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At least 55 records · Page 3

Immunological Correlates of the HIV-1 Replication-Competent Reservoir Size

Understanding what shapes the latent human immunodeficiency virus type 1 (HIV-1) reservoir is critical for developing strategies for cure. Here, we measured frequency of persistent HIV-1 infection after 5 years of suppressive antiretroviral therapy initiated during chronic infection. Pretreatment CD8 + T-cell activation, nadir CD4 count, and CD4:CD8 ratio predicted reservoir size.

60 APPLIED LIFE SCIENCES↗

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure

Background: Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility. Methods: This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode. Results: Metals analysis of WS particulate matter (PM) revealed significantly increased levels of 63 Cu, 182 W, 208 Pb, and 238 U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1β, TNF-α, CXCL-1, CCL-5, TGF-β, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1β, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1β, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche. Conclusions: In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression of proinflammatory cytokines, chemokines, lung mRNA gene expression, and related functional networks linked to signaling pathways. These differences potentially act as mediators of sex-specific and hormonal influences in the systemic inflammatory response to acute WS exposure during a wildfire event. Understanding the regulatory roles of genes expressed differentially under environmental stressors holds considerable implications, aiding in identifying sex-specific therapeutic targets for addressing acute lung inflammation and injury.

59 BASIC BIOLOGICAL SCIENCES↗

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure

Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility.

59 BASIC BIOLOGICAL SCIENCES↗

A study of immunological reactions in dogs exposed to prolonged chronic radiation

Immunomorphological studies on dog tissues exposed to long term gamma irradiation show that the number of cells containing antibodies increased and that the blast transformation reaction was activated. Prolonged radiation did not cause a reliable change in the synthesis of nucleic acids in spleen cells.

Konstantinova, I. V.↗

Immunological analyses of U.S. Space Shuttle crewmembers

Changes in the immunoresponsiveness of 'T' lymphocytes following space flight have been reported previously. Additional data collected before and after 11 Shuttle space flights show that absolute lymphocyte numbers, lymphocyte blastogenic capability, and eosinophil percent in the peripheral blood of crewmembers are generally depressed postflight. These responses resemble those associated with physical and emotional stress and may not be related to flight per se. Additional data from Space Shuttle flights 41B and 41D, involving 11 crewmembers, indicate a postflight decrease in cells reacting with 'B' lymphocyte and monocyte monoclonal antibody tags. Further, the loss of 'T' lymphocyte blast capability correlates with the decreased monocyte count (correlation coefficient = 0.697). This finding implies that the previously reported loss of blastogenic capability may be a function of decreased monocyte control, as noted in several nonspaceflight related studies.

Taylor, G. R.↗

Space immunology - Past, present and future

Research results on the causes and mechanisms of change in immune systems during spaceflight are briefly reviewed. The most reliable conclusion from the sparse existing data is that postflight crew members exhibit a transient neutrophilia, eosinopenia, monocytopenia, reduced numbers of circulating T cells, and an often pronounced decrease in the ability of their T cells to respond to mitogen stimulation. Clinically, no direct predictive relationship between any of these measurements and increased health risk or disease has been established. Future areas of research are suggested in light of NASA's emerging requirements to support long-duration missions.

Coulter, Gary R.↗

Cosmos: 1989 immunology studies

The effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM were determined. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies performed on Cosmos 1887. Spleen and bone marrow cells were obtained from flown, vivarium control, synchronous control, and suspended rats. The cells were stained with a series of monoclonal antibodies directed against rat leukocyte cell surface antigens. Control cells were stained with a monoclonal antibody directed against an irrelevant species or were unstained. Cells were then analyzed for fluorescence using a FACSCAN flow cytometer. Bone marrow cells were placed in culture with GM-CSF in McCoy's 5a medium and incubated for 5 days. Cultures were then evaluated for the number of colonies of 50 cells or greater.

Sonnenfeld, Gerald↗

Altered immunological response in mice subjected to stress and exposed to fungal spores

Space flight and related factors such as stress appear to have an adverse effect on astronauts' immune systems. The presence of potentially pathogenic microbes including several genera of fungi reported from spacecraft environment may be a cause of concern in such situations. In order to study the role of such organisms in causing opportunistic or allergic diseases in crewmembers, we have tried to develop an animal model. BALB/c mice were suspended upside down for varying periods of time to induce stress, and their lymphocyte functions were evaluated. These studies indicate that the stress resulted in lowered mitogen induced lymphocyte stimulation as represented by 3H-thymidine uptake. We have also studied the ability of these animals to respond to Aspergillus fumigatus spores. The results of the study clearly demonstrate a definite down-regulation in T-cell proliferation and a higher incidence of infection with A. fumigatus.

Kurup, Viswanath P.↗

Immunological Influences on the Vestibular System

The goals of this project were to examine the influence of immune signaling molecules on the survival and replacement of sensory hair cells in the vestibular organs. We have made considerable progress toward that goal, particularly in the characterization of mechanisms that underlie hair cell death.

Warchol, Mark E.↗

Consequences of contamination of the spacecraft environment: immunologic consequences

Long-term space voyages pose numerous known and unknown health hazards, to the human immune system. Well-studied clinical examples of secondary immunodeficiencies created on Earth, lead one to predict that the conditions of prolonged space flight would weaken the human immune responses that normally hold infection and cancer in check. From evidence gathered from humans flown for prolonged periods in space and from human models of space flight studied on Earth it is reasonable to suspect that space travelers to the planet Mars would experience a weakening of immunity. Subtle defects of immune cell structure and function have been observed in astronauts, such as weakening of specific T-lymphocyte recall of specific antigens. Ground-based models also have demonstrated alterations of immune function, such as the elevation of neuroendocrine immune system messengers, interleukin-6, and soluble tumor necrosis factor-alpha receptor in sleep deprivation. Since severe immune compromise the clinical consequences of reactivation of latent virus infections and the development of cancer, has yet to be seen in space flight or in the Earth models, it is extremely important to begin to quantify early changes in immunity to predict the development of immune system collapse with poor clinical outcomes. This approach is designed to validate a number of surrogate markers that will predict trouble ahead. Inherent in this research is the development of countermeasures to reduce the risks of infection and cancer in the first humans going to Mars.

Non-NASA Center↗

Immunological and biochemical evidence for nuclear localization of annexin in peas

Immunofluorescent localization of annexins using an anti-pea annexin polyclonal antibody (anti-p35) in pea (Pisum sativum) leaf and stem epidermal peels showed staining of the nuclei and the cell periphery. Nuclear staining was also seen in cell teases prepared from pea plumules. The amount of nuclear stain was reduced both by fixation time and by dehydration and organic solvent treatment. Observation with confocal microscopy demonstrated that the anti-p35 stain was diffusely distributed throughout the nuclear structure. Immunoblots of purified nuclei, nuclear envelope matrix, nucleolar, and chromatin fractions showed a cross-reactive protein band of 35 kDa. These data are the first to show annexins localized in plant cell nuclei where they may play a role in nuclear function.

Non-NASA Center↗