Innate and adaptive immunity at mucosal surfaces of the female reproductive tract : stratification and integration of immune protection against the transmission of sexually transmitted infections

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract.

TLR2, but Not TLR4, is required for effective host defence against Chlamydia respiratory tract infection in early life

Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (−/−), 4−/− or 2/4−/− BALB/c mice. Wt mice had moderate disease and infection. TLR2−/− mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4−/− mice were asymptomatic. TLR2/4−/− mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4−/− mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)γ in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2−/− mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4−/− mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases.

IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms

Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4+ and CD8+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1−/− mice or in mice depleted of CD4+ and/or CD8+ cells than in normal mice. The tumors in RAG1−/− mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.

Adaptive immunity to rhinoviruses: Sex and age matter

Background: Rhinoviruses (RV) are key triggers in acute asthma exacerbations. Previous studies suggest that men suffer from infectious diseases more frequently and with greater severity than women. Additionally, the immune response to most infections and vaccinations decreases with age. Most immune function studies do not account for such differences, therefore the aim of this study was to determine if the immune response to rhinovirus varies with sex or age. Methods: Blood mononuclear cells were isolated from 63 healthy individuals and grouped by sex and age (≤50 years old and ≥52 years old). Cells were cultured with rhinovirus 16 at a multiplicity of infection of 1. The chemokine IP-10 was measured at 24 h as an index of innate immunity while IFNγ and IL-13 were measured at 5 days as an index of adaptive immunity. Results: Rhinovirus induced IFNγ and IL-13 was significantly higher in ≤50 year old women than in age matched men (p < 0.02 and p < 0.05) and ≥52 year old women (p < 0.02 and p > 0.005). There was no sex or age based difference in rhinovirus induced IP-10 expression. Both IFNγ and IL-13 were negatively correlated with age in women but not in men. Conclusions: This study suggests that pre-menopausal women have a stronger adaptive immune response to rhinovirus infection than men and older people, though the mechanisms responsible for these differences remain to be determined. Our findings highlight the importance of gender and age balance in clinical studies and in the development of new treatments and vaccines.

SNAREing immunity : the role of SNAREs in the immune system

The trafficking of molecules and membranes within cells is a prerequisite for all aspects of cellular immune functions, including the delivery and recycling of cell surface proteins, secretion of immune mediators, ingestion of pathogens and activation of lymphocytes. SNARE (soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptor)-family members mediate membrane fusion during all steps of trafficking, and function in almost all aspects of innate and adaptive immune responses. Here, we provide an overview of the roles of SNAREs in immune cells, offering insight into one level at which precision and tight regulation are instilled on immune responses.

Interpersonal pattern dynamics and adaptive behavior in multiagent neurobiological systems : conceptual model and data

Ecological dynamics characterizes adaptive behavior as an emergent, self-organizing property of interpersonal interactions in complex social systems. The authors conceptualize and investigate constraints on dynamics of decisions and actions in the multiagent system of team sports. They studied coadaptive interpersonal dynamics in rugby union to model potential control parameter and collective variable relations in attacker–defender dyads. A videogrammetry analysis revealed how some agents generated fluctuations by adapting displacement velocity to create phase transitions and destabilize dyadic subsystems near the try line. Agent interpersonal dynamics exhibited characteristics of chaotic attractors and informational constraints of rugby union boxed dyadic systems into a low dimensional attractor. Data suggests that decisions and actions of agents in sports teams may be characterized as emergent, self-organizing properties, governed by laws of dynamical systems at the ecological scale. Further research needs to generalize this conceptual model of adaptive behavior in performance to other multiagent populations.

Building climate change resilience and adaptive capacity in Australia’s community sector using social media and technology innovation

Public and private sector organisations worldwide are putting strategies in place to manage the commercial and operational risks of climate change. However, community organisations are lagging behind in their understanding and preparedness, despite them being among the most exposed to the effects of climate change impacts and regulation. This poster presents a proposal for a multidisciplinary study that addresses this issue by developing, testing and applying a novel climate risk assessment methodology that is tailored to the needs of Australia’s community sector and its clients. Strategies to mitigate risks and build resilience and adaptive capacity will be identified including new opportunities afforded by urban informatics, social media, and technologies of scale making.

An assessment of timber dwellings typical of the Queenslander era, and constraints associated with their relocation, component and adaptive reuse when considering 'regeneration'

This paper presents an explanation of why the reuse of building components after demolition or deconstruction is critical to the future of the construction industry. An examination of the historical cause and response to climate change sets the scene as to why governance is becoming increasingly focused on the built environment as a mechanism to controlling waste generation associated with the process of demolition, construction and operation. Through an annotated description to the evolving design and construction methodology of a range of timber dwellings (typically 'Queenslanders' during the eras of 1880-1900, 1900-1920 & 1920-1940) the paper offers an evaluation to the variety of materials, which can be used advantageously by those wishing to 'regenerate' a Queenslander. This analysis of 'regeneration' details the constraints when considering relocation and/ or reuse by adaption including deconstruction of building components against the legislative framework requirements of the Queensland Building Act 1975 and the Queensland Sustainable Planning Act 2009, with a specific examination to those of the Building Codes of Australia. The paper concludes with a discussion of these constraints, their impacts on 'regeneration' and the need for further research to seek greater understanding of the practicalities and drivers of relocation, adaptive and building components suitability for reuse after deconstruction.

Fault diagnosis of induction motor based on decision trees and adaptive neuro-fuzzy inference

This paper presents a fault diagnosis method based on adaptive neuro-fuzzy inference system (ANFIS) in combination with decision trees. Classification and regression tree (CART) which is one of the decision tree methods is used as a feature selection procedure to select pertinent features from data set. The crisp rules obtained from the decision tree are then converted to fuzzy if-then rules that are employed to identify the structure of ANFIS classifier. The hybrid of back-propagation and least squares algorithm are utilized to tune the parameters of the membership functions. In order to evaluate the proposed algorithm, the data sets obtained from vibration signals and current signals of the induction motors are used. The results indicate that the CART–ANFIS model has potential for fault diagnosis of induction motors.

The link between age, career goals, and adaptive development for work-related learning among local government employees

More recently, lifespan development psychology models of adaptive development have been applied to the workforce to investigate ageing worker and lifespan issues. The current study uses the Learning and Development Survey (LDS) to investigate employee selection and engagement of learning and development goals and opportunities and constraints for learning at work in relation to demographics and career goals. It was found that mature age was associated with perceptions of preferential treatment of younger workers with respect to learning and development. Age was also correlated with several career goals. Findings suggest that younger workers’ learning and development options are better catered for in the workplace. Mature aged workers may compensate for unequal learning opportunities at work by studying for an educational qualification or seeking alternate job opportunities. The desire for a higher level job within the organization or educational qualification was linked to engagement in learning and development goals at work. It is suggested that an understanding of employee perceptions in the workplace in relation to goals and activities may be important in designing strategies to retain workers.

β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice

Objective The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17–dependent inflammatory arthritis developed after dectin 1–mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process. Methods SKG mice and control BALB/c mice were injected once with curdlan or mannan. Arthritis was scored weekly, and organs were assessed for pathologic features. Anti–IL-23 monoclonal antibodies were injected into curdlan-treated SKG mice. CD4+ T cells were transferred from curdlan-treated mice to SCID mice, and sera were analyzed for autoantibodies. Results After systemic injection of curdlan, SKG mice developed enthesitis, wrist, ankle, and sacroiliac joint arthritis, dactylitis, plantar fasciitis, vertebral inflammation, ileitis resembling Crohn's disease, and unilateral uveitis. Mannan triggered spondylitis and arthritis. Arthritis and spondylitis were T cell– and IL-23–dependent and were transferable to SCID recipients with CD4+ T cells. SpA was associated with collagen- and proteoglycan-specific autoantibodies. Conclusion Our findings indicate that the SKG ZAP-70W163C mutation predisposes BALB/c mice to SpA, resulting from innate and adaptive autoimmunity, after systemic β-glucan or mannan exposure.

Tangible cultural heritage and adaptive reuse: the Old Government House, Brisbane, Australia

The Old Government House, a former residence of the Queen’s representatives in Brisbane, Australia, symbolises British cultural heritage of Colonial Queensland. Located on the campus of the Queensland University of Technology, it is one of the oldest surviving examples of a stately residence in Queensland. Built in 1860s, the Old Government House was originally intended as a temporary residence for the first governor of the newly independent colony of Queensland. However, it remained the vice-regal residence until 1909, serving eleven succeeding governors. Nearly seven decades later, it became the first building in Queensland to be protected under heritage legislation. Thus its importance, as an excellent exemplar that demonstrates the significance of cultural heritage, was established. The Old Government House has survived 150 years of restoration work, refurbishments, and additions. Through these years, it has served the people of Queensland in a multitude of roles. This paper aims to investigate the survival of heritage listed buildings through their adaptive re-use. Its focus will be on the adaptive reuse of the Old Government House through its refurbishments and additions over a period of 150 years. Through a qualitative research process this paper will endeavour to establish the significance of restoration work on the Old Government house; the new opportunities that has opened up as a result of the restoration work; the continued maintenance and management of the building through adaptive re-use; the economic benefits of restoration work; and its contribution to the on-going interest in the preservation of the Tangible Cultural Heritage.

An interactive and adaptive building layer : strategies for allowing people to become advanced building-users

This paper reports outcomes of a pilot study to develop a conceptual framework to allow people to retrofit a building-layer to gain better control of their own built- environments. The study was initiated by the realisation that discussions surrounding the improvement of building performances tend to be about top-down technological solutions rather than to help and encourage bottom-up involvement of building-users. While users are the ultimate beneficiaries and their feedback is always appreciated, their direct involvements in managing buildings would often be regarded as obstruction or distraction. This is largely because casual interventions by uninformed building-users tend to disrupt the system. Some earlier researches showed however that direct and active participation of users could improve the building performance if appropriate training and/or systems were introduced. We also speculate this in long run would also make the built environment more sustainable. With this in mind, we looked for opportunities to retrofit our own office with an interactive layer to study how we could introduce ad-hoc systems for building-users. The aim of this paper is to describe our vision and initial attempts followed by discussion.

Understanding IT value : a multilevel, complex, and adaptive system perspective

One remaining difficulty in the Information Technology (IT) business value evaluation domain is the direct linkage between IT value and the underlying determinants of IT value or surrogates of IT value. This paper proposes a research that examines the interacting effects of the determinants of IT value, and their influences on IT value. The overarching research question is how those determinants interact with each other and affect the IT value at organizational value. To achieve this, this research embraces a multilevel, complex, and adaptive system view, where the IT value emerges from the interacting of underlying determinants. This research is theoretically grounded on three organizational theories – multilevel theory, complex adaptive systems theory, and adaptive structuration theory. By integrating those theoretical paradigms, this research proposes a conceptual model that focuses on the process where IT value is created from interactions of those determinants. To answer the research question, agent-based modeling technique is used in this research to build a computational representation based on the conceptual model. Computational experimentation will be conducted based on the computational representation. Validation procedures will be applied to consolidate the validity of this model. In the end, hypotheses will be tested using computational experimentation data.