Local effects of ultraviolet radiation on cutaneous immune responses

Depletion of stratospheric ozone and changes in lifestyles have led to increased concern about the harmful effects of ultraviolet radiation (UVR). Exposure to UVR has been shown to induce both local and systemic suppression of immune responses initiated through the skin. The mechanism of dysregulation of immune responses following UV exposure is complex, and is initiated by chromophores. One such chromophore is urocanic acid (UCA), which is isomerised from the trans- to the cis-isoform by UVR, in the epidermis. The primary antigen presenting cell (APC) of the skin, the Langerhans cell (LC), plays a critical role in cutaneous immune responses. UVR alters LC frequency within the irradiated epidermis, and also exerts effects on the mature form of LC, the dendritic cells (DC), within lymph nodes draining irradiated sites. These changes appear to be concurrent with an alteration in T cell cytokine profiles. UVR suppresses immune responses which are normally characterised by Th1 -like cytokine profiles, possibly by immune deviation to Th2 -like cytokine profiles.The contact hypersensitivity (CH) response is commonly used to demonstrate cutaneous immunity. A model of CH in C3H/HeN mice was established. This model was utilised to examine the effects of local UVB irradiation before induction of contact sensitisation. Cytokine profiles within lymph nodes draining the site of elicitation of CH, or the site of contact sensitisation were investigated. Results suggest that UVB has no effect on cytokine production during the sensitisation phase of CH, but that it downregulates Th1 -like cytokine production upon elicitation of CH.Effects of UVR and UCA application were examined in relation to LC frequency within the epidermis. UVA1 (340- 400nm) irradiation, or trans-UCA application, did not alter the LC numbers within the exposed site. UVB (280-315nm) irradiation and cis-UCA application depleted LC, and timecourses for LC depletion were established for both treatments. Injection of antibodies against either IL-1ß or TNF-α before UVB irradiation or cis-UCA treatment completely abrogated their effects on LC numbers. Thus, the UVB-mediated reduction of LC is dependent on the cytokines IL-1P and TNF-α. Despite reports that UVA1 irradiation protects mice from subsequent immunosuppression by UVB exposure, UVA1 irradiation did not affect the decrease in LC numbers induced by UVB.Despite the differences in effects on LC frequency, both UVA1 and UVB induced an accumulation of DC within lymph nodes draining the site of irradiation. For both irradiation regimens, the accumulation of DC was dependent on IL-1ß. This was identified by injecting neutralising IL-1ß antibodies before irradiation, which inhibited the accumulation of DC within draining lymph nodes following irradiation. Similar experiments indicated that accumulation of DC following UVB irradiation, but not following UVA1 irradiation, was also dependent upon TNF-α.Induction of cytokines within irradiated skin was examined. UVB exposure increased the expression of IL-10 and TNF-α proteins at the irradiated site. Attempts to identify the source of these cytokines were inconclusive, as both keratinocyte (PAM-212) and melanocyte (B16) cell lines failed to secrete these cytokines following UVB irradiation. Intracellular stores of TNF-α decreased as the dose of radiation increased. The technique of reverse transcription polymerase chain reaction (RT -PCR) was established to examine expression of cytokine mRNA in irradiated skin. Following UVB irradiation, TNF -a mRNA was upregulated and there was induction of IL-10 mRNA. UVA1 irradiation did not result in such changes. There were also differences in the timecourse of IL-1ß mRNA upregulation. IL-1ß mRNA expression peaked transiently 4h after UVB irradiation. Following UVA1 irradiation, IL-1ß mRNA expression did not peak until 24h, and remained upregulated at 48h, after exposure

Advances toward diagnostic tools for managing zoonotic visceral leishmaniasis

Visceral leishmaniasis (VL) is a life-threatening outcome of Leishmania infantum or Leishmania donovani infection. Dogs are the primary domestic reservoir of L. infantum parasites, and ownership of infected dogs increases the risk of human VL. Controlling infection within dog populations is regarded as critical to VL management in endemic countries, both preventing progression of canine disease and limiting parasite transmission to humans and dogs. Here we discuss various strategies that are used to diagnose canine visceral leishmaniasis (CVL) and the possibilities of adapting these for use within population screening and control programs. In addition, given the variable transmissibility of L. infantum to the sand fly vector, we outline some possibilities for the preferential identification of ‘super-spreader’ dogs among the overall infected population

A GNSS-based method to define athlete manoeuvrability in field-based team sports

This study presented a method of quantifying the manoeuvrability of two field-based team sport athletes and investigated its relationship with running velocity during competition. Across a season, 10 Hz Global navigation satellite system (GNSS) devices were worn during matches by 62 athletes (Australian Football League [AFL]; n = 36, 17 matches, National Rugby League [NRL]; n = 26, 21 matches). To quantify manoeuvrability, tortuosity was calculated from the X and Y coordinates from match GNSS files (converted from latitude and longitude). Tortuosity was calculated as 100 x natural logarithm of the chord distance (distance travelled between X and Y coordinates), divided by the straight-line distance. The maximal tortuosity was then quantified for each 0.5 m∙s-1 speed increment, ranging from 0 to the highest value for each game file. A quadratic model was fitted for each match file, controlling for the curvilinear relationship between tortuosity and velocity. A comparison of the quadratic coefficients between sports, and within sport between positions was investigated using linear mixed models. Resulting standard deviations (SDs) and mean differences were then assessed to establish standardized effect sizes (ES) and 90% confidence intervals (CI). A curvilinear relationship exists between maximal tortuosity and running speed, reflecting that as speed increases, athletes’ ability to deviate from a linear path is compromised (i.e., run in a more linear path). Compared to AFL, NRL had a greater negative quadratic coefficient (a) (ES = 0.70; 0.47 to 0.93) for the 5 second analysis, meaning that as speed increased, NRL athletes’ manoeuvrability reduced at a faster rate than when compared to AFL. There were no positional differences within each sport. GNSS derived information can be used to provide a measure of manoeuvrability tortuosity during NRL and AFL matches. The curvilinear relationship between tortuosity and speed demonstrated that as speed increased, manoeuvrability was compromised

Adjuvants for Leishmania vaccines: from models to clinical application

Two million new cases of leishmaniasis occur every year, with the cutaneous leishmaniasis (CL) presentation accounting for approximately two-thirds of all cases. Despite the high incidence rates and geographic expansion of the disease, CL remains a neglected tropical disease without effective intervention strategies. Efforts to address this deficit have given rise to the experimental murine model of CL. By virtue of its simplicity and pliability, the CL model has been used to provide substantial information regarding cellular immunity, as well as in the discovery and evaluation of various vaccine adjuvants. The CL model has facilitated in vivo studies of the mechanism of action of many adjuvants, including the TLR4 agonist monophosphoryl lipid A, the TLR7/8 agonist imiquimod, the TLR9 agonist CpG, adenoviral vectors, and the immunostimulatory complexes. Together, these studies have helped to unveil the requirement for certain types of immune responses at specific stages of CL disease and provide a basis to aid the design of effective second-generation vaccines for human CL. This review focuses on adjuvants that have been tested in experimental CL, outlining how they have helped advance our understanding of the disease and ultimately, how they have performed when applied within clinical trials against human CL

Immunologically reactive M. leprae antigens with relevance to diagnosis and vaccine development

<p>Abstract</p> <p>Background</p> <p>Leprosy is a chronic infectious disease caused by <it>Mycobacterium leprae </it>that can manifest a wide variety of immunological and clinical outcomes ranging from potent humoral responses among borderline lepromatous (BL) and lepromatous (LL) patients to strong cellular responses among tuberculoid (TT) and borderline tuberculoid (BT) patients. Until recently, relatively little has been known about the immune responses to individual proteins of <it>M. leprae </it>recognized during leprosy.</p> <p>Methods</p> <p>The immune reactivity to a panel of 33 <it>M. leprae </it>recombinant proteins was evaluated among leprosy patients and controls from a high endemic area for leprosy (Goiania/GO, Central Brazil). Serum IgG responses were measured by ELISA (45 participants/group) and T cell responses (20 participants/group) were evaluated by IFN-gamma production in 24 hours whole blood cultures with antigen (whole blood assay-WBA). Study groups were newly diagnosed, untreated TT/BT and BL/LL leprosy patients classified by Ridley Jopling criteria and household contacts of BL/LL patients (HHC). Control groups were HIV-1 negative pulmonary tuberculosis patients (TB) and healthy individuals from the same endemic area (EC). In silico predictions indicated the level of identity of <it>M. leprae </it>proteins with homologues in other mycobacteria and the presence of T cell and B cell epitopes.</p> <p>Results</p> <p>Despite the prediction that all proteins would be reactive, 16 of 33 (48%) of the single proteins tested were immunogenic (recognized in WBA or ELISA) and seventeen were non-immunogenic (not recognized in either assay). Among the 16 immunogenic proteins, 9 were considered leprosy specific in WBA inducing cell-mediated IFN-gamma secretion from TT/BT patients and HHC. Three of these proteins were also leprosy specific in serology being recognized by serum IgG from LL/BL patients. Seven of the immunogenic proteins were not leprosy specific.</p> <p>Conclusions</p> <p>New <it>M. leprae </it>antigens recognized by antibody responses of BL/LL patients and cellular responses of TT/BT leprosy patients were identified. An improved serological diagnostic test for leprosy could be developed by incorporating these IgG-reactive antigens to the current PGL-I based tests. Moreover our data indicate that the WBA is a robust, relatively simple and user friendly format for a T cell based diagnostic test. The field use of these test formats in leprosy endemic countries could contribute to early leprosy diagnosis before the development of deformities and disabilities.</p

Integrative literature review of the reported uses of serological tests in leprosy management

An integrative literature review was conducted to synthesize available publications regarding the potential use of serological tests in leprosy programs. We searched the databases Literatura Latino-Americana e do Caribe em Ciências da Saúde, Índice Bibliográfico Espanhol em Ciências da Saúde, Acervo da Biblioteca da Organização Pan-Americana da Saúde, Medical Literature Analysis and Retrieval System Online, Hanseníase, National Library of Medicine, Scopus, Ovid, Cinahl, and Web of Science for articles investigating the use of serological tests for antibodies against phenolic glycolipid-I (PGL-I), ML0405, ML2331, leprosy IDRI diagnostic-1 (LID-1), and natural disaccharide octyl-leprosy IDRI diagnostic-1 (NDO-LID). From an initial pool of 3.514 articles, 40 full-length articles fulfilled our inclusion criteria. Based on these papers, we concluded that these antibodies can be used to assist in diagnosing leprosy, detecting neuritis, monitoring therapeutic efficacy, and monitoring household contacts or at-risk populations in leprosy-endemic areas. Thus, available data suggest that serological tests could contribute substantially to leprosy management.

Neurological disability in leprosy: incidence and gender association in Sergipe, Brazil

Leprosy remains a public health problem in many countries. The disease affects skin and peripheral nerves and can cause irreversible disabilities. In Brazil, the detection rate of new cases is 18.2/100,000 inhabitants and leprosy control is considered a priority in the state of Sergipe. Studies showing the epidemiological profile and geographical distribution of leprosy cases are needed for effective epidemiological control measures. The objective of this study was to assess the detection rate of new cases, the geographical distribution and association with gender and clinical forms in Sergipe. Data were obtained from the Brazilian Institute of Geography and Statistics and the Information System for Notifiable Diseases. Maps indicating the geographical distribution of leprosy cases and the degree of neurological disabilities of all municipalities of the state were created using Spring, version 5.1.8 and ArcGIS, version 9.3.1. Hyper-endemic leprosy municipalities exist in Sergipe, indicating that the disease remains a major public health problem. The leprosy cases were found to be in municipalities with a higher number of dwellings with nine people per house. A detection rate of 33.0/100,000 inhabitants was noted in 2005, followed by a progressive reduction in the number of new cases until 2010. However, in the same period, an increase of cases with neurological disability was observed. A significant association of males with the multi-bacillary form and neurological disability was observed. This predisposition to severe forms of leprosy in males may be due to a delay in diagnosis and treatment emphasising the need for special attention by the leprosy control programme

Challenges and considerations in determining the quality of electronic performance & tracking systems for team sports

Electronic performance &amp; tracking systems (EPTS) are commonly used to track the location and velocity of athletes in many team sports. A range of associated applications using the derived data exist, such as assessment of athlete characteristics, informing training design, assisting match adjudication and providing fan insights for broadcast. Consequently the quality of such systems is of importance to a range of stakeholders. The influence of both systematic and methodological factors such as hardware, software settings, sample rate and filtering on this resulting quality is non-trivial. Highlighting these allows for the user to understand their strengths and limitations in various decision-making processes, as well as identify areas for research and development. In this paper, a number of challenges and considerations relating to the determination of EPTS validity for team sport are outlined and discussed. The aim of this paper is to draw attention of these factors to both researchers and practitioners looking to inform their decision-making in the EPTS area. Addressing some of the posited considerations in future work may represent best practice; others may require further investigation, have multiple potential solutions or currently be intractable