957 resultados para Immunology and Allergy


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Background Neutrophils play a role in the pathogenesis of asthma, chronic obstructive pulmonary disease, and pulmonary infection. Impaired neutrophil phagocytosis predicts hospital-acquired infection. Despite this, remarkably few neutrophil-specific treatments exist. 

Objectives We sought to identify novel pathways for the restoration of effective neutrophil phagocytosis and to activate such pathways effectively in neutrophils from patients with impaired neutrophil phagocytosis. 

Methods Blood neutrophils were isolated from healthy volunteers and patients with impaired neutrophil function. In healthy neutrophils phagocytic impairment was induced experimentally by using β2-agonists. Inhibitors and activators of cyclic AMP (cAMP)-dependent pathways were used to assess the influence on neutrophil phagocytosis in vitro. 

Results β2-Agonists and corticosteroids inhibited neutrophil phagocytosis. Impairment of neutrophil phagocytosis by β2-agonists was associated with significantly reduced RhoA activity. Inhibition of protein kinase A (PKA) restored phagocytosis and RhoA activity, suggesting that cAMP signals through PKA to drive phagocytic impairment. However, cAMP can signal through effectors other than PKA, such as exchange protein directly activated by cyclic AMP (EPAC). An EPAC-activating analog of cAMP (8CPT-2Me-cAMP) reversed neutrophil dysfunction induced by β2-agonists or corticosteroids but did not increase RhoA activity. 8CPT-2Me-cAMP reversed phagocytic impairment induced by Rho kinase inhibition but was ineffective in the presence of Rap-1 GTPase inhibitors. 8CPT-2Me-cAMP restored function to neutrophils from patients with known acquired impairment of neutrophil phagocytosis. 

Conclusions EPAC activation consistently reverses clinical and experimental impairment of neutrophil phagocytosis. EPAC signals through Rap-1 and bypasses RhoA. EPAC activation represents a novel potential means by which to reverse impaired neutrophil phagocytosis.

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Background: In November 2013, the Queensland Department of Health announced its intention to pilot pharmacist vaccination for influenza in the 2014 flu season. The Pharmaceutical Society of Australia Queensland Branch was tasked with developing a training program for the pilot. Aim: The aim was to develop, implement and evaluate a training program for pharmacist vaccination relevant to the needs of Australian pharmacists. Method: Background content was delivered via two online modules, while training for practical injection skills and anaphylaxis management were provided in a face-to-face workshop. Participants were required to complete the Australasian Society of Clinical Immunology and Allergy (ASCIA) anaphylaxis e-training for pharmacists, and hold a current First-Aid and CPR certificate. On completion of the course, pharmacists were asked to evaluate the training program. Results: Overall, 157 pharmacists across Queensland completed the training. Participants rated the training highly on a 5-point Likert scale (>4.4 for all fields) for relevance to practice, comfort with the skill, confidence to do the task and relevance of the learning objectives to the training. Qualitative feedback indicated that a key component of the training was the ability to practice injections on each other. Conclusion: The findings demonstrate participants felt prepared for vaccination following completion of the training program, as reflected in the high level of confidence reported. A follow-up post-pilot will explore if this confidence was translated into practice during the implementation phase.

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Langerhans cells (LCs) are prominent dendritic cells (DCs) in epithelia, but their role in immunity and tolerance is poorly defined. 'Knockin' mice expressing enhanced green fluorescent protein (EGFP) under the control of the langerin (CD207) gene were recently developed in order to discriminate epidermal LCs from other DC subsets and at the same time to track their dynamics under steady-state or inflammatory conditions in vivo. Additional knockin mice expressing a diphtheria toxin receptor fused to EGFP were used to conditionally ablate LCs and assess their role in triggering hapten-specific T cell effectors through skin immunization. We review the insights that have been provided by these various knockin mice and discuss gaps in our knowledge of LCs that need to be filled.

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Pregnancy is proposed to be a Th2 phenomenon, where Th2 cytokines inhibit Th1 responses to improve fetal survival. The importance of interleukin-10 (IL-10), an immunomodulatory cytokine produced by Th2 cells, in the maintenance of normal pregnancy is becoming increasingly apparent. In a longitudinal case-control study, the physiological effect of pregnancy on plasma IL-10 was investigated. The plasma concentration of IL-10 was determined using an ELISA technique in 99 pregnant women sampled at 12, 20 and 35 weeks of gestation, 38 non-pregnant control subjects sampled in parallel and in a subgroup of women sampled at 3 days post-partum (n, pregnant 21, non-pregnant 21). Plasma IL-10 was significantly higher in pregnant women at 12, 20 and 35 weeks of gestation (p