The Effects of Spaceflight on the Immune System

1. 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

2. 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.

3. How the Immune System Works:Cell 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/immune00.htm

4. 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/immune00.htm

5. Two types of Immunity: Innate and Acquired

6. 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

7. 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.

8. 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.

9. 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

10. Macrophages and their role with respect to T cells and B cells: Antibody Production

11. 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/immune00.htm

12. 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!!

13. Bone marrow Stem cells Differentiation • T-cells • Helper T-cells • Cytotoxic T-cells • Natural Killer Cells • B-cells • Turn into plasma cells • Secrete antibodies

14. Thymus • Two functions: • BM T-cell maturation • Release of mature T-cells into bloodstream BM = bone marrow

15. 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.

16. 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

17. Reviewing Article in Time Life Magazine: http://www.westom.com/coolsite/life_imm.htm

18. 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?

19. Space Flight-related Factors Affecting Immunity • Nutrition / SMS • Circadian rhythm and sleep patterns • Radiation? • Stress? • Other effects?

20. 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

21. 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

22. 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.

23. 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.

24. 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.

25. 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

26. 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)

27. Analogous environments on Earth • Submarines • Polar stations • Oil platforms • Stressors: • Confinement • Sociological dynamics of isolation

28. Analogous environments on Earth • Deep sea labs • In case of emergency, immediate return to Earth’s surface is not viable • Astronauts, just like deep sea divers, experience the confinement of a decompression chamber before an EVA

29. 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)

30. STS-107 Experiments • Stress and the immune system • Two experiments: • Impairment of system’s ability to fight infections? (innate immunity) • Stress-related reactivation of latent viruses? (acquired immunity)

31. STS-107 Experiments Stress compromises the immune system by releasing hormones that make the body prone to infection and viral reactivation.

32. STS-107 Experiments Some viruses remain latent within the body and are never expressed until sufficient immunosuppression occurs (i.e. Herpes)

33. STS-107 Experiments Astronauts have reported a reduced ability to recover from cuts and abrasions in microgravity.

34. 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.

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

36. 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

37. Take home lessons • The immune system’s 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).

38. 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).

39. Good Sources • National Cancer Institute http://press2.nci.nih.gov/sciencebehind/immune/immune00.htm • The On-line Medical Dictionary • http://cancerweb.ncl.ac.uk/cgi-bin/omd?action=Home&query= • How Stuff Works http://www.howstuffworks.com/immune-system.htm • The Inner Body http://www.innerbody.com/image/lympov.html

40. Questions?