scholarly journals Antigen-specific competitive inhibition of CD4+ T cell recruitment into the primary immune response

2020 ◽  
Author(s):  
Alexandra J. Spencer ◽  
Adrian L. Smith ◽  
Barbara Fazekas de St Groth
Keyword(s):  
Immune Response ◽  
Competitive Inhibition ◽  
Inverse Function ◽  
Primary Response ◽  
Primary Immune Response ◽  
Specific Response ◽  
Cell Recruitment ◽  
Secondary Infections ◽  
Proliferation And Differentiation ◽  
Additional Antigen

AbstractPrevious studies suggest that recruitment of naïve T cells into a program of cell division and differentiation is a highly synchronous process under tight regulation. However it is not known whether antigen availability is the major regulator of this process, or whether other factors such as ongoing responses to unrelated antigens can affect the size of the primary response. We have developed an adoptive transfer system to investigate the efficiency with which additional antigen specific cells are recruited into an ongoing primary immune response. Recruitment of additional cells is an inverse function of the size of the response and is progressively inhibited with time. Cells recruited late into the response proliferate less, and fewer secrete IL-2 and IFN-γ. Thus the size of the response changes very little as a result of late recruitment. The inhibition of recruitment, proliferation and differentiation affects only cells of the same specificity as the ongoing response, indicating that the size of an antigen specific response is independent of any shared factors such as access to APCs, costimulation or cytokines. Thus, during infection, the immune system retains the ability to respond as necessary to secondary infections or antigens not presented until later stages of the response.

scholarly journals In Situ Studies of the Primary Immune Response to (4-Hydroxy-3-Nitrophenyl)Acetyl. V. Affinity Maturation Develops in Two Stages of Clonal Selection

1998 ◽  
Vol 187 (6) ◽  
pp. 885-895 ◽  
Author(s):  
Yoshimasa Takahashi ◽  
Pinaki R. Dutta ◽  
Douglas M. Cerasoli ◽  
Garnett Kelsoe
Keyword(s):  
Immune Response ◽  
Clonal Selection ◽  
Cd40 Ligand ◽  
Primary Response ◽  
Affinity Maturation ◽  
Primary Immune Response ◽  
Cellular Interactions ◽  
Serum Antibodies ◽  
High Affinity ◽  
Selection Of

To examine the role of germinal centers (GCs) in the generation and selection of high affinity antibody-forming cells (AFCs), we have analyzed the average affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific AFCs and serum antibodies both during and after the GC phase of the immune response. In addition, the genetics of NP-binding AFCs were followed to monitor the generation and selection of high affinity AFCs at the clonal level. NP-binding AFCs gradually accumulate in bone marrow (BM) after immunization and BM becomes the predominant locale of specific AFCs in the late primary response. Although the average affinity of NP-specific BM AFCs rapidly increased while GCs were present (GC phase), the affinity of both BM AFCs and serum antibodies continued to increase even after GCs waned (post-GC phase). Affinity maturation in the post-GC phase was also reflected in a shift in the distribution of somatic mutations as well as in the CDR3 sequences of BM AFC antibody heavy chain genes. Disruption of GCs by injection of antibody specific for CD154 (CD40 ligand) decreased the average affinity of subsequent BM AFCs, suggesting that GCs generate the precursors of high affinity BM AFCs; inhibition of CD154-dependent cellular interactions after the GC reaction was complete had no effect on high affinity BM AFCs. Interestingly, limited affinity maturation in the BM AFC compartment still occurs during the late primary response even after treatment with anti-CD154 antibody. Thus, GCs are necessary for the generation of high affinity AFC precursors but are not the only sites for the affinity-driven clonal selection responsible for the maturation of humoral immune responses.

scholarly journals Oligoclonal expansion of major histocompatibility complex class I-restricted cytolytic T lymphocytes during a primary immune response in vivo: direct monitoring by flow cytometry and polymerase chain reaction.

1993 ◽  
Vol 177 (5) ◽  
pp. 1487-1492 ◽  
Author(s):  
H R MacDonald ◽  
J L Casanova ◽  
J L Maryanski ◽  
J C Cerottini
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Polymerase Chain Reaction ◽  
Cytotoxic T Lymphocyte ◽  
Cell Receptor ◽  
Primary Response ◽  
Primary Immune Response ◽  
Chain Reaction ◽  
Polymerase Chain

Previous T cell receptor (TCR) sequence analysis of a panel of 23 H-2Kd restricted cytotoxic T lymphocyte (CTL) clones recognizing the decapeptide HLA-CW3 170-179 revealed a striking conservation of TCR structure, in that all clones examined used V beta 10 and J alpha pHDS58 segments. We show here that the primary response in vivo after intraperitoneal injection of DBA/2 mice with HLA-CW3 expressing transfectants of syngeneic P815 (H-2d) tumor cells is characterized by a dramatic expansion of CD8+ V beta 10+ CTL in the peritoneal cavity and draining (mesenteric) lymph node, as well as in peripheral blood. Additional analysis of TCR on HLA-CW3 immune populations by flow cytometry and polymerase chain reaction further indicates that the vast majority of responding CD8+ cells express restricted V alpha domains, a dominant J alpha segment (pHDS58), and a conserved CDR3 length for both alpha and beta chains. This novel system provides a unique opportunity to directly monitor an oligoclonal primary antigen specific immune response in vivo at the single cell level independently of functional assays.

scholarly journals COMPETITION OF 19S AND 7S ANTIGEN RECEPTORS IN THE REGULATION OF THE PRIMARY IMMUNE RESPONSE

1968 ◽  
Vol 128 (1) ◽  
pp. 133-152 ◽  
Author(s):  
Claudia Henry ◽  
Niels K. Jerne
Keyword(s):  
Immune Response ◽  
Animal Species ◽  
Fold Increase ◽  
Primary Response ◽  
Red Cells ◽  
Primary Immune Response ◽  
Temporary Increase ◽  
Antigen Receptors ◽  
Enhancing Effect ◽  
Kinetics Of

Prior to sheep red cells (SRC) mice were given 7S or 19S anti-SRC antibodies or mixtures of both. All 7S preparations suppressed the immune response. All 19S preparations enhanced the primary response, as measured by an up to 15-fold increase in the number of PFC per spleen. Results obtained with mixtures showed that 7S and 19S antibodies are competitive in their effect. The kinetics of the appearance of PFC in the mouse spleen after injection of SRC suggest that the depressive effect of 7S antibody simulates a reduction in SRC dose, whereas the enhancing effect of 19S antibody appears as a temporary increase in the rate at which PFC appear. Antibodies from one animal species are quite effective in another species.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

Effects of a primary immune response to T-cell dependent antigen on serotonin metabolism in frontal cortex: in vivo microdialysis study in freely moving Fischer 344 rat

1994 ◽  
Vol 645 (1-2) ◽  
pp. 150-156 ◽  
Author(s):  
Alain M. Gardier ◽  
Sébastien Kachaner ◽  
Elisabeth Khan Shaghaghi ◽  
Christian Blot ◽  
Claude Bohuon ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
In Vivo Microdialysis ◽  
Primary Immune Response ◽  
Serotonin Metabolism ◽  
Fischer 344 ◽  
Fischer 344 Rat ◽  
Freely Moving ◽  
Microdialysis Study
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