宇宙飞行对免疫的影响

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宇宙飞行对免疫的影响

  1. 1. The Effects of Spaceflight on the Immune System <ul><li>Crash course on the immune system </li></ul><ul><li>Space Flight-related factors to immunosuppression </li></ul><ul><li>Current knowledge </li></ul><ul><li>STS-107 experiments </li></ul><ul><li>BioMEMS sensor </li></ul>
  2. 2. What is the Immune System? <ul><li>It is a complex network of organs, chemicals and specialized cells that work together to protect the body from foreign or local damaging material. </li></ul>
  3. 3. How the Immune System Works: Cell recognition <ul><li>One of the primary functions of the immune system is to distinguish between self and non-self cells. </li></ul><ul><li>Problem in organ transplant. </li></ul>http://press2.nci.nih.gov/sciencebehind/immune/immune00.htm
  4. 4. Substance Recognition <ul><li>Antigens are substances that are capable of triggering an immune response. </li></ul><ul><li>Foreign molecules carry distinctive markers that differentiate them. </li></ul>http://press2.nci.nih.gov/sciencebehind/immune/immune00.htm
  5. 5. Two types of Immunity: Innate and Acquired
  6. 6. Innate Immunity <ul><li>We are born with it. </li></ul><ul><li>Physical barriers: skin, mucous membranes </li></ul><ul><li>Protective chemicals: acid pH, surface lipids </li></ul><ul><li>Enzymes: saliva, digestive tract enzymes </li></ul><ul><li>Macrophages and complement </li></ul><ul><li>Non-specific to antigens </li></ul>
  7. 7. Acquired Immunity <ul><li>Antigen-specific: recognizes antigens, which can be proteins, carbohydrates, lipids and nucleic acids. </li></ul><ul><li>Memory: results in increased reactivity upon repeated exposures to the antigen or infectious agent (i.e. vaccines). </li></ul><ul><li>Regulation: discriminates between self and non-self, prevents autoimmune reactions in most individuals. </li></ul>
  8. 8. Cells of the Immune System <ul><li>T-cells: </li></ul><ul><ul><li>Helper T-cells (CD4+) </li></ul></ul><ul><ul><ul><li>Coordinators of immune regulation (cytokines) </li></ul></ul></ul><ul><ul><ul><li>Augment or tone down immune responses </li></ul></ul></ul><ul><ul><li>Cytotoxic Killer Cells (CD8+) </li></ul></ul><ul><ul><ul><li>Deal with tumor and virus infected cells </li></ul></ul></ul><ul><ul><li>Natural Killer Cells (CD8+) </li></ul></ul><ul><ul><ul><li>Also deal with tumor cells, but do not need to pass through the lymphoid organs. </li></ul></ul></ul>
  9. 9. Cells of the Immune System <ul><li>B-cells: </li></ul><ul><ul><li>Plasma cells </li></ul></ul><ul><ul><ul><li>Antibody production. </li></ul></ul></ul><ul><ul><ul><li>Antibodies initiate the ‘complement’ destroying cascade (chemically punctures antigens). </li></ul></ul></ul><ul><li>Macrophages: </li></ul><ul><ul><li>T-cell and B-cell stimulation </li></ul></ul>
  10. 10. Macrophages and their role with respect to T cells and B cells: Antibody Production
  11. 11. The Organs of the Immune System: The Bone Marrow <ul><li>Spongy tissue found in the center of most large bones </li></ul><ul><li>All cells in the IS initially derive from it </li></ul><ul><li>Produces RBCs and platelets </li></ul>http://press2.nci.nih.gov/sciencebehind/immune/immune00.htm
  12. 12. The Organs of the Immune System: The Bone Marrow <ul><li>Stem cells, reside within the BM (unspecialized cells) </li></ul><ul><li>Most radiation sensitive tissue of the human body!! </li></ul>
  13. 13. Bone marrow <ul><li>B-cells </li></ul><ul><li>Turn into plasma cells </li></ul><ul><li>Secrete antibodies </li></ul><ul><li>T-cells </li></ul><ul><li>Helper T-cells </li></ul><ul><li>Cytotoxic T-cells </li></ul><ul><li>Natural Killer Cells </li></ul>Stem cells Differentiation
  14. 14. Thymus <ul><li>Two functions: </li></ul><ul><ul><li>BM T-cell maturation </li></ul></ul><ul><ul><li>Release of mature T-cells into bloodstream </li></ul></ul>BM = bone marrow
  15. 15. Spleen <ul><li>Immunological filter of the blood. </li></ul><ul><li>Antigens are brought by macrophages or carried by the blood itself. B and T-cells are activated. </li></ul><ul><li>Old RBCs are destroyed. </li></ul>
  16. 16. Lymph Nodes <ul><li>Immunological filters of the body fluid called lymph. </li></ul><ul><li>Lymph is drained from most of our tissues. </li></ul><ul><li>Antigens are filtered before returning to circulation. </li></ul>http://www.innerbody.com/image/lympov.html
  17. 17. Reviewing Article in Time Life Magazine: http://www.westom.com/coolsite/life_imm.htm
  18. 18. Space Flight-related Factors Affecting Immunity <ul><li>Launch/Landing </li></ul><ul><li>Weightlessness? </li></ul><ul><ul><li>Cephalic fluid shift </li></ul></ul><ul><ul><ul><li>Affects lymphatic system (lymph nodes) </li></ul></ul></ul><ul><ul><li>Loss of body fluid affects plasma protein concentration and osmolality </li></ul></ul><ul><ul><li>Bone loss? </li></ul></ul>
  19. 19. Space Flight-related Factors Affecting Immunity <ul><li>Nutrition / SMS </li></ul><ul><li>Circadian rhythm and sleep patterns </li></ul><ul><li>Radiation? </li></ul><ul><li>Stress? </li></ul><ul><li>Other effects? </li></ul>
  20. 20. Current Studies <ul><li>Factors that can influence physiologic functions*: </li></ul><ul><ul><li>Microgravity </li></ul></ul><ul><ul><li>Isolation </li></ul></ul><ul><ul><li>Radiation </li></ul></ul><ul><ul><li>Microbial contamination </li></ul></ul><ul><ul><li>Sleep disruption </li></ul></ul><ul><ul><li>Insufficient nutrition </li></ul></ul><ul><li>Interaction with other body systems (pituitary gland) </li></ul>*Sonnenfeld et. al , 2002
  21. 21. Current Studies <ul><li>Stress-related immunosuppression </li></ul><ul><li>Stressors: </li></ul><ul><ul><li>Pre-flight physical training </li></ul></ul><ul><ul><li>Discomfort of lift-off and landing </li></ul></ul><ul><ul><li>Heavy in-flight work and exercise schedules </li></ul></ul><ul><ul><li>Forced adaptation to the confined environment of the spacecraft </li></ul></ul>
  22. 22. Current Studies <ul><li>Observed changes: </li></ul><ul><ul><li>Reduction in T-cell counts (cell-mediated immunity) </li></ul></ul><ul><ul><li>Natural killer cells: decrease in functionality and concentration. </li></ul></ul><ul><ul><li>Constant immunoglobulin levels (antibodies) </li></ul></ul><ul><ul><li>Immune cells mediators: Interleukin-2 decreases. </li></ul></ul>
  23. 23. Radiation effects <ul><li>Radiation effects : cumulative and long-term exposure promotes the formation of cancer and tumors </li></ul><ul><li>Low-level ionizing radiation stimulates the immune system </li></ul><ul><ul><li>could reduce cancer frequency </li></ul></ul><ul><ul><li>increase growth and longevity (factors that will be crucial to humans in interplanetary voyages ) </li></ul></ul><ul><li>Bone marrow stem cell production impaired. </li></ul>
  24. 24. Diet <ul><li>Astronauts are bound to the same recommended daily allowances (RDA) with regard to micronutrients as people on Earth. </li></ul><ul><li>A decrease in the intake of necessary minerals and vitamins will certainly affect the immune system. </li></ul>
  25. 25. Exercise <ul><li>Moderate exercise has been shown to enhance immune activity </li></ul><ul><li>However, an increased load in exercise can also lead to an overall depression in certain immune responses: </li></ul><ul><ul><li>augments chances for viral and bacterial attacks </li></ul></ul><ul><ul><li>makes astronauts more susceptible to infection </li></ul></ul>
  26. 26. Exercise <ul><li>Effects such as protein aberrations were observed during the first Apollo flights that were not seen in the Skylab missions* </li></ul><ul><li>Major difference between the two programs: an increased exercise load for the Skylab crews compared to their predecessors </li></ul>*(Criswell-Hudak, 1991)
  27. 27. Analogous environments on Earth <ul><li>Submarines </li></ul><ul><li>Polar stations </li></ul><ul><li>Oil platforms </li></ul><ul><li>Stressors: </li></ul><ul><ul><li>Confinement </li></ul></ul><ul><ul><li>Sociological dynamics of isolation </li></ul></ul>
  28. 28. Analogous environments on Earth <ul><li>Deep sea labs </li></ul><ul><ul><li>In case of emergency, immediate return to Earth’s surface is not viable </li></ul></ul><ul><ul><li>Astronauts, just like deep sea divers, experience the confinement of a decompression chamber before an EVA </li></ul></ul>
  29. 29. Analogous environments on Earth <ul><li>On deep sea diving: </li></ul><ul><ul><li>Neutrophil granulocyte (allergens) activity has been shown to increase* </li></ul></ul><ul><ul><li>Results in decreased resistance to skin and other infections. </li></ul></ul><ul><li>During early spaceflights astronauts frequently suffered from otitis and skin infections** </li></ul><ul><ul><li>*(Benestad et al., 1990) </li></ul></ul><ul><ul><li>**(Schmitt and Schaffar, 1993) </li></ul></ul>
  30. 30. STS-107 Experiments <ul><li>Stress and the immune system </li></ul><ul><li>Two experiments: </li></ul><ul><ul><li>Impairment of system’s ability to fight infections? (innate immunity) </li></ul></ul><ul><ul><li>Stress-related reactivation of latent viruses? (acquired immunity) </li></ul></ul>
  31. 31. STS-107 Experiments <ul><li>Stress compromises the immune system by releasing hormones that make the body prone to infection and viral reactivation. </li></ul>
  32. 32. STS-107 Experiments Some viruses remain latent within the body and are never expressed until sufficient immunosuppression occurs (i.e. Herpes)
  33. 33. STS-107 Experiments Astronauts have reported a reduced ability to recover from cuts and abrasions in microgravity.
  34. 34. Immunological Analysis <ul><li>Collecting immunological data during flight is very difficult… </li></ul><ul><ul><li>Blood samples degrade with time and do not represent current state. </li></ul></ul><ul><ul><li>Traditional lab equipment is too big to fly and a hassle to operate. </li></ul></ul>
  35. 35. BioMEMS Sensor <ul><li>Monitor astronaut immune response </li></ul><ul><li>Measure immune markers (i.e. Cytokines) </li></ul><ul><li>Minimally invasive </li></ul><ul><li>MEMS technology </li></ul>
  36. 36. What are MEMS? <ul><li>Microelectromechanical Systems </li></ul><ul><ul><li>Integration of mechanical elements, sensors, actuators, and electronics on a common silicon substrate through microfabrication technology. </li></ul></ul><ul><li>Lab-on-a-chip </li></ul><ul><ul><li>In vitro (Ph.D. work) </li></ul></ul><ul><ul><li>In vivo (ultimate goal) </li></ul></ul>Raiteri et. al , 2001
  37. 37. Take home lessons <ul><li>The immune system’s main functions: </li></ul><ul><ul><li>Self vs. Non-self </li></ul></ul><ul><ul><li>Foreign or domestic damaging cells </li></ul></ul><ul><li>It is composed of engulfing cells (Macrophages), coordinators (Helper T-cells), destroyers (Killer T-cells) and antibody producers (B-cells). </li></ul>
  38. 38. Take home lessons <ul><li>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. </li></ul><ul><li>Better analytical techniques are needed to assess immune system status real-time (BioMEMS). </li></ul>
  39. 39. Good Sources <ul><li>National Cancer Institute </li></ul><ul><li>http://press2.nci.nih.gov/sciencebehind/immune/immune00.htm </li></ul><ul><li>The On-line Medical Dictionary </li></ul><ul><li>http://cancerweb.ncl.ac.uk/cgi-bin/omd?action=Home&query = </li></ul><ul><li>How Stuff Works </li></ul><ul><li>http://www.howstuffworks.com/immune-system.htm </li></ul><ul><li>The Inner Body </li></ul><ul><li>http://www.innerbody.com/image/lympov.html </li></ul>
  40. 40. Questions?

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