Transcript Slide 1

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.
THE BOHR EFFECT
7.) This phenomenon is called _____________
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 FrankStarling 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 acutephase response to local injury”
Pedersen & Nieman (1998)
Two Sides of the “Immune” Coin
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Immunological System & Exercise
1.) regular moderate exercise is beneficial to a
person’s health by stimulating the immunoresponse
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)
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
Cells of the Immune System
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Leukocytes (white blood cells)
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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
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Comprised of T cells, B cells, and NKC
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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?
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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)
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Glycoproteins found in ALL bodily fluids
ALL antibodies  immunoglobins
But not vice-versa
Combat infections through direct & indirect means
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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
Function
% of total pool
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)
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Regulate growth factors
Involved with immediate inflammatory response
Soluble (in plasma)
Commonly types
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Interleukuen (IL)
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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
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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) Response
A. Acute Exercise
B. Long Term
II.
III.
IV.
V.
Phagocytic Cell Function
Cytokines & Complement System
Immunoglobulins
Athlete Immune Reponse
Leukocyte
Effect of Acute Exercise
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Circulating leukocyte [ ]’s ↑ after an acute bout of
exercise
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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
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150-180% above resting values
Decline begins 30-60min post-exercise
Can remain elevated up to 2hrs depending on exercise dose
Leukocyte
Effect of Acute Exercise (continued)
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Endurance Exercise
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Circulating levels may increase 2-3 fold during exercise
May remain elevated up to 6hr post-exercise
Lymphocyte Response
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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
Neutrophil
Effect of Heavy Training Volume
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Pyne et al. (1995)
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Mature WBC
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Represent about 54-65% of
leukocyte count normally
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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
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Natural Killer Cells (NKC)
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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
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Baseline NKC values
substantial higher
Substantial reduction
following marathon
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Implications?
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Still at the sedentary values
Leukocyte
Effect of Long-Term Training
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Research studies (cross sectional design) have
shown no differences in athletes vs.
nonathletes
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BUT leukocyte values may be affected during
periods of heavy training volume as opposed
to smaller training volume
Leukocyte
Effect of Long-Term Training (continued)
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Training Volume ↑  ↓ Leukocyte count
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Increased susceptibility to infectious attack
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Training Intensity ↑  no change in leukocyte count
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Response also sensitive to type of exercise (aerobic vs anaerobic)
Phagocytic Cell Function
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Increased circulating phagocytic values does NOT
indicate anything about cell function (be careful not to assume
activity when reading articles)
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Acute exercise  positive effect
Prolonged Training program  deleterious effect
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20-30% less phagocytic activity in endurance athletes
Also overall decreases in:
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Migrating ability
Neutrophil adherence
Granule content
Sensitivity to stimulation
Phagocytic Cell Function (con’t)
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What is the significance of decreased
phagocytic cell activity in endurance
athletes?
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More susceptible to infection
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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
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Reminder: these are mediators of the
INNATE immune system
Effect on Complement System from acute
exercise
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Contradictory results
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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 System
Endurance Athletes
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Have lower resting levels and response following a
graded exercise protocol as compared to nonathletes
Significant Adaptation?
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Lowered response thought to reflect long-term adaptation to
chronic inflammation from intense daily running
Cytokine Response
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Conflicting reports – difficult to determine response
Some report no resting differences between athletes and
non-athletes
Immunoglobins
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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 highintensity 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?
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Moderate Exercise
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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
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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.
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Recovery of running performance following
muscle-damaging exercise: Relationship to
brain IL-1β
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Exercise immunology: integration and
regulation
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Exercise-induced immune changes – an
influence on metabolism