Containment of Mycobacterium tuberculosis (Mtb) infection requires T cell recognition of infected macrophages. Mtb has evolved to tolerate, evade, and subvert host immunity. Despite a vigorous and ...sustained CD8+ T cell response during Mtb infection, CD8+ T cells make limited contribution to protection. Here, we ask whether the ability of Mtb-specific T cells to restrict Mtb growth is related to their capacity to recognize Mtb-infected macrophages. We derived CD8+ T cell lines that recognized the Mtb immunodominant epitope TB10.44-11 and compared them to CD4+ T cell lines that recognized Ag85b240-254 or ESAT63-17. While the CD4+ T cells recognized Mtb-infected macrophages and inhibited Mtb growth in vitro, the TB10.4-specific CD8+ T cells neither recognized Mtb-infected macrophages nor restricted Mtb growth. TB10.4-specific CD8+ T cells recognized macrophages infected with Listeria monocytogenes expressing TB10.4. However, over-expression of TB10.4 in Mtb did not confer recognition by TB10.4-specific CD8+ T cells. CD8+ T cells recognized macrophages pulsed with irradiated Mtb, indicating that macrophages can efficiently cross-present the TB10.4 protein and raising the possibility that viable bacilli might suppress cross-presentation. Importantly, polyclonal CD8+ T cells specific for Mtb antigens other than TB10.4 recognized Mtb-infected macrophages in a MHC-restricted manner. As TB10.4 elicits a dominant CD8+ T cell response that poorly recognizes Mtb-infected macrophages, we propose that TB10.4 acts as a decoy antigen. Moreover, it appears that this response overshadows subdominant CD8+ T cell response that can recognize Mtb-infected macrophages. The ability of Mtb to subvert the CD8+ T cell response may explain why CD8+ T cells make a disproportionately small contribution to host defense compared to CD4+ T cells. The selection of Mtb antigens for vaccines has focused on antigens that generate immunodominant responses. We propose that establishing whether vaccine-elicited, Mtb-specific T cells recognize Mtb-infected macrophages could be a useful criterion for preclinical vaccine development.
This paper is a work-in-progress account of ideas and propositions about resilience in social-ecological systems. It articulates our understanding of how these complex systems change and what ...determines their ability to absorb disturbances in either their ecological or their social domains. We call them “propositions” because, although they are useful in helping us understand and compare different social-ecological systems, they are not sufficiently well defined to be considered formal hypotheses. These propositions were developed in two workshops, in 2003 and 2004, in which participants compared the dynamics of 15 case studies in a wide range of regions around the world. The propositions raise many questions, and we present a list of some that could help define the next phase of resilience-related research.
We review the evidence of regime shifts in terrestrial and aquatic environments in relation to resilience of complex adaptive ecosystems and the functional roles of biological diversity in this ...context. The evidence reveals that the likelihood of regime shifts may increase when humans reduce resilience by such actions as removing response diversity, removing whole functional groups of species, or removing whole trophic levels; impacting on ecosystems via emissions of waste and pollutants and climate change; and altering the magnitude, frequency, and duration of disturbance regimes. The combined and often synergistic effects of those pressures can make ecosystems more vulnerable to changes that previously could be absorbed. As a consequence, ecosystems may suddenly shift from desired to less desired states in their capacity to generate ecosystem services. Active adaptive management and governance of resilience will be required to sustain desired ecosystem states and transform degraded ecosystems into fundamentally new and more desirable configurations.
Resilience is the magnitude of disturbance that can be tolerated before a socioecological system (SES) moves to a different region of state space controlled by a different set of processes. ...Resilience has multiple levels of meaning: as a metaphor related to sustainability, as a property of dynamic models, and as a measurable quantity that can be assessed in field studies of SES. The operational indicators of resilience have, however, received little attention in the literature. To assess a system's resilience, one must specify which system configuration and which disturbances are of interest. This paper compares resilience properties in two contrasting SES, lake districts and rangelands, with respect to the following three general features: (a) The ability of an SES to stay in the domain of attraction is related to slowly changing variables, or slowly changing disturbance regimes, which control the boundaries of the domain of attraction or the frequency of events that could push the system across the boundaries. Examples are soil phosphorus content in lake districts woody vegetation cover in rangelands, and property rights systems that affect land use in both lake districts and rangelands. (b) The ability of an SES to self-organize is related to the extent to which reorganization is endogenous rather than forced by external drivers. Self-organization is enhanced by coevolved ecosystem components and the presence of social networks that facilitate innovative problem solving. (c) The adaptive capacity of an SES is related to the existence of mechanisms for the evolution of novelty or learning. Examples include biodiversity at multiple scales and the existence of institutions that facilitate experimentation, discovery, and innovation.
Shooting the Rapids Olsson, Per; Gunderson, Lance H.; Carpenter, Steve R. ...
Ecology and society,
06/2006, Volume:
11, Issue:
1
Journal Article
Peer reviewed
Open access
The case studies of Kristianstads Vattenrike, Sweden; the Northern Highlands Lake District and the Everglades in the USA; the Mae Nam Ping Basin, Thailand; and the Goulburn-Broken Catchment, ...Australia, were compared to assess the outcome of different actions for transforming social-ecological systems (SESs). The transformations consisted of two phases, a preparation phase and a transition phase, linked by a window of opportunity. Key leaders and shadow networks can prepare a system for change by exploring alternative system configurations and developing strategies for choosing from among possible futures. Key leaders can recognize and use or create windows of opportunity and navigate transitions toward adaptive governance. Leadership functions include the ability to span scales of governance, orchestrate networks, integrate and communicate understanding, and reconcile different problem domains. Successful transformations rely on epistemic and shadow networks to provide novel ideas and ways of governing SESs. We conclude by listing some rules of thumb” that can help build leadership and networks for successful transformations toward adaptive governance of social-ecological systems.
Screening for colorectal neoplasms has become the standard of care in advanced medical settings worldwide. Identifying asymptomatic colorectal neoplastic lesions has been shown to reduce colorectal ...cancer incidence and the overall cost of medical care. Clinicians have several alternatives at their disposal as they consider screening for their respective patient population. Two important methods to consider are optical colonoscopy and computed tomographic colonography (CTC). The purpose of this article is to make the case that gastroenterologists should read CTC. Central to the argument that gastroenterologists read CTC is the benefit of experience with video-assisted colonic imaging and the physician-patient relationship.
The lakes in the northern highlands of Wisconsin, USA, the lakes and wetlands of Kristianstads Vattenrike in southern Sweden, and the Everglades of Florida, USA, provide cases that can be used to ...compare the linkages between ecological resilience and social dynamics. The erosion of ecological resilience in aquatic and wetland ecosystems is often a result of past management actions and is manifest as a real or perceived ecological crisis. Learning is a key ingredient in response to the loss of ecological resilience. Learning is facilitated through networks that operate in distinct arenas and are structured for dialogue, synthesis, and imaginative solutions to chart alternative futures. The networks also help counter maladaptive processes such as information control or manipulation, bureaucratic inertia, or corruption. The networks help create institutional arrangements that provide for more learning and flexibility and for the ability to change. Trust and leadership appear to be key elements for adaptability and transformability.
The US strategy in Afghanistan has fallen short of neutralizing the insurgency that threatens the future stability. The primary insurgency's leadership council, the Quetta Shura, has effectively ...managed influence through a shadow government and superior tactics in recruiting marginalized tribal leaders, leading to a questionable outcome once Coalition forces withdraw in 2014. This article summarizes the threat posed by the Quetta Shura, coinciding with the deficiencies in the current US policy, and recommends a more viable strategy conducive to the current circumstances, based on historical and cultural precedence. Coalition forces have put a great amount of time, money, and effort into establishing a more stable Afghanistan. The USA needs a more aggressive strategy to counter the aspirations of the insurgency, thereby giving the Afghans the opportunity to further progress in the future. Under the current circumstances and policies, a peaceful transition after the Coalition withdrawal is becoming more unlikely.
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