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Immunological System

Immunological System. Dr. Moran October 12, 2005 EXS 558. Review Questions #1, 2. 1.) TRUE/FALSE Normal and trained athletes have approximately the same resting cardiac outputs. 2.) Explain how this apparent discrepancy can occur.

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Immunological System

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  1. Immunological System Dr. Moran October 12, 2005 EXS 558

  2. Review Questions #1, 2 1.) TRUE/FALSE Normal and trained athletes have approximately the same resting cardiac outputs. 2.) Explain how this apparent discrepancy can occur. Endurance trained athletes have a larger stroke volume (EDV-ESV) than sedentary individuals and as a result have a lower resting HR. Recall that cardiac output (Q) equals the product of HR and SV.

  3. Review Question #3 3.) Explain the extent and mechanisms that blood is redistributed during exercise as opposed to at rest? At rest only ~16% of blood is directed towards skeletal muscle with the majority of blood flow going to internal organs (i.e. liver + kidneys). During exercise this % increases to 84%. This redistribution is possible through selective vasoconstriction and vasodilation of the vasculature system. Capillary diameter is manipulated through both (1) autoregulation and through (2) extrinsic neural control.

  4. Review Question #4 4.) Which of the following is NOT a function of blood? a.) buffer and balance acidic levels b.) regulate temperature c.) transport gas, nutrients, and wastes d.) metabolize plasma FFA

  5. Review Question #5 5.) Explain the changes in blood plasma and hematocrit following a marathon training program. Following endurance training the blood plasma levels increase as does the red blood cell count, however, since the blood plasma gains are greater than the RBC gains overall hematocrit levels are LOWER post-training program. An increased blood plasma level decreases blood viscosity and lowers systolic blood pressure, further aiding in oxygen transport.

  6. Review Question #6, 7 6.) TRUE/FALSE Due to the increased metabolic needs, the hemoglobin affinity of oxygen is increased when blood pH levels are lowered. 7.) This phenomenon is called _____________ THE BOHR EFFECT

  7. Review Question #8 8.) Explain the primary reasons why stroke volume values can be up to 60% higher in endurance trained athletes than sedentary people. The major reason that stroke volumes are increased in endurance trained athletes is because of positive changes of EDV. EDV can be increased through (1) increased left ventricle chamber size, (2) suctioning mechanism, (3) increased blood plasma levels.

  8. Review Question #9 9.) Explain the significance of the Frank-Starling mechanism. With an increased EDV the left ventricle walls becomes stretched stimulating the viscoelastic properties of the smooth cardiac muscle walls. This stretch allows a greater passive muscle contribution and thus a more powerful ejection force. As a result of the more forceful contraction less blood remains in the chamber and cardiac efficiency is improved.

  9. Review Question #10 10.) TRUE/FALSE The primary factor influencing V0 max is arteriovenous (A-V) oxygen difference. The primary factor is CARDIAC OUTPUT!!!

  10. Exercise Immunology “Exercise can be employed as a model of temporary immunosuppression that occurs after severe physical stress. Furthermore, exercise that is associated with muscle damage may represent a model of the acute-phase response to local injury” Pedersen & Nieman (1998)

  11. Two Sides of the “Immune” Coin • Immunological System & Exercise 1.) regular moderate exercise is beneficial to a person’s health by stimulating the immuno-response 2.) intense training may increase the athlete’s susceptibility to infection (i.e. upper respiratory infection) Research focused on the effect of exercise volume and intensity on the immune response!

  12. Functional Immune Divisions INNATE 1.) body’s natural response 2.) first line of defense against infectious agents 3.) does not get better from exposure (it is what it is) ADAPTIVE 1.) used if innate system unable to destroy infectious agent 2.) infectious-specific reaction 3.) has a memory 4.) antibodies produced to quickly & efficiently respond to infectious threats COMPLEMENT 1.) also part of innate system response 2.) includes: a.) lysozymes b.) phagocytes c.) natural killer (NK) cells

  13. Cells of the Immune System • Leukocytes (white blood cells) • Composed of: 1.) Lymphocytes (20%):have receptors for antigens a.) T cells: develop in thymus b.) B cells: develop in bone marrow c.) Natural Killer Cells (NKC) 2.) Monocytes (10%):produce cytokines (stimulate inflammatory response) 3.) Granulocytes (70%):part of initial response to foreign pathogens (PHAGOCYTOSIS) a.) Neutrophils: attracted to sites of infection/injury b.) Eosinophils: parasitic infection c.) Basophils & Mast Cells: allergies and inflammatory reactions

  14. Lymphocytes • Comprised of T cells, B cells, and NKC • each have separate function • T cells/B cells: major effectors of adaptive immunity • NKC: innate immunity capability • Part of initial immune system • Responsible for: 1.) produce cytokines 2.) producing antibodies 3.) cytotoxicity 4.) memories of previous infections

  15. What is phagocytosis? • Phagocytic cells brought to sites of infection and inflammation • Have surface receptors  increases affinity to variety of microorganisms • After attachment  phagocytes engulf and destroy microorganism

  16. Immunoglobulin (Antibodies) • Glycoproteins found in ALL bodily fluids • ALL antibodies  immunoglobins • But not vice-versa • Combat infections through direct & indirect means • DIRECT: bind to antigens on microorganisms to prevent it from entering host • INDIRECT: stimulate other phagocytic cells that kill organism (more prevalent) • 5 distinct classes

  17. Immunoglobin Classes (TABLE 5.1)

  18. Cytokines (TABLE 5.2) • Regulate growth factors • Involved with immediate inflammatory response • Soluble (in plasma) • Commonly types • Interleukuen (IL) • Inflammatory mediation • Enhance phagocytic function • Stimulate further cytokine function • IL-6: increased substantially following muscle damaging activity • IL-1β: elevated levels in brain following a faitguing downhill run in mice (Carmichael et al., 2005).

  19. IL-6 linked to Muscle Damage

  20. Complement System • Group of proteins found in blood • Primary Function: initiate and amplify inflammatory response • Biological Functions: 1.) recruit macrophages and neutrophils to site of injury 2.) lysis of bacteria 3.) opsonization of pathogens Opsonization = process that alters bacteria by adding an antibody (C3b-component), this increases the likelihood that they will be engulfed by phagocyte

  21. Opsonization & Phagocytosis

  22. Exercise Induced Changes • Leukocyte (including lymphocytes) Response A. Acute Exercise B.Long Term • Phagocytic Cell Function • Cytokines & Complement System • Immunoglobulins • Athlete Immune Reponse

  23. Leukocyte Effect of Acute Exercise • Circulating leukocyte [ ]’s ↑ after an acute bout of exercise • Most notable within neutrophils but also within monocytes and lymphocytes • Magnitude of change dependent on both DURATION and INTENSITY • Positive relationship • Short-duration, high intensity • 150-180% above resting values • Decline begins 30-60min post-exercise • Can remain elevated up to 2hrs depending on exercise dose

  24. Leukocyte Effect of Acute Exercise (continued) • Endurance Exercise • Circulating levels may increase 2-3 fold during exercise • May remain elevated up to 6hr post-exercise • Lymphocyte Response • Consistent increase during and immediately after exercise • After prolonged OR intense workouts NKC levels may be decreased below resting levels for several hours OR even days post-exercise

  25. NeutrophilEffect of Heavy Training Volume • Pyne et al. (1995) • Mature WBC • Represent about 54-65% of leukocyte count normally • Neutrophil counts were suppressed in elite swimmers following periods of heavy training • Counts raised during a “peaking” or tapering phase leading into the NCAA championships

  26. Natural Killer Cells (NKC) • Part of the initial immune response • Kill a large number of cells through secretion of toxic substances • Levels not affected during a 2.5-3.0 hour run • Levels diminished significantly for up to 6 hours post-operative • T cells and B cells (lymphatic tissue) display a similar trend during this experiment Leukocytes NKC

  27. NKC Following a Marathon • Baseline NKC values substantial higher • Substantial reduction following marathon • Implications? • Still at the sedentary values

  28. Leukocyte Effect of Long-Term Training • Research studies (cross sectional design) have shown no differences in athletes vs. nonathletes • BUT leukocyte values may be affected during periods of heavy training volume as opposed to smaller training volume

  29. Leukocyte Effect of Long-Term Training (continued) • Training Volume ↑ ↓ Leukocyte count • Increased susceptibility to infectious attack • Training Intensity ↑ no change in leukocyte count • Response also sensitive to type of exercise (aerobic vs anaerobic)

  30. Phagocytic Cell Function • Increased circulating phagocytic values does NOT indicate anything about cell function (be careful not to assume activity when reading articles) • Acute exercise  positive effect • Prolonged Training program  deleterious effect • 20-30% less phagocytic activity in endurance athletes • Also overall decreases in: • Migrating ability • Neutrophil adherence • Granule content • Sensitivity to stimulation

  31. Phagocytic Cell Function (con’t) • What is the significance of decreased phagocytic cell activity in endurance athletes? • More susceptible to infection • OR • Smith et al. (1990) argues that lower sensitivity of neutrophil function indicates a good adaptation that limits inflammatory response to chronic tissue damage

  32. Cytokines & Complement System • Reminder: these are mediators of the INNATE immune system • Effect on Complement System from acute exercise • Contradictory results • MacKinnon (1999): complement system levels may remain elevated for several hours post-exercise and are responsible for cleaning proteolytic fragments released from muscles

  33. Cytokines & Complement SystemEndurance Athletes • Have lower resting levels and response following a graded exercise protocol as compared to non-athletes • Significant Adaptation? • Lowered response thought to reflect long-term adaptation to chronic inflammation from intense daily running • Cytokine Response • Conflicting reports – difficult to determine response • Some report no resting differences between athletes and non-athletes

  34. Immunoglobins • Important for the adaptive immune system • For athletes (runners, cyclists) serum levels of immunoglobin did not alter much during or after exercise. • However, response was elevated up to 1.5 hrs following exercise for overweight females • Resting salivary IgA levels reduced in athletes involved high-intensity training programs • Suppressed immunoglobin levels may indicate greater chance of upper respiratory tract infection (URTI) in athletes • 40-60% ↓ of IgA following an acute exercise bout (can remained lower for up to 24 hrs - IMPLICATIONS)

  35. URTI

  36. URTI – is it really a risk? • Moderate Exercise • Nieman et al. (1993) reported that a 50% reduction in URTI in women exercising 5 days a week compared with sedentary age-matched controls • Intense/Prolonged Exercise Bout • Larabee (1901) – he noted that the WBC differential in four runners at the Boston Marathon paralleled those seen in diseased conditions • Neiman et al. (1990) reported that 12.9% of runners in a marathon experienced URTI symptoms the week after the race as compared to 2.2% of control runners. • Greater URTI incidence seems to occur during the 2 weeks following a hard race/run greater than 2-3 hours in duration • Appears to be limited to endurance athletes (marathon, triathlon, orienteering, etc.)

  37. Is infection risk linked to exercise workload?Medicine & Science in Sports & Exercise. 32(7) Supplement:S406-S411, July 2000 Abstract:Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1- to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. Although it naturally follows that infection risk should in some way be linked to acute and chronic exercise-induced alterations in immunity, attempts thus far to measure this association have been unsuccessful. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Some attempts have been made through chemical or nutritional means (e.g., indomethacin, glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune changes after intensive exercise to lower the risk of infection. No consistent relationship between nutritional interventions, exercise immunology, and alteration in URTI risk has yet been established.

  38. Research Articles • Recovery of running performance following muscle-damaging exercise: Relationship to brain IL-1β • Exercise immunology: integration and regulation • Exercise-induced immune changes – an influence on metabolism

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