This viewgraph presentation reviews the lessons learned from manned space flight on the International Space Station. The contents include: 1) Overview of space flight effects on crewmembers; 2) General overview of immune system; 3) How does space flight alter immune system? 4) What factors associated with space flight inteact with crewmember immune function and impact health risks? 5) What is the current understanding of space flight effects on the immune system? and 6) Why should NASA be interested in immunology? Why is it significant

Sams, Clarence F.

NASA Technical Reports Server

The Human in Space:
Lessons from ISS 
Clarence F. Sams, Ph.D.
NASA/JSC
https://ntrs.nasa.gov/search.jsp?R=20090031882 2019-08-30T07:52:33+00:00Z
Content
• Overview of space flight effects on crewmembers
• General overview of immune system
• How does space flight alter immune system?
• What factors associated with space flight interact 
with crewmember immune function and impact 
health risks?
• What is the current understanding of space flight 
effects on the immune system?
• Why should NASA be interested in immunology? 
Why is it significant?
Consists primarily of white blood cells 
(WBCs) located in lymph nodes, the 
peripheral blood and other tissues. 
Responsible for protection against viruses 
and bacteria, tumor surveillance, wound 
healing, etc.
Dysfunction results in increased infection 
rate, malignancy, autoimmunity, allergy, 
etc.
THE IMMUNE SYSTEM
IMMUNE SYSTEM
Innate Immunity
• Barriers to Infection
1. Non-Specific Chemicals
2. Non-Specific Cells
3. Microbial Flora
Acquired Immunity
• Lymphocytes
1. B-cells
• Plasma cells
• Memory cells
2. T-Cells
• First line defense acting 
within mins-hrs
• Is a primitive response, 
largely conserved 
throughout evolution
• Non-specifically defends 
the body against 
infection
• Late response
• Recognizes and attacks 
specific protein sequences of 
the foreign “intruder,” it also 
remembers them 
HUMAN 
BLOOD 
CELLS
+WHITE BLOOD CELLS RED BLOOD CELLS
GRANULOCYTES                           MONOCYTES                        LYMPHOCYTES
NEUTROPHILS           BASOPHILS         EOSINOPHILS
CD4+             CD8+
Th1           Th2 Memory          Naive
‘Helper’                   ‘Cytotoxic’
T CELLS          B CELLS          NK CELLS
Type 1 & Type 2 cytokine Response
IL-2
IFN-γ
IL-12
IL-4
IL-5
IL-10
Type 2Type 1
Cell-mediated Immunity,
Delayed Hypersensitivity
Humoral Immunity,
B cell differentiation
Content
• General overview of immune system
• How does space flight alter immune system?
• What factors associated with space flight interact 
with crewmember immune function and impact 
health risks?
• What is the current understanding of space flight 
effects on the immune system?
• Why should NASA be interested in immunology? 
Why is it significant?
Cardiovascular
↑ resting heart rate
↑ stroke volume early in flight
↑ PACs & PVCs
↓ fluid volume
↓ orthostatic tolerance
↓ aerobic & anaerobic capacity
↓ resting blood pressure postflight
↓ central venous pressure (indirect)
↓ cardio/thoracic (CK) ratio postflight
Ocular
↑ intraocular pressure in flight
↑ retinal blood vessel constriction
postflight
↓ visual motor task performance
↓ contrast discrimination
↓ visual field postflight
↓ intraocular pressure postflight
Neurosensory
↑ vestibular disturbances
↑ space motion sickness
early in flight
↓ postural stability
↓ sensorimotor function
Body Fluids
↑ hemoglobin & hematocrit 
postflight
↓ total body water
↓ plasma & urine volumes
postflight
Electrolytes
↑ urinary Ca, PO4 postflight
↓ plasma K & Mg postflight
↓ urinary Na, K, Cl, Mg
Hormones
↑ plasma ADH, ANF
↑ urinary aldosterone
↑ urinary ADH, cortisol postflight
↓ urinary epinephrine,
androsterone postflight
↓ plasma ACTH, aldosterone,
cortisol
Metabolites
↑ plasma glucose, creatinine, BUN
postflight
↓ albumin, cholesterol,
triglycerides, uric acid
Musculoskeletal/Bone
↓ muscle mass
↓ muscle endurance & strength
↓ bone mineral content
↓ bone integrity
Adaptations to Long-Duration Space Flight
Integrating Hypothesis: 
Stress-induced Dysregulation
Characteristics of the mission and  the spacecraft 
environment represent a physiological and 
psychological stress to the crewmember.  
Regulation of the  immune system is altered during 
the period of stress and such alterations may 
induce specific medical risks to the crews.
IMMUNE DYSREGULATION
CRF, ACTH, Cortisol &
Other Pituitary - Adrenal Hormones
Modulate Immune Function
Latent virus
Reactivation
Space Flight
Hypersensitivity
& allergies
Delayed healing
Increased
infections Autoimmune 
disorders
Reduced tumor 
surveillance
Increased cancer 
risk
Content
• General overview of immune system
• How does space flight alter immune system?
• What factors associated with space flight interact 
with crewmember immune function and impact 
health risks?
• What is the current understanding of space flight 
effects on the immune system?
• Why should NASA be interested in immunology? 
Why is it significant?
Immune system 
function
Environmental
risk factors
• microgravity
• radiation
• others
Crewmember Health:
a balancing act
Interplay of factors determines health outcome
Spacecraft Environmental Factors
• crowded, closed environment
• recycled air & water
• potential toxic exposures
• microgravity
• particulate exposures
• limited personal hygiene
• skin abrasion/injury
• continuous radiation 
exposure
• altered growth/virulence
• unique microbial ecosystem
• unique challenge scenarios
• psychological, physical stress
Unique challenge scenarios
• Due to microgravity there is 
increased potential for 
mucosal ocular exposure
• Systems failures may 
aggravate problem
• Some opportunistic pathogens 
may infect unique locations 
due to microgravity supported 
transmission routes
Continuous radiation exposure
• Radiation exposure can be 
significant for LD flight 
and exploration sorties
• Radiation directly reduces 
immune function
• Immune system restricts 
tumor development
• Interplay between these 
factors potentially 
increases crew risks
Content
• General overview of immune system
• How does space flight alter immune system?
• What factors associated with space flight interact 
with crewmember immune function and impact 
health risks?
• What is the current understanding of space flight 
effects on the immune system?
• Why should NASA be interested in immunology? 
Why is it significant?
• Reduced blastogenic response
• Altered cytokine production
• Decreased NK cell function
• Altered phagocytosis and oxidative burst
• Changes in circulating leukocyte populations
– Increased granulocytes
– Decreased lymphocytes and NK cells
– Variable monocyte changes
Immune Responses to Space Flight
(Pre- vs. Postflight)

Neutrophils: Decreased Function
Innate Immunity Responses to flight
Monocytes: Decreased Function
NK-Cells: Decreased Function
Phagocytosis ↓
Oxidative Burst ↓
Degranulation:  No Change
Kaur et al. Brain, Behavior, & Immunity, 2004
Phagocytosis ↓
Oxidative Burst ↓
Degranulation ↓
Kaur et al. Brain, Behavior, & Immunity, 2005
Cytotoxicity ↓
Mehta et al., J. Applied Physiology 2001
• Decreased cell-mediated 
immune function
• Distinct inflight and 
postflight circulating WBC 
phenotype
• Potentially altered NK cell 
function
• Normal antibody response 
to vaccination
• Altered in vitro lymphocyte 
activation & migration
Immune Responses to Space Flight
(during flight)
in vivo Cell-Mediated Immunity 
reduced during flight
• Cell- mediated immunity tested during short and 
long duration flight
• Used commercial CMI multi-test assay
– 7 antigen test panel and control
– Configured into applicator device
• Reduced response observed in both short and 
long-duration crewmembers
• Similar observations from analogue studies
010
20
30
40
50
L - 150 L - 35 FD - 11 R + 0 R + 9
DAY
NK Cells
%
 o
f t
ot
al
 ly
m
ph
oc
yt
es
Natural Killer Cells decrease postflight
l NK cells decreased 
after landing
l NK cell cytotoxicity 
decreased at landing
l Potentially decreased 
function during long 
duration flight
Lymphocytes decrease postflight
0
10
20
30
40
50
L - 150 L - 35
Ly
m
ph
-3
 p
ar
t d
iff
.
FD - 11 R + 0 R + 9
DAY
Lymphs
• Lymphocytes decrease 
on landing day
• Numbers return to 
baseline within 3 days
• Mitogen-induced 
proliferation is lower
• May reflect delayed S-
phase entry
Granulocytes increase postflight
• Granulocytes increase at 
landing
• Demargination of  grans 
into circulation
• Similar to changes  
induced with exercise
• Resolves quickly after 
landing (3 days) 0
20
40
60
80
100
L - 150 L - 35 FD - 11
G
ra
ns
 - 
3 
pa
rt 
di
ff.
R + 0 R + 9
DAY
Grans
Overview of in-flight phenotype
• Gross phenotype of circulating WBCs late in-
flight similar to pre-flight values
• Landing day phenotype significantly altered
• Must be factored into assessments of pre- & post 
studies of immune system
• Post-flight analysis may not reflect in-flight 
functional status
Humoral Immunity 
Experimental Objectives
Determine ability of crewmembers to 
respond to an immune challenge 
during flight
Method:
Assess antigen specific response to an 
immunization during space flight
1) vaccinate crewmember inflight
2) measure antibody response 
First vaccination of a crewmember 
during flight
• elderly individuals with 
depressed immune systems
• AIDS patients
• patients on life support
• patients in confined 
environments (ICUs, rest 
homes, etc)
• Pneumococcal vaccine    
selected for use 
• Vaccine is used to prevent   
respiratory infections 
• 2 million doses/year US
• Low incidence of adverse 
events  
Target PopulationVaccine
Response to immunization
403020100
0
1000
2000
type 3
type 7F
type 9N
type 14
Days after immunizat ion
Average antibody titers 
   (control subjects) 
Se
ru
m
 A
nt
ib
od
y 
T
ite
rs
   
   
(n
g 
A
b 
N
/m
l)
Protective antibodies
are produced within
2-4 weeks after the 
Immunization
Doubling of  baseline 
antibody titer or 
levels exceeding 800 
ng Ab N/ml are 
positive
Experiment timeline
L-150 L-30 TO 14
I+0        +7    +11   +14   +17  +21       +28
Two preflight samples
Approximately mid-mission 
a) in-flight baseline
b) immunization
Post immunization samples at
7, 11, 14, 17, 21 & 28 days 
Launch
TP-9N
0
1
2
3
4
5
6
7
8
I-0 I+7 I+11 I+14 I+17 I+21 I+28
Control
Flight
TP-12F
0
1
2
3
4
5
6
7
8
9
I-0 I+7 I+11 I+14 I+17 I+21 I+28
Control
Flight
TP-7F
0
1
2
3
4
5
6
7
8
9
10
I-0 I+7 I+11 I+14 I+17 I+21 I+28
Control
Flight
TP-8
0
1
2
3
4
5
6
7
8
9
I-0 I+7 I+11 I+14 I+17 I+21 I+28
Control
Flight
Overview of HI Results
• All crewmembers responded well to all 
measured antigens compared to control groups
• 2 of 7 crewmembers immunized during flight 
developed significant injection site reactions
• One of approx 24 control subjects had 
reportable adverse response to vaccination
• Possible increased hypersensitivity response 
during space flight
• Data from HI study suggests humoral immunity 
is not reduced by space flight
Cellular studies indicate reduced 
immune cell function in microgravity
• Reduced proliferation
• Reduced migration
• Altered signal transduction
• Altered cytoskeletal structure
• Indicates sensitivity of immune 
cell to mechanical forces 
• Reflects a direct effect of 
microgravity on cells
T CELL ACTIVATION
1xG
T CELL ACTIVATION
0xG (clinorotation)
Summary Immune Observations
• Reduced cell-mediated immunity
• Humoral function maintained
• Possible increased allergic hypersensitivity
• Altered cytokine patterns
• Data suggest a dysregulation of immune 
system
• Data are consistent with that observed in 
some model scenarios
Inflight studies are relatively simplistic due to 
operational constraints
Further assessment of immune status during flight is 
required for determining immune-related crew 
health risks
Limitations of currently available data
Pre- and postflight data may not accurately reflect
immune parameters existing during flight
-effects of reentry and re-ambulation
-time before assay (recovery effects)
Some systems have received little study
-Target specific cellular responses
Content
• General overview of immune system
• How does space flight alter immune system?
• What factors associated with space flight interact 
with crewmember immune function and impact 
health risks?
• What is the current understanding of space flight 
effects on the immune system?
• Why should NASA be interested in immunology? 
Why is it significant?
– Relationship to immune standards
– Relationship to Immune SMO
Immune-Related Disorders
With Potential Mission Impact
• respiratory congestion
• infections 
• delayed healing of wounds
• hypersensitivity/allergic 
reactions
• rashes/skin disorders
• reactivation of latent 
viruses
INFECTIOUS DISEASES IN ASTRONAUTS
STS-1 Through STS-108
Source: Medical Informatics & Health Care Systems Branch Epidemiology Section; July 2002
• Fungal infections
• Flu-like syndrome
• Urinary tract infections
• Aphthous stomatitis
• Viral gastrointestinal disease
• Subcutaneous skin infections
• Other viral diseases
• URI (common cold, sore throat)
• Sty
IMMUNE-RELATED SYMPTOMS
• Allergic rhinitis
• Hypersensitivity
• Coughing/Sneezing
• Rashes/Skin disorders
• Infections
• Delayed wound healing
Critical immune events
• Considered de-orbiting crewmember due to a 
sustained contact hypersensitivity (28 days)
• UTI that progressed to near sepsis
• Pronounced injection site reactions during 
vaccination (2 of 7 inflight, no equivalents in 24 
ground)
• Significant hypersensitivity or infection can 
threaten crewmember within course of mission
• Will present as challenge/response problem
Exploration Concerns
• Infections or hypersensitivity can progress to critical within course 
of mission
– Appear to have heightened hypersensitivity and reduced CMI
• CMI performs tumor surveillance and restricts latent virus 
expression.  
– appears to be down regulated during flight
– may interact with radiation increasing risk of tumors
• Immune system has an integrating role in maintenance of some 
other systems (e.g., bone)
• Viral reactivation approaches clinical thresholds and has unique 
characteristics not common terrestrially
• Understanding this system is necessary to set requirements for 
vehicle and ops 
Bone and Immune
• Cytokines directly modulate bone 
metabolism
• Immune cells produce bone regulatory 
factors
• Immune cells interact with bone cells at 
sites of remodeling
• Immune cells are involved in osteoclast 
differentiation and development
• Evidence for burst of osteoclast production 
early in flight
RANK picture
Immune standard
• Written to terrestrial clinical limit values 
• Values chosen for lack of ambiguity in terrestrial clinical settings
• Std indicates immune monitoring must be performed but does not 
define full scope
• Immune SMO is designed to develop this immune monitoring 
strategy
– Will fill existing knowledge gap for immune changes during flight
– Allow evidence-based risk prediction
• Immune SMO will also require improved clinical incidence 
tracking
Conclusion
• Critically need to close the knowledge gap of 
what happens to immune system during flight
• Immune SMO is required to do this
• Completion of SMO will support revision of 
standards and risk assessments
• Remaining time is very limited to accomplish this 
within life of ISS


The Human in Space: Lesson from ISS

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