scholarly journals STUDIES ON THE REGULATION OF AVIDITY AT THE LEVEL OF THE SINGLE ANTIBODY-FORMING CELL

1970 ◽  
Vol 132 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Birger Andersson
Keyword(s):  
Immune Response ◽  
Present Method ◽  
Low Dose ◽  
Cellular Level ◽  
Plaque Formation ◽  
High Dose ◽  
High Avidity ◽  
Specific Inhibition ◽  
Cellular Events ◽  
Free Antigen

The hemolytic plaque formation of cells producing antibody against heterologous albumins was tested for sensitivity to specific inhibition by free antigen. The inhibition characteristics of plaques in this system were found to be a measure for the avidity of the antibody produced by the plaque-forming cells (PFC:s). High avidity-producing PFC:s were more sensitive to inhibition than low avidity PFC:s. Immunization with a high dose of antigen induced PFC:s that produced antibody with a lower avidity as compared to PFC:s from animals immunized with a low dose. The avidity was increased with time. Determinations of avidity at the serum level were also made, and the results were in agreement with the findings at the cellular level. The present method made it possible to demonstrate differences in avidity of antibody at the level of the single antibody-forming cell. It may also constitute a useful tool for the analysis of the cellular events leading to the production of antibodies with varying affinities during the immune response.

IGF-I inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-I infusion rates

1997 ◽  
Vol 272 (3) ◽  
pp. E352-E358 ◽  
Author(s):  
N. Porksen ◽  
M. A. Hussain ◽  
T. L. Bianda ◽  
B. Nyholm ◽  
J. S. Christiansen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Low Dose ◽  
Insulin Concentration ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Specific Inhibition ◽  
Igf I ◽  
Concentration Time Series ◽  
Functional Features ◽  
Pulsatile Insulin Secretion

Insulin-like growth factor I (IGF-I) shares structural and functional features with insulin, affects carbohydrate metabolism, and inhibits insulin secretion. Insulin secretion is pulsatile, and it is regulated by changing frequency and/or mass of secretory bursts. To examine the mechanism of IGF-I's inhibition of insulin secretion, eight healthy volunteers were studied three times. During glucose infusion (2.5 mg x kg(-1) x min(-1)) blood was sampled minutely at time 75-200 min for triplicate insulin concentration measurements by enzyme-linked immunosorbent assay (ELISA; coefficient of variation 2.1%). Time 125 min infusion of saline, low-dose IGF-I (0.025 microg x kg(-1) x min(-1)) or high-dose IGF-I (0.15 microg x kg(-1) x min(-1)) was commenced and continued until 200 min. Data were compared before (75-125 min) vs. during infusion (150-200 min). Insulin concentration time series were deconvolved, using validated pulse-detection criteria, to assess insulin secretory burst mass and frequency. During saline infusion no time effect occurred. After IGF-I infusion, serum C-peptide decreased (582 +/- 85 vs. 481 +/- 82 pM, low-dose IGF-I, P < 0.05; 539 +/- 84 vs. 427 +/- 69 pM, high-dose IGF-I, P < 0.01). Total insulin secretion rates decreased by 17 and 21%, respectively, via specific inhibition of the insulin secretory burst mass (31 +/- 8 vs. 20 +/- 4 pmol/ml, low-dose IGF-I, P = 0.06; 22 +/- 4 vs. 17 +/- 3 pmol/ml, high-dose IGF-I, P < 0.05), whereas the frequency was not affected (10.5 +/- 1.3 vs. 10.7 +/- 1.3 pulses/h, low-dose IGF-I, P = 0.85; 8.7 +/- 1.0 vs. 11.1 +/- 1.2 min/pulse, high-dose IGF-I, P = 0.15). We conclude that IGF-I inhibits pulsatile insulin secretion by specific inhibition of mass but not frequency of secretory bursts.

scholarly journals Mycobacterium tuberculosis in Chemokine Receptor 2-Deficient Mice: Influence of Dose on Disease Progression

2002 ◽  
Vol 70 (11) ◽  
pp. 5946-5954 ◽  
Author(s):  
Holly M. Scott ◽  
JoAnne L. Flynn
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Cell Migration ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Low Dose ◽  
High Dose ◽  
Long Term Effects ◽  
Spread Of Infection ◽  
Oxide Synthase

ABSTRACT Within a Mycobacterium tuberculosis-induced granuloma, lymphocytes and macrophages work together to control bacterial growth and limit the spread of infection. Chemokines and chemokine receptors are involved in cell migration and are logical candidates for a role in granuloma formation. In the present study we addressed the role of CC chemokine receptor 2 (CCR2) in M. tuberculosis infection. In previous studies (W. Peters et al., Proc. Natl. Acad. Sci. USA 98:7958-7963, 2001), CCR2−/− mice were found to be highly susceptible to a moderate or high dose of H37Rv administered intravenously (i.v.). We have expanded those studies to demonstrate that the susceptibility of CCR2−/− mice is dose dependent. After low-dose aerosol or i.v. infection of CCR2−/− mice with M. tuberculosis, there was a substantial delay in cell migration to the lungs and delayed expression of gamma interferon and inducible nitric oxide synthase. The CCR2−/− mice had a severe and prolonged deficiency in the number of macrophages in the lungs and an early increase in the number of neutrophils. Despite these deficiencies in cell migration, the CCR2−/− mice did not have increased bacterial loads in the lungs compared to wild-type (C57BL/6) mice and successfully formed granulomas. This finding is in contrast to CCR2−/− mice infected with a high dose of M. tuberculosis administered i.v. These results indicate that with low-dose infection, a delay in immune response in the lungs does not necessarily have detrimental long-term effects on the progression of the disease. The fact that CCR2−/− mice survive with substantially fewer macrophages in the low-dose models implies that the immune response to low-dose M. tuberculosis infection in mice is more robust than necessary to control the infection. Finally, these data demonstrate that, in cases of infectious disease in knockout models, clear phenotypes may not be evident when one is solely evaluating bacterial numbers and survival. Functional assays may be necessary to reveal roles for components of the multifactorial immune system.

scholarly journals Relationship between chorionic gonadotropin immunomodulating effects and the initial functional activity of the splenocytes mediating the adoptive immune response

1993 ◽  
Vol 39 (1) ◽  
pp. 54-57 ◽  
Author(s):  
S. V. Shirshev ◽  
N. N. Kevorkov
Keyword(s):  
Immune Response ◽  
Chorionic Gonadotropin ◽  
Functional Activity ◽  
Low Dose ◽  
Interleukin 2 ◽  
Prostaglandin Synthesis ◽  
High Dose ◽  
Transfer System ◽  
Male Mice ◽  
Stimulation Of

CBA and (СВАхC57BL/6) F1 male mice were used in experiments. One hour incubation of splenocytes with chorionic gonadotropin in doses 10 or 50 MU/ml statistically significantly reduced the count of antibody-producing cells detectable in the syngeneic transfer system. Addition of conA or recombinant human interleukin 2 to the splenocyte culture did not alter the processes of the formation of antibodyproducing cells. Addition of chorionic gonadotropin simultaneously with conA resulted in discontinuation of the immunosuppression induced by a low hormone dose, whereas 50 MU/ml of chorionic gonadotropin in the presence of conA had a marked immunodepressant effect. Combination of interleukin 2 with chorionic gonadotropin lead either to immunosuppression cessation (10 MU/ml) or to more than twofold stimulation of the adoptive immune response (50 MU/ml). Voltaren a cycloxygenase inhibitor, was used in some experiments to elucidate the degree of endogenic prostaglandin relationships with the mechanisms of chorionic gonadotropin immunomodulating effects. Cycloxygenase activity was found to be related to the immunosuppressive effect of chorionic gonadotropin low dose, whereas the costimulating effect of a high dose of the hormone in the presence of interleukin 2 was unrelated to endogenic prostaglandin synthesis.

scholarly journals A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yinghua Zhao ◽  
Liyan Sui ◽  
Ping Wu ◽  
Wenfang Wang ◽  
Zedong Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Low Dose ◽  
Nuclear Translocation ◽  
Innate Immune ◽  
High Dose ◽  
Type I ◽  
Innate Immune Responses ◽  
N Protein

AbstractThe recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and overactive immune response in the late stage of infection; However, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein dually regulated the phosphorylation and nuclear translocation of IRF3, STAT1, and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress the ubiquitination and activation of retinoic acid-inducible gene I (RIG-I). Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.

Differences in Clinical Disease and Immune Response of Pigs Challenged with a High-Dose versus Low-Dose Inoculum of Porcine Reproductive and Respiratory Syndrome Virus

2008 ◽  
Vol 21 (3) ◽  
pp. 315-326 ◽  
Author(s):  
Crystal L. Loving ◽  
Susan L. Brockmeier ◽  
Amy L. Vincent ◽  
Kelly M. Lager ◽  
Randy E. Sacco
Keyword(s):  
Immune Response ◽  
Low Dose ◽  
Clinical Disease ◽  
Respiratory Syndrome Virus ◽  
High Dose

scholarly journals STUDIES ON ANTIBODY AFFINITY AT THE CELLULAR LEVEL

1972 ◽  
Vol 135 (2) ◽  
pp. 312-322 ◽  
Author(s):  
Birger Andersson
Keyword(s):  
Antibody Production ◽  
Low Dose ◽  
Cellular Level ◽  
Plaque Formation ◽  
Memory Cells ◽  
Antibody Affinity ◽  
Antigen Dose ◽  
High Affinity ◽  
Plastic Bead ◽  
Similar Affinity

Heterogeneity with regard to affinity of anti-hapten antibody was demonstrated at the cellular level in mice. The heterogeneity was shown at the level of single antibody-forming cells using hapten inhibition of hemolytic antibody plaque formation as a measure of affinity. The affinity increased with time after immunization. A high antigen dose initially resulted in relatively low affinity antibody production as compared to the affinity of the antibody production in animals immunized with a low dose. Affinity specialization of immunological memory cells was demonstrated, since it was possible to specifically fractionate such cells with regard to affinity on hapten-protein-coated plastic bead columns. High affinity memory cells showed a higher tendency to become retained in the columns than did low affinity memory cells. The data in a direct way demonstrate that memory cells carrying membrane-associated receptors of a certain affinity for the antigen are determined to release antibody of a similar affinity after stimulation with antigen.

scholarly journals Assessing the Immune Response of Atlantic Salmon (Salmo salar) after the Oral Intake of Alginate-Encapsulated Piscirickettsia salmonis Antigens

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 450
Author(s):  
Daniela Sotomayor-Gerding ◽  
José Miguel Troncoso ◽  
Alejandro Pino ◽  
Felipe Almendras ◽  
Mónica Rubilar Diaz
Keyword(s):  
Immune Response ◽  
Atlantic Salmon ◽  
Salmo Salar ◽  
Low Dose ◽  
Oral Vaccine ◽  
Fish Growth ◽  
High Dose ◽  
Fish Feed ◽  
Atlantic Salmon Salmo Salar ◽  
Piscirickettsia Salmonis

Salmon rickettsial septicaemia (SRS) is the infectious disease that produces the highest losses in the Chilean salmon industry. As a new strategy for the control of SRS outbreaks, in this study we evaluated the effect of alginate-encapsulated Piscirickettsia salmonis antigens (AEPSA) incorporated in the feed as an oral vaccine to induce the immune response in Atlantic salmon (Salmo salar). Fish were distributed into three vaccination groups (injectable, oral high dose, oral low dose). Feed intake and fish growth were recorded during the trial. The P. salmonis-specific IgM levels in blood plasma were measured by ELISA. Alginate microparticles containing the antigen were effectively incorporated in fish feed to produce the oral vaccine. Incorporation of AEPSA did not affect the palatability of the feed or the fish appetite. Furthermore, the oral vaccine did not have a negative effect on fish growth. Finally, the oral vaccine (high and low dose) produced an acquired immune response (IgM) similar to the injectable vaccine, generating a statistically significant increase in the IgM levels at 840-degree days for both experimental groups. These findings suggest that AEPSA incorporated in the feed can be an effective alternative to boost the immune response in Atlantic salmon (S. salar).

scholarly journals Use of an Experimental Model To Test the Efficacy of Planned Exposure to Live Porcine Reproductive and Respiratory Syndrome Virus

2007 ◽  
Vol 14 (12) ◽  
pp. 1572-1577 ◽  
Author(s):  
Tanja Opriessnig ◽  
Rodney B. Baker ◽  
Patrick G. Halbur
Keyword(s):  
Immune Response ◽  
Low Dose ◽  
Respiratory Syndrome Virus ◽  
Control Group ◽  
High Dose ◽  
Efficacy And Safety ◽  
Copy Numbers ◽  
Group A ◽  
Prrsv Strain ◽  
Autogenous Vaccine

ABSTRACT The objectives of this study were to test the efficacy and safety of planned exposure to porcine reproductive and respiratory syndrome virus (PRRSV) in protecting naïve and previously exposed pigs against PRRSV challenge and to gain information on the dose of PRRSV necessary to induce a protective immune response. Fifty 2-week-old pigs were randomly assigned to one of five groups: a group exposed to a low dose of autogenous PRRSV vaccine (the L-VAC group), a group exposed to a high dose of autogenous vaccine (the H-VAC group), a group exposed to a low dose of a heterologous PRRSV strain (strain SDSU73) prior to planned exposure (the SDSU73-L-VAC group), a group exposed to a high dose of a heterologous PRRSV strain (strain SDSU73) prior to planned exposure (the SDSU73-H-VAC group), and a control group. All groups were challenged with PRRSV VR2385 5 weeks after the planned exposure. Necropsy was done 2 weeks after the PRRSV challenge. The H-VAC, SDSU73-L-VAC, and SDSU73-H-VAC groups had significantly (P < 0.05) less severe clinical disease (sneezing, respiratory scores, and weight gain), significantly (P < 0.05) less severe macroscopic and microscopic lung lesions, and significantly (P < 0.05) lower numbers of PRRSV genomic copy numbers in their sera compared to the results for the control group. Planned exposure to live PRRSV can be used as an inexpensive and effective way to decrease the severity of PRRSV-induced disease following subsequent challenge.

scholarly journals Protective Effects of Ophiocordyceps lanpingensis on Glycerol-Induced Acute Renal Failure in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yanyan Zhang ◽  
Yaxi Du ◽  
Hong Yu ◽  
Yongchun Zhou ◽  
Feng Ge
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Low Dose ◽  
Treated Group ◽  
High Dose ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Immune Organ

Objective. Oxidative stress and immune response are associated with acute renal failure (ARF). Ophiocordyceps lanpingensis (OL) might be an antioxidant and immunopotentiator. In this study, we explored the protective effects of OL on glycerol-induced ARF. Methods. Male mice were randomly divided into four groups, specifically, glycerol-induced ARF model group, low-dose OL-treated group (1.0 g/kg/d), high-dose OL-treated group (2.0 g/kg/d), and control group. Renal conditions were evaluated using kidney index, serum creatinine (Cr), blood urea nitrogen (BUN), and histological analysis. Rhabdomyolysis was monitored using creatine kinase (CK) level. Oxidative stress was determined using kidney tissue glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Immune status was evaluated using immune organ indices and immunoglobulin G (IgG) level. Results. OL could relieve renal pathological injury and decrease the abnormal levels of kidney index, serum Cr, CK, BUN, and MDA, as well as increase the immune organ indices and the levels of IgG, GSH, and SOD. Treatment with a high dose of OL had more positive therapeutic effects on ARF than using a low dose of OL. Conclusion. OL could ameliorate renal dysfunction in glycerol-induced ARF in mice by inhibiting oxidative stress and enhancing immune response.

scholarly journals A Local and Low-Dose Chemotherapy/Autophagy-Enhancing Regimen Treatment Markedly Inhibited the Growth of Established Solid Tumors Through a Systemic Antitumor Immune Response

2021 ◽  
Vol 11 ◽  
Author(s):  
Jia Yuan ◽  
Xianlin Yuan ◽  
Kunlong Wu ◽  
Junxia Gao ◽  
Liangping Li
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Low Dose ◽  
Local Delivery ◽  
Antitumor Immune Response ◽  
High Dose ◽  
Chemotherapeutic Drugs ◽  
Cell Immunity ◽  
Drug Concentrations ◽  
Low Dose Chemotherapy

Chemotherapy is one of the main options for the treatment of a variety of malignant tumors. However, the severe side effects resulting from the killing of normal proliferating cells limit the application of cancer-targeting chemotherapeutic drugs. To improve the efficacy of classic systemic chemotherapy, the local delivery of high-dose chemotherapeutic drugs was developed as a method to enhance local drug concentrations and minimize systemic toxicity. Studies have demonstrated that chemotherapy is often accompanied by cancer-associated immunogenic cell death (ICD) and that autophagy is involved in the induction of ICD. To improve the efficacy of local cancer chemotherapy, we hypothesized that the local delivery of chemotherapeutic plus autophagy-enhancing agents would enhance the promotive effects of ICD on the antitumor immune response. Here, we report that a low-dose chemotherapy/autophagy enhancing regimen (CAER) not only resulted in the increased death of B16F10 and 4T1 tumor cells, but also induced higher levels of autophagy in vitro. Importantly, the local delivery of the CARE drugs significantly inhibited tumor growth in B16F10 and 4T1 tumor-bearing mice. Systemic antitumor T-cell immunity was observed in vivo, including neoantigen-specific T-cell responses. Furthermore, bioinformatic analysis of human breast cancer and melanoma tissues showed that autophagy-associated gene expression was upregulated in tumor samples. Increased autophagy and immune cell infiltration in tumor tissues were positively correlated with good prognosis of tumor patients. This work highlights a new approach to improve the effects of local chemotherapy and enhance systemic antitumor immunity.

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