The Effects of Spaceflight on the Immune System

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The Effects of Spaceflight on the Immune System

• Crash course on the immune system
• Space Flight-related factors to immunosuppression
• Current knowledge
• STS-107 experiments
• BioMEMS sensor

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What is the Immune System?

• It is a complex network of organs, chemicals and
  specialized cells that work together to protect
  the body from foreign or local damaging material.

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How the Immune System WorksCell recognition

• One of the primary functions of the immune system
  is to distinguish between self and non-self
  cells.
• Problem in organ transplant.

http//press2.nci.nih.gov/sciencebehind/immune/imm
une00.htm
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Substance Recognition

• Antigens are substances that are capable of
  triggering an immune response.
• Foreign molecules carry distinctive markers that
  differentiate them.

http//press2.nci.nih.gov/sciencebehind/immune/imm
une00.htm
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Two types of Immunity

• Innate and Acquired

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Innate Immunity

• We are born with it.
• Physical barriers skin, mucous membranes
• Protective chemicals acid pH, surface lipids
• Enzymes saliva, digestive tract enzymes
• Macrophages and complement
• Non-specific to antigens

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Acquired Immunity

• Antigen-specific recognizes antigens, which can
  be proteins, carbohydrates, lipids and nucleic
  acids.
• Memory results in increased reactivity upon
  repeated exposures to the antigen or infectious
  agent (i.e. vaccines).
• Regulation discriminates between self and
  non-self, prevents autoimmune reactions in most
  individuals.

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Cells of the Immune System

• T-cells
• Helper T-cells (CD4)
• Coordinators of immune regulation (cytokines)
• Augment or tone down immune responses
• Cytotoxic Killer Cells (CD8)
• Deal with tumor and virus infected cells
• Natural Killer Cells (CD8)
• Also deal with tumor cells, but do not need to
  pass through the lymphoid organs.

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Cells of the Immune System

• B-cells
• Plasma cells
• Antibody production.
• Antibodies initiate the complement destroying
  cascade (chemically punctures antigens).
• Macrophages
• T-cell and B-cell stimulation

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Macrophages and their role with respect to T
cells and B cells Antibody Production
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The Organs of the Immune System The Bone Marrow

• Spongy tissue found in the center of most large
  bones
• All cells in the IS initially derive from it
• Produces RBCs and platelets

http//press2.nci.nih.gov/sciencebehind/immune/imm
une00.htm
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The Organs of the Immune System The Bone Marrow

• Stem cells, reside within the BM (unspecialized
  cells)
• Most radiation sensitive tissue of the human
  body!!

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Bone marrow
Stem cells
Differentiation

• T-cells
• Helper T-cells
• Cytotoxic T-cells
• Natural Killer Cells

• B-cells
• Turn into plasma cells
• Secrete antibodies

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Thymus

• Two functions
• BM T-cell maturation
• Release of mature T-cells into bloodstream

BM bone marrow
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Spleen

• Immunological filter of the blood.
• Antigens are brought by macrophages or carried by
  the blood itself. B and T-cells are activated.
• Old RBCs are destroyed.

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Lymph Nodes

• Immunological filters of the body fluid called
  lymph.
• Lymph is drained from most of our tissues.
• Antigens are filtered before returning to
  circulation.

http//www.innerbody.com/image/lympov.html
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Reviewing
Article in Time Life Magazine http//www.westom.c
om/coolsite/life_imm.htm
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Space Flight-related Factors Affecting Immunity

• Launch/Landing
• Weightlessness?
• Cephalic fluid shift
• Affects lymphatic system (lymph nodes)
• Loss of body fluid affects plasma protein
  concentration and osmolality
• Bone loss?

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Space Flight-related Factors Affecting Immunity

• Nutrition / SMS
• Circadian rhythm and sleep patterns
• Radiation?
• Stress?
• Other effects?

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Current Studies

• Factors that can influence physiologic
  functions
• Microgravity
• Isolation
• Radiation
• Microbial contamination
• Sleep disruption
• Insufficient nutrition
• Interaction with other body systems (pituitary
  gland)

Sonnenfeld et. al, 2002
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Current Studies

• Stress-related immunosuppression
• Stressors
• Pre-flight physical training
• Discomfort of lift-off and landing
• Heavy in-flight work and exercise schedules
• Forced adaptation to the confined environment of
  the spacecraft

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Current Studies

• Observed changes
• Reduction in T-cell counts (cell-mediated
  immunity)
• Natural killer cells decrease in functionality
  and concentration.
• Constant immunoglobulin levels (antibodies)
• Immune cells mediators Interleukin-2 decreases.

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Radiation effects

• Radiation effects cumulative and long-term
  exposure promotes the formation of cancer and
  tumors
• Low-level ionizing radiation stimulates the
  immune system
• could reduce cancer frequency
• increase growth and longevity (factors that will
  be crucial to humans in interplanetary voyages )
• Bone marrow stem cell production impaired.

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Diet

• Astronauts are bound to the same recommended
  daily allowances (RDA) with regard to
  micronutrients as people on Earth.
• A decrease in the intake of necessary minerals
  and vitamins will certainly affect the immune
  system.

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Exercise

• Moderate exercise has been shown to enhance
  immune activity
• However, an increased load in exercise can also
  lead to an overall depression in certain immune
  responses
• augments chances for viral and bacterial attacks
• makes astronauts more susceptible to infection

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Exercise

• Effects such as protein aberrations were observed
  during the first Apollo flights that were not
  seen in the Skylab missions
• Major difference between the two programs an
  increased exercise load for the Skylab crews
  compared to their predecessors

(Criswell-Hudak, 1991)
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Analogous environments on Earth

• Submarines
• Polar stations
• Oil platforms
• Stressors
• Confinement
• Sociological dynamics of isolation

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Analogous environments on Earth

• Deep sea labs
• In case of emergency, immediate return to Earths
  surface is not viable
• Astronauts, just like deep sea divers, experience
  the confinement of a decompression chamber before
  an EVA

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Analogous environments on Earth

• On deep sea diving
• Neutrophil granulocyte (allergens) activity has
  been shown to increase
• Results in decreased resistance to skin and other
  infections.
• During early spaceflights astronauts frequently
  suffered from otitis and skin infections

(Benestad et al., 1990) (Schmitt and Schaffar,
1993)
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STS-107 Experiments

• Stress and the immune system
• Two experiments
• Impairment of systems ability to fight
  infections? (innate immunity)
• Stress-related reactivation of latent viruses?
  (acquired immunity)

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STS-107 Experiments

• Stress compromises the immune system by releasing
  hormones that make the body prone to infection
  and viral reactivation.

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STS-107 Experiments
Some viruses remain latent within the body and
are never expressed until sufficient
immunosuppression occurs (i.e. Herpes)
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STS-107 Experiments
Astronauts have reported a reduced ability to
recover from cuts and abrasions in microgravity.
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Immunological Analysis

• Collecting immunological data during flight is
  very difficult
• Blood samples degrade with time and do not
  represent current state.
• Traditional lab equipment is too big to fly and a
  hassle to operate.

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BioMEMS Sensor

• Monitor astronaut immune response
• Measure immune markers (i.e. Cytokines)
• Minimally invasive
• MEMS technology

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What are MEMS?

• Microelectromechanical Systems
• Integration of mechanical elements, sensors,
  actuators, and electronics on a common silicon
  substrate through microfabrication technology.
• Lab-on-a-chip
• In vitro (Ph.D. work)
• In vivo (ultimate goal)

Raiteri et. al, 2001
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Take home lessons

• The immune systems main functions
• Self vs. Non-self
• Foreign or domestic damaging cells
• It is composed of engulfing cells (Macrophages),
  coordinators (Helper T-cells), destroyers (Killer
  T-cells) and antibody producers (B-cells).

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Take home lessons

• There are several factors that may influence
  immunosuppression in space flight (stress,
  malnutrition, confinement, microgravity?), but up
  to now, the data is inconclusive due to the low
  frequency of experimentation.
• Better analytical techniques are needed to
  assess immune system status real-time (BioMEMS).

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Good Sources

• National Cancer Institute
• http//press2.nci.nih.gov/sciencebehind/immune/imm
  une00.htm
• The On-line Medical Dictionary
• http//cancerweb.ncl.ac.uk/cgi-bin/omd?actionHome
  query
• How Stuff Works
• http//www.howstuffworks.com/immune-system.htm
• The Inner Body
• http//www.innerbody.com/image/lympov.html

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Questions?