Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2002. / Härtill 4 uppsatser.

Background: Throughout human history infectious agents such as viruses have been one of the biggest threats to public health. One example of infectious agents that can cause severe malignant conditions in humans is the Epstein-Barr virus (EBV). This virus has been researched for decades but still a lot of its potential malignant functions remain to be elucidated. Autoimmunity, and especially multiple sclerosis (MS), has been strongly associated to EBV infection for a long time but the exact mechanisms behind this relationship are still largely unknown. Aim: The main aim of this study was to investigate the evidence connecting an EBV-specific dysregulated immune response to MS. Methods: This paper is written as a systematic review examining the latest science within the studied field. PubMed was searched for articles published between 2010-2020. Results: In total 15 studies were reviewed. Five out of seven studies found an altered antibody response towards EBV in patients with MS, while one demonstrated somewhat mixed results and one could not support such a pattern. Seven out of eight studies found an altered T cell response towards EBV in MS patients, while one could only support such a trend. Conclusions: This review confirms that there is strong evidence for a dysregulated EBV-specific immune response in MS patients. Evidence for a causal relationship between the failure to control a reactivated EBV infection and the progression of disease is suggestive, but this needs to be confirmed by further studies.

No description available.

Brucella abortus (BA) are gram-negative, facultative intracellular bacteria that cause abortions in cattle and debilitating illness in humans. The US is now virtually free of bovine brucellosis, but the disease is endemic in wildlife. The official brucellosis vaccine in the US is strain RB51 (RB51). It elicits protective cell-mediated immunity (CMI) against BA infections. Mycobacterium avium subspecies paratuberculosis (MAP) causes paratuberculosis in ruminants. It is a slow growing intracellular parasite that requires CMI for its control, belongs to the genus Mycobacterium, and is closely related to M. avium avium (MA). Using RB51 as a vector that induces strong protective CMI may be useful to protect against MAP if it expresses MAP protective antigens. Therefore, MAP 85A and 35kDa proteins were expressed at low levels in RB51, and the immune responses elicited by these vaccines in BALB/c mice were evaluated. Strong anti-Brucella immunity was generated, but the anti-mycobacterial response was low. To evaluate protective efficacy, a BALB/c model using MA was developed. When mice were challenged with MA, protection was obtained in some experiments but was inconsistent. This may be due to the low expression of MAP antigens in RB51. Another objective was to evaluate the effect of an ongoing Brucella-infection on the efficacy of RB51 vaccination, and whether vaccination of already infected animals could have a curative effect. Mice acutely or chronically infected with virulent BA, rapidly cleared the RB51 vaccine organisms, but there was no significant decrease in the number of virulent BA. Brucella spp. have been developed as biological weapons, but there are no vaccines to protect humans. The development of a very attenuated protective vaccine is necessary to prevent human infections, as well as to protect wildlife. To generate such a vaccine, RB51 based vaccines were irradiated to render them non-replicative, but metabolically active. We demonstrated that in general, irradiated and non-irradiated RB51 vaccines remain protective at levels similar to those elicited by the live vaccines. Therefore, irradiation of strain RB51 is an effective means of attenuating the strain without affecting its protective characteristics, and could eventually be used as a vaccine for wildlife and humans. / Ph. D.

La maladie de Newcastle est une maladie virale hautement contagieuse et dévastatrice chez la volaille. Bien que la biosécurité et lhygiène puissent savérer suffisantes pour lutter contre lintroduction de la maladie, la vaccination préventive est considérée comme une précaution supplémentaire et a été rendue obligatoire dans la plupart des pays européens dès les années 90 suite aux épidémies de ND. Cependant, lobservation dépizooties sporadiques témoigne des limites des programmes de prévention actuels. Dans ce contexte, de nombreuses alternatives vaccinales sont étudiées afin de limiter le risque dune infection par le NDV et de réduire la transmission virale, tout en prévenant les signes cliniques et la mortalité. Durant ce travail, la vaccination à un jour à laide dun vaccin atténué a été privilégiée et lamélioration de son efficacité par la co-administration avec ladjuvant chitosan et une primo-vaccination in ovo avec un vaccin recombinant rHVT-ND a été investiguée. Lobjectif de cette thèse consiste à étudier de manière approfondie limmunité induite chez le poulet par la vaccination contre la ND et à établir une corrélation entre les réponses immunitaires mesurées et la protection. Ces expériences ont montré linfluence du tropisme de la souche vaccinale de NDV sur linduction de limmunité à médiation cellulaire et sur le degré de la réponse immune locale en anticorps au niveau des tractus respiratoire et digestif. Cette réponse immune cellulaire spécifique du NDV a pu être renforcée par la co-administration du chitosan avec le vaccin atténué. Linterférence des anticorps maternels sur linduction dune réponse immune spécifique lors dune vaccination à un jour a également été validée. Cet impact négatif a pu être limité par une primo-vaccination in ovo avec un vaccin recombinant rHVT-ND. Enfin, le programme de vaccination combinant une primo-vaccination in ovo avec une vaccination à un jour avec un vaccin atténué co-administré avec le chitosan a permis daméliorer la protection contre les signes cliniques de la maladie mais également de diminuer lexcrétion virale lors dune infection virulente. Cette plus forte protection peut être corrélée avec linduction dune meilleure immunité à médiation cellulaire et une réponse immune locale accrue. Newcastle disease is a highly contagious and devastating condition of poultry. Although good biosecurity and hygiene practices can be sufficient to fight against this disease, the preventive vaccination is thought to be an additional precaution and is rendered compulsory in many European Union countries since the 90 after ND epidemic. Nevertheless, enzootics and epizootics that are sometimes reported point out the limitations of current vaccination regimens. In this context, different approaches have been investigated in order to prevent infection by NDV, reduce the transmission of the virus and eliminate clinical signs and mortality. In this work, we have selected the vaccination at day-old with attenuated ND vaccine and we have attempted to increase its efficacy by the co-administration with chitosan adjuvant and by an in ovo injection of a rHVT-ND vaccine. The aim of this present work was to evaluate the immunity induced by ND vaccination and the establishment of the correlation between the recorded measurement and the protection. These experiments showed the influence of the tropism of the ND vaccine strain on the NDV-specific antibody-mediated immunity in the respiratory and digestive tracts and on the cell-mediated immunity. This NDV-specific cellular immune response was improved by the co-administration of chitosan with the ND attenuated vaccine. It was also observed that the presence of MDA interferes with the establishment of a persisting good protective immunity after a single day-old vaccination. The use of rHVT-ND vaccine applied in ovo as primo-vaccination allowed overcoming this negative interference of MDA. Finally, the innovative rHVT-ND/live ND-chitosan vaccination regimen provided the highest protection against mortality and morbidity as well as the strongest reduction of virus shedding, which could be related to a higher measured cellular immune response and local antibody-mediated immunity.

<p>The aim of this study was to investigate the effects of Sutherlandia frutescens on the inflammatory response and T cell differentiation in vitro using cytokines as biomarkers. Whole blood cells containing various concentrations of Sutherlandia frutescens were stimulated in vitro with either Lipopolysaccharide (LPS) or Phytohaemagglutinin (PHA). Results show that Sutherlandia frutescens is not toxic at any of the concentrations tested. The addition of Sutherlandia frutescens at high concentrations to the stimulated whole blood cell cultures reflects a significant down regulation of Interleukin(IL) 6 and IL-10 compared to the control (P&lt / 0.05) hence suppressed the inflammatory and humoral immune response. Results obtained for Inteferon-gamma (IFN ) shows that Sutherlandia frutescens is donor specific as it reflects both up and down regulation in the release of IFN at the concentrations tested. The in vitro data generated by this study supports the use of Sutherlandia frutescens in the management of inflammatory conditions and allergies such as asthma. However the effects of Sutherlandia frutescens on cell mediated immunity was found to be donor specific. Further investigation of Sutherlandia frutescens on cellular immunity is advised.</p>

<p>The aim of this study was to investigate the effects of Sutherlandia frutescens on the inflammatory response and T cell differentiation in vitro using cytokines as biomarkers. Whole blood cells containing various concentrations of Sutherlandia frutescens were stimulated in vitro with either Lipopolysaccharide (LPS) or Phytohaemagglutinin (PHA). Results show that Sutherlandia frutescens is not toxic at any of the concentrations tested. The addition of Sutherlandia frutescens at high concentrations to the stimulated whole blood cell cultures reflects a significant down regulation of Interleukin(IL) 6 and IL-10 compared to the control (P&lt / 0.05) hence suppressed the inflammatory and humoral immune response. Results obtained for Inteferon-gamma (IFN ) shows that Sutherlandia frutescens is donor specific as it reflects both up and down regulation in the release of IFN at the concentrations tested. The in vitro data generated by this study supports the use of Sutherlandia frutescens in the management of inflammatory conditions and allergies such as asthma. However the effects of Sutherlandia frutescens on cell mediated immunity was found to be donor specific. Further investigation of Sutherlandia frutescens on cellular immunity is advised.</p>

Magister Scientiae - MSc / The aim of this study was to investigate the effects of Sutherlandia frutescens on the inflammatory response and T cell differentiation in vitro using cytokines as biomarkers. Whole blood cells containing various concentrations of Sutherlandia frutescens were stimulated in vitro with either Lipopolysaccharide (LPS) or Phytohaemagglutinin (PHA). Results show that Sutherlandia frutescens is not toxic at any of the concentrations tested. The addition of Sutherlandia frutescens at high concentrations to the stimulated whole blood cell cultures reflects a significant down regulation of Interleukin(IL) 6 and IL-10 compared to the control (P&lt;0.05) hence suppressed the inflammatory and humoral immune response. Results obtained for Inteferon-gamma (IFN ) shows that Sutherlandia frutescens is donor specific as it reflects both up and down regulation in the release of IFN at the concentrations tested. The in vitro data generated by this study supports the use of Sutherlandia frutescens in the management of inflammatory conditions and allergies such as asthma. However the effects of Sutherlandia frutescens on cell mediated immunity was found to be donor specific. Further investigation of Sutherlandia frutescens on cellular immunity is advised. / South Africa

The interleukin (IL)-12 family of cytokines plays a key role in the orchestration of cellular immune responses, bridging innate and adaptive immunity. The founding member, IL-12, was discovered in the late 1980s as the first heterodimeric cytokine, composed of a 40 kDa (p40) and 35 kDa (p35) subunit. Years of basic and clinical research on this prototypical T helper type (Th)1 cytokine revealed its importance in immunity to intracellular non-viral infections, as well as in cancer and autoimmune diseases. Since the discovery of IL-23 as another cytokine composed of the p40 subunit of IL-12 in the year 2000, IL-23, rather than IL-12, could be shown to be the key player in rodent models of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. With accumulating evidence revealing IL-23 as the crucial regulator of a non-classical pathway of cellular immunity which is hallmarked by IL-17 producing T cells it is intriguing to gain understanding of the importance of such findings in immunity to infections. The present work describes a series of in vivo studies investigating the role of endogenous as well as exogenous IL-23 in a murine model of chronic fungal infection, cryptococcosis. To address the role of endogenous IL-23, wild-type (WT), IL-12- (IL-12p35-/-), IL-23- (IL-23p19-/-) deficient, as well as IL-12- and IL-23- double deficient (p40-deficient) mice on a C57BL/6 background were infected with Cryptococcus neoformans (C. neoformans). Following infection, p40-deficient mice demonstrated higher mortality than IL-12p35-/- mice. Reconstitution of p40-deficient mice with recombinant murine IL-23 prolonged their survival to levels similar to IL-12p35-/- mice. IL-23p19-/- mice showed a moderately reduced survival time and delayed fungal clearance in the liver. While interferon (IFN)-γ production was similar in WT and IL-23p19-/- mice, production of IL-17 was strongly impaired in the latter. IL-23p19-/- mice produced fewer hepatic granulomata relative to organ burden and showed defective recruitment of mononuclear cells to the brain. Moreover, activation of microglia cells and expression of IL-1β, IL-6, and MCP-1 in the brain was impaired. SUMMARY - 80 - The second part of the present work explores the mechanisms underlying the IL-23 effects by characterizing the role of exogenous IL-23. C. neoformans-infected C57BL/6 WT mice treated with recombinant murine IL-23 showed significantly prolonged survival time as compared to mock-treated control mice. However, complete survival throughout the observation period (100 days) was only achieved following IL-12 treatment. At day 21 post infection (p.i.) the IL-23-treated mice as well as the IL-12 group had a significantly lower fungal burden in the brain than the control mice. However, while IL-12 treatment was associated with elevated serum levels of the proinflammatory mediators IFN-γ, tumor necrosis factor (TNF)-α and nitric oxide, IL-23-treated animals, although more resistant, developed a Th2 response similar to the control group as measured by serum IgE levels. Further experiments to assess the mechanism of action were based on the finding of reduced fungal burden at the site of infection, the peritoneal cavity, at day 8 p.i. following IL-23 treatment. This microbicidal effect was also seen in p40-deficient as well as in T and B cell deficient (RAG-deficient) mice. Administration of IL-23 led to enhanced recruitment of inflammatory cells, not only of T cells but also cells of the innate immune system such as DCs, natural killer cells and granulocytes to the infected site. Although numbers of macrophages were not altered following IL-23 treatment, co-stimulatory molecules were markedly up-regulated on such cells. The chemokine/cytokine pattern induced by IL-23 treatment was hallmarked by proinflammatory mediators such as MCP-1, IL-1β, IL-6, TNF-α and IL-17, but also the Th2 associated cytokine IL-5. From these results it can be concluded that a non-classical immune pathway induced by IL-23 complements the more dominant role of IL-12 in protection against C. neoformans. This novel immune response is characterized by an enhancement of the inflammatory cell response and the production of a proinflammatory cytokine pattern hallmarked by IL-1β, IL-6, TNF-α and IL-17.

<p>This study shows that herbs can be effectively screened for potiential bio-activity using in vitro methods. Further studies will be needed to better explore Artemisia afra&rsquo / s effect on immunoregulation, particularly long term effects of the herb on the immune system and its effect on other disease states.</p>