belief sports is healthy and strengthens immunity sports is healthy and strengthens immunity

BeliefBelief

Sports is healthy

and

strengthens immunity

Sports is healthy

and

strengthens immunity

Exercise Immunity?Acute

Chronic

ScopeScope

• host immune response

• acute exercise & IR

• chronic exercise & IR

• neuro-endocrine &immunity

• clinical implication

Immune Response

Target cellInflammatory process

Th

lymphokine mediatedcytotoxicity

Target cell

Th

activated macrophage

Th

Tc

K

Cytotoxic NK-cell

Effector T-cells

NK

Ab mediated

cytotoxic T

YY

Th

NK

Tc

K

B

Complement

YY

Th

protease

NK

Tc

K

B

YY

Th

NK

Tc

K

B

Confrontation with infectious agent, do I get ill or not?

Confrontation with infectious agent, do I get ill or not?

non-spimmunity

non-spimmunity

adaptive immunity

adaptive immunity

illness recovery

2 Types of Host Defense

2 Types of Host Defense

Natural (non-specific)

innate IR

Acquired(specific)

• active• passive

Non-specific immune response

(Innate immunity)

Non-specific immune response

(Innate immunity)

barrier : skin, mucosa

monocytes / macrophages

PMN

cytokines

complements

The first lines of defense: body surfaceThe first lines of defense: body surface

lysozymein saliva

acid

mucus

cilia mucus

no

rmal

gu

t fl

ora

lysozymewashingaction

Fat

ty a

cid

sN

orm

al b

acte

rial

skin

flo

ra

washingaction ofurine

Cellular innate IR Cellular innate IR

• neutrophil

• macrophage• monocyte• NK cells

adhearance, chemotaxis, phagocytosis, oxidative burst, degranulation, IC killing

complement

bacteriaphagocytebacteria

2. chemotaxis

C5a

3. opsonization

C3b

1. lysis

C9C5b

phagocyte opsonin binding

_ +

C3b ++

Ab +

Ab + C3b ++++Y

Y

2 Types of Specific IR

2 Types of Specific IR

HIR (B-cell)

CMIR

(T-cell)

Ab production • T-cells• B-cells

Antigen

Antigen Presenting Cell

Antigen

T-lymphocyte

Antigen Presenting Cell

IL-1TNF-GM-CSFIL-6

IFN-IL-2IL-4IL-6

IL-1TNF-GM-CSFIL-6

IFN-IL-2IL-4IL-6

chemokinesMIF

FibroblastSynoviocyte

IL-1TNF-GM-CSFIL-6

IFN-IL-2IL-4IL-6IL-5

B-lymphocyte

IgG

IL-1TNF-GM-CSFIL-6

IFN-IL-2IL-4IL-6

IgG

Effector T-cells K Tc NK

IL-1TNF-GM-CSFIL-6

IFN-IL-2IL-4IL-6

IgG

Activatedmacrophage

effectorT-cells

IL-1TNF-GM-CSFIL-6

IFN-IL-2IL-4IL-6

IgG

Blood vessel

effectorT-cells

IL-1TNF-GM-CSFIL-6

IFN-IL-2IL-4IL-6

IgG

VCAM-1 ICAM-1

effectorT-cells

IL-1TNF-GM-CSFIL-6

IFN-IL-2IL-4IL-6

IgG

effectorT-cells

ScopeScope






enhance impair

Sport Immunity

?

Contradictive DataContradictive Data

less cold during 5 yr.

catch cold immediately

following a race

study 1

enhancein general

impairafter excercise

Common cold in marathonCommon cold in marathon

9/10

7/10

study 2

heavy trainingathletes

participatedin competition

plan, but not participate in competition

Common cold in marathonCommon cold in marathon

2x

6ximpair

coldfreq.

study 3Animal trailsAnimal trails

moderate exercise intense exercise

Protected Susceptibility

infectioninfection

enhance impair

study 4

45 min walk, 5 days a week15 weeks

days with colddays with cold

enhance

5.1+1.2

36 women

10.8 + 2.3

study 5

enhance

8

% who took a cold

during 12 weeks

21

50

very active& fit

mod. active& fit

inactiveless fit

enhance impair

Sport Immunity?

Difficulty in studyDifficulty in study

Immune changes after acute exerciseImmune changes after acute exercise

variable results intensity & duration

transient effects

Cross sectional study (case control)

Immune changes after chronic exerciseImmune changes after chronic exercise

• many confounding factors influence immunity

• difficult to study during actual resting period

Longitudinal study study (RCT)

• inadequate duration of chronic exercise

Factors influence immune functionFactors influence immune function

ImmunityImmunity

Sleep

Social burdens

Environmental factors

Psychological loads

Malnutrition

Physical stress

Age

Inherited factors

Immune Response

to

Acute Exercise

Immune Response

to

Acute Exercise

CD16,56 (NK cell)

CD19 (B cell)

(CD4/CD8)CD8 (T suppressor)

CD4 (T helper)

Lymphocyte count

Monocyte count

Neutrophil count

afterduringNumber of immune cells

Effect of strenuous exercise on the immune system

• most CD4, CD8 are memory cells (contain CD45RO)

• overall, NK cells increase more than other lymphocyte subpopulation

non-specific

specific

Effect of short strenuous exercise on the number of WBC

Effect of short strenuous exercise on the number of WBC

120600 5 15 30 Minutes

% change

0

100

50

resting value

stopexercise

7 3 2 2 3 3

number of studies performed

• increases by 50%

• recovers within 2 hours

• shift from central pool.

• increases by 50%

• recovers within 2 hours

• shift from central pool.

% change from resting

5

20

220

120

090

Minutes after exercise stopped

6040

80100

140160180200

6 h

Effect of prolonged exercise (3h)on the number of WBC

Effect of prolonged exercise (3h)on the number of WBC

• increase are more advance• continue after run• take more time to recover• shift from the central pool

• increase are more advance• continue after run• take more time to recover• shift from the central pool

most = neutrophilia

effect of cortisol

most = neutrophilia

effect of cortisol

Effect of short strenuous exercise on number of lymphocytes

Effect of short strenuous exercise on number of lymphocytes

% change

0

200

60

120600 5 15 30 Minutes

- 80

120

10 3 2 3 5 5number of studies performed

• increase by 100%

• recover quickly

• shift from cells sitting at rest on blood vessels wall

• increase by 100%

• recover quickly

• shift from cells sitting at rest on blood vessels wall

Effect of prolonged exercise on # lymphocytes Effect of prolonged exercise on # lymphocytes

Marathon race (42.6 km)

0

1

2

3

4

2days before Run (arrival) 2days after

Giga/l

Change isnot significant


Effect of prolonged exercise on # T-cellsEffect of prolonged exercise on # T-cells


Change isnot significantMarathon race (42.6 km)

0

1

2

3


Giga/l


Killer cell activity (lymphokine activated)

NK cell activity *

Delayed type hypersensitivity

Salivary IgA

Ab response in vitro

Proliferative response

Lymphocyte apoptosis

after exercise

during exercise

Function of immune cells

• NK cells activity intensity > duration of exercise,

• mod. exercise NK cell activity, while intense exercise NK cell activity.

number L.

Ab production

L. activity

Effect of prolonged exercise on T-cell activationEffect of prolonged exercise on T-cell activation

0

1

2


Marathon race (42.6 km)change is

significant

change is

significant

ConA test

Effect of prolonged exercise on IgGEffect of prolonged exercise on IgG

21 km run (workout intensity) : total IgG

00

5 10 15 20 25 30 35 days

4

8

12

16g/l

no significant changesno significant changes


MIP-1

IL-10

TNF-R

IL-8

IL-1ra

IL-6

IL-1

TNF

Neopterin

C-reactive protein

after exercise

during exercise

acute phase protein and cytokines

proinflammatory cytokines

anti-inflammatory cytokines

acute phase protein

infection disease recovery

days

acute phase protein (unit)

100

10

1

2 4 6 8 10 12 14

acute phase protein CRP, proteasepart of HIbind with bacteria & fungiwork with complement

acute phase protein CRP, proteasepart of HIbind with bacteria & fungiwork with complement

InflammationInflammation

Acute phase protein & cytokine levelAcute phase protein & cytokine level

Before AfterDuring

3hr. run to exhaustion

1h 3h 24h 48h

pla

sma

con

cen

trat

ion

Elastase

-1 antitrypsine

Neopterin

TNF

ScopeScope






stress hormone release

attenuate specific immune defense

? tissue damage

Too much and continuous stress and distress can lead to

permanent depression of specific immune response

Neuro-endocrine & immunityNeuro-endocrine & immunity

epinephrine

norepinephrine

growth hormone

-endorphin

insulin

cortisol

Plasma level of stress hormonePlasma level of stress hormone

Runconc

etra

tion

Time (h)1 2 3 4 5 6 7 87

cortisol: psychological stress

catecholamine: physical stress

CD16,56 (NK cell)

CD19 (B cell)

(CD4/CD8)CD8 (T suppressor)

CD4 (T helper)

Lymphocyte count

Monocyte count

Neutrophil count

afterduringNumber of immune cells


E

E, GH, cortisol

cortisol



NK cell activity *


Salivary IgA




after exercise

during exercise


- endorphin – maintain NK activity in chronic exercise only

sex H

sex H

PsychoneuroimmunologyPsychoneuroimmunology

Adrenals

Macrophages T-cells B-cells

Lymphokines

stress (physical, psychological)

CNS

Hypothalamus

Corticotropin RF (CRF)

Hypophysis

ACTH

corticosteroids

innervations oflymphatic tissue

catecholamines

sympathetic nervous system

IL1TNFIL-6Neopterin

IFIL-2

CRFcorticosteroidcatecholaminesendorphineencephaline

ScopeScope






viral infection (myocartitis, poliomyelitis,URI)

cancer prevention

HIV patient care

Clinical implication ?Clinical implication ?

in



NK cell activity


Salivary IgA




after exercise

during exercise


• mod. exercise NK cell activity, while intense exercise NK cell activity.

number L.

Ab production

L. activity

• clinical findings : normal Ab response to vaccine, skin test

viral infection (myocartitis, poliomyelitis,URI)

cancer prevention

HIV patient care

Clinical implication ?Clinical implication ?

in

Can sports support treatment ofimmunodeficiency diseases & cancer ?

Can sports support treatment ofimmunodeficiency diseases & cancer ?

enhances immune function

low to moderate intensity

It is helpful: as long as you have fun

If one does not like sport: workout means stress,

and this may impair immune functions.

If one does not like sport: workout means stress,

and this may impair immune functions.

Psychological stress alone can affect immune systemPsychological stress alone can affect immune system

Test exam (students)

Mourning(death of relative)

General distress

↓ NK

↓ IL-2

↓ lymphocyte activation

↑susceptibility to infection

Sports and immunity: the “dose” is the key element

Sports and immunity: the “dose” is the key element

+

-

non-

spec

ific

adap

tatio

n

positiveadaptation

effects of stress and distress overweight

overcompensation

number, volume &intensity of physical &psychological load.(workout, competition..)

benefit

impair

SUMMARYSUMMARY• host immune response

window of decrease host protection (CMIR)

increase NK cell activity

catecholaminecortisol

-endorphin

• precaution of infection after heavy training

• limit physical activity during incubation period





belief sports is healthy and strengthens immunity sports is healthy and strengthens immunity

Documents

ifng tcells

il vesseleffectortcellsil

immune system

immunityexercise immunity

immunity difficult

memory cells

number of wbc increase

competitioncommon cold