The role of dendritic cells in response to cytokine gene adjuvants

DNA vaccination is a novel means of expressing antigens in vivo for the generation of humoral and cell-mediated immune responses. DNA vaccines elicit protective immunity in mice; however, DNA vaccination in outbred species requires optimisation. Dendritic cells (DC) are unique in that they are the only cells capable of stimulating naive T cells, the major requirement of successful vaccination. Lack of efficacy of DNA vaccines may be due to inefficient targeting of DC. One strategy to improve DNA vaccines is to use cytokine gene adjuvants to recruit DC, such as GMCSF and IL-3.The aim of the work carried out in this thesis was to investigate the effects of GM-CSF and IL-3 after gene-gun vaccination. Initial studies focused on the histological effects of GM-CSF and IL-3 in ovine skin. GM-CSF induced a linear increase in IL-lp transcripts from 1-24 hours concomitant with pronounced neutrophilic infiltration and micro-abscess formation by 24 hours. Maximal GMCSF and IL-3 mRNA expression was evident at approximately 4 hours, whereas IL-ip and TNF-a transcripts remained highly elevated up to 96 hours. Infiltration of DC, coordinately with a rise in MHC class II DRa expression in perivascular regions, was observed 72-96 hours after GM-CSF administration. Recruitment of eosinophils and neutrophils was evident 24-48 hours after administration of IL-3, whereas infiltates of B cells and DC were observed at 24 and 72 hours, respectively.Subsequent work characterised DC draining skin before and after GM-CSF administration by means of cannulation of the pseudoafferent lymphatics. Two sub-populations of afferent lymph DC (ALDC) were isolated based on differential expression of SIRPa as described in both cattle and rats. Ovine SIRPa+ ALDC constitutively express high levels of IL-ip, IL-18 and IL-10 mRNA. Conversely, SIRPa ALDC do not express IL-10 but express high levels of IL-12p40. SIRPa+ ALDC may contain Langerhans' cells since both ATPase and langerin were detected. Both subpopulations express Toll like receptor 3 (TLR3) and TLR9, whereas SIRPa" ALDC uniquely express TLR4 (+/- CD14). Gene-gun vaccination with pGM-CSF resulted in increased cytokine transcripts in both ALDC subpopulations and an upregulation of surface MHC class Ila, CD lb, CD40, CD86 and CD 11c. These studies have extended the knowledge of GM-CSF and IL-3 as adjuvants and highlight the use of the cannulation model to further decipher the immune mechanisms of adjuvants. This work has demonstrated that GM-CSF not only recruits DC into skin but also activates DC, possibly as a result of increased expression of "danger signals" including IL-1|3 and TNF-a

Splenopancreatic ductal adenocarcinoma with multiorgan metastasis in a northern water snake (Nerodia sipedon)

A 16-yr-old northern water snake (Nerodia sipedon) presented with a large, firm midcoelomic swelling. A complete blood count, survey radiographs, coelomic ultrasound, and fine needle aspirate of the mass were performed. Survey radiographs revealed a soft tissue opacity mass. Ultrasonographic examination confirmed the presence of the mass but could not aid in its visceral localization. After 2 weeks, the snake presented again because of continued anorexia and poor quality of life. Euthanasia was performed. Gross necropsy revealed a multilobulated mass attached to and effacing the splenopancreas. Histologically, the mass was composed of cuboidal to columnar neoplastic epithelial cells forming tubules surrounded by variable amounts of fibrovascular stroma. Histological examination and immunohistochemical staining of other tissues revealed local invasion in the subserosa and tunica muscularis of the stomach, metastasis within the liver, in the mesovarium, and an intravascular metastasis within the ventricle of the heart surrounded by a thrombus

Briefing note. Severity of the February 2020 floods - preliminary analysis

The purpose of this Briefing Note is to highlight some of the key points from the monthly Hydrological Summary, and to provide some additional context beyond the space and format constraints of the Summary. Neither the Hydrological Summary nor this Briefing Note provide a fully comprehensive review of the severity of the February 2020 floods

Hydrological summary for the United Kingdom: November 2019

The monthly summary of hydrological conditions in the United Kingdom is compiled as part of the National Hydrological Monitoring Programme (a joint UKCEH and BGS enterprise). The report features contemporary data for rainfall, river flow, reservoir and groundwater levels in the form of maps and graphs. A commentary is provided on the status of the nation’s water resources and any notable hydrological events during the month. The National River Flow and National Groundwater Level Archives help provide an historical context for these contemporary assessments. Financial support for the production of the Hydrological Summaries is provided by Defra, the Environment Agency, the Scottish Environment Protection Agency, the Rivers Agency in Northern Ireland and the Office of Water Services

Promoting students' psychological well-being through volunteering: What works and why?

Objectives: The study adopted a qualitative approach to explore the motives and experiences of university student volunteers who engage in volunteering to understand how they manage and sustain their volunteering, and how volunteering affects their well-being. Design: The study utilised semi-structured interviews consisting of a series of open questions, permitting flexibility and in-depth discussion. . Methods: Participants were a purposive sample of 45 university student volunteers aged 18 years or over and studying at British universities. Participants were volunteering or had undertaken regular voluntary work relating to chronic illness, psychological difficulties or disability within the twelve months prior to the interview. Using grounded theory a three phase model was developed which comprises five themes capturing key elements of the development and maintenance of student volunteering. Results: Phase one - 'Getting involved' outlines the 'Motives and catalysts' for students starting to volunteer. Phase two - 'Maintaining commitment' includes three themes ('Making connections' 'Developing resilience' and 'Keeping the balance'), which represent important components of sustained volunteering participation. Phase three - 'Reaping the rewards' focuses on the benefits of volunteering identified by participants around self-development and employability. We discuss our findings in relation to how successful volunteering enhances key components of psychological well-being and facilitates ‘flourishing’ among student volunteers. Conclusions: The findings provide valuable insight into the initiation and maintenance of student volunteering. Further, they have implications for educational institutes such as universities involved in initiatives which include the training, mentoring and support of student volunteers, as well as promoting their well-being

Time of day of vaccination affects SARS-CoV-2 antibody responses in an observational study of health care workers

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time of day of vaccination has been reported to influence host immune responses to multiple pathogens, we quantified the influence of SARS-CoV-2 vaccination time, vaccine type, participant age, sex, and days post-vaccination on anti-Spike antibody responses in health care workers. The magnitude of the anti-Spike antibody response is associated with the time of day of vaccination, vaccine type, participant age, sex, and days post-vaccination. These results may be relevant for optimising SARS-CoV-2 vaccine efficacy