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Results for “Dose-Response Relationship, Immunologic”

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At least 19 recordsLinked to original sources
PubMed1976

Induction of increased graft-versus-host disease by mouse spleen cells sensitized in vitro to allogeneic tumor.

The aim of our study was to sensitize cells in vitro, follow their proliferative and cytotoxic responses, and determine their ability to cause lethal graft-versus-host disease (GVHD). C57BL/6 (H2b) spleen cells were incubated with irradiated BALB/C (H2d) Moloney lymphoma cells (LSTRA) in mixed leukocyte culture conditions for 2, 4, or 6 days and then tested. The maximal proliferative response occurred after 4 days. In vitro cytotoxic reactivity against 51Cr-labeled LSTRA was generated by 4 days (76.3+/-3.1% 51Cr released) and 6 days (133.0+/-4.8%) of sensitization but not by 2 days (-0.2+/-1.1%). Induction of fatal GVHD was assayed by injecting graded doses of the C57BL/6 spleen cells i.v. into adult BALB/c mice pretreated with cyclophosphamide, 180 mg/kg. Cells sensitized for 2 days were effective but no more so than were (control) cells cultured with irradiated C57BL/6 spleen cells. However, cells sensitized longer were far more active than the control cells. Cells sensitized for 4 days killed 70 of 88 mice (80%), and those sensitized for 6 days killed 37 of 48 mice (77%), whereas control cells killed only 42 of 90 mice (47%) (P less than 0.005). Thus, cells sensitized in vitro exhibited an increased ability to induce GVHD in vivo, which was temporally associated with the development of cytotoxicity in vitro.

Animals↗
PubMed1976

Cytotoxicity in graft-versus-host reaction. II. Lysis of target cells of parental genotyppe by F1 hybrid macrophages.

Graft-versus-host (GVH) reactions were induced in adult F1 hybrid mice with the i.p. injection of parental strain spleen cells. Peritoneal exudate and spleen cells of the F1 hybrids taken 8 days after the induction of GVH reaction had a nonspecific in vitro cytotoxic effect which was measured by using 51Cr-labeled target cells of parental genotype. The cytotoxic cells in the peritoneal exudates were shown to be macrophages which adhered to plastic surfaces and were sensitive to the toxic action of crystalline silica particles. Moreover, the injection of partially purified syngeneic macrophages into the F1 hybrids undergoing GVH reactions increased the cytotoxic activity of the peritoneal exudate cells obtained from these animals. These results suggest that during GVH reaction host macrophages are activated into a state of nonspecific cytotoxicity.

Animals↗
PubMed1976

B cell tolerance induced by polymeric antigens. I. Comparison of the dose and epitope density requirements for inactivation of primed and unprimed B cells in vivo.

Hapten [2,4-dinitrophenyl (DNP)]-specific tolerance was induced in nonimmune or DNP-hemocyanin (DNP-KLH) primed mice by administering hapten-conjugated type 3 pneumococcal polysaccharide (DNP-lys-S3). The dose of DNP-lys2.5-S3 required to suppress the primary anti-DNP antibody responses was approximately ten times higher than that required to suppress the secondary response. Large doses of lightly substituted antigen (DNP-lys0.6-S3) had no effect on primary antibody responses, while small doses of this conjugate suppressed 90-95% of the secondary response. The conclusion from this (presumably B cell) tolerance model is that B lymphocytes "mature" in their susceptibility to tolerization following primary contact with immunogen, since primed cells are inactivated by lower doses of tolerogen, and by tolerogen with lower epitope density, than nonimmune B cells. These and other data suggest that the tolerance threshold of B lymphocytes is related to their state of differentiation, and especially to their antigen-binding characteristics.

Animals↗
PubMed1975

Role of epitope density in the induction of immunity and tolerance with thymus-independent antigens. I. Studies with 2,4-dinitrophenyl conjugates in vitro.

The effect of different degrees of conjugation of levan, dextran, pneumococcal polysaccharide SIII and the copolymer of D-glutamic acid and D-lysine with the 2,4-dinitrophenyl determinant (DNP) on the immunogenic and tolerogenic capacity of its haptenic conjugates was investigated in vitro. A strikingly uniform effect of hapten conjugation was observed despite the marked difference in the mol. wt. and structure (branched or linear) of the carrier molecules. Regarding the anti-DNP response, low density conjugates were immunogenic but not tolerogenic (even at high doses), higher conjugates were both, depending on concentration, while very high density conjugates were only tolerogenic. These results confirm and extend earlier findings made with DNP conjugates of polymeric flagellin and indicate the probable generality of this principle. Together with parallel in vivo studies (Eur. J. Immunol. 1975. 5:541), they reaffirm the importance of epitope density in the discrimination between immunity and tolerance.

Animals↗
PubMed1976

Blastogenic response of human lymphocytes to oral bacterial antigens: comparison of individuals with periodontal disease to normal and edentulous subjects.

Cell-mediated immunity in humans to antigens derived from oral plaque bacteria was investigated by using the lymphocyte blastogenesis assay. Subjects with varying severities of periodontal disease including normal, gingivitis, periodontitis, and edentulous were compared. Mononuclear leukocytes were separated from peripheral blood and cultured with antigens prepared by sonication of Actinomyces viscosus (AV), Actinomyces naeslundii (AN), Veillonella alcalescens (VA), Leptotrichia buccalis (LB), Bacteroides melaninogenicus (BM), and homologous dental plaque (DP). The lymphocyte response of subjects with gingivitis or periodontitis was significantly greater than that of normal subjects to antigens of AV, AN, and DP, but did not differ from the response of edentulous subjects. Periodontitis subjects were significantly more reactive than edentulous and normal subjects in response to VA, LB, and BM. These findings suggest that the tested gram-negative bacteria and the host response they evoke are associated with advanced periodontal destruction.

Actinomyces↗
PubMed2026

Dose-dependent IFN programs in myeloid cells after mRNA and adenovirus COVID-19 vaccination.

BACKGROUNDThe SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.METHODSWe longitudinally profiled SARS-CoV-2-naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).RESULTSWe discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1-2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was characterized by ISGF3 complex activation and its target genes (e.g., MX1, MX2, DDX58), with transcriptional and epigenetic profiles distinct from the robust IFN program observed after mRNA boosting or a single Ad26.COV2.S dose (ISG-high). In vitro stimulation of human monocytes showed that IFN-α alone recapitulates ISG-dim, whereas both IFN-α and IFN-γ are required for ISG-high.CONCLUSIONThese findings define dose-dependent IFN programming in human myeloid cells and highlight mechanistic differences between priming and boosting, with implications for optimizing vaccine platform choice, dose scheduling, and formulation.FUNDINGNIH grants AI142086, U19 AI135972, U01 AI165452, U01 AI165452, R01 AI160706, and P30 AG067988.

Humans↗
PubMed1976

Reduction of the graft-versus-host reactivity of mouse and rat spleen cells by 5alpha-androstane-3,17-dione.

The local graft-versus-host reaction as evaluated by the popliteal lymph node enlargement was used for studying the immunosuppressive potency of placental steroid 5alpha-androstane-3,17-dione. Spleen cells from virgin female mice and rats injected subcutaneously with this steroid compound produced in appropriate F1 recipients a significantly weaker reaction (P less than 0.001) than spleen cells from untreated or medium-treated control animals. On the other hand, the pretreatment of cell donors either with 5beta-androstane-3,17-dione or testosterone, the compounds which are not present in the mouse and rat placenta, did not influence the normal graft-versus-host reactivity.

Androstanes↗
PubMed1977

Assay and partial characterization of the solubilized cell surface receptor for immunoglobulin E.

The cell surface component (receptor) which specifically binds immunoglobulin E (IgE) presumably forms an integral part of the functional chain involved in the antigen-induced IgE-mediated degranulation of histamine-containing mast cells and basophils. This paper describes a simple (NH4)2SO4 predipitation assay with which the interaction of IgE with detergent-solubilized receptors can be reproducibly quantitated. Receptor saturation was demonstrated and a linear response to receptor concentration over at least a 30-fold rang obtained. By means of the assay it was shown that (a) all assayable receptors of rat basophil leukemia cells are cell surface expressed; (b) receptor specificity remains intact during solubilization; (c) the binding constants of the solubilized IgE receptors are similar to those determined on intact cells. Utilizing agarose gel filtration, preliminary estimates of the molecular weight of the active free solubilized receptor and of its complex with IgE suggest that the receptor is univalent.

Ammonium Sulfate↗
PubMed1977

Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen.

The immune response to a thymus-dependent antigen was depressed in vivo and in vitro in spleen cells from mice injected with LPS i.p. a few days before challenge with the antigen. Spleen cells from LPS-injected mice could, however, respond with increase DNA synthesis after activation with polyclonal B and T cell activators in vitro. The LPS-activated spleen cells could actively suppress normal cells in their response to the antigen sheep red blood cells. The suppressor cells contained in the LPS-activated spleens were most likely B lymphocytes, and the possible mechanism for their inhibitory function is discussed.

Animals↗
PubMed1977

Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide I. Comparison of the suppression induced by con A and low dose paralysis.

Concanavalin A (Con A) administered at the time of immunization induces suppression of the in vivo splenic plaque-forming cell (PFC) response to type III pneumococcal polysaccharide (SSS-III). As with low dose paralysis of the PFC response to SSS-III, Con A-induced suppression could not be demonstrated in congenitally athymic (nu/nu) mice and could be eliminated partially by treatment with anti-lymphocyte serum (ALS). The kinetics for Con A-induced suppression paralleled those for low dose paralysis of the antibody response to SSS-III. These findings support the view that Con A-induced suppression is produced in vivo by suppressor T cells and that this form of suppression shares with low dose paralysis a common pathway through which suppression is mediated.

Animals↗
PubMed1976

[Immunobiological means of identifying hypersensitivity to anesthetics and adjuvants].

The diagnosis of hypersensitivity to anesthetics and adjuvants is based chiefly on immunobiological tests which involve:-sensitized lymphocytes; -IgE or IgG antibodies; -sensitized target cells; -determination of chemical mediators. Comparison between these different methods is only possible for techniques involving the sensitized lymphocyte, such as the LTT and EA rosettes for examples, or T.D.B.H. and liberation of histamine. Comparison between the LTT and RAST is difficult, since the first technique investigates the sensitized lymphocyte while the second involves radio-immune antibody assay. An attempt to establish a correlation between these two types of methods is difficult but they can, however, complement each other.

Adjuvants, Pharmaceutic↗
PubMed1976

Antigenicity of type-specific pneumococcal polysaccharides in rats.

Hemagglutinating antibody responses of Lewis-Wistar and Sprague-Dawley rats to graded doses of type-specific pneumococcal polysaccharide were measured. Rats given a small dose (0.2 to 50 mug)of type 1 or 8 polysaccharide intraperitoneally developed type-specific hemagglutinating antibody. Rats given larger doses of polysaccharide (greater than or equal to200 mug) did not develop detectable hemagglutinating antibody, and they were unresponsive to a subsequence injection of a small (and normally antigenic) dose of polysaccharide. There was prolonged antigenemia in rats injected with a large dose of polysaccharide. There was prolonged antigenemia in rats injected with a large dose of polysaccharide, and the kinetics of antigen clearance in these animals resembled that reported for mice with polysaccharide immunological paralysis. These results indicate that a phenomenon resembling immunological paralysis with type-specific pneumococcal polysaccharides can be produced in rats.

Animals↗