Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nitrohydroxyiodophenylacetate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1986

Induction of in vitro antigen-specific antibody production against NIP-KLH in nonadherent cells derived from human peripheral blood mononuclear cells.

A primary in vitro antibody response to 4-hydroxy-3-iodo-5-nitrophenylacetyl keyhole limpet hemocyanin (NIP-KLH) by plastic dish nonadherent human peripheral blood mononuclear cells (PBMC) was examined. Nonadherent cells of most donors produced an anti-NIP antibody when they were cultured with the antigen at a cell density of 2.5 X 10(6)/ml in the presence of Staphylococcus aureus Cowan I (SAC) at a concentration of 0.003% for 5 days, washed and further cultured in the absence of the antigen and SAC for an additional 5 or 6 days. Nonadherent cells of 'low-responders' responded to NIP-KLH plus SAC and produced anti-NIP antibody when they were cultured with not only NIP-KLH plus SAC but also with the culture supernatant obtained on phytohemagglutinin (PHA) stimulation of a mixture of PBMC from 2 donors. Furthermore, it was found that the PHA supernatants could be very effectively substituted for by human recombinant interleukin-2.

Antibody Formation↗
PubMed2003

The phytoestrogen genistein suppresses cell-mediated immunity in mice.

The soy phytoestrogen, genistein, induces thymic atrophy when administered to ovariectomized mice by injection or in the diet. Injected genistein also causes decreased humoral immunity, but the effects of genistein on cell-mediated immunity have not been addressed. Here we examined effects of injected and dietary genistein on cell-mediated immune responses. Female C57BL/6 mice (25- to 27-days-old) were ovariectomized, then placed on phytoestrogen-free feed 5 days later. Seven days after ovariectomy, they were given daily subcutaneous injections of either dimethylsulfoxide (DMSO) or genistein (8, 20, 80 mg/kg) for 28 days; some mice were given 80 mg/kg genistein plus the anti-estrogen ICI 182,780 (5 mg/kg/week). Cell-mediated immune response was tested by analyzing the delayed-type hypersensitivity (DTH) response to a hapten, 4-hydroxy-3-nitrophenyl acetyl succinimide (NP-O-SU), at the end of treatment. Reversibility of the effects of genistein was tested by measuring the DTH response in mice that were given genistein (20 or 80 mg/kg) for 28 days, then allowed to recover for 28 days. To determine if dietary genistein could affect cell-mediated immunity, mice ovariectomized as above were fed genistein at 0, 1000 or 1500 parts per million (ppm) for 28 days. There was a 46-67% decrease in the DTH response in the footpads of mice injected with 8-80 mg/kg genistein compared with controls (P<0.05 vs control for all treatment groups); these effects were reversible. On histopathological examination of the feet, there was decreased cell infiltration in genistein-treated animals compared with controls, and the numbers of CD4(+) and CD8(+) T cells in popliteal lymph nodes were reduced. The effects of genistein are mediated through both estrogen receptor (ER) and non-ER pathways, as the anti-estrogen ICI 182,780 only partially blocked the effects of genistein on the DTH response. Dietary genistein (1000 or 1500 ppm) decreased cell-mediated immunity while producing serum genistein concentrations in the physiological range for humans under certain nutritional conditions. Further work is needed to determine if dietary genistein and phytoestrogen exposure can produce effects on cell-mediated immunity in humans or other animals under various nutritional conditions.

Animals↗
PubMed1994

Expression of a recombinant sheep IgE gene.

An ovine cosmid library was screened with a bovine C epsilon gene probe. IgE and IgA constant region genes (C epsilon and C alpha, respectively) were isolated within a single 26 kb cosmid insert. The C epsilon gene was cloned into an expression vector which contained the rearranged VDJ genomic segment encoding an anti-(4-hydroxy-3-iodo-5-nitrophenyl) acetic acid (anti-NIP) VH chain. This chimeric construct was transfected into murine hybridoma cells producing L chain with anti-NIP antibody specificity and stable transfectomas secreting chimeric ovine-murine IgE anti-NIP antibodies were obtained. Chimeric antibody, affinity purified from culture supernatants of transfected cells on a NIP-sepharose column, was characterised by SDS-PAGE and shown to contain H and L chains of expected size. These experiments demonstrated the power of advanced molecular genetic techniques to generate immunological reagents against low abundance immunoglobulin isotypes thus facilitating monoclonal antibody production for further immunological studies.

Animals↗
PubMed2003

CD40, but not CD154, expression on B cells is necessary for optimal primary B cell responses.

CD40 is an important costimulatory molecule for B cells as well as dendritic cells, monocytes, and other APCs. The ligand for CD40, CD154, is expressed on activated T cells, NK cells, mast cells, basophils, and even activated B cells. Although both CD40(-/-) and CD154(-/-) mice have impaired ability to isotype switch, form germinal centers, make memory B cells, and produce Ab, it is not entirely clear whether these defects are intrinsic to B cells, to other APCs, or to T cells. Using bone marrow chimeric mice, we investigated whether CD40 or CD154 must be expressed on B cells for optimal B cell responses in vivo. We demonstrate that CD40 expression on B cells is required for the generation of germinal centers, isotype switching, and sustained Ab production, even when other APCs express CD40. In contrast, the expression of CD154 on B cells is not required for the generation of germinal centers, isotype switching, or sustained Ab production. In fact, B cell responses are completely normal when CD154 expression is limited exclusively to Ag-specific T cells. These results suggest that the interaction of CD154 expressed by activated CD4 T cells with CD40 expressed by B cells is the primary pathway necessary to achieve B cell activation and differentiation and that CD154 expression on B cells does not noticeably facilitate B cell activation and differentiation.

Animals↗
PubMed2004

Differential segmental flexibility and reach dictate the antigen binding mode of chimeric IgD and IgM: implications for the function of the B cell receptor.

Mature, naive B cells coexpress IgD and IgM with identical binding sites. In this study, the binding properties of such IgM and IgD are compared to determine how size and shape may influence their ability to bind Ag and thus function as receptors. To dissect their intrinsic binding properties, recombinant IgM and IgD were produced in soluble form as monomers of the basic H(2)L(2) Ab architecture, each with two Ag binding sites. Since these sites are connected with a hinge region in IgD and structural Ig domains in IgM, the two molecules differ significantly in this region. The results show that IgD exhibited the larger angle and longer distance between its binding sites, as well as having the greater flexibility. Relative functional affinity was assessed on two antigenic surfaces with high or low epitope density, respectively. At high epitope density, IgM had a higher functional affinity for the Ag compared with IgD. The order was reversed at low epitope density due to a decrease in the functional affinity of IgM. Studies of binding kinetics showed similar association rates for both molecules. The dissociation rate, however, was slower for IgM at high epitope density and for IgD at low epitope density. Taken together, the results show that IgM and IgD with identical Ag binding regions have different Ag binding properties.

Amino Acid Sequence↗
PubMed2005

The influence of immune complex-bearing follicular dendritic cells on the IgM response, Ig class switching, and production of high affinity IgG.

It is believed that Ag in immune complexes (ICs) on follicular dendritic cells (FDCs) selects high affinity B cells and promotes affinity maturation. However, selection has been documented in the absence of readily detectable ICs on FDCs, suggesting that FDC-ICs may not be important. These results prompted experiments to test the hypothesis that IC-bearing murine FDCs can promote high affinity IgG responses by selecting B cells after stimulating naive IgM(+) cells to mature and class switch. Coculturing naive lambda(+) B cells, FDCs, (4-hydroxy-3-nitrophenyl)acetyl-chicken gamma-globulin (CGG) + anti-CGG ICs, and CGG-primed T cells resulted in FDC-lymphocyte clusters and production of anti-4-hydroxy-5-iodo-3-nitrophenyl acetyl. Class switching was indicated by a shift from IgM to IgG, and affinity maturation was indicated by a change from mostly low affinity IgM and IgG in the first week to virtually all high affinity IgG anti-4-hydroxy-5-iodo-3-nitrophenyl acetyl in the second week. Class switching and affinity maturation were easily detectable in the presence of FDCs bearing appropriate ICs, but not in the absence of FDCs. Free Ag plus FDCs resulted in low affinity IgG, but affinity maturation was only apparent when FDCs bore ICs. Class switching is activation-induced cytidine deaminase (AID) dependent, and blocking FDC-CD21 ligand-B cell CD21 interactions inhibited FDC-IC-mediated enhancement of AID production and the IgG response. In short, these data support the concept that ICs on FDCs can promote AID production, class switching, and maturation of naive IgM(+) B cells, and further suggest that the IC-bearing FDCs help select high affinity B cells that produce high affinity IgG.

Animals↗
PubMed1975

Specifically cytotoxic human and mouse lymphoid cells induced with antibody or antigen-antibody complexes.

Human or mouse lymphoid cells could be "armed" with anti-NIP antibodies to become cytotoxic to NNP-conjugated fowl erythrocytes (NNP and NIP are closely related haptens). The arming factor was neutralized by a sufficient concentration of NIP-BSA (twice the concentration causing maximal precipitation) but low concentrations (e.g., 7% of the maximal precipitation concentration) increased the arming capacity.

Animals↗
PubMed1988

A new strain-specific cross-reactive idiotope with possible regulatory function expressed on BALB/c anti-alpha (1-3) dextran antibodies.

We obtained a mAb, B5, defining a major crossreactive Id, the B5 Id, having an in vivo regulatory function. BALB/c mice immunized against the bacterial dextran Ag B1355S produce lambda 1-bearing anti-alpha (1-3) glucosidic linkage of dextran B1355S (DEX) antibodies. Of these antibodies 30% expressed the B5 Id determinant. As was observed for the IdX-Id, B5 idiotope expression was also linked to the BALB/c H chain allotype. The antibody family expressing the B5 Id included IdX+ as well as IdX- defined monoclonal anti-alpha (1-3) DEX antibodies. Injection into BALB/c mice of mAb B5 conjugated to keyhole limpet hemocyanin led to enhancement of serum anti-alpha (1-3) DEX antibody synthesis, and to a strong increase in B5+ Ig lacking dextran-binding activity. IdX+ serum Ig were also increased in these mice. Injection of this mAb into allotype congenic nonresponder C.B20 mice induced a significant serum lambda 1-bearing anti-alpha (1-3) dextran antibody response (5 to 50 micrograms/ml). However, in A/J nonresponder mice, a similar treatment induced only the dextran-nonbinding component, which reached high levels (approximately 7 mg/ml) in the sera of these mice. In the majority of these A/J mice, we detected a specific anti-(4-hydroxy-5-iodo-3-nitrophenyl)acetyl antibody response characterized by B5 Id-positive antibodies. This observation can be explained by an in vivo regulatory idiotope-mediated cross-regulation.

Adjuvants, Immunologic↗
PubMed1976

Single cell studies on the antibody-forming potential of fractionated, hapten-specific B lymphocytes.

This study addresses itself to the problem of antibody formation in vitro by mouse splenic B lymphocytes enriched for reactivity to the hapten NIP by the hapten-gelatine binding and melting technique of Haas and Layton (1975). Small numbers of NIP-gelatine-bound B cells were placed in microcultures either by bulk dispensing of dilute cell suspensions, or by micromanipulation under direct microscopic visualization. Antibody formation was induced by the T cell-independent hapten-protein conjugate NIP-polymierized flagellin, using 10(4) thymus cells per microlitre as 'filler' cells. The frequency of precursors of NIP-specific antibody-forming cells among bound cells was about 2-2 X 10(-2) (one cell in forty-five) by both statistical and direct evaluation, after adjustment for a background frequency of 6-10 X 10(-8) precursors in the thymus filler cells. Single clones commenced antibody secretion asynchronously, as shown by the fact that the incidence of positive cultures continued to rise over the whole three days of culture, and that very small clones of one to four plaque-forming cells (PFC) were still found on day 3. The mean PFC number per positive culture rose from 1-2 at day 1 to 4-7 at day 2 and about 20 at day 3.

Animals↗
PubMed1983

The diversity of T cell receptors specific for self MHC gene products.

Cytolytic and helper T cells exhibit, in addition to their specificity for foreign antigen, a restriction specificity for self MHC gene products. The present study was designed to assess the degree of diversity within the repertoire of receptors that are involved in T cell recognition of self MHC gene products. For this purpose, we generated a series of murine cytolytic T lymphocyte (CTL) clones specific for a hapten antigen and restricted to the self MHC gene product H-2Kb. An analysis of the hapten fine specificity of these clones by using hapten analogues revealed the presence of substantial diversity within the repertoire of CTL receptors specific for the hapten. The degree of diversity within the repertoire of self H-2 recognition structures on these clones was assessed by testing clones on panels of syngeneic, congenic H-2K disparate, and H-2Kb mutant target cells bearing varying amounts of antigen. A striking degree of heterogeneity in H-2K recognition was found among these H-2Kb restricted CTL. We estimate that there are probably a minimum of 65 different patterns of H-2K recognition among these clones. Our results suggest a high degree of diversity exists within the repertoire of self MHC recognition structures on antigen-specific T cells restricted to a single self MHC gene product.

Animals↗
PubMed1983

Analysis of true anti-hapten cytotoxic clones in limit dilution microcultures after correction for "anti-self" activity: precursor frequencies, Ly-2 and Thy-1 phenotype, specificity, and statistical methods.

By the use of split culture techniques we have been able to demonstrate conclusively that the "anti-self" activity and the spontaneous anti-hapten activity within an apparent anti-hapten cytotoxic T cell response is a clonal phenomenon and is not caused by cross-reactivity between anti-self and true anti-hapten clones. With the knowledge of this clonality we have been able formally to prove that the true hapten-generated, hapten-specific response can be obtained by subtracting the response generated by "self" but directed against modified targets from the response generated by modified self and directed against modified targets. Unbiased statistical estimators, which do not make assumptions about the origin (0 responder cells, 100% negative cultures), have been developed to plot accurately limit dilution data (maximal likelihood estimator and minimal chi-square estimator), and the analysis demonstrates that all the components of an apparent anti-hapten response obey zero order (single hit) kinetics. By specifically identifying true anti-hapten and true anti-self clones, we have been able to study the phenotype of their precursors as well as the effectors themselves at the clonal level. Precursors of true anti-hapten and anti-self clones are Thy-1+, Ly-2+. However, anti-hapten and anti-self effector cells show marked clonal variation with respect to Ly-2, as some clones are almost completely insensitive to anti-Ly-2 and complement whereas others show minimal to complete sensitivity. All anti-hapten clones are completely sensitive to anti-Thy-1 and complement, whereas about one-third of anti-self clones show only partial sensitivity, with the most lytic clones showing the most sensitivity. Hapten-specificity and anti-self-specificity have been examined clonally. Ten percent of anti-TNP clones recognize NIP, 10% of anti-NIP clones recognize TNP, and 20% of anti-self clones recognize an allo-target. These figures are in accordance with the overall specificity of effectors generated in bulk culture in the presence of CAS (concanavalin A-stimulated spleen cell conditioned medium). However, hapten specificity and H-2 restriction of bulk generated effectors are improved if CAS is omitted from cultures.

Animals↗
PubMed1976

Long-term antibody synthesis in vitro- IV. Independent segregation of antibodies directed to different determinants of an antigen molecule in its native configuration.

Independent segregation of antibody populations directed to different portions of E. coli beta-d-galactosidase occurs during the immune response against the enzyme. Anti-enzyme antibodies able to interact and activate a naturally occurring ligand, the mutant-defective enzyme AMEF (Antibody Mediated Enzyme Factor), do not parallel anti-enzyme antibodies which are measured by a coprecipitation assay involving precipitation of the wild-type molecule. Dissociation of the two antibody populations is best achieved in microcultures sustaining long-lasting responses. Similarly, anti-NIP (4-hydroxy-3-iodo-5-nitrophenylacetic acid) antibodies could be elicited without concomitant synthesis of anti-carrier antibodies by short-term challenge in vitro of ovalbumin-NIP-primed lymph nodes with a heterologous conjugate in which the hapten NIP was coupled to a carrier known to be non-immunogenic under the conditions of challenge. The potential applications of these findings are indicated, namely: large-scale production of monospecific antibodies in vitro; and the possibility of studying the regulatory role of antibodies directed towards on portion of the immunogenic molecule on the response to other regions of the same molecule.

Animals↗
PubMed1984

Adjuvant effect of bacterial LPS and/or alum precipitation in responses to polysaccharide and protein antigens.

A conjugate of a hapten (NIP) and a strongly antigenic protein chicken gamma globulin (CGG), when injected in soluble form into mice, induced weak primary responses, as weak as responses induced by conjugates of NIP (or other haptens) to polysaccharides Ficoll or alpha (-1-6) dextran. Mean concentrations of anti-hapten antibodies on day 14 varied within the range of 37-105 micrograms/ml (C57BL mice) or 14-38 micrograms/ml (CBA mice). The NIP-protein conjugate administered in alum-precipitated form induced 100 times higher primary antibody responses. Alum-precipitation of NIP-Ficoll made it a modestly stronger antigen than soluble NIP-Ficoll. When lipopolysaccharide (LPS) was injected together with any of the soluble antigens, the mice produced plenty of anti-hapten antibodies regardless of whether the antigen was hapten-polysaccharide or hapten-protein conjugate. Concentrations on day 14 varied from around 400 micrograms/ml to approximately 1600 micrograms/ml. LPS had a similar adjuvant effect on antidextran responses. LPS alone induced a polyclonal immunoglobulin production, and the immunoglobulin produced included 'anti-NIP' or 'anti-dextran' detectable in the solid phase antibody assay. These 'antibodies' induced by LPS alone were almost totally mercapto-ethanol-sensitive and poorly detectable by Farr assay or the bacteriophage assay. The response to the LPS+antigen combination was specific for the antigen and included both mercapto-ethanol-sensitive and resistant antibodies.

Adjuvants, Immunologic↗
PubMed1978

Induction of a stable hapten-specific immunosuppression by a hapten conjugated to poly(N-vinylpyrrolidone) (PVP).

The ability of a hapten coupled to a clinically permissive synthetic polymer (NIP-PVP) to induce suppression was investigated. NIP coupled to the low molecular weight non-immunogenic form of poly(N-vinylpyrrolidone) (PVP) was found to be capable of inducing a hapten-specific longlasting suppression of both primary and secondary responses. The previous use of PVP as a plasma expander in humans makes this polymer a potentially suitable tool for the induction of specific immunosuppression to a variety of clinically important drug and tissue specific epitopes. The possible use of low molecular weight PVP for that purpose will be investigated further, specifically with larger antigenic components.

Animals↗
PubMed1976

Estimation of hapten-specific antibody-forming cell precursors in microcultures.

The immune response of mouse spleen cells to hapten-conjugated polymer of flagellin (DNP-POL, NIP-POL) was studied using a microculture system. When increasing numbers of spleen cells were added to a 'filler' cell system, negative feedback effects became apparent and resulted in the generation of progressively lower numbers of plaque-forming cells (PFC) per input cell. This feedback inhibition was shown to be antigen-specific and mediated by factors released into the culture medium. The effect precludes calculation of the frequency of PFC precursors in cultures containing spleen cells alone and complicates the analysis of tolerance using in vitro assay systems. The addition of small numbers of spleen cells to a constant number of thymocytes provided a system in which Poisson analysis could be used to determine the frequency of PFC precursors capable of being activated by hapten-POL conjugates. This system was used to estimate the frequency of anti-NIP-PFC precursors in CBA spleen cells.

Animals↗