scholarly journals Antigen structural requirements for immunoglobulin isotype switching in mice

1980 ◽  
Vol 152 (6) ◽  
pp. 1670-1683 ◽  
Author(s):  
P Chen ◽  
DE Nitecki ◽  
GK Lewis ◽  
JW Goodman
Keyword(s):  
Guinea Pigs ◽  
Indirect Evidence ◽  
Keyhole Limpet Hemocyanin ◽  
Antibody Responses ◽  
T Helper ◽  
Structural Requirements ◽  
Immunoglobulin Isotypes ◽  
Rigid Rod ◽  
Rats And Mice

L-Tyrosine-p-azobenzene-p-arsonate (RAT) is immunogenic and serves as a carrier for anti-hapten antibody responses in guinea pigs, rats, and mice. However, the murine anti-N-2,4-dinitrophenyl (DNP) plaque-forming cell (PFC) response to the bifunctional antigen 2,4-dinitrophenyl-6-amino-caproyl-L- tyrosine-p-azobenzene-p-arsonate (DNP-SAC-RAT; or BI-1) is extremely weak (2,000-4,000 PFC/spleen) and exclusively IgM in both primary and secondary responses. The 6-amino-caproyl group serves as a spacer in this antigen between the DNP haptenic and RAT carrier epitopes. In view of recent evidence indicating that different T helper cells synergize for optimal antibody responses, a trifunctional antigen, N-2,4- dinitrophenyl-6-amino-caproyl-L-tyrosine-p-azobenze-p-arsonate-(proline)9-L- tyrosine-p-azobenzene-p-arsonate (DNP-SAC-RAT-PRO(9)-RAT; or TRI), was prepared to investigate the effect of adding a second RAT epitope to BI-1. The nonaproline spacer between the two RAT epitopes in TRI is assumed to be a rigid rod of approximately 28 A. TRI induced about twice as many PFC as BI-1 in primary responses of A/J mice, and induced both IgM and IgG PFC in secondary responses. Furthermore, TRI induced IgG PFC responses in mice primed with p-azobenzene-p-arsonate-keyhole limpet hemocyanin, BI-1, or RAT, whereas boosting with BI-1 failed to induce IgG PFC, even in mice primed with TRI. These findings indicate that the minimum antigen structural requirements for inducing IgG PFC in mice are two carrier epitopes and one haptenic epitope. In addition, priming with a mono-epitope carrier (RAT) is sufficient preparation for IgG responses to a trifunctional immunogen. Because TRI differs from BI-1 by the (proline)(9) spacer as well as the additional RAT epitope, two other compounds, N-2,4-dinitrophenyl-6-amino- caproyl-(proline)(9)-L-tyrosine-p-azobenzene-p-arsonate (DNP-SAC-PRO(9)-RAT; or BI-2) and N-2,4-dinitrophenyl-6-amino-caproyl-(proline)(9)-L-tyrosine-p- azobenzene-arsonate (DNP-SAC-RAT-PRO(10); or BI-3), were prepared to evaluate the possible role of the spacer in the observed responses. BI-2, but not BI-3, induced IgG as well as IgM PFC in TRI-primed mice. However, BI-2 failed to induce IgG responses in RAT-primed mice, indicating that TRI and BI-2 were not equivalent immunogens. Because anti-prolyl antibodies had been found in guinea pigs immunized with N-2,4-dinitrophenyl-(proline)10-L-tyrosine-p- azobenzene-p-arsonate (DNP-PRO(10)-RAT), it seemed possible that priming with TRI might induce anti-prolyl antibodies, which, in turn, could cross-link BI-2 molecules into aggregates containing at least two carrier epitopes. To help resolve this question, mice were immunized with acetyl-(proline)10-L- tyrosine-p-azobenzene-p-arsonate and boosted with BI-2. IgG PFC responses were detected, suggesting that anti-prolyl antibodies were indeed responsible, because priming with RAT and boosting with BI-2 did not induce IgG formation. Accordingly, the observations that IgG responses in RAT-primed mice were induced only by TRI and not by any of the bifunctional antigens indicate that two carrier epitopes per antigen molecule are indeed required for IgG induction. They also provide indirect evidence for synergistic help in the switching of immunoglobulin isotypes.

scholarly journals Alterations by peroxisome proliferators of acyl composition of hepatic phosphatidylcholine in rats, mice and guinea-pigs. Role of stearoyl-CoA desaturase

1986 ◽  
Vol 235 (1) ◽  
pp. 251-255 ◽  
Author(s):  
Y Kawashima ◽  
A Hirose ◽  
H Kozuka
Keyword(s):  
Guinea Pigs ◽  
Liver Microsomes ◽  
Clofibric Acid ◽  
Chain Elongation ◽  
Peroxisome Proliferators ◽  
Acyl Composition ◽  
Stearoyl Coa Desaturase ◽  
Rats And Mice ◽  
Chlorophenoxyisobutyric Acid

Rats, mice and guinea-pigs were administered p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2′-(decamethylenedithio)diethanol (tiadenol). The treatments of rats and mice with either clofibric acid or tiadenol increased markedly the activities of stearoyl-CoA desaturase, palmitoyl-CoA chain elongation, 1-acylglycerophosphate (1-acyl-GP) acyltransferase and 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase, but not 2-acylglycerophosphocholine (2-acyl-GPC) acyltransferase in liver microsomes. The treatment of guinea-pigs with clofibric acid did not cause any change in the activities of these enzymes. The treatment of guinea-pigs with tiadenol caused a slight, but significant, increase in the activities of 1-acyl-GP acyltransferase and 1-acyl-GPC acyltransferase. The treatment of rats and mice with either clofibric acid or tiadenol increased markedly the proportion of 18:1 and decreased greatly the proportion of 18:0 in liver microsomal phosphatidylcholine. However, there is a considerable difference in the effects of the two peroxisome proliferators on the composition of polyunsaturated fatty acids in phosphatidylcholine between rats and mice. The treatment of guinea-pigs with either of the two peroxisome proliferators caused no change in acyl composition of phosphatidylcholine. The possible role of stearoyl-CoA desaturation in the regulation of acyl composition of phosphatidylcholine was discussed.

scholarly journals Role of B7 Costimulatory Molecules in Immune Responses and T-Helper Cell Differentiation in Response to Recombinant HagB from Porphyromonas gingivalis

2004 ◽  
Vol 72 (2) ◽  
pp. 637-644 ◽  
Author(s):  
Ping Zhang ◽  
Michael Martin ◽  
Qiu-Bo Yang ◽  
Suzanne M. Michalek ◽  
Jannet Katz
Keyword(s):  
Cell Differentiation ◽  
Immune Responses ◽  
Porphyromonas Gingivalis ◽  
Costimulatory Molecules ◽  
Antibody Responses ◽  
T Helper Cell ◽  
Wild Type ◽  
T Helper ◽  
Serum Igg

ABSTRACT In addition to antigen-specific signals mediated through the T-cell receptor, T cells also require antigen nonspecific costimulation for activation. The B7 family of molecules on antigen-presenting cells, which include B7-1 (CD80) and B7-2 (CD86), play important roles in providing costimulatory signals required for development of antigen-specific immune responses. Hemagglutinin B (HagB) is a nonfimbrial adhesin of the periodontopathic microorganism Porphyromonas gingivalis and is thought to be involved in the attachment of the bacterium to host tissues. However, the immune mechanisms involved in responses to HagB and their roles in pathogenesis have yet to be elucidated. Therefore, the purpose of this study was to determine the role of B7 costimulatory molecules on T-helper-cell differentiation for the induction of immune responses to HagB. Mice deficient in either or both of the costimulatory molecules B7-1 and B7-2 were used to explore their role in immune responses to HagB after subcutaneous immunization. B7-1−/− mice had levels of immunoglobulin G (IgG) anti-HagB antibody activity in serum similar to those of wild-type mice, whereas lower serum IgG anti-HagB antibody responses were seen in B7-2−/− mice. Moreover, significantly lower numbers of IgG antibody-secreting cells and lower levels of CD4+-T-cell proliferation were observed in B7-2−/− mice compared to wild-type mice. No serum IgG response to HagB was detected in B7-1/B7-2−/− mice. Analysis of the subclass of the serum IgG responses and the cytokines induced in response to HagB revealed that B7-2−/− mice had significantly lower IgG1 and higher IgG2a anti-HagB antibody responses compared to wild-type mice. The B7-2−/− mice also had significantly reduced levels of interleukin-4 (IL-4) and IL-5 and enhanced level of gamma interferon. Furthermore, assessment of B7-1 and B7-2 expression on B cells and macrophages derived from wild-type BALB/c mice after in vitro stimulation with HagB revealed a predominant upregulation in the expression of the B7-2 costimulatory molecule on B cells and macrophages. Essentially no change was seen in the expression of B7-1. Taken together, these results suggest a critical role for B7, especially B7-2, for the preferential induction of a Th2-like response to HagB.

Role of T helper cell precursor frequency on vesicular stomatitis virus neutralizing antibody responses in a T cell receptor β chain transgenic mouse

1995 ◽  
Vol 25 (5) ◽  
pp. 1410-1416 ◽  
Author(s):  
Giulia Freer ◽  
Christoph Burkhart ◽  
Thomas Rülicke ◽  
Emilia Ghelardi ◽  
Urs Hoffmann Rohrer ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Cell Receptor ◽  
Antibody Responses ◽  
T Helper Cell ◽  
T Helper ◽  
Cell Precursor ◽  
Vesicular Stomatitis ◽  
Precursor Frequency ◽  
Β Chain

scholarly journals Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction

2019 ◽  
Vol 221 (1) ◽  
pp. 21-32 ◽  
Author(s):  
Sarah Lartey ◽  
Fan Zhou ◽  
Karl A Brokstad ◽  
Kristin G-I Mohn ◽  
Steffen A Slettevoll ◽  
...  
Keyword(s):  
Hemagglutination Inhibition ◽  
Inverse Correlation ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Helper ◽  
Post Vaccination ◽  
Cell Responses ◽  
Tfh Cells

Abstract Background Influenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown. Methods We collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay. Results We report that LAIV induced early (3–7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV. Conclusions Our data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans.

Assessment of the role of T Helper 17 cells in the pathogenesis of Acne Vulgaris

2019 ◽  
Vol 10 (12) ◽  
pp. 1435
Author(s):  
Nahla Maher ◽  
HebatAllah Ismail Gawdat ◽  
Heba Helmy El Hadidi ◽  
Olfat Gamil Shaker
Keyword(s):  
Acne Vulgaris ◽  
T Helper ◽  
T Helper 17 ◽  
T Helper 17 Cells

scholarly journals Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape

2021 ◽  
Vol 9 (5) ◽  
pp. 899
Author(s):  
Anthony Torres-Ruesta ◽  
Rhonda Sin-Ling Chee ◽  
Lisa F.P. Ng
Keyword(s):  
Diagnostic Tests ◽  
Inflammatory Arthritis ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Chikv Infection ◽  
Wide Range ◽  
Susceptible Populations ◽  
Humoral Responses

Alphaviruses are mosquito-borne pathogens distributed worldwide in tropical and temperate areas causing a wide range of symptoms ranging from inflammatory arthritis-like manifestations to the induction of encephalitis in humans. Historically, large outbreaks in susceptible populations have been recorded followed by the development of protective long-lasting antibody responses suggesting a potential advantageous role for a vaccine. Although the current understanding of alphavirus antibody-mediated immunity has been mainly gathered in natural and experimental settings of chikungunya virus (CHIKV) infection, little is known about the humoral responses triggered by other emerging alphaviruses. This knowledge is needed to improve serology-based diagnostic tests and the development of highly effective cross-protective vaccines. Here, we review the role of antibody-mediated immunity upon arthritogenic and neurotropic alphavirus infections, and the current research efforts for the development of vaccines as a tool to control future alphavirus outbreaks.

scholarly journals AB0925-PARE A NARRATIVE REVIEW ASSESSING THE ROLE OF DIETARY SALT AS AN ENVIRONMENTAL RISK FACTOR FOR THE ONSET AND SEVERITY OF RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1484.1-1484
Author(s):  
S. Ahmed ◽  
E. Nikiphorou ◽  
J. Bayliss
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factor ◽  
Autoimmune Disease ◽  
Environmental Risk ◽  
Narrative Review ◽  
Environmental Risk Factor ◽  
T Helper ◽  
Dietary Salt ◽  
Salt Consumption

Background:The role of dietary salt consumption in the etiopathogenesis of Rheumatoid Arthritis (RA), and autoimmune disease in general, has received renewed interest. This has been fueled by the increased prevalence of autoimmune disease worldwide correlating with western diets and heightened consumption of salt rich foods and also studies at the cellular level demonstrating induction of IL 17 producing T helper cells (Th17) by dietary salt.Objectives:To conduct a narrative review of observational studies and clinical trials on the role of dietary salt as an environmental risk factor for the onset and development of RA.Methods:A comprehensive search was done of the literature from 2010 to 2021, using the search terms dietary salt and RA; the native interfaces EBSCO and Ovid were used. Databases searched included Pubmed, Embase, EMCare, Medline and CINAHL using a Population, Exposure and Outcome framework; the MESH terms RA, risk factors, nutrition and salt were used. Data was extracted by an independent reviewer.Results:Out of the 72 studies initially identified, 50 were included in this review. Studies in murine models have demonstrated that high concentrations of sodium chloride promote the differentiation of T helper lymphocytes, via the serum- and glucocorticoid- inducible kinase 1 (SGK1) mediator towards the proinflammatory Th17 driven immune response. Six studies were carried out in human subjects. Study design ranged from cross sectional observational to nested case control studies. Sodium intake amongst participants characterized as having high intake, or being placed in the higher quartiles, ranged from 4.5-5grams per day. 5 out of 6 studies demonstrated that increased dietary salt consumption is associated with earlier onset RA. One study suggested an association between high salt intake and erosive disease at diagnosis and the development of anti-citrullinated protein antibodies (ACPA), although evidence was weak and from a single study only. Another study found that increased consumption of salt was only associated with risk of RA in smokers, highlighting the need to explore confounding variables further.Conclusion:This narrative review of the literature provides some evidence that supports a role of excess dietary salt consumption as a risk factor for the onset and severity of RA.Disclosure of Interests:None declared

Immunology of the inner ear: Response of the inner ear to antigen challenge

1983 ◽  
Vol 91 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Jeffrey P. Harris
Keyword(s):  
Inner Ear ◽  
Blood Brain Barrier ◽  
Guinea Pigs ◽  
Keyhole Limpet Hemocyanin ◽  
Host Immunity ◽  
Brain Barrier ◽  
Antigen Challenge ◽  
Antibody Titers ◽  
Relationship Of ◽  
The Relationship

The relationship of the inner ear to host immunity and the immunoresponsiveness of the inner ear to antigen challenge were investigated. A radioimmunoassay was used to quantitate antibody titers to keyhole-limpet hemocyanin generated in the serum, perilymph, and CSF of guinea pigs following systemic or inner ear immunizations. The results of these experiments demonstrate (1) the blood-labyrinth barrier is analogous to the blood-brain barrier with respect to immunoglobulin equilibrium, (2) the inner ear is capable of responding to antigen challenge, and (3) the inner ear is an effective route for systemic immunization.

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