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.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.

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.

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

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.

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

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.

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.

Review Question #10

10.) TRUE/FALSE

The primary factor influencing V0 max is arteriovenous (A-V) oxygen difference.

The primary factor is CARDIAC OUTPUT!!!

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)

Two Sides of the “Immune” Coin

Immunological System & Exercise1.) 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!

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)

COMPLEMENT1.) also part of innate system response

2.) includes:

a.) lysozymes

b.) phagocytes

c.) natural killer (NK) cells

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

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

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

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

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

Immunoglobin Classes (TABLE 5.1)

Immunoglobin % of total pool Function

IgG 70-75% Major antibody of secondary immune response

IgA 15-20% In saliva & mucous membranes and acts against infections entering through mucous

IgM 10% In mucosal secretions and seen early in immune response

IgD <1% On membrane of circulating B cells

IgE trace Associated with immediate sensitivity to asthma and hay fever

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).

IL-6 linked to Muscle Damage

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

Opsonization & Phagocytosis

Exercise Induced Changes

I. Leukocyte (including lymphocytes) ResponseA. Acute Exercise

B. Long Term

II. Phagocytic Cell Function

III. Cytokines & Complement System

IV. Immunoglobulins

V. Athlete Immune Reponse

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

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

Leukocyte Effect of Acute Exercise (continued)

Neutrophil Effect 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

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

NKC Following a Marathon

Baseline NKC values substantial higher

Substantial reduction following marathon Implications?

Still at the sedentary values

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

Leukocyte Effect of Long-Term Training

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)

Leukocyte Effect of Long-Term Training (continued)

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

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

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

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

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)

URTI

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.)

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.

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