scholarly journals REGULATION OF ANTIBODY RESPONSE BY CELLS EXPRESSING HISTAMINE RECEPTORS

1972 ◽  
Vol 136 (5) ◽  
pp. 1302-1307 ◽  
Author(s):  
G. M. Shearer ◽  
Kenneth L. Melmon ◽  
Yacob Weinstein ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Serum Albumin ◽  
Sheep Erythrocyte ◽  
Antibody Responses ◽  
Rabbit Serum ◽  
Spleen Cells ◽  
Surface Receptors ◽  
Cell Responses ◽  
A Cell

Spleen cells from immunized and unimmunized mice were either passed over histamine-rabbit serum albumin-Sepharose columns or rabbit serum albumin-Sepharose control columns. The immune response potential of 5 x 106 cells excluded from the two columns were compared with each other, and with an equal number of unfiltered cells by injection of the cell suspensions mixed with sheep erythrocytes into irradiated, syngeneic recipients. The direct and indirect anti-sheep erythrocyte plaque-forming cell responses generated by the cells passed over the histamine-bead column were significantly greater than the responses resulting from the inocula of unfiltered cells or cells passed over control columns. These results indicate the existence of a cell population expressing surface receptors for histamine, which functions to regulate antibody responses.

scholarly journals Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial

Diabetologia ◽  
2021 ◽  
Author(s):  
Robin Assfalg ◽  
Jan Knoop ◽  
Kristi L. Hoffman ◽  
Markus Pfirrmann ◽  
Jose Maria Zapardiel-Gonzalo ◽  
...  
Keyword(s):  
Immune Response ◽  
Type 1 Diabetes ◽  
Randomised Controlled Trial ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Antibody Responses ◽  
Oral Insulin ◽  
Cell Responses ◽  
Randomised Controlled

Abstract Aims/hypothesis Oral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome. Methods A phase I/II randomised controlled trial was performed in a single clinical study centre in Germany. Participants were 44 islet autoantibody-negative children aged 6 months to 2.99 years who had a first-degree relative with type 1 diabetes and a susceptible HLA DR4-DQ8-containing genotype. Children were randomised 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months using a web-based computer system. The primary outcome was immune efficacy pre-specified as induction of antibody or T cell responses to insulin and measured in a central treatment-blinded laboratory. Results Randomisation was performed in 44 children. One child in the placebo group was withdrawn after the first study visit and data from 22 insulin-treated and 21 placebo-treated children were analysed. Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in children who received both insulin (54.5%) and placebo (66.7%), and the trial did not demonstrate an effect on its primary outcome (p = 0.54). In exploratory analyses, there was preliminary evidence that the immune response and gut microbiome were modified by the INS genotype Among children with the type 1 diabetes-susceptible INS genotype (n = 22), antibody responses to insulin were more frequent in insulin-treated (72.7%) as compared with placebo-treated children (18.2%; p = 0.03). T cell responses to insulin were modified by treatment-independent inflammatory episodes. Conclusions/interpretation The study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptible INS genotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells. Trial registration Clinicaltrials.gov NCT02547519 Funding The main funding source was the German Center for Diabetes Research (DZD e.V.) Graphical abstract

Dual effect of meningococcal antigens on a T cell dependent immune response

1983 ◽  
Vol 29 (12) ◽  
pp. 1619-1625 ◽  
Author(s):  
Brian G. Sparkes
Keyword(s):  
Immune Response ◽  
Inhibitory Activity ◽  
Sheep Erythrocyte ◽  
Subsequent Development ◽  
Plaque Formation ◽  
Adherent Cells ◽  
Spleen Cells ◽  
Dual Effect ◽  
Adjuvant Activity ◽  
Nonadherent Cells

Meningococcal antigens (MA) showed adjuvant activity when administered to mice at the same time as antigen (sheep erythrocyte (SE)), by increasing the splenocyte plaque-forming response in a dose-related manner. However, when SE were given 1 day after MA administration, the subsequent plaque formation was diminished from normal in proportion to the dose of MA injected. Splenocytes taken from mice up to 5 days after MA injection actively inhibited plaque formation when mixed with splenocytes immunized with SE 4 days earlier. Two days after MA injection the nonspecific inhibition of plaque formation was mainly due to adherent spleen cells, while at 5 days nonadherent cells had acquired the inhibitory activity. It appears that it is the degree of activation of adherent cells resulting from the timing and dosage of MA which modulates the subsequent development and secretion of antibody-forming cells.

scholarly journals Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of a Plasmodium falciparum Protein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

2008 ◽  
Vol 76 (4) ◽  
pp. 1709-1718 ◽  
Author(s):  
Ariane Rodríguez ◽  
Jaap Goudsmit ◽  
Arjen Companjen ◽  
Ratna Mintardjo ◽  
Gert Gillissen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Recombinant Adenovirus ◽  
Antibody Responses ◽  
T Cell Immunity ◽  
Adenovirus Serotype ◽  
Liver Stage ◽  
Cell Responses ◽  
Cell Immunity ◽  
Ifn Γ

ABSTRACT Prime-boost vaccination regimens with heterologous antigen delivery systems have indicated that redirection of the immune response is feasible. We showed earlier that T-cell responses to circumsporozoite (CS) protein improved significantly when the protein is primed with recombinant adenovirus serotype 35 coding for CS (rAd35.CS). The current study was designed to answer the question whether such an effect can be extended to liver-stage antigens (LSA) of Plasmodium falciparum such as LSA-1. Studies with mice have demonstrated that the LSA-1 protein induces strong antibody response but a weak T-cell immunity. We first identified T-cell epitopes in LSA-1 by use of intracellular gamma interferon (IFN-γ) staining and confirmed these epitopes by means of enzyme-linked immunospot assay and pentamer staining. We show that a single immunization with rAd35.LSA-1 induced a strong antigen-specific IFN-γ CD8+ T-cell response but no measurable antibody response. In contrast, vaccinations with the adjuvanted recombinant LSA-1 protein induced remarkably low cellular responses but strong antibody responses. Finally, both priming and boosting of the adjuvanted protein by rAd35 resulted in enhanced T-cell responses without impairing the level of antibody responses induced by the protein immunizations alone. Furthermore, the incorporation of rAd35 in the vaccination schedule led to a skewing of LSA-1-specific antibody responses toward a Th1-type immune response. Our results show the ability of rAd35 to induce potent T-cell immunity in combination with protein in a prime-boost schedule without impairing the B-cell response.

scholarly journals Depletion of Complement Has Distinct Effects on the Primary and Secondary Antibody Responses to a Conjugate of Pneumococcal Serotype 14 Capsular Polysaccharide and a T-Cell-Dependent Protein Carrier

2005 ◽  
Vol 73 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Samuel T. Test ◽  
Joyce K. Mitsuyoshi ◽  
Yong Hu
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Antibody Response ◽  
Complement Activation ◽  
Capsular Polysaccharide ◽  
Antibody Responses ◽  
Primary Immunization ◽  
Protein Carrier ◽  
Dependent Protein

ABSTRACT Complement activation plays a critical role in the immune response to T-cell-dependent and T-cell-independent antigens. However, the effect of conjugation of T-cell-dependent protein carriers to T-cell-independent type 2 antigens on the requirement for complement in the humoral immune response to such antigens remains unknown. We studied the role of complement activation on the antibody response of BALB/c mice immunized with the T-cell-independent type 2 antigen serotype 14 pneumococcal capsular polysaccharide (PPS14), either in unmodified form or conjugated to ovalbumin (OVA). In mice immunized with either PPS14 or PPS14-OVA, depletion of endogenous complement at the time of primary immunization by treatment with cobra venom factor (CVF) diminished serum anti-PPS14 concentrations after primary immunization but enhanced antibody responses after secondary immunization. The secondary immunoglobulin G (IgG) anti-PPS14 antibody response after immunization with PPS14-OVA was especially enhanced by complement depletion, was observed at doses as low as 0.2 μg of antigen, and was maximal when CVF was administered within 2 days of immunization. The avidity and opsonophagocytic functions of IgG anti-PPS14 antibodies were comparable in mice immunized with PPS14-OVA with or without complement depletion. Serum anti-PPS14 antibody concentrations were near normal, and the enhancing effects of CVF treatment on the secondary anti-PPS14 antibody response were also apparent in splenectomized mice immunized with PPS14-OVA. These results demonstrate that complement activation can have distinct effects on the primary and secondary antibody responses to a T-cell-independent type 2 antigen, either unmodified or conjugated to a T-cell-dependent protein carrier. These differences should be taken into consideration when using complement to modulate the immune response to vaccines.

scholarly journals Defining Antibody Seroprevalence and Duration of Humoral Responses to SARS-CoV-2 Infection and/or Vaccination in a Greek Community

2021 ◽  
Vol 19 (1) ◽  
pp. 407
Author(s):  
Ourania S. Kotsiou ◽  
Dimitrios Papagiannis ◽  
Evangelos C. Fradelos ◽  
Dimitra I. Siachpazidou ◽  
Garifallia Perlepe ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Severe Disease ◽  
Vaccination Status ◽  
Antibody Responses ◽  
Antibody Testing ◽  
Mild Disease ◽  
Antibody Titers ◽  
Humoral Responses ◽  
Pandemic Wave

Background: In this work we aimed to evaluate antibody-response longevity to SARS-CoV-2 infection and/or vaccination in one of the Greek communities that was worst hit by the pandemic, Deskati, five months after a previous serosurveillance and nine months after the pandemic wave initiation (October 2020). Methods: The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. Results: A total of 69 subjects, who previously tested positive or negative for COVID-19 antibodies, participated in the study. We found that 48% of participants turned positive due to vaccination and 27% of participants were both previously infected and vaccinated. All previously infected participants retained antibodies to the virus, irrespective of their vaccination status. The antibody titers were significantly higher in previously infected participants that had been vaccinated than those who were unvaccinated and in those that had been previously hospitalized for COVID-19 than those with mild disease. Conclusions: Antibody responses to SARS-CoV-2 infection were maintained nine months after the pandemic. Vaccination alone had generated an immune response in almost half of the population. Higher antibody titers were found in the case of vaccination in previously infected subjects and especially in those with severe disease leading to hospitalization

The immune response of inbred strains of guinea-pigs to polylysyl rabbit serum albumin

1966 ◽  
Vol 3 (6) ◽  
pp. 491-494 ◽  
Author(s):  
Shlomo Ben-Efraim ◽  
Ruth Arnon ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Serum Albumin ◽  
Guinea Pigs ◽  
Inbred Strains ◽  
Rabbit Serum

scholarly journals Immunosuppressive factors from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10. IV. Lack of strain restrictions among allogeneic, nonresponder donors and recipients.

1978 ◽  
Vol 147 (4) ◽  
pp. 997-1006 ◽  
Author(s):  
J A Kapp
Keyword(s):  
T Cells ◽  
Lymphoid Cells ◽  
Antibody Responses ◽  
Gene Complex ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
T Cell Factor ◽  
Cell Responses ◽  
Specific Suppressor T Cells ◽  
Immunosuppressive Factors

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder mice but stimulates development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT plaque-forming cell responses to GAT complexed to methylated bovine serum albumin (MBSA). Extracts from lymphoid cells of GAT-primed but not control, nonresponder (DBA/1) mice contain a T-cell factor (GAT-TsF) that also specifically suppresses responses to GAT-MBSA by normal syngeneic spleen cells. The experiments reported in this communication demonstrate that: (a) extracts from all GAT-primed nonresponder mice tested contain GAT-TsF; (b) non-H-2 genes do not restrict the production of GAT-TsF; (c) all nonresponder strains of mice regardless of their non-H-2 genes are suppressed by GAT-TsF from all other strains bearing the nonresponder H-2p,q,s haplotypes; (d) suppression of GAT-MBSA responses by both syngeneic and allogeneic nonresponder spleen cells is mediated by a molecule encoded by the H-2 gene complex; and (e) both syngeneic and allogeneic nonresponder mice are suppressed by purified GAT-TsF that lacks immunoreactive GAT.

scholarly journals SELECTIVE ROLES OF THYMUS-DERIVED LYMPHOCYTES IN THE ANTIBODY RESPONSE

1974 ◽  
Vol 140 (1) ◽  
pp. 239-252 ◽  
Author(s):  
Tomio Tada ◽  
Toshitada Takemori
Keyword(s):  
T Cells ◽  
B Cells ◽  
Antibody Response ◽  
Suppressive Effect ◽  
Antibody Responses ◽  
Cell Transfer ◽  
Spleen Cells ◽  
Igg Antibody ◽  
Igm Antibody

Passively transferred thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) exerted differential suppressive effect on IgM and IgG antibody responses of syngeneic recipients immunized with DNP-KLH depending primarily on the time when KLH-primed cells were transferred. This was demonstrated by the decrease in the numbers of DNP-specific direct and indirect PFC in the spleen of the recipients given KLH-primed cells at different times during primary and secondary immunization. Whereas the cell transfer simultaneously with or 2 days after the primary immunization produced only slight suppression of the peak IgM antibody response, it caused profound suppression of late IgM and IgG antibody responses. By contrast, the cell transfer 3 days after the immunization produced immediate suppression of the ongoing IgM antibody response resulting in its earlier termination, while being unable to prevent the induction of IgG antibody response. KLH-primed cells could moderately suppress the secondary anti-DNP antibody response, in which IgG antibody response was found to be slightly more sensitive than IgM antibody response to the suppressive influence of KLH-primed cells. The suppressive effect of the KLH-primed spleen cells was completely eliminated by the in vitro treatment of the cells with anti-θ and C before cell transfer, indicating that cells responsible for the suppression are, in fact, T cells. The suppression of DNP-specific antibody response by KLH-primed T cells was achieved only if the recipients were immunized with DNP-KLH but not with DNP-heterologous carrier, suggesting that direct interaction between T and B cells is necessary for the suppression of the antibody response. It is concluded that susceptibility of B cells to the specific suppressive influence of T cells is inherently different depending on the differentiation stage of B cells and on the immunoglobulin class they are destined to produce.

scholarly journals CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

1968 ◽  
Vol 128 (3) ◽  
pp. 437-457 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz ◽  
Mary St. James Connell ◽  
R. L. Priore
Keyword(s):  
Cellular Differentiation ◽  
Sheep Erythrocyte ◽  
Donor Cell ◽  
Cell Suspensions ◽  
Antibody Responses ◽  
Primary Immune Response ◽  
Cell Populations ◽  
Spleen Cells ◽  
Experimental Conditions ◽  
Antibody Class

Spleen cell suspensions of unprimed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice. In the presence of antigen (sheep erythrocytes) these precursors, called antigen-sensitive units, gave rise to progeny cells secreting specific antibody. We studied quantitatively the production of cells releasing IgM hemolysins (direct plaque-forming cells), IgG hemolysins (indirect plaque-forming cells), and hemagglutinins (cluster-forming cells). We found that each of these immunocyte populations was distinct, i.e., that cells releasing agglutinins did not, as a rule, release hemolysins, and vice versa. We also found that cell populations secreting IgM hemolysins did not shift, under certain experimental conditions, to the production of IgG hemolysins during the primary immune response. By transplanting graded numbers of spleen cells, we succeeded in limiting to one or a few the number of antigen-sensitive units that reached the recipient spleen. We estimated thereby the frequency of antigen-sensitive units in donor cell suspensions and tested their potential for production of immunocytes of more than one type. Our results indicated that antigen-sensitive units were unipotent for they displayed in the spleens of unprimed donors the same restrictions of function and heterogeneity (antibody-specificity differentiation, antibody-class differentiation) found among antibody-forming cells. Furthermore, antigen-sensitive precursors for direct plaque-forming cells, indirect plaque-forming cells, and cluster-forming cells were detected in the spleens of unprimed mice in different frequencies, i.e., 1 in ∼ 106, 1 in ∼ 7 x 106, and 1 in ∼ 19 x 106 spleen cells, respectively. We concluded that relatively advanced differentiation of potentially competent cells occurs before sheep erythrocyte administration. The relevance of this finding for the broad spectrum of immunologic reactivities and for the heterogeneity of antibody responses to given antigens was discussed.

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