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Search Results: 1 - 10 of 151780 matches for " Adam F. Cunningham "
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Rapid Development of Th2 Activity During T Cell Priming
Adam F. Cunningham,Kai-Michael Toellner
Clinical and Developmental Immunology , 2003, DOI: 10.1080/10446670310001598537
Abstract: The paradigm of T helper-1 (Th-1) and Th-2 cells developing from non-committed naïve precursors is firmly established. Th1 cells are characterized by IFN production and, in mice, the selective switching to IgG2a. Conversely IL-4 production and selective switching to IgG1 and IgE characterize Th2 cells. Analysis of Th2 induction in vitro indicates that this polarization develops gradually in T cells activated by anti-CD3 in the presence of IL-4; conversely anti-CD3 and IFN induce Th1 cells. In this report, we explore evidence that indicates that the T helper cell polarization in vivo cannot solely be explained by the cytokine environment. This is provided by studying the early acquisition of Th1 and Th2 activities during responses to a mixture of Th1 and Th2-inducing antigens. It is shown that these divergent forms of T cell help can rapidly develop in cells within a single lymph node. It is argued that early polarization to show Th-1 or Th-2 behavior can be induced by signals delivered during cognate interaction between virgin T cells and dendritic cells, in the absence of type 1 or type 2 cytokines. This contrasts with the critical role of the cytokines in reinforcing the Th-phenotype and selectively expanding T helper clones.
The Stability of Complement-Mediated Bactericidal Activity in Human Serum against Salmonella
Colette M. O’Shaughnessy, Adam F. Cunningham, Calman A. MacLennan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049147
Abstract: The complement cascade includes heat-labile proteins and care is required when handling serum in order to preserve its functional integrity. We have previously used a whole human serum bactericidal assay to show that antibody and an intact complement system are required in blood for killing of invasive isolates of Salmonella. The aim of the present study was to evaluate the conditions under which human serum can be stored and manipulated while maintaining complement integrity. Serum bactericidal activity against Salmonella was maintained for a minimum of 35 days when stored at 4°C, eight days at 22°C and 54 hours at 37°C. Up to three freeze-thaw cycles had no effect on the persistence of bactericidal activity and hemolytic complement assays confirmed no effect on complement function. Delay in the separation of serum for up to four days from clotted blood stored at 22°C did not affect bactericidal activity. Dilution of serum resulted in an increased rate of loss of bactericidal activity and so serum should be stored undiluted. These findings indicate that the current guidelines concerning manipulation and storage of human serum to preserve complement integrity and function leave a large margin for safety with regards to bactericidal activity against Salmonella. The study provides a scheme for determining the requirements for serum handling in relation to functional activity of complement in other systems.
B1b Cells Recognize Protective Antigens after Natural Infection and Vaccination
Adam F. Cunningham,Saeeda Bobat,Charlotte N. L. Cook,Constantino Lopez-Macias,Ian R. Henderson
Frontiers in Immunology , 2014, DOI: 10.3389/fimmu.2014.00535
Abstract: There are multiple, distinct B-cell populations in human beings and other animals such as mice. In the latter species, there is a well-characterized subset of B-cells known as B1 cells, which are enriched in peripheral sites such as the peritoneal cavity but are rare in the blood. B1 cells can be further subdivided into B1a and B1b subsets. There may be additional B1 subsets, though it is unclear if these are distinct populations or stages in the developmental process to become mature B1a and B1b cells. A limitation in understanding B1 subsets is the relative paucity of specific surface markers. In contrast to mice, the existence of B1 cells in human beings is controversial and more studies are needed to investigate the nature of these enigmatic cells. Examples of B1b antigens include pneumococcal polysaccharide and the Vi antigen from Salmonella Typhi, both used routinely as vaccines in human beings and experimental antigens such as haptenated-Ficoll. In addition to inducing classical T-dependent responses some proteins are B1b antigens and can induce T-independent (TI) immunity, examples include factor H binding protein from Borrelia hermsii and porins from Salmonella. Therefore, B1b antigens can be proteinaceous or non-proteinaceous, induce TI responses, memory, and immunity, they exist in a diverse range of pathogenic bacteria, and a single species can contain multiple B1b antigens. An unexpected benefit to studying B1b cells is that they appear to have a propensity to recognize protective antigens in bacteria. This suggests that studying B1b cells may be rewarding for vaccine design as immunoprophylactic and immunotherapeutic interventions become more important due to the decreasing efficacy of small molecule antimicrobials.
Tuberculin Skin Testing and Treatment Modulates Interferon-Gamma Release Assay Results for Latent Tuberculosis in Migrants
Matthew K. O'Shea, Thomas E. Fletcher, Nicholas J. Beeching, Martin Dedicoat, David Spence, Helen McShane, Adam F. Cunningham, Duncan Wilson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097366
Abstract: Background Identifying latent tuberculosis infection (LTBI) in people migrating from TB endemic regions to low incidence countries is an important control measure. However, no prospective longitudinal comparisons between diagnostic tests used in such migrant populations are available. Objectives To compare commercial interferon (IFN)-gamma release assays (IGRAs) and the tuberculin skin test (TST) for diagnosing LTBI in a migrant population, and the influence of antecedent TST and LTBI treatment on IGRA performance. Materials and Methods This cohort study, performed from February to September 2012, assessed longitudinal IGRA and TST responses in Nepalese military recruits recently arrived in the UK. Concomitant T-SPOT.TB, QFT-GIT and TST were performed on day 0, with IGRAs repeated 7 and 200 days later, following treatment for LTBI if necessary. Results 166 Nepalese recruits were prospectively assessed. At entry, 21 individuals were positive by T-SPOT.TB and 8 individuals by QFT-GIT. There was substantial agreement between TST and T-SPOT.TB positives at baseline (71.4% agreement; κ = 0.62; 95% CI:0.44–0.79), but only moderate concordance between positive IGRAs (38.1% agreement; κ = 0.46; 95% CI:0.25–0.67). When reassessed 7 days following TST, numbers of IGRA-positive individuals changed from 8 to 23 for QFT-GIT (p = 0.0074) and from 21 to 23 for T-SPOT.TB (p = 0.87). This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88). Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5%) provided a positive IGRA and of these 13 were TST negative. Two hundred days after the study commenced and three months after treatment for LTBI was completed by those who were given chemoprophylaxis, 23 and 21 participants were positive by T-SPOT.TB or QFT-GIT respectively. When individual responses were examined longitudinally within this population 35% of the day 7 QFT-GIT-positive, and 19% T-SPOT.TB-positive individuals, were negative by IGRA. When the change in the levels of secreted IFN-γ was examined after chemoprophylaxis the median levels were found to have fallen dramatically by 77.3% from a pre-treatment median concentration of IFN-γ 2.73 IU/ml to a post-treatment median concentration IFN-γ 0.62 (p = 0.0002). Conclusions This study suggests differences in the capacity of commercially available IGRAs to identify LTBI in the absence of antecedent TST and that IGRAs, in the time periods examined, may not be the optimal tests to determine the success of chemoprophylaxis for LTBI.
Transpersonal Education: Problems, Prospects and Challenges
Paul F. Cunningham
International Journal of Transpersonal Studies , 2006,
Abstract: Despite its substantial scientific, academic, and professional achievements, transpersonal psychology hasnot been fully incorporated within traditional undergraduate psychology curricula. One reason is conventional psychology’s prejudiced perception of humanity’s spiritual nature. Other reasons lie within the field of transpersonal psychology itself, including the lack of agreed-upon general curricular models, absence of normative educational (student) outcomes, unstructured courses with restricted content coverage, and conceptual and methodological disagreements among experts. One of the most pressing challenges facing contemporary transpersonal education is the publication of an authoritative, standard textbook that would effectively introduce undergraduate students to transpersonal psychology and facilitate the progress of the discipline’s further integration into mainstream psychology.
The Challenge, Prospects, and Promise of Transpersonal Psychology
Paul F. Cunningham
International Journal of Transpersonal Studies , 2007,
Abstract: Several substantial critiques remain a source of fractionalizing debate within transpersonal psychology, including the weakness of its definition, whether it is redundant with Wilber’s integral psychology, whether it is a scientific field, whether it is too metaphysical, whether it neglects the problem of evil, and what contribution can it make to mainstream psychology. This article explicates these and related areas of critique and provides a response that identifies the essential challenges and future prospects of transpersonal psychology. The article also emphasizes the field’s unique role as a potential bridge connecting psychological science with the transpersonal psyche in a way that can more fully recognize the importance of the latter.
Self-Convergence of Radiatively Cooling Clumps
Kristopher Yirak,Adam Frank,Andrew J. Cunningham
Physics , 2009, DOI: 10.1088/0004-637X/722/1/412
Abstract: Numeric convergence studies demonstrate that the evolution of an adiabatic clump is well-captured by roughly 100 cells per clump radius. The presence of radiative cooling, however, imposes limits on the problem due to the removal of thermal energy. Numerical studies which include radiative cooling typically adopt the 100--200 cells per clump radius resolution. In this paper we present the results of a convergence study for radiatively cooling clumps undertaken over a broad range of resolutions, from 12 to 1,536 cells per clump radius, employing adaptive mesh refinement (AMR) in a 2D axisymmetric geometry ("2.5D"). We also provide a fully 3D simulation, at 192 cells per clump radius, which supports our 2.5D results. We find no appreciable self-convergence at ~100 cells per clump radius as small-scale differences owing to increasingly resolving the "cooling length" have global effects. We therefore conclude that self-convergence is an insufficient criterion to apply on its own when addressing the question of sufficient resolution for radiatively cooled shocked clump simulations. We suggest the adoption of alternate criteria to support a statement of sufficient resolution, such as the demonstration of adequate resolution of the cooling layers behind shocks. We discuss an associated refinement criteria for AMR codes.
Mutational and Topological Analysis of the Escherichia coli BamA Protein
Douglas F. Browning, Sophie A. Matthews, Amanda E. Rossiter, Yanina R. Sevastsyanovich, Mark Jeeves, Jessica L. Mason, Timothy J. Wells, Catherine A. Wardius, Timothy J. Knowles, Adam F. Cunningham, Vassiliy N. Bavro, Michael Overduin, Ian R. Henderson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0084512
Abstract: The multi-protein β-barrel assembly machine (BAM) of Escherichia coli is responsible for the folding and insertion of β-barrel containing integral outer membrane proteins (OMPs) into the bacterial outer membrane. An essential component of this complex is the BamA protein, which binds unfolded β-barrel precursors via the five polypeptide transport-associated (POTRA) domains in its N-terminus. The C-terminus of BamA contains a β-barrel domain, which tethers BamA to the outer membrane and is also thought to be involved in OMP insertion. Here we mutagenize BamA using linker scanning mutagenesis and demonstrate that all five POTRA domains are essential for BamA protein function in our experimental system. Furthermore, we generate a homology based model of the BamA β-barrel and test our model using insertion mutagenesis, deletion analysis and immunofluorescence to identify β-strands, periplasmic turns and extracellular loops. We show that the surface-exposed loops of the BamA β-barrel are essential.
Genotypic and Phenotypic Characterisation of Enteroaggregative Escherichia coli from Children in Rio de Janeiro, Brazil
Fernanda L. S. Fran?a, Timothy J. Wells, Douglas F. Browning, Raquel Tayar Nogueira, Felipe Silva Sarges, Ana Claudia Pereira, Adam F. Cunningham, Kely Lucheze, Ana Claudia Paula Rosa, Ian R. Henderson, Maria das Gra?as de Luna
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069971
Abstract: Enteroaggregative Escherichia coli (EAEC) is a significant cause of diarrhoeal illness in both children and adults. Genetic heterogeneity and recovery of EAEC strains from both healthy and diseased individuals complicates our understanding of EAEC pathogenesis. We wished to establish if genetic or phenotypic attributes could be used to distinguish between strains asymptomatically colonising healthy individuals and those which cause disease. Genotypic screening of a collection of twenty four EAEC isolates from children with and without diarrhoea revealed no significant differences in the repertoire of putative virulence factors present in either group of strains. In contrast, EAEC strains from phylogroup A were more strongly associated with asymptomatic groups whereas strains from phylogroup D were more associated with cases of diarrhoea. Phenotypic screening revealed no differences in the ability of strains from either cohort of children to form biofilms, to adhere to and invade cells in tissue culture or to cause disease in the Caenorhabditis elegans model of infection. However, the latter assay did reveal significant reduction in nematode killing rates when specific virulence factors were deleted from human pathogenic strains. Our results suggest that current models of infection are not useful for distinguishing avirulent from pathogenic strains of EAEC but can be useful in studying the effect of specific virulence factors.
Helios Is Associated with CD4 T Cells Differentiating to T Helper 2 and Follicular Helper T Cells In Vivo Independently of Foxp3 Expression
Karine Serre, Cécile Bénézech, Guillaume Desanti, Saeeda Bobat, Kai-Michael Toellner, Roger Bird, Susan Chan, Philippe Kastner, Adam F. Cunningham, Ian C. M. MacLennan, Elodie Mohr
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020731
Abstract: Background Although in vitro IL-4 directs CD4 T cells to produce T helper 2 (Th2)-cytokines, these cytokines can be induced in vivo in the absence of IL-4-signalling. Thus, mechanism(s), different from the in vitro pathway for Th2-induction, contribute to in vivo Th2-differentiation. The pathway for in vivo IL-4-independent Th2-differentiation has yet to be characterized. Findings Helios (ikzf2), a member of the Ikaros transcription regulator family, is expressed in thymocytes and some antigen-matured T cells as well as in regulatory T cells. It has been proposed that Helios is a specific marker for thymus-derived regulatory T cells. Here, we show that mouse ovalbumin-specific CD4 (OTII) cells responding to alum-precipitated ovalbumin (alumOVA) upregulate Th2 features - GATA-3 and IL-4 - as well as Helios mRNA and protein. Helios is also upregulated in follicular helper T (TFh) cells in this response. By contrast, OTII cells responding to the Th1 antigen - live attenuated ovalbumin-expressing Salmonella - upregulate Th1 features - T-bet and IFN-γ - but not Helios. In addition, CD4 T cells induced to produce Th2 cytokines in vitro do not express Helios. The kinetics of Helios mRNA and protein induction mirrors that of GATA-3. The induction of IL-4, IL-13 and CXCR5 by alumOVA requires NF-κB1 and this is also needed for Helios upregulation. Importantly, Helios is induced in Th2 and TFh cells without parallel upregulation of Foxp3. These findings suggested a key role for Helios in Th2 and TFh development in response to alum-protein vaccines. We tested this possibility using Helios-deficient OTII cells and found this deficiency had no discernable impact on Th2 and TFh differentiation in response to alumOVA. Conclusions Helios is selectively upregulated in CD4 T cells during Th2 and TFh responses to alum-protein vaccines in vivo, but the functional significance of this upregulation remains uncertain.
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