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Belief
Sports is healthy
and
strengthens immunity
Acute
Exercise
Chronic
?
Immunity
Scope
• host immune response
• acute exercise & IR
• chronic exercise & IR
• neuro-endocrine &immunity
• clinical implication
Inflammatory
process
Target cell
Immune Response
Th
lymphokine
mediated
cytotoxicity
Target cell
Th
activated
macrophage
Th
Effector T-cells
Ab mediated
K
cytotoxic T
Tc
Cytotoxic NK-cell
NK
Th
B
s
s
Complement
K
Tc
NK
Th
B
s
s
K
Tc
NK
protease
Th
B
s
s
K
Tc
NK
Confrontation with infectious agent,
do I get ill or not?
non-sp
immunity
non-sp
immunity
adaptive
immunity
illness
recovery
adaptive
immunity
2 Types of Host Defense
Natural
(non-specific)
innate IR
Acquired
(specific)
• active
• passive
Non-specific immune response
(Innate immunity)
 barrier : skin, mucosa
 monocytes / macrophages
 PMN
 cytokines
 complements
Fatty acids
Normal bacterial
skin flora
The first lines of defense: body surface
cilia
mucus
lysozyme
in saliva
lysozyme
washing
action
mucus
acid
washing
action of
urine
Cellular innate IR
• macrophage
• monocyte
• NK cells
adhearance, chemotaxis, phagocytosis, oxidative burst, degranulation, IC killing
• neutrophil
complement
bacteria
1. lysis
C5b
C9
phagocyte
bacteria
2. chemotaxis
3. opsonization
C5a
C3b
phagocyte
Y Y
opsonin
binding
_
+
C3b
++
Ab
+
Ab + C3b
++++
2 Types of Specific IR
HIR
(B-cell)
CMIR
(T-cell)
Ab production
• T-cells
• B-cells
Antigen
Antigen
Antigen Presenting Cell
T-lymphocyte
Antigen Presenting Cell
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-6
chemokines
MIF
Fibroblast
Synoviocyte
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-6
IgG
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-5
IL-6
B-lymphocyte
IgG
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-6
Effector
T-cells
K
Tc
NK
IgG
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-6
effector
T-cells
Activated
macrophage
Blood vessel
IgG
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-6
effector
T-cells
VCAM-1
ICAM-1
IgG
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-6
effector
T-cells
IgG
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-6
effector
T-cells
IgG
IL-1
TNF-a
IFN-g
IL-2
GM-CSF
IL-4
IL-6
IL-6
effector
T-cells
Scope
• host immune response
• acute exercise & IR
• chronic exercise & IR
• neuro-endocrine &immunity
• clinical implication
?
Sport
Immunity
enhance impair
Contradictive Data
study 1
Common cold in marathon
9/10
less cold
during 5 yr.
enhance
in general
7/10
catch cold
immediately
following a race
impair
after excercise
study 2
Common cold in marathon
cold
freq.
heavy training
athletes
2x
impair
6x
plan, but not
participated
participate in
competition
in competition
study 3
Animal trails
moderate exercise
intense exercise
enhance
Protected
impair
Susceptibility
infection
study 4
45 min walk,
5 days a week
15 weeks
36 women
days with cold
enhance
5.1+1.2
10.8 + 2.3
study 5
% who took a cold
during 12 weeks
enhance
50
8
very active
& fit
21
mod. active
& fit
inactive
less fit
Sport
?
Immunity
enhance impair
Difficulty in study
Immune changes after acute exercise
variable results
a
intensity & duration
transient effects
Immune changes after chronic exercise
Cross sectional study (case control)
• many confounding factors influence immunity
• difficult to study during actual resting period
Longitudinal study study (RCT)
• inadequate duration of chronic exercise
Factors influence immune function
Sleep
Age
Psychological
loads
Social burdens
Immunity
Malnutrition
Environmental
factors
Inherited
factors
Physical
stress
Immune Response
to
Acute Exercise
Effect of strenuous exercise on the immune system
Number of immune cells
during
after
Neutrophil count
non-specific
Monocyte count
Lymphocyte count

CD4 (T helper)






CD8 (T suppressor)


specific
(CD4/CD8)
CD19 (B cell)


CD16,56 (NK cell)


• most CD4, CD8 are memory cells (contain CD45RO)
• overall, NK cells increase more than other lymphocyte subpopulation
Effect of short strenuous exercise
on the number of WBC
% change
100
• increases by 50%
• recovers within 2 hours
• shift from central pool.
50
resting
value
0
0 5
7 3
stop
exercise
15
30
60
120 Minutes
2
2
3
3
number of studies performed
Effect of prolonged exercise (3h)
on the number of WBC
% change
from resting
• increase are more advance
• continue after run
• take more time to recover
• shift from the central pool
220
200
180
160
140
120
100
80
60
40
most = neutrophilia
effect of cortisol
20
0
5
90
Minutes after exercise stopped
6h
Effect of short strenuous exercise on
number of lymphocytes
% change
• increase by 100%
200
• recover quickly
• shift from cells sitting at rest on blood vessels wall
120
60
0
- 80
0 5
15
30
10 3
2
3
60
5
number of studies performed
120 Minutes
5
Effect of prolonged exercise on
Marathon race (42.6 km)
# lymphocytes
Change is
not significant
4
Giga/l
3
2
1
0
2days before
Run (arrival)
2days after
Effect of prolonged exercise on
Marathon race (42.6 km)
# T-cells
Change is
not significant
3
Giga/l
2
1
0
2days before
Run (arrival)
2days after
Effect of strenuous exercise on the immune system
Function of immune cells
Lymphocyte apoptosis
Proliferative response
Ab response in vitro
Salivary IgA
during
exercise
after
exercise














number L.
Ab production
Delayed type hypersensitivity
L. activity
NK cell activity *
Killer cell activity
(lymphokine activated)
• NK cells activity
a intensity > duration of exercise,
• mod. exercise  NK cell activity, while intense exercise  NK cell activity.
Effect of prolonged exercise on
T-cell activation
Marathon race (42.6 km)
change is
significant
2
ConA test
1
0
2days before
Run (arrival)
2days after
Effect of prolonged exercise on
IgG
21 km run (workout intensity) : total IgG
g/l
16
12
8
no significant changes
4
0
0
5
10
15
20
25
30
35
days
Effect of strenuous exercise on the immune system
acute phase protein and cytokines
C-reactive protein
Neopterin
proinflammatory cytokines
IL-6
IL-1ra
IL-10
TNF-R
after
exercise














acute phase protein
TNFa
IL-1
during
exercise
anti-inflammatory cytokines
MIP-1b

IL-8

Inflammation
acute phase
protein (unit)
infection
disease
recovery
100
10
1
2
4
6
acute phase protein
8
10
12
14
days
CRP, protease
part of HI
bind with bacteria & fungi
work with complement
Acute phase protein & cytokine level
plasma concentration
Elastase
a-1 antitrypsine
Neopterin
TNF
Before
During
After
3hr. run to
exhaustion
1h
3h
24h
48h
Scope
• host immune response
• acute exercise & IR
• chronic exercise & IR
• neuro-endocrine &immunity
• clinical implication
stress hormone release
attenuate
specific immune defense
Too much and continuous stress and distress can lead to
permanent depression of specific immune response
? tissue damage
Neuro-endocrine & immunity
epinephrine
norepinephrine
growth hormone
b-endorphin
cortisol
insulin
Plasma level of stress hormone
cortisol: psychological stress
concetration
catecholamine: physical stress
Run
1
2
3
4
Time (h)
5
6
7
8
Effect of strenuous exercise on the immune system
Number of immune cells
Neutrophil count
Monocyte count
Lymphocyte count
during

CD4 (T helper)


CD8 (T suppressor)

E, GH,
(CD4/CD8)
CD19 (B cell)

CD16,56 (NK cell)

after
 cortisol

 cortisol



E

Effect of strenuous exercise on the immune system
Function of immune cells
Lymphocyte apoptosis
Proliferative response
Ab response in vitro
Salivary IgA
Delayed type hypersensitivity
NK cell activity *
Killer cell activity
(lymphokine activated)
during
exercise







after
exercise

 sex H



 sex H

b- endorphin – maintain NK activity in chronic exercise only
Psychoneuroimmunology
stress (physical, psychological)
IL1
TNFa
IL-6
Neopterin
IFg
IL-2
CRF
corticosteroid
catecholamines
endorphine
encephaline
Macrophages
CNS
Hypothalamus
Corticotropin RF (CRF)
sympathetic
nervous system
Hypophysis
ACTH
Adrenals
corticosteroids
T-cells
Lymphokines
catecholamines
innervations of
lymphatic tissue
B-cells
Scope
• host immune response
• acute exercise & IR
• chronic exercise & IR
• neuro-endocrine &immunity
• clinical implication
Clinical implication ?
in
viral infection (myocartitis, poliomyelitis,URI)
cancer prevention
HIV patient care
Effect of strenuous exercise on the immune system
Function of immune cells
Lymphocyte apoptosis
Proliferative response
Ab response in vitro
Salivary IgA
number L.
Ab production
Delayed type hypersensitivity
L. activity
NK cell activity
Killer cell activity
(lymphokine activated)
during
exercise
after
exercise














• mod. exercise  NK cell activity, while intense exercise  NK cell activity.
• clinical findings : normal Ab response to vaccine,  skin test
Clinical implication ?
in
viral infection (myocartitis, poliomyelitis,URI)
cancer prevention
HIV patient care
Can sports support treatment of
immunodeficiency diseases & cancer ?
low to moderate intensity
enhances immune function
It is helpful: as long as you have fun
If one does not like sport: workout means stress,
and this may impair immune functions.
Psychological stress alone can affect immune system
Test exam
Mourning
(students)
(death of relative)
General
distress
↓ NK
↓ lymphocyte
↑susceptibility
↓ IL-2
activation
to infection
Sports and immunity:
the “dose” is the key element
+
number, volume &
intensity of physical &
psychological load.
(workout, competition..)
impair
-
non-specific
adaptation
benefit
positive
adaptation
effects of stress
over
and distress
overweight compensation
SUMMARY
• host immune response
• acute exercise & IR
window of decrease
host protection (CMIR)
• chronic exercise & IR
increase NK cell activity
• neuro-endocrine &immunity
• clinical implication
catecholamine
cortisol
b-endorphin
• precaution of infection after heavy training
• limit physical activity during incubation period