Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “immunization”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2007

Validation of Procedures for Monitoring Crewmember Immune Function SDBI-1900, SMO-015 - Integrated Immune

There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk from prolonged immune dysregulation during space flight are not yet determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight condition. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flight-compatible immune monitoring strategy. Characterization of the clinical risk and the development of a monitoring strategy are necessary prerequisite activities prior to validating countermeasures. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers immune system. Pre-flight, in-flight and post-flight assessments of immune status, immune function, viral reactivation and physiological stress will be performed. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter landing day assessments. The overall status of the immune system during flight (activation, deficiency, dysregulation) and the response of the immune system to specific latent virus reactivation (known to occur during space flight) will be thoroughly assessed. Following completion of the SMO the data will be evaluated to determine the optimal set of assays for routine monitoring of crewmember immune system function, should the clinical risk warrant such monitoring.

Crucian, Brian↗
DOE OSTI2021

Antitumor T-cell Immunity Contributes to Pancreatic Cancer Immune Resistance

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States. Pancreatic tumors are minimally infiltrated by T cells and are largely refractory to immunotherapy. Accordingly, the role of T-cell immunity in pancreatic cancer has been somewhat overlooked. Here, we hypothesized that immune resistance in pancreatic cancer was induced in response to antitumor T-cell immune responses and that understanding how pancreatic tumors respond to immune attack may facilitate the development of more effective therapeutic strategies. We now provide evidence that T-cell–dependent host immune responses induce a PDAC-derived myeloid mimicry phenomenon and stimulate immune resistance. Three KPC mouse models of pancreatic cancer were used: the mT3-2D (Kras +/LSL-G12D ; Trp53 +/LSL-R172H ; Pdx1-Cre) subcutaneous and orthotopic models, as well as the KP1 (p48-CRE/LSL-Kras/Trp53 flox/flox ) subcutaneous model. KPC cancer cells were grown in immunocompetent and immunodeficient C57BL/6 mice and analyzed to determine the impact of adaptive immunity on malignant epithelial cells, as well as on whole tumors. We found that induced T-cell antitumor immunity, via signal transducer and activator of transcription 1 (STAT1), stimulated malignant epithelial pancreatic cells to induce the expression of genes typically expressed by myeloid cells and altered intratumoral immunosuppressive myeloid cell profiles. Targeting the Janus Kinase (JAK)/STAT signaling pathway using the FDA-approved drug ruxolitinib overcame these tumor-protective responses and improved anti–PD-1 therapeutic efficacy. Overall, these findings provide future directions for treatments that specifically disable this mechanism of resistance in PDAC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection

Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus’s direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2020

A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni

The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen’s virulence factors and the host immune system. Campylobacter jejuni is the leading bacterial cause of diarrhea worldwide due to its near-ubiquitous zoonotic association with poultry. One of the outstanding questions is to what extent the bacteria are responsible for the diarrheal symptoms via intestinal cell necrosis versus immune cell initiated tissue damage. To determine the stepwise process of inflammation that leads to diarrhea, we used a piglet ligated intestinal loop model to study the intestinal response to C. jejuni. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine. We found that the abundance of neutrophil related proteins increased in the intestinal lumen during C. jejuni infection, including proteins related to neutrophil migration (neutrophil elastase and MMP9), actin reorganization (Arp2/3), and antimicrobial proteins (lipocalin-2, myeloperoxidase, S100A8, and S100A9). The appearance of neutrophil proteins also corresponded with increases of the inflammatory cytokines IL-8 and TNF-a. Compared to infection with the C. jejuni wild-type strain, infection with the noninvasive C. jejuni ?ciaD mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by C. jejuni virulence and that neutrophils are the predominant cell type responding to C. jejuni infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.

disease model, INNATE IMMUNITY, proteomics, intest↗
NASA NTRS2014

2013 Immune Risk Standing Review Panel Research Plan Review for: The Risk of Crew Adverse Health Event Due to Altered Immune Response

The 2013 Immune Risk Standing Review Panel (from here on referred to as the SRP) participated in a meeting with representatives from the Human Research Program (HRP) Human Health Countermeasures (HHC) Element and HRP management on February 3-4, 2014 in Houston, TX to review the updated Research Plan for the Risk of Crew Adverse Health Event Due to Altered Immune Response in the HRP Integrated Research Plan. The SRP is impressed with the work the immune discipline has done since the 2012 SRP review and agrees with the new wording of the Gaps, no longer questions, now statements. The SRP also likes the addition of adding targets for closing the Gaps, but it is not clear how they got to some of the interim stages (interval percentages). A major concern that the SRP has mentioned since the initial 2009 SRP meeting is that there is still not enough emphasis on the interdisciplinary aspect of the immune risk associated with other risks (i.e., nutrition, radiation, etc.). The SRP recommends that a "translational SRP" or advisory group be developed that is composed of members from all of the HRP SRPs. The SRP also thinks that the immune discipline should consider a more systems biology approach. Lastly, the SRP is concerned that the risks observed in research from low Earth orbit (LEO) missions may not accurately reflect all the risks of longer duration flight beyond LEO. Also, there does not seem to be a concern for immune responses that may occur when someone is in space longer than six months, for example, a Mars mission would take three years. The absence of disease in past and current flight scenarios does not mean the risk may not be there in future flight settings.

Steinberg, Susan↗
DOE OSTI2018

Active immunization using hand-push emulsification method increases the operator's risk of transcutaneous immunization

Highlights: • Researchers have the right to be told the relevant risks of immunological experiments. • Susceptible individuals to allergic diseases are suggested to be more careful when they perform immunological experiments. Setting up an animal model by using active immunization methods is a common means of studying immune-related diseases or producing antibodies with high titer and high activities. However, the security during the process of pathogen emulsification remains unclear. In a physical examination, we unexpectedly noticed high levels of angiotensin II type 1 receptor autoantibody (AT1-AA) specific to the immunizing antigen in the sera of some researchers who had participated in setting up active immunization animal models, and we were puzzled about the cause of AT1-AA production. In this study, we intended to investigate whether the emulsified antigen was the source of infection in these researchers, and if so, how to prevent it from occurring. AT1-AA was detected by advanced ELISA method. The participants presented higher levels of AT1-AA compared with non-participants of the same laboratory. This phenomenon remained that some factors during the process of rat model establishment may contribute to AT1-AA production. Animal and glove penetration studies indicated the emulsified antigen infection was attributed to neither aerosol or fur touch nor penetrating through gloves. However, AT1-AA level was largely decreased in the participants after they used an automatic emulsification device. Because of the strong permeability of the adjuvant, we speculated that emulsified antigen might get access to the unprotected skin of the participants accidentally during the immunization process. These results demonstrated that accidental contacts of emulsified antigens may infect researchers during the process of traditional hand-push emulsification, resulting in high specific autoantibody levels, which can be prevented by using appropriate tools.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1997

Studies of Cell-Mediated Immunity Against Immune Disorders Using Synthetic Peptides and Rotating Bioreactor System

Our proposed experiments included: (1) immunzing mice with synthetic peptides; (2) preparing spleen and lymph node cells; (3) growing them under conventional conditions as well as in the rotatory vessel in appropriate medium reconstituting with synthetic peptides and/or cytokines as needed; and (4) comparing at regular time intervals the specific CTL activity as well as helper T-cell activity (in terms of both proliferative responses and cytokine production) using established procedures in my laboratory. We further proposed that once we demonstrated the merit of rotatory vessel technology to achieve desired results, these studies would be expanded to include immune cells from non-human primates (rhesus monkeys and chimpanzees) and also humans. We conducted a number of experiments to determine CTL induction by the synthetic peptides corresponding to antigenic proteins in HIV and HPV in different mouse strains that express MHC haplotypes H-2b or H-2d. We immunized mice with 100 ug of the synthetic peptide, suspended in sterile water, and emulsified in CFA (1:1). The immune lymph node cells obtained after 7 days were restimulated by culturing in T25 flask, HARV-10, or STLV-50, in the presence of the peptide at 20 ug/ml. The results from the 5'Cr-release assay consistently revealed complete abrogation of CTL activity of cells grown in the bioreactors (both HARV and STLV), while significant antigen-specific CTL activity was observed with cells cultured in tissue culture flasks. Thus, overall the data we generated in this study proved the usefulness of the NASA-developed developed technology for understanding the known immune deficiency during space travel. Additionally, this ex vivo microgravity technology since it mimics effectively the in vivo situation, it is also useful in understanding immune disorders in general. Thus, our proposed studies in TMC-NASA contract round II application benefit from data generated in this TMC-NASA contract round I study.

Sastry, Jagannadha K.↗
DOE OSTI2025

Methods integrating innate and adaptive immune responses in human in vitro immunization assays

Rapid vaccine development and innovative immunotherapeutics are critical in the fight against emerging outbreaks and global pandemic threats, yet the high costs and prolonged timelines for developing new vaccines underscore the urgent need for robust, predictive pre-clinical testing platforms. The rapid down-selection of vaccine candidates and identification of optimal vaccine formulations can be performed using human in vitro immunization (IVI) assays that recapitulate the complex interactions of the innate and adaptive human immune response. In this review, we present a comprehensive evaluation of three key IVI platforms: the whole blood assay (WBA), monocyte-derived dendritic cell (MoDC) assay with dendritic cell-T cell interface assay (DTI), and the microphysiological human tissue construct assay (HTC). The WBA offers a cost-effective and straightforward approach, while the MoDC + DTI system represents the current gold standard for balancing experimental efficiency with immunological complexity. The HTC assay, by mimicking both spatial and temporal aspects of immune interactions, provides enhanced physiological relevance. We discuss the methodological advantages and limitations of each platform, explore their roles in rapid vaccine candidate screening, and propose strategies for integrating these assays with complementary in vivo models. These insights pave the way for refining IVI assays and accelerating the translational pipeline for next-generation vaccines and immunotherapies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Bradbury Science Museum NOTEs Program Docs: Building Immunity: How fighting HIV and other viruses helps us understand our immune system

Building Immunity is a unique opportunity to journey through the history and development of your immune system. Our interactive touch table invites each user to choose their own, unique experience as they learn about how fighting HIV and other viruses helps researchers understand how our own immune systems work to keep us healthy. From the Bradbury Science Museum of Los Alamos National Laboratory, the exhibit presents remarkable insight into one of the most ancient and well-traveled organisms on the planet, viruses. Viral epidemics like the H1N1 flu, which killed over 40 million people in 1918, devastate communities around the world and destabilize regions around the globe. Additionally, their ability to mutate quickly creates a “Red Queen” effect, or loop of treated and then treatment-resistant strains of deadly diseases. Increased understanding of the relationships between viruses and our own immune system is crucial to the development of improved treatments and novel vaccines and this research is happening right now at Los Alamos National Laboratory.

60 APPLIED LIFE SCIENCES↗
NASA NTRSDate not supplied

Pilot Assessment of Immune Dysregulation, Stress and Latent Herpesvirus Reactivation at Palmer, Antarctica - Platform for validation of Immune Countermeasures?

Recent studieshave characterized adverse health events potentially relatedto immune system dysregulation, latent herpesvirus reactivation, and clinical incidence for crewmembers onboard ISS. Both areview article describing potential spaceflight countermeasures related to immunityand a specific countermeasures protocol for deep space missions were recently published. An appropriate ground analogto enable spaceflight countermeasures has yet to be validated, although winterover in Antarctica (AWO) seems a highly relevant mission parallel to spaceflight. AWO consists of prolonged deployment, extreme environment, circadian misalignment, personal isolation, station lifestyle (varies by base), and personal risk. Through several studies, AWO at several European bases has beencharacterized, and to date the data has revealed that (immunologically) deployment to interior bases at elevation and with persistent hypobaric hypoxia possesses certaindissimilarities to spaceflight. This proposal seeks to collect low cost pilot data assessing stress, immunity and viral reactivation during AWOat thecoastalU.S. Palmer Station. Even among coastal bases, lifestyle, available crew time/workload and logistical access can vary considerably. Considering all factors, if validated, Palmer may be the most feasible location to evaluate NASA countermeasures. The goal of this pilot study is to ascertain if Palmer may serve as a spaceflight analog option for ground validation of immune countermeasures.The study initiatedwith the crew deployed for winterover at Palmer in 2020.A second crew participated in the recently concluded WO2021 season.All participatingcrew havecollectedand preservedsaliva, plasma and hair samples. On location, the crewmembers alsoperformeda fingerstick blood collection for immediate analysis of basic peripheral leukocyte subsets. Preserved biosamples have beenreturned for analysis, with the WO2020 samples received, and the WO2021 samples currently en-route to Houston. It should be noted that COVID-19 had significant impacts on operations, including training and the collection of pre-mission baseline samples. Preliminary data from the 2020 crewmembers indicate that a relatively mild but detectable immune dysregulation persists at Palmer Station, including alterations in concentration of some plasma cytokines and consistent increases in the incidence of EBV reactivation. Final study data will be tabulated upon receipt of the 2021 crew samples.

Stephanie Krieger↗
DOE OSTI2018

TICAM-1 is dispensable in STING-mediated innate immune responses in myeloid immune cells

Highlights: • A previous paper described that STING signal requires TICAM-1 in mouse MEF. • We have checked TICAM-1 function in STING signal in macrophage/dendritic cells (DCs). • Unlike MEF, mouse macrophages and DCs respond to STING ligands without TICAM-1. • TICAM-1 is dispensable for STING signal in such myeloid cells. Stimulator of interferon genes (STING) is an essential molecule for the production of type I interferon (IFN), and other inflammatory cytokines, in response to cytosolic DNA. STING contributes to host defense against infection and anti-tumor responses. Previous reports have demonstrated that STING signaling is required by the adaptor Toll-IL-1 receptor-containing adaptor molecule-1 (TICAM-1), which has been identified as a TLR3-adaptor molecule using mouse embryonic fibroblasts. Here, we demonstrate that TICAM-1 does not affect STING-mediated innate immune responses, as increases in the mRNA expression levels of IFN-β, IL-6, and CCL5 were observed in bone marrow-derived or splenic myeloid cells. Moreover, STING ligand-enhanced co-stimulatory molecule expression, including CD80, CD86, and CD40, was detected on splenic CD11c + DCs, even in Ticam-1-deficient mice. Our results suggest that STING-mediated innate immune responses and dendritic cell maturation do not require TICAM-1 in myeloid lineage immune cells. TICAM-1 is ubiquitously expressed, even in cell types which do not express TLR3. Therefore, TICAM-1 may possess different functions depending on cell type and signaling purposes.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2014

2013 Immune Risk Standing Review Panel Evidence Review for: The Risk of Crew Adverse Health Event Due to Altered Immune Response

The 2013 Immune Risk Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on February 3-4, 2014. The SRP reviewed the new Evidence Report for the Risk of Crew Adverse Health Event Due to Altered Immune Response (from here on referred to as the 2013 Immune Evidence Report), as well as the Research Plan for this Risk that is in the current version of the Human Research Program’s (HRP) Integrated Research Plan (IRP).

Steinberg, Susan↗
NASA NTRS2003

Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. I. Immune population distributions

There are several aspects of the spaceflight environment that may lead to changes in immunity: mission-related psychological stress, radiation, and changes in gravity. On December 5, 2001, the space shuttle Endeavor launched for a 12-day mission to examine these effects on C57BL/6 mice for the first time. On their return, assays were performed on the spleen, blood, and bone marrow. In response to flight, there were no significant differences in the general circulating leukocyte proportions. In contrast, there was an increase in splenic lymphocyte percentages, with a corresponding decrease in granulocytes. There was an overall shift in splenic lymphocytes away from T cells toward B cells, and a decrease in the CD4-to-CD8 ratios due to a decrease in T helpers. In contrast, there were proportional increases in bone marrow T cells, with decreases in B cells. Although the blast percentage and count were decreased in flight mice, the CD34(+) population was increased. The data were more consistent with a shift in bone marrow populations rather than a response to changes in the periphery. Many of the results are similar to those using other models. Clearly, spaceflight can influence immune parameters ranging from hematopoiesis to mature leukocyte mechanisms.

Non-NASA Center↗
DOE OSTI2019

Foreground-Immune Cosmic Microwave Background Lensing with Shear-Only Reconstruction

Cosmic microwave background (CMB) lensing from current and upcoming wide-field CMB experiments such as AdvACT, SPT-3G and Simons Observatory relies heavily on temperature (versus polarization). In this regime, foreground contamination to the temperature map produces significant lensing biases, which cannot be fully controlled by multifrequency component separation, masking, or bias hardening. Here in this Letter, we split the standard CMB lensing quadratic estimator into a new set of optimal “multipole” estimators. On large scales, these multipole estimators reduce to the known magnification and shear estimators, and a new shear B-mode estimator. We leverage the different symmetries of the lensed CMB and extragalactic foregrounds to argue that the shear-only estimator should be approximately immune to extragalactic foregrounds. We build a new method to compute, separately and without noise, the primary, secondary, and trispectrum biases to CMB lensing from foreground simulations. Using this method, we demonstrate that the shear estimator is, indeed, insensitive to extragalactic foregrounds, even when applied to a single-frequency temperature map contaminated with cosmic infrared background, thermal Sunyaev-Zel’dovich, kinematic Sunyaev-Zel’dovich, and radio point sources. This dramatic reduction in foreground biases allows us to include higher temperature multipoles than with the standard quadratic estimator, thus, increasing the total lensing signal-to-noise ratio beyond the quadratic estimator. In addition, magnification-only and shear B-mode estimators provide useful diagnostics for potential residuals.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS1998

Studies of Cell-Mediated Immunity Against Immune Disorders Using Synthetic Peptides and Rotating Bioreactor System

We conducted a series of experiments using mouse immune-precursor cells, and observed that bioreactor culturing results in the loss of antigen-specific cytotoxic T lymphocyte (CTL) function. The reason for the abrogation of CTL function is microgravity conditions in the bioreactor, but not the antigen per se or its MHC restriction. Similarly, we observed that allostimulation of human PBMC in the bioreactor, but not in the T flask, resulted in the blunting of both allo-CTL function and the NK activity, indicating that the microgravity-associated functional defects are not unique to the mouse system. These results provide further confirmation to the microgravity-associated immune dysfunction, and constitute ground-based confirmatory data for those related to space-travel.

Sastry, Jagannadha K.↗