS extracted from Escherichia coli 08, 09 and 0128, and Salmonella typhosa exhibited relatively strong action. The difference in strength of the action of the high and low active LPS in induction of delayed-type hypersensitivity could be observed at any doses of OA and LPS. The strength of the adjuvant activity of LPS in induction of delayed-type hypersensitivity roughly correlated with that of their adjuvant activity in augmenting immunological memory for the secondary antibody response to OA and also their ability to enlarge the regional lymph node, whereas it did not apparently correlate with that of their activity to stimulate B cells polyclonally and their ability to enlarge the spleen.

Adjuvants, Immunologic↗
PubMed1982

Alterations in the immunogenic properties of sheep erythrocytes by sonic disruption.

A solubilized sheep red blood cell (SRBC) antigen (supernatant fraction obtained by centrifuging 10(7)-2 x 108 sonicated SRBC at 6 x 10(4) g for 30 min [Sup-SRBC]), whose ability to inhibit anti-SRBC plaque formation was 70% of that of the original sonicated SRBC, was unable to elicit a detectable antibody response in either unprimed or SRBC-primed mice. However, Sup-SRBC as well as intact SRBC antigens generated memory for the secondary response, which was transferable to irradiated syngeneic recipients by injection of immune spleen cells. The memory generated by Sup-SRBC involved helper memory for anti-trinitrophenyl group (TNP) response to challenge with TNP-conjugated SRBC. Increase in the helper T cell memory in the spleens of Sup-SRBC-primed mice was also demonstrated by an in vitro culture experiment and by an adoptive cell transfer experiment. In contrast, no detectable B cell memory was generated by Sup-SRBC. Repeated stimulation with Sup-SRBC never induced significant antibody response but reduced the level of memory. A single injection of a low dose (10(6)) of SRBC also failed to induce a definite primary antibody response generating memory for the secondary response. However, repeated stimulation with this dose of SRBC induced a high antibody response and generated good memory. From these results it is suggested that the intact structure of SRBC is required for the activation of B cells, but is not necessary for the stimulation of T cells.

Animals↗
PubMed1982

Further studies of the polysaccharide of Klebsiella pneumoniae possessing strong adjuvanticity. III. Augmentation of the antibody response to subcutaneously injected sheep red blood cells by the adjuvant polysaccharide.

The adjuvant action of the O3 antigen of Klebsiella (KO3) on the antibody response to sheep red blood cells (SRBC) was elucidated by injecting both KO3 and SRBC subcutaneously at the right inguinal region of SMA mice. We demonstrated that KO3 exhibits a novel ability to augment anti-SRBC plaque-forming cell responses in both the local lymph node and the spleen at a relatively late stage of immunization. Escherichia coli lipopolysaccharide, dextran sulfate and concanavalin A showed such an action only minimally. In parallel with the development of the adjuvant action, KO3 definitely activated B cells in the local lymph node polyclonally for either IgM or IgG synthesis, suggesting that the mechanism of the adjuvant action includes direct stimulation of B cells by KO3 at the late stage. Neither increase in trapping of lymphocytes in the local lymph node nor change in tissue distribution of antigen was shown to be primarily involved in the mechanism of the adjuvant action.

Adjuvants, Immunologic↗
PubMed1981

Primary antibody responses to hapten-modified syngeneic cells: exceptional immunogenicity of erythrocytes.

Intravenous injection of fluorescein isothiocyanate-modified syngeneic spleen cells (FITC-SSC) into mice induced T cell-independent, anti-hapten plaque-forming cell responses. In contrast to the high immunogenicity of FITC-coupled SSC or bone marrow cells, thymus, lymph node or peritoneal exudate cells were poorly immunogenic. Further analysis showed that FITC-syngeneic peripheral blood red cells were as immunogenic as FITC-SSC containing a similar number of red cells. The immunogenicity of the red cells was confirmed by treatment of FITC-SSC with 0.83% ammonium chloride before sensitization with FITC. This procedure almost totally abolished the immunogenicity regardless of the concentration of hapten with which they were sensitized. In addition, heat treatment or fixation with glutaraldehyde destroyed the immunogenicity of FITC-SSC.

Ammonium Chloride↗
PubMed1981

Suppression of B-memory cell function by polyclonal lymphocyte activators.

When various polyclonal lymphocyte activators (PLA), such as the capsular polysaccharide of Klebsiella pneumoniae (CPS-K), E. coli lipopolysaccharide (LPS), concanavalin A (Con A), dextran sulfate (DS), phytohemagglutinin (PHA), and pokeweed mitogen (PWM) were injected into mice primed with sheep red blood cells (SRBC), anti-SRBC secondary plaque-forming cell (PFC) responses in vitro of their spleen cells to SRBC and to polyclonal B cell activatory (PBA) were more or less decreased. The decrease in the responsiveness was accompanied by the decrease in the number of SRBC-specific rosette-forming cells (RFC) of B-cell type (B memory cells). This resulted neither from emigration of RFC out of the spleen, nor from change of RFC to antibody-forming cells. Further, we revealed that the decreased responsiveness occurs exclusively in the B cell-rich fraction of the spleen cells from PLA-treated SRBC-primed mice, but not in their T cell-rich fraction. It is concluded therefore that PLA exhibited a common action to reduce selectively B-memory cell function by decreasing the number of B memory cells without differentiation to their end cells, although the strength of the action of various PLA varied.

Animals↗
PubMed1981

Formation of mononuclear phagocyte (macrophage) colonies by mouse spleen cells in liquid culture. II. Its inhibition by the capsular polysaccharide of Klebsiella pneumoniae.

The effect of the capsular polysaccharide of Klebsiella pneumoniae type 1 Kasuya strain (CPS-K) on the formation of macrophage colonies in cultures of mouse spleen cells was investigated by the liquid culture technique during an incubation period of 7-8 days. CPS-K markedly inhibited further generation of macrophage colonies when added at any time after the beginning of culture, whereas it showed no destructive effect on macrophage colonies which were already formed before its addition. When CPS-K was present throughout the incubation period, such a low concentration as 0.05 micrograms/ml significantly inhibited colony formation, and the intensity of its inhibitory effect depended on its dose in the range of 0.005-50 micrograms/ml. The inhibitory effect persisted even if CPS-K was washed out after spleen cells were kept in contact with 20 micrograms of CPS-K per ml at 37 C for 6 hr. It was found that the inhibitory effect of CPS-K on colony formation was not mediated through its action on T cells, B cells or macrophages, and that it was not due to the generation of suppressor cells capable of inhibiting colony formation. It is concluded therefore that CPS-K directly inhibits the proliferation of macrophage colony-forming cells. The active substance responsible for the inhibitory effect of CPS-K on colony formation is the neutral polysaccharide fraction of CPS-K.

Animals↗
PubMed1981

Further Studies of the polysaccharide of Klebsiella pneumoniae possessing strong adjuvanticity. I. Production of the adjuvant polysaccharide by noncapsulated mutant.

In culture fluid, Klebsiella pneumoniae type 1 Kasuya strain produces polysaccharide exhibiting a strong adjuvant effect. The active substance responsible for the strong adjuvant effect of the polysaccharide isn ot its acidic polysaccharide fraction (the type-specific capsular antigen) but the neutral polysaccharide fraction. In the present study, a mutant which did not produce the type-specific capsular polysaccharide was isolated from ultraviolet-irradiated cells of K. pneumoniae type 1 Kasuya strain which had been labeled with leucine-requiring marker by selecting unagglutinable cells with the antiserum to he type-specific capsular polysaccharide. Serological tests showed that the type-specific acidic capsular polysaccharide was present neither on the cells surface nor in the culture fluid of the mutant. Electron microscopically, the mutant did not possess any capsular material. On the other hand, nearly an equal amount of neutral polysaccharide antigen as produced in culture fluids of the noncapsulated mutant polysaccharide antigen was produced in culture fluids of te noncapsulated mutant and the parent strain. The neutral polysaccharide antigen produced by the noncapsulated mutant exhibited the same degree of strong adjuvant effect on antibody response to bovine gammaglobulin in mice as that produced by the parent strain. The relationship between the neutral polysaccharide antigen in culture fluid and the O antigen of K. pneumoniae was discussed.

Adjuvants, Immunologic↗
PubMed1981

Further studies of the polysaccharide of Klebsiella pneumoniae possessing strong adjuvanticity. II. Serological relationship between the adjuvant polysaccharide and O3 antigen of Klebsiella.

The serological specificity of the neutral polysaccharide possessing extraordinarily strong adjuvanticity originally isolated from the culture supernatant of Klebsiella K1 strain Kasuya has been investigated. Among all of the reference strains (K1-K82) of Klebsiella obtained from the International Escherichia and Klebsiella Center, Statens Seruminstitut, Copenhagen, only 13 strains have been shown to produce the adjuvant polysaccharide by the passive hemagglutination inhibition test. All of these 13 strains belong to the O3 group, and the strains which belong to other O groups of which were not identifiable did not produce it. The gel precipitation test has demonstrated that the adjuvant polysaccharide is antigenically identical to O3 antigen isolated from the cells of the decapsulated mutant (strain LEN 1) of Klebsiella K1 strain Kasuya and to O9 antigen of Escherichia coli isolated from either the culture supernatant or the cells, which has already been shown to be antigenically and structurally identical to the O3 antigen of Klebsiella.

Adjuvants, Immunologic↗
PubMed1981

Induction of tumor resistance by hybrid cell lines between human acute lymphocytic leukemia cells and mouse myeloma cells.

Three hybrid cell lines were derived from the fusion of BALB/c mouse NS-1 myeloma cells and human acute lymphocytic leukemia cells. Hybrid clones contained almost all of the mouse chromosomes and a few human chromosomes, and induced tumors in BALB/c and BALB/c nu/nu mice when inoculated subcutaneously. However, the tumors of BALB/c mice subsided spontaneously within one month. The mice which survived the inoculation of 5 approximately 10 X 10(6) hybrid cells were able to reject a subsequent challenge with 5 X 10(6) NS-1 cells. Spleen cells or lymph node cells from immune mice were injected into BALB/c mice. These mice lived longer than the mice which received normal spleen cells or normal lymph node cells, when challenged with 5 X 10(6) NS-1 cells. These results suggest that a rearrangement of tumor-specific antigens on human/mouse hybrid cells can induce immunogenicity.

Animals↗
PubMed1980

Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. VIII. Its effect on the size and the number of cells of regional lymph node and other lymphoid organs.

Changes in the number of cells and the weight of various lymphoid organs of mice, such as the regional lymph node (right inguinal node), spleen, thymus, bone marrow, and peripheral blood, were followed after the subcutaneous injection of the capsular polysaccharide of Klebsiella pneumoniae (CPS-K). For comparison, the changes after injection of various polyclonal lymphocyte activators (PLA) including various preparations of bacterial lipopolysaccharide (LPS) were concurrently studied. The number of cells of all of the lymphoid organs tested and that of nucleated cells in the peripheral blood decreased significantly within a few days after injection of CPS-K, and increased later. Above all, the increase in the number of cells and in the weight of the regional lymph node was most prominent (about 10 times larger than that of the normal control). Such a marked increase in the number of cells of the regional lymph node was not induced by the injection of any preparation of LPS or any other PLA tested. The initial decrease in the number of cells after CPS-K injection was most marked and long lasting in the thymus. Although LPS prepared by Westphal's method from Escherichia coli 055 or Salmonella enteritidis exhibited a stronger decreasing effect on the number of cells of the thymus, the effect of LPS prepared by Westphal's method from E. coli O111 or that by Boivin's method from E. coli O55 was similar to that of CPS-K. It is concluded therefore that CPS-K has the ability to decrease the number of cells of various lymphoid organs, especially that of the thymus, initially after injection, which is a property in common with LPS, and CPS-K has a unique ability to increase markedly the cells of various lymphoid organs, especially those of the regional lymph node, at later stages after injection. Considering that CPS-K exhibits a much stronger adjuvant effect on the antibody response than does LPS or other polyclonal lymphocyte activators, it is suggested that this extraordinarily potent activity of CPS-K in increasing the number of cells of the regional lymph node is closely related to its strong adjuvant action.

Adjuvants, Immunologic↗
PubMed1980

Formation of mononuclear phagocyte (macrophage) colonies by mouse spleen cells in liquid culture. I. Kinetics of appearance of colonies and characterization of macrophage colony-forming cells.

When spleen cells of the adult mouse were tested for the formation of mononuclear phagocyte (macrophage) colonies by the liquid culture technique with an incubation period of 7--8 days, about 100 macrophage colonies were produced from 1 X 10(6) cells. The number of macrophage colonies appearing after 2 days of incubation was small, but thereafter increased progressively up to at least 8 days. In the later stages of incubation (after day 6) large colonies consisting of more than 100 cells appeared. Macrophage colonies in the early stages consisted almost solely of macrophages. On day 6 significant numbers of small round mononuclear cells with no detectable phagocytic activity were seen in the center of large colonies, and by day 8 marked crowding of these cells had occurred. The peripheral region of the large colonies consisted mainly of macrophages and the intermediate region of middle-sized round or slightly stretched cells with weak phagocytic activity. Approximately two-thirds of the colony-forming cells still remained after glass-adherent cells were removed from the spleen cells by passing over a glass-bead column. In cultures of glass-nonadherent cells macrophage colonies were not generated in the early stage. The number of colony-forming cells did not change significantly even after actively phagocytic cells were rigorously removed from the spleen cells. In addition, no macrophage colonies were generated in cultures of spleen cells treated with mitomycin C.

Animals↗
PubMed1980

Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. IX. Its effect on the histology of the regional lymph node and other lymphoid organs.

The sequence of histological changes in the regional lymph node and other lymphoid organs of mice injected with the capsular polysaccharide of Klebsiella pneumoniae (CPS-K) or bacterial lipopolysaccharide (LPS) was followed. Injection of CPS-K, but not LPS, induced the following characteristic histological changes in the regional lymph node. In the early stage there was a marked decrease in the number of small lymphocytes, accompanied by the appearance of scattered fragmented nuclei and infiltration of polymorphonuclear neutrophilic leukocytes, and in the late stage there was marked proliferation of macrophage-like cells and pyroninophilic cells. Histological changes in the thymus and spleen and changes in cell populations in the bone marrow and peripheral blood after CPS-K injection were essentially the same as after LPS injection. Since CPS-K has a much stronger adjuvant action on antibody response than does LPS, it is suggested that the characteristic histological changes in the regional lymph node after injection of CPS-K are closely related to its extraordinarily strong adjuvant action.

Adjuvants, Immunologic↗
PubMed1980

Microbial adjuvant and autoimmunity. IV. Production of lesions in the exocrine pancreas of mice by repeated injection of syngeneic pancreatic extract together with the capsular polysaccharide of Klebsiella pneumoniae.

Definite lesions in the exocrine pancreas were produced when SMA mice were immunized eight times at intervals of 30 days with a mixture of extract of pooled pancreas from syngeneic mice and the capsular polysaccharide of Klebsiella pneumoniae type I Kasuya strain (CPS-K), whereas no pancreatic lesions were produced in mice given CPS-K alone or pancreatic extract alone. The typical histological changes were characterized by infiltration with lymphocytes, plasma cells, and other mononuclear cells, degeneration and lysis of the acinar cells, destruction of the lobular architecture, and replacement of fatty tissue and fibrous connective tissue. The endocrine islets were well preserved. No specific histological changes were produced in the organs other than the pancreas in these mice. Most of mice immunized with pancreatic extract mixed with CPS-K produced serum precipitins to syngeneic pancreatic antigens. However, severe pancreatic lesions were also produced in mice showing no definite precipitin production.

Adjuvants, Immunologic↗
PubMed1980

Interferon and cytotoxic factor (cytotoxin) released in the blood of mice infected with Mycobacterium bovis BCG. III. Interferon and cytotoxin induced by the specific antigen as compared with those induced by bacterial lipopolysaccharide.

The time course of development and decline of the ability of BCG-infected mice to produce interferon in the serum in response to the intravenous infection of purified protein derivative of tuberculin (PPD) was very similar to that of their systemic hypersensitivity to PPD. A cytotoxic factor (cytotoxin) was produced in parallel with interferon in the serum of BCG-infected mice after stimulation with PPD. The duration of the period in which cytotoxin-production responsiveness to PPD was definitely detectable was much shorter than that for interferon-production responsiveness although the periods for the maximum production of interferon and cytotoxin coincided. The kinetics of release of interferon in the serum of BCG-infected mice after stimulation with PPD did not parallel that of release of cytotoxin. The four kinds of activities, interferons and cytotoxins induced by PPD and lipopolysaccharide (LPS) in the serum of BCG-infected mice, were compared for their stability to heating at 56 C and to treatment at pH 2. The kinetics of inactivation of these four activities differed significantly, when the serum was either heated at 56 C or treated at pH 2. Interferon produced in response to LPS could be neutralized by anti-L cell(NDV) interferon rabbit serum as easily as L cell (NDV) interferon, 16 times as much antiserum was required to neutralize the same amount of interferon in response to PPD, but cytotoxins induced by PPD and LPS were not neutralized at all by the antiserum. From these findings it is thought likely that interferons and cytotoxins induced by PPD and LPS in the serum of BCG-infected mice are different substances, although the antigenic relationship between cytotoxins induced by PPD and LPS remains unknown.

Animals↗