Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station (Functional Immune) - 10.04.18

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Science Objectives for Everyone
The human immune system is altered during spaceflight, which may increase the likelihood of adverse health events in crew members. The Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station (Functional Immune) investigation analyzes blood and saliva samples to determine the changes taking place in crew members’ immune systems during flight. The changes in the immune system are also compared with crew members’ self-reported health information. Results are expected to provide new insight into the possible health risks of long-duration space travel, including future missions to Mars, asteroids, or other distant destinations.
Science Results for Everyone
Information Pending

The following content was provided by Brian E. Crucian, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Functional Immune

Principal Investigator(s)
Brian E. Crucian, Ph.D., NASA Johnson Space Center, Houston, TX, United States
Honglu Wu, Ph.D., NASA Johnson Space Center, Houston, TX, United States
Richard J. Simpson, Ph.D., Department of Health and Human Performance, Houston, TX, United States
Kanokporn Rithidech, Ph.D., State University of New York Stony Brook School of Medicine, Stony Brook, NY, United States

Duane L. Pierson, Ph.D., NASA Johnson Space Center, Houston, TX, United States
Satish K. Mehta, Ph.D., Enterprise Advisory Services Incorporated, Houston, TX, United States
Raymond P. Stowe, Ph.D., Microgen Laboratories, La Marque, TX, United States
Alexander Choukèr, M.D., University of Munich, Munich, Germany
Robert J. Ploutz-Snyder, Ph.D., University of Michigan School of Nursing, Ann Arbor, MI, United States
Hawley E. Kunz, Ph.D., KBRwyle, Houston, TX, United States

NASA Johnson Space Center, Human Research Program, Houston, TX, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
NASA Research Office - Human Research Program (NASA Research-HRP)

Research Benefits
Scientific Discovery, Earth Benefits, Space Exploration

ISS Expedition Duration
September 2016 - April 2019; -

Expeditions Assigned

Previous Missions
Integrated Immune

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Experiment Description

Research Overview

  • The Functional Immune Alterations, Latent Herpes Virus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station (Functional Immune) investigation builds on previous research completed during the Integrated Immune Study.
  • This study analyzes ambient, live blood samples, saliva samples, urine samples, and skin swabs.
  • Previously uninvestigated areas of immunity and latent viral reactivation are examined, as well as other interdisciplinary physiological interactions.
  • Data is collected on the in-flight incidence of adverse clinical events and medication usage, to correlate with immune alterations.
  • This study aims to completely characterize many aspects of immune-regulation as they occur during flight.
  • Information obtained from this investigation can be used to assess the need for immune countermeasures to maintain and protect crew health on deep space missions.


The Functional Immune Alterations, Latent Herpes Virus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station (Functional Immune) experiment is a comprehensive immunity flight investigation that uses longitudinally repeated measures to assess several aspects of immunity during long-duration spaceflight. This builds on the successful sampling architecture of the former Integrated Immune flight study, which for the first time returned ambient, live blood samples from space to allow for cellular functional assays. Blood (ambient, live) and saliva samples are collected before, during, and following spaceflight. Previously uninvestigated live cell assays are performed to assess cellular function during spaceflight. Unique, solicited content from external investigators assess natural killer cell and dendritic cell function, DNA breaks, transcriptomics, and proteomics. Measures of inflammation, stress, antimicrobial activity, etc. are assessed in blood, saliva, and/or urine. The reactivation of a panel of herpes viruses is assessed both during flight and post-flight until shedding resolves. Array technology is utilized to allow maximal information to be derived from minimal in-flight samples. Additionally, a swab of any inflight rash that might develop is requested if the crewmember is willing. After collection, the swab is frozen until return to Earth, where it is analyzed.
Functional Immune has three aims:
  1. To examine the effect of spaceflight on previously uninvestigated areas of innate and adaptive immunity. Innate immunity can be described as nonspecific and immediate cellular responses. Adaptive immunity is that portion of the immune system that is composed of a specific response to a particular pathogen. Therefore, adaptive responses take several days for the proper specific immune cells to develop and complete their function.
  2. To determine the effect of spaceflight on various soluble markers of in-vivo immune physiological status, including plasma, salivary and urinary markers of stress, inflammation, cytokine profiles, and latent viral reactivation.
  3. To correlate, when possible, findings of immune status with astronaut environmental, human, and stress factors such as sleep/wake data, crew work schedules, surveys of in-flight symptomology and/or medication use (voluntary), vehicle docking/undocking, EVA activity, etc. This correlative work should help to inform NASA’s scientific and operational communities about the influence of spaceflight specific environmental factors on immunity, factors which may potentially be modulated in accordance with countermeasures development.

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Space Applications
Previous research has shown crew members experience alterations in their immune systems during spaceflight, but this investigation is the first to examine unique immune-related changes, such as the distribution of white blood cells, particular aspects of innate immunity, and reactivation of latent viruses. Biological changes are also compared with crew members’ self-reported information on stress, sleep disruption and other factors that are known to impact the immune system. By understanding spaceflight-related immune system challenges, countermeasures that can keep the crew healthy on future missions can be devised, if they are needed.

Earth Applications
The immune system works unnoticed to protect the body, but alterations in immunity may be linked to the onset of disease and development of symptoms. This study provides a unique view of the subtle changes in the immune system that may occur before symptoms present, such as those associated with stress or microgravity. Understanding these subtle changes may help scientists pinpoint the onset of illness, and suggest monitoring strategies, or treatments, that can boost the immune system and prevent full-blown infections and diseases.

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Operational Requirements and Protocols

Functional Immune requires 10 inflight subjects.
Pre-flight at Launch (L)-180 days and again at L-45 days, blood, urine, and saliva samples are collected and a health questionnaire is completed. Three types of saliva samples are obtained. Liquid saliva samples are collected by rolling a nylon swab from cheek to cheek allowing the swab to get completely saturated. This occurs once a day over five consecutive days and is associated with the blood collections. A second liquid saliva sample is collected once per sampling session on the day of the blood draw and is obtained by a passive drool method. Dry saliva samples are collected using the Dry Saliva Booklet at prescribed intervals throughout a single day. Each sample is collected on a separate page of the booklet corresponding to the prescribed time interval (Wake, Wake +30 min, Wake +6 hours, Wake +10 hours, Retire).
In-flight at approximately mid-mission and again at Return (R)-1 day, blood samples are collected. These samples remain ambient through return to the ground via Soyuz. Additionally, saliva samples (liquid samples using nylon swabs that are frozen, and dry samples using a booklet that remain ambient) are collected. A health questionnaire is completed at the mid-mission point only. Neither urine nor passive drool saliva collections are performed on-orbit.
Swabs (for skin samples) may be collected and frozen at crew discretion up to two times during the flight.
Liquid saliva samples and swabs are stored in the Minus Eighty-Degree Laboratory Freezer for ISS (MELFI) and remain frozen through return on the next available flight. Blood samples remain ambient and are returned to the Principal Investigator on the ground via Soyuz spacecraft within 48 hours of collection, so blood should be drawn as close to hatch closure as possible. Dry book saliva samples also remain ambient and return to Earth with the blood samples.
Health Questionnaires are completed using the Data Collection Tool (DCT) and are downlinked to the ground.
Post-flight at each of R+1, R+30, and R+90, blood, urine, and all three types of saliva samples are collected, and a health questionnaire is completed.

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Decadal Survey Recommendations

Animal and Human Biology AH13
Animal and Human Biology AH14

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Results/More Information

Information Pending

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Related Websites

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NASA Image: ISS030E257689 - European Space Agency (ESA) Andre Kuipers, Expedition 30 Flight Engineer (FE), during Integrated Immune Blood Sample Draw at the Human Research Facility (HRF), in the Columbus Module. Photo taken during Expedition 30.

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