Human macrophage model for selective evaluation of CD8⁺ and γδ⁺ cytotoxic T cell function in tuberculosis

The human macrophage cell line U937 was investigated as an in vitro model for human macrophage function in mycobacterial infections. This involved evaluating the ability of differentiated U937 cells to phagocytose Mycobacterium tuberculosis, control intracellular mycobacterial growth, and present mycobacterial antigens to human HLA class I-matched cytotoxic T lymphocytes (CTLs). Differentiation of U937 cells usmg IFN-γ, 1,25-(OH)₂ vitamin D₃, or PMA significantly enhanced their ability to phagocytose M. tuberculosis but failed to induce a subsequent respiratory burst response. Following infection, U937 cells were found to be permissive to the intracellular growth of both the virulent H37Rv strain of M. tuberculosis and the attenuated vaccine strain of M. bovis BCG. U937 cells have been shown to constitutively express high levels of cell surface HLA class I while expressing undetectable levels of HLA class II both at the mRN A level and at the cell surface. HLA class II expression was neither up-regulated following infection with M. tuberculosis nor inducible using IFN-γ, 1,25-(OH)₂ vitamin D₃, PMA, GM-CSF or a combination of these agents. In contrast, chronic infection of U937 cells with virulent H37Rv M. tuberculosis (but not with BCG) resulted in the cell surface expression of HLA class I being significantly up-regulated. Taken together, these characteristics made U937 cells a very attractive model for further investigations into their ability to present mycobacterial antigens to human HLA class I-restricted CTLs. Differentiation of U937 cells was found to completely abrogate their sensitivity to non-antigen specific cytolysis mediated by NK or LAK cells. Following infection with M. tuberculosis, U937 target cells were lysed by M. tuberculosis-primed CTLs from HLA class I-matched donors in an antigen-specific manner and with a similar efficiency to autologous macrophage targets. This cytolytic activity was restricted to live organisms since only U937 cells infected with virulent H37Rv M. tuberculosis and BCG but not those pulsed with soluble PPD were lysed by the HLA class I-matched effector cells. On the other hand, M. tuberculosisstimulated but ALA-mismatched CTLs failed to lyse infected U937 cells in an antigen-specific manner. T cell subset fractionation of the HLA class I-matched M. tuberculosis-primed CTL population and limiting dilution cloning demonstrated that the cytolytic activity was mediated by CD8⁺ cytolytic T cells and confirmed that CD4⁺ T cells showed no significant ability to lyse infected U937 target cells. Furthermore, this study found that M. tuberculosis-infected U937 target cells were lysed by CD8⁺ CTLs more rapidly and strongly than similarly infected autologous macrophage targets demonstrating the sensitivity of this in vitro model as an indicator for CD8⁺ cytolytic function in mycobacterial infections. M. tuberculosis-infected U937 cells were found to be highly sensitive to mycobacterial antigenspecific cytolysis mediated by γδ⁺ CTL. Mycobacterial antigen-specific γδ⁺ CTLs consistently showed stronger cytolytic activity against infected U937 target cells than γδ⁺ CTL but were not restricted to classical HLA class I or class II molecules. A panel of cytolytic human M. tuberculosis-reactive γδ⁺ CTL clones was established to investigate more thoroughly the role of γδ⁺ CTL lytic activity in human mycobacterial infections. This study examined the mechanism of cellular cytotoxicity used by these mycobacterial-specific γδ⁺ CTL clones against infected U93 7 targets and further investigated the effect of γδ⁺ T cell-mediated cytolysis on intracellular mycobacterial survival. Cytolysis mediated by the γδ⁺ T cell clones was found to be dependent on cell-to-cell contact. Furthermore, the ability of the γδ⁺ CTL clones to lyse infected targets was found to be strongly Ca²⁺-dependent, sensitive to cyclosporine A (a specific inhibitor of granule exocytosis ), and completely abrogated following Sr²⁺-induced de-granulation of the γδ⁺ T cell effectors, indicating that cytoxicity was mediated predominantly by the granule exocytosis/ perforin pathway. Despite being strongly cytolytic against infected U937 cells, however, the γδ⁺ CTL clones did not have any impact on the survival of intracellular M. tuberculosis. The major conclusions of this study are that U937 cells not only provide a useful in vitro human macrophage model allowing for selective evaluation of HLA class I-restricted CD8⁺ CTL function in mycobacterial infections but also provided a highly sensitive indicator for γδ⁺ CTL cytolytic activity

Mental health outcomes of ethnic identity and acculturation among British-born children of immigrants from Turkey

Identity development can be challenging for adolescents, particularly those from immigrant families who are required to make sense of their identity whilst accommodating themselves into different cultures. For second-generation ethnic minority adolescents, these identity formation processes may range from harmony/effectiveness to conflict/stress, having consequences for acculturation and for mental health. Focusing on an underexplored area of research, the present study aimed to examine the relationships between ethnic identity, acculturation orientations, and mental health outcomes among second-generation Turkish adolescents (16–18 years old) in England. Data were collected using a self-report survey (N = 220) and analyzed using structural equation modelling. Results demonstrated that ethnic identity was positively associated with positive mental health and that each ethnic identity component (exploration, resolution, affirmation) was differently associated with life satisfaction, self-esteem, psychological well-being, and depression. Ethnic identity was also positively related to separation and negatively to marginalization whilst no relationships were observed between integration, separation or marginalization, and mental health. Mediation analysis determined that ethnic identity was negatively associated with assimilation and in turn, more positive mental health. Findings demonstrate the complexity of understanding the nature and effects of ethnic identity for second-generation adolescents and have important implications for theory and practice

The Higher Education Landscape for Student Service Members and Veterans in Indiana

The road to higher education can be long and challenging. The demands of academic work combined with employment, family, friends, and social life prove insurmountable for somestudents. Students who are now servingor have served their country in the Armed Forces and want to attend college may face unique obstacles that impede their progress. In this report, we consider the needs of student service members and veterans and the readiness of campuses across Indiana to serve them. We also highlight innovative programming across the nation that addresses gaps in support for student service members and veterans. The United States is currently experiencing the longest and largest-scale sustained involvement in war in recent history. Over 1.6 million deployments have occurred to support Operation Iraqi Freedom (OIF) in Iraq and/or Operation Enduring Freedom (OEF) in Afghanistan and over 420,000 troops have served on multiple deployments. The drawdown in the size of the Armed Forces during the 1990s increased the role of the National Guard and Reserves in our nation's military. As a result, members of the National Guard and Reserves are currently serving longer, more frequent deployments than since World War II, with approximately 38% deployed, and 84,000 deploying more than once. When they are not on active duty, many members of the National Guard and Reserves are students at institutions of higher learning. After completing their service, many active duty military members pursue higher education using the benefits they receive via the GI Bill. The presence of student service members and veterans on college campuses -- and their families -- is likely to increase given recent expansions in GI Bill benefits and continued large-scale deployments

Structural Approaches to Health Promotion: What Do We Need to Know About Policy and Environmental Change?

Although the public health literature has increasingly called on practitioners to implement changes to social, environmental, and political structures as a means of improving population health, recent research suggests that articles evaluating organization, community, or policy changes are more limited than those focused on programs with individuals or their social networks. Even when these approaches appear promising, we do not fully understand whether they will benefit all population groups or can be successful in the absence of accompanying individually oriented programs. The role of this broad category of approaches, including both policy and environmental changes, in decreasing health disparities is also unclear, often benefiting some communities more than others. Finally, the political nature of policy and environmental change, including the impact on personal autonomy, raises questions about the appropriate role for public health professionals in advancing specific policies and practices that alter the conditions in which people live. This article addresses these issues and ends with a series of questions about the effectiveness and ethical implementation of what we have termed “structural initiatives.

Structural Approaches to Health Promotion: What Do We Need to Know About Policy and Environmental Change?

Although the public health literature has increasingly called on practitioners to implement changes to social, environmental, and political structures as a means of improving population health, recent research suggests that articles evaluating organization, community, or policy changes are more limited than those focused on programs with individuals or their social networks. Even when these approaches appear promising, we do not fully understand whether they will benefit all population groups or can be successful in the absence of accompanying individually oriented programs. The role of this broad category of approaches, including both policy and environmental changes, in decreasing health disparities is also unclear, often benefiting some communities more than others. Finally, the political nature of policy and environmental change, including the impact on personal autonomy, raises questions about the appropriate role for public health professionals in advancing specific policies and practices that alter the conditions in which people live. This article addresses these issues and ends with a series of questions about the effectiveness and ethical implementation of what we have termed “structural initiatives.

Vaginal microbiomes associated with aerobic vaginitis and bacterial vaginosis

A healthy vaginal microbiota is considered to be significant for maintaining vaginal health and preventing infections. However, certain vaginal bacterial commensal species serve an important first line of defense of the body. Any disruption of this microbial barrier might result in a number of urogenital conditions including aerobic vaginitis (AV) and bacterial vaginosis (BV). The health of the vagina is closely associated with inhabitant microbiota. Furthermore, these microbes maintain a low vaginal pH, prevent the acquisition of pathogens, stimulate or moderate the local innate immune system, and further protect against complications during pregnancies. Therefore, this review will focus on vaginal microbial “health” in the lower reproductive tract of women and on the physiological characteristics that determine the well-being of reproductive health. In addition, we explore the distinct versus shared characteristics of BV and AV, which are commonly associated with increased risk for preterm delivery

Upending the Social Ecological Model to Guide Health Promotion Efforts Toward Policy and Environmental Change

Efforts to change policies and the environments in which people live, work, and play have gained increasing attention over the past several decades. Yet health promotion frameworks that illustrate the complex processes that produce health-enhancing structural changes are limited. Building on the experiences of health educators, community activists, and community-based researchers described in this supplement and elsewhere, as well as several political, social, and behavioral science theories, we propose a new framework to organize our thinking about producing policy, environmental, and other structural changes. We build on the social ecological model, a framework widely employed in public health research and practice, by turning it inside out, placing health-related and other social policies and environments at the center, and conceptualizing the ways in which individuals, their social networks, and organized groups produce a community context that fosters healthy policy and environmental development. We conclude by describing how health promotion practitioners and researchers can foster structural change by (1) conveying the health and social relevance of policy and environmental change initiatives, (2) building partnerships to support them, and (3) promoting more equitable distributions of the resources necessary for people to meet their daily needs, control their lives, and freely participate in the public sphere