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At least 19 recordsLinked to original sources
PubMed1976

In vitro immune response to the 2,4,6-trinitrophenyl determinant in aged C57BL/6J mice:changes in the humoral immune response to, avidity for the TNP determinant and responsiveness to LPS effect with aging.

An in vitro anti-TNP response of the spleen cells from aged C57BL/6J mice showed approximately 4-fold less PFC than did that from young adult mice. Anti-theta serum-treated young spleen cells gave an anti-TNP response that was definitely greater than the response of the anti-theta serum-treated aged spleen cells in the presence of the exogenous activated thymus cells as helper cells. These results suggest that the deficits in B cells may be partly responsible for the imparied anti-TNP response of the aged spleen cells. To examine further the capacity of stem cells in the bone marrow to generate B cells responsible for anti-TNP response in the spleen, we injected i.v. 1.5 to 2.0 times 10(7) bone marrow cells from young or aged mice into lethally irradiated syngeneic recipients that had previously been thymectomized. Four to 6 weeks later, 10(7) spleen cells from the two groups of these recipient mice were immunized with TNP-SRBC in the presence of the exogenous activated thymus cells and assayed for anti-TNP PFC. The response of the aged marrow-derived B cells was approximately one-half of that of the young marrow-derived B cells. The avidity for TNP determinant of the antibodies produced by the PFC was determined by the plaque-inhibition technique. The avidity of the antibodies produced by the aged mice was approximately 33 times lower than that by the young mice. Anti-TNP response of the young spleen cells were markedly enhanced by the addition of LPS to the cultures, whereas no or little enhancement of the response was induced in the aged spleen cells even in the presence of high concentration of LPS. In contrast, DNA synthesis of both the young and aged spleen cells was comparably stimulated by 1 mug/ml and 10 mug/ml of LPS, however, it was rather less in the aged spleen cells at a concentration of 100 mug/ml. Mechanisms responsible for the changes in avidity and responsiveness to LPS with aging are discussed.

Aging↗
PubMed1979

T-lymphocyte response to cytochrome c. I. Demonstration of a T-cell heteroclitic proliferative response and identification of a topographic antigenic determinant on pigeon cytochrome c whose immune recognition requires two complementing major histocompatibility complex-linked immune response genes.

The T-lymphocyte proliferative response to pigeon cytochrome c was studied in the mouse. H-2a and H-2k strains were responders to this antigen whereas H-2b, H-2d, H-2f, H-2ja, H-2p, H-2q, H-2r, H-2s, and H-2u strains were low or nonresponders. Genetic mapping demonstrated that two major histocompatibility complex (MHC)-linked Ir genes control the response, one in I-A, the other in I-E/I-C. The major antigenic determinant recognized in this response was localized by cross-stimulations with species variants and cyanogen bromide cleavage fragments of cytochrome c. It was found to be a topographic surface determinant composed of an isoleucine for valine substitution at residue 3, a glutamine for lysine substitution at residue 100 and a lysine for glutamic acid substitution at residue 104. Tobacco hornworm moth cytochrome c, which contains a glutamine at residue 100 but a terminal lysine at residue 103 (one amino acid closer to the glutamine), stimulated pigeon cytochrome c immune T cells better than the immunogen. This result demonstrates for the first time a functional T-cell heteroclitic proliferative response in a system under Ir gene control. Immunization with the cyanogen bromide cleavage fragments revealed that only pigeon cytochrome c fragment 81-104 was immunogenic. This fragment primed for a T-cell proliferative response whose specificity was nearly identical to that of the T-cell response primed for by the whole molecule, suggesting that the glutamine at 100 and the lysine at 104 form the immunodominant portion of the antigenic site. Furthermore, mixing experiments using the two cross-reacting antigens, hippopotamus cytochrome c and Pekin duck or chicken cytochrome c fragment (81-104), each of which contains only one of the two immunodominant substitutions, demonstrated that the T lymphocytes responding to the major antigenic determinant comprise a single family of clones that recognize both amino acids as part of the same determinant. Thus, two complementing MHC-linked Ir genes can control the immune response to a single antigenic determinant.

Animals↗
PubMed1978

Cellular and genetic control of antibody responses in vitro. III. Immune response gene regulation of accessory cell function.

The possibility was investigated that Ir genes regulate the function of cells other than T or B cells in the primary IgM responses to the synthetic antigens trinitrophenylated poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys [TNP-(T,G)-A--L]and trinitrophenylated poly-,-(His,Glu)-poly-D, L-Ala--poly-L-Lys [TNP-(H,G)-A--L]. The primary responses of (B10 x B10.A)F(1) spleen cells to both antigens were abrogated by Sephadex G-10 passage, and restored by the addition of spleen adherent cells. The cell type in the spleen adherent cell population active in reconstituting the responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L was a non-T, non-B, radiation-resistant, glass-adherent spleen cell. The responses of Sephadex G-10-passed (responder x nonresponder)F(1) spleen cells to TNP-(T,G)-A--L or TNP-(H,G)-A--L were reconstituted by spleen adherent cells from only responder strains. Spleen adherent cells from F(1) mice reconstituted the responses to both antigens. Spleen adherent cells from each of the strains tested reconstituted the non- Ir gene-controlled response to a third antigen, TNP-keyhole limpet hemocyanin. The inability of spleen adherent cells from nonresponder strains to reconstitute the responses to either TNP-(T,G)-A--L or TNP-(H,G)-A--L was not a result of active suppression induced by the presence of nonresponder adherent cells, since a mixture of responder and nonresponder spleen adherent cells reconstituted the responses to both antigens. The use of spleen adherent cells from recombinant strains demonstrated that the autosomal dominant genes controlling the ability of spleen adherent cells to function as accessory cells in the responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L are located in the K or I-A regions of the responder H-2 complex, the same region(s) of H-2 as the Ir genes controlling overall in vitro and in vivo responsiveness to these antigens.

Animals↗
PubMed2026

Characterization of the Immune Response after Oral Cholera Vaccination (OCV) and Effects of Mycophenolate Mofetil on Priming of this Immune Response-A Randomized, Placebo-Controlled Trial.

Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used by solid organ transplant recipients. Although it is known that MMF suppresses immune responses, its exact effects on specific vaccinations have not been investigated yet. Mucosal vaccinations are increasingly used, such as a cholera vaccination consisting of two oral immunizations (oral cholera vaccination; OCV). This study aimed to investigate the specific immunosuppressive effects of MMF use during the first dose of OCV in a randomized, placebo-controlled trial in healthy volunteers. Moreover, the study aimed to characterize the immune response provoked by OCV in detail. This randomized, placebo-controlled, single-blind trial included 16 healthy volunteers, each receiving two doses of Dukoral® and an intranasal rechallenge. Outcome measures were serum antibody responses (IgA and IgG) and IgA levels in saliva. Additionally, peripheral blood mononuclear cells (PBMCs) of participants were investigated for ex vivo cytokine production and expression of tissue-specific homing markers after OCV. There were considerable serum IgA and IgG responses after vaccination. MMF-treated volunteers still showed a significant cholera antibody response, though data suggest a potential suppression by MMF without reaching statistical significance. There was no substantial IgA response in saliva. Investigation of PBMCs from OCV-treated participants showed a Th2 skewing with increased ex vivo production of TNF, IL-2, IL-5, IL-13, and IL-22 compared to the placebo group. Taken together, this study provides a framework for future clinical pharmacology studies building on OCV as a challenge model and for further investigation of specific effects of MMF on mucosal vaccination responses.

Humans↗
PubMed1979

Genetic control of the immune response to collagen. II. Antibody responses produced in fetal liver restored radiation chimeras and thymus reconstituted F1 hybrid nude mice.

The level of antibody produced in response to calf skin collagen in mice is influenced by genes which are closely linked to the I region of the H-2 major histocompatibility complex. This influence is shown to be expressed during lymphoid maturation by testing the antibody responsiveness to collagen in two types of chimeric mice. First, high responder and low responder parental strain mice were lethally irradiated and restored with fetal liver cells from (high X low responder) F1 mice. These F1 leads to parent chimeras exhibited an immune response phenotype characteristic of the irradiated parental strain animals, establishing that H-2 determinants of the host affect antigen responsiveness. Second, (high X low responder) F1 congenitally athymic (nude) mice were restored with fetal thymus transplants from either high or low responder parental strain mice. After a period of maturation these mice were shown to be competent for a T-dependent IgG response to SRBC. The responsiveness to collagen in these mice was characteristic of the parental strain thymus donors, indicating that the expression of H-2 determinants in thymic tissue during lymphoid maturation influences the antibody response phenotype expressed by mice.

Animals↗
PubMed1979

Human immune responses to hapten-conjugated cells. II. The roles of autologous and allogeneic histocompatibility determinants in proliferative responses in vitro.

Proliferative responses of human lymphocytes primed in vitro to autologous TNP-cells were found to be associated with autologous D-region determinants irrespective of HLA-B locus antigens. Family studies of secondary TNP-conjugate proliferative responses demonstrated a gene dosage effect in this phenomenon. Moreover, co-culture with allogeneic cells did not affect the net TNP-conjugate proliferative responses of primed responder cells, suggesting that HLA-D region preference was due to a requirement for representation of TNP-molecules in association or combination with autologous MHC structures. Alloantigens were found to influence the sensitization of lymphocytes to autologous hapten-conjugated cells. Co-culture of allogeneic and TNP-modified autologous stimulator cells in primary cultures enhanced the secondary TNP proliferative response. Sensitization of human lymphocytes to allogeneic cells alone did not prime responses to autologous modified cells. However, priming lymphocytes to modified autologous cells potentiated responses to allogeneic cells. The data suggest a complex relationship between responses to alloantigens and modified autologous cells.

Antibody Formation↗
PubMed1979

Genetic control of the immune response to mammalian chymotrypsins in mice. I. The immune response to high doses of bovine alpha-chymotrypsin.

The primary and secondary immune response to the antigen bovine pancreatic alpha-chymotrypsin was investigated in inbred mice. It was found that strain differences in the immune response only became apparent after secondary immunization. The genetic control of the immune response was investigated in twelve different strains of mice, F1, F2 and F1 backcross hybrids, following secondary immunization. A continuous distribution for the mean antibody responsiveness was obtained. High responsiveness was associated with both the H-2 haplotype and three non-H-2 loci. Furthermore the F1 hybrids produced a greater quantitative antibody response to chymotrypsin than either of the corresponding parental strains.

Animals↗
PubMed1977

Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide. II. Ability of suppressor T cells to act on both B cells and amplified T cells to limit the magnitude of the antibody response.

When administered 2 days after immunization with 0.5 microgram Type III pneumococcal polysaccharide (SSS-III), the T lymphocyte mitogen concanavalin A (Con A) stimulates a 2.6-to 7-fold enhancement of the plaque-forming cells (PFC) response to SSS-III in vivo. This enhancement requires the presence of amplified T cells, which act by driving PFC or their precursors to extra rounds of proliferation. The extra proliferation that can be stimulated by Con A is not seen in the normal primary response to SSS-III; but treatment with anti-lymphocyte serum (ALS) to remove suppressor T cells will permit the additional proliferation to occur. This indicates that in the primary response to SSS-III, suppressor T cells act on amplifier T cells to limit the magnitude of the antibody response. Only suppression of B cells can account for the further suppression induced by Con A given at the time of immunization or by low-dose paralysis of the SSS-III response. The relatively late development of amplified activity compared to suppressor activity appears to account for the absence of amplifier activity after primary immunization with SSS-III. It is apparent that one can explain the regulatory effects observed during the development of an immune response to SSS-III only by considering both T cell- B cell and T cell- T cell interactions, together with the temporal relationships involved in those interactions.

Animals↗
PubMed1977

Immune response genes in chickens: the multifarious responsiveness to (T,G)-A--L.

Immune response in chickens to the multichain copolymer (T,G)-A--L 2030 is analysed. Previous work has shown that responsiveness is not linked to the B-complex. Three different antibody specificities could be distinguished. From the data it is proposed that the response to the backbone of (T,G)-A--L (poly-DL-alanine) influences the responses to the side chain determinants (primarily the (T,G)-determinant). Thus the anti-(T,G) response in chickens is determined by at least two different loci, the B-complex, and another, as yet unidentified locus which determines the response to the poly-DL-alanine determinant. A third antibody specificity is directed against G-A--L and is only detectable in chickens which are high responders to poly-DL-alanine.

Alanine↗
PubMed2024

PSEUDO-RESPONSE REGULATOR 3b and transcription factor ABF3 modulate abscisic acid-dependent drought stress response in soybean.

The circadian system plays a pivotal role in facilitating the ability of crop plants to respond and adapt to fluctuations in their immediate environment effectively. Despite the increasing comprehension of PSEUDO-RESPONSE REGULATORs and their involvement in the regulation of diverse biological processes, including circadian rhythms, photoperiodic control of flowering, and responses to abiotic stress, the transcriptional networks associated with these factors in soybean (Glycine max (L.) Merr.) remain incompletely characterized. In this study, we provide empirical evidence highlighting the significance of GmPRR3b as a crucial mediator in regulating the circadian clock, drought stress response, and abscisic acid (ABA) signaling pathway in soybeans. A comprehensive analysis of DNA affinity purification sequencing and transcriptome data identified 795 putative target genes directly regulated by GmPRR3b. Among them, a total of 570 exhibited a significant correlation with the response to drought, and eight genes were involved in both the biosynthesis and signaling pathways of ABA. Notably, GmPRR3b played a pivotal role in the negative regulation of the drought response in soybeans by suppressing the expression of abscisic acid-responsive element-binding factor 3 (GmABF3). Additionally, the overexpression of GmABF3 exhibited an increased ability to tolerate drought conditions, and it also restored the hypersensitive phenotype of the GmPRR3b overexpressor. Consistently, studies on the manipulation of GmPRR3b gene expression and genome editing in plants revealed contrasting reactions to drought stress. The findings of our study collectively provide compelling evidence that emphasizes the significant contribution of the GmPRR3b-GmABF3 module in enhancing drought tolerance in soybean plants. Moreover, the transcriptional network of GmPRR3b provides valuable insights into the intricate interactions between this gene and the fundamental biological processes associated with plant adaptation to diverse environmental conditions.

Glycine max↗
PubMed1976

Cell-mediated immune response to herpes simplex virus: type-specific lymphoproliferative responses in lymph nodes draining the site of primary infection.

Cell-mediated immune responses to type 1 and type 2 HSV were studied in rabbits using an in vitro lymphocyte transformation assay. The footpad route of inoculation was used to allow us to study the specificity and degree of localization of the responses. Rabbits inoculated in the hind footpads with infectious HSV-I or HSV-II mount type-specific lymphocyte transformation responses that are localized to draining lymphoid organs. Type-specificity requires careful control of all in vitro culture conditions and reflects the extensive cross-reactivity demonstrated by serologic techniques. While lymphocyte transformation responses can be detected with immune SL and PBL, presumably the result of early escape of antigen into the systemic circulation, responses by draining LNL are significantly greater in magnitude. Distant LNL have not been shown to respond. It is postulated that the augmented local immune response to HSV plays a significant role in controlling recurrent HSV infections.

Animals↗
PubMed1976

Cellular and humorial immune responses in mice. III. Acceleration of delayed hypersensitivity response by presensitization with suboptimal dose of antigen.

Delayed hypersensitivity (DH) response in mice induced by subcutaneous (s.c.) injection of optimal dose of sheep red blood cells (SRBC) 10(8)) was accelerated by s.c. injection of the antigen of 10(3) or more doses, given 2 or more days earlier. The accelerated response appeared soon after the injection of optimal antigen dose, that is, 1 or 2 days earlier than the response of non-presensitized control. The acceleration was antigen specific. The accelerated response was generally accompanied by an acceleration and/or enhancement of humoral antibody response. Parallel to the acceleration of DH response, the proliferation of regional lymph node cells in the presensitized mice was induced immediately after the following injection of 10(8) SRBC, 1 day earlier than that of non-presensitized animals. These results suggest that presensitization of mice with the antigen induces DH-related memory cells which proliferate immediately after the following injection and function as effector cells for DH reactions, and that the development of DH-related memory cells occurs in close relation to that of helper thymus-derived (T) cells for antibody production.

Animals↗
PubMed1977

Cell-mediated and humoral immune responses in mice. III. Dynamic balance between delayed-type hypersensitivity and antibody response.

Delayed-type hypersensitivity in mice to bovine serum albumin (BSA) which would be induced by a s.c. injection of BSA in Freund's complete adjuvant was interrupted by an i.v. injection of alum-precipitated BSA plus bacterial endotoxin (AP-BSA plus ET). In contrast, s.c. injection of BSA restrained the antibody response in the spleen of the mice receiving AP-BSA plus ET. Subcutaneous injection of either the adjuvant alone or an unrelated antigen in the adjuvant did not affect the anti-BSA antibody response in the spleen. The antibody response to other antigens in the spleen was not affected by the s.c. injection of BSA. The reduction of the antibody response in the spleen does not seem to be attributable to suppressor cells, since the suppressor cell activity against the antibody response of normal mice and that of irradiated recipients of primed spleen cells was not observed in the spleen cells of mice given s.c. immunization. The results indicated that the reduced antibody response in the spleen may be caused by the migration of some part of the antigen reactive cells or their precursors from the spleen to the s.c. region.

Animals↗
PubMed1979

B-cell subsets responsive to fluorescein-conjugated antigens. III. Differential effect of E. Coli lipopolysaccharide on T-dependent and T-independent responses in vivo.

The effect of E. coli lipopolysaccharide (LPS) on the induction of both hapten-specific immunity and tolerance was studied in an in vivo system utilizing putative T-cell dependent (TD) or T-cell independent (TI) challenge antigens. The administration of LPS 1 day prior to challenge preempted the response of C3D2 mice to a TD antigen (FL-KLH) but had little effect on the response to FL-Ficoll, a TI antigen. LPS did not affect the responsiveness of C3H/HeJ mice, an LPS-unresponsive strain, to either antigen. The reduction of the response to a putative T-dependent antigen by LPS pre-treatment was only temporary since mice challenged 7 days after LPS responded normally in vivo. We also confirmed that LPS administered shortly after a tolerogen prevented FL-specific IgG tolerence induction and produced B-cell priming to a subsequent T-dependent antigenic challenge. LPS, however, did not significantly interfere with tolerance induction in terms of the IgM responce to either challenge antigen. These results suggest that LPS acts either directly or indirectly on a subpopulation of B cells responsive to a TD antigen. Our data further reflect the heterogeneity of B-cell subpopulations responsive to various polyclonal activators.

Animals↗
PubMed2025

GWAS of CRP response to statins further supports the role of APOE in statin response: A GIST consortium study.

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response. CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing &#x223c;10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts. Our GWAS identified two genome-wide significant (P&#x202f;<&#x202f;5e-8) loci: APOE and HNF1A for CRP statin response corrected for baseline CRP. The missense lead variant rs429358 at APOE, contributing to the APOE-E4 haplotype, is a risk locus for dyslipidaemia, Alzheimer's and coronary artery disease (CAD). The HNF1A locus is associated with diabetes, cholesterol levels, and CAD. Both loci are also associated with baseline CRP levels, and neither locus achieved a significant (P&#x202f;<&#x202f;0.05) result from the statin v. placebo interaction meta-analysis using randomized clinical trial data. However, the interaction result (P-int=0.09) for APOE was suggestive and possibly underpowered. The APOE-E4 signal may therefore be associated with both CRP and LDL-cholesterol statin response. Combined with suggestions in the literature that APOE also leads to differential statin benefit in Alzheimer's, the APOE locus warrants further investigation for potential genetic effects on healthcare with statin treatment.

Humans↗
PubMed1975

Suppression of the immune response by alpha-fetoprotein on the primary and secondary antibody response.

Mouse amniotic fluid was shown to contain a noncytotoxic inhibitor of primary gammaM and secondary gammaM, gammaG subclass splenic plaque forming cells in vitro to SRBC. The suppressive effect was not abolished by exhaustive dialysis or by absorption of mouse amniotic fluid (MAF) with SRBC. Polyacrylamide gel analysis showed that dialyzed MAF was composed of three major protein components, transferrin, albumin, and alpha-fetoprotein (AFP). The selective removal of each of these patients from MAF by affinity chromatography suggested that AFP was the immunosuppressive substance in MAF. This conclusion was verified by the demonstration that pure AFP suppressed in vitro antibody synthesis in microgram quantities whereas equivalent amounts of normal mouse serum, transferrin, or albumin did not. Dose-response studies showed that the effect of AFP in the isolated form was equivalent to the suppressive effect of comparable amounts of AFP in MAF. gammaA and gammaG plaque-forming cell (PFC) responses were suppressed by a significantly lower concentration of AFP than was the gammaM PFC response. The degree of suppression watration of AFP than was the gammaM PFC response. The degree of suppression was dependent on the time at which AFP was added to the cultures; MAF added to antigen-stimulated cultures up to 24 h after initiation of cultures was immunosuppressive whereas similar additions of MAF at 48 h after initiation or later did not suppress. The duration of exposure of spleen cells to MAF in cultures without antigen necessary to achieve suppression of a subsequent primary immune response was determine-d to be approximately 8 h. The results suggest that AFP may have an immunoregulatry function. This has potentially important implications in the maternal-fetal relationship, the immune capabilities of the fetus and newborn, and in certain malignant and nonmalignant diseases in which AFP is elevated.

Alpha-Globulins↗
PubMed1978

Genetic control of immune response to sperm whale myoglobin in mice. I. T lymphocyte proliferative response under H-2-linked Ir gene control.

Studies on the genetic control of immune response to sperm whale myoglobin were initiated. As demonstrated in this paper, the T lymphocyte proliferative response to whale myoglobin is under H-2-linked Ir gene control. Mice of H-2d, H-2f, and H-2s haplotypes were high responders to the myoglobin, whereas haplotypes H-2b, H-2k, H-2p, H-2q, and H-2r were low responders. The Ir gene(s) was localized between H-2K and H2D regions, since the recombinant strain A.TL (KsIkSkDd) was a low responder and A.TH (KsIsSsDd) was a high responder. Further studies with recombinant strains revealed that the expression of the high-responder I-Ad or Ias alleles was sufficient to give a good response, since strains D2.GD (d d b b b b b b) and B10.HTT (s s s s k k k d) were high responders. The expression of the I-Cd allele in strains B10.A (k k k k k d d d) and B10.A(5R) (b b b k k d d d) also gave high response, and thus suggested a second Ir gene, derived from the H-2d haplotype. The finding that expression of the I-Cs allele in B10.S(8R) (k k ? ? s s s s) did not result in high response suggests the lack of the second Ir gene in the high-responder H-2s haplotype.

Animals↗