Exercise and immunity

Question 1

What is the acute response to exercise?

Answer 1

Research as shown that an acute bout of exercise can compromise the immune response for a few hours/ day, depending on stress levels induced – high changes of upper respiratory trace infections

After a workout as stress levels increase, working capacity decreases from homeostatic baseline status.
Then there will be a recovery period back to homeostasis – diet is important to modulate recovery, 10-15g protein can help enhance immune response
For a few hours or days, working capacity is much higher than baseline
During this period, the immune response can be compromised.
2-3 hours after exercise there is an enhanced absorption of vitamins and mineral –> after exercise if food is not eaten, mitochondrial function can increase but there is an risk to immune function

A study found that the prevalence of URTI, was higher in marathon runners than the control (non-runners)

Question 2

What happen if you don’t eat after exercise?

Answer 2

Mitochondrial function can increase
Risk to immune function

Question 3

What are different curves of the acute response to exercise?

Answer 3

J-shaped curve
- Suggests that exercise at moderate intensity is much more effective than at higher intensity to reduce risk of URTI
- When the combination of intensity, duration and frequency is too much/ high, this can increase risk of infection risk, even above level of those who are not very active

S-shaped curve
- Suggests highest peak is at high and then decreases for elite
- Low higher than moderate
- If exercise done at a level than physiological level it can compromise the immune response
- In well trained athletes, the physiological response is different as they are used to the intensity and they recover much quicker. Can tolerate higher intensity exercise than others –> risk of infection is similar to that at low intensity

Question 4

What is the Open Window Theory?

Answer 4

Short term suppression of the immune system following an acute bout of endurance exercise leading to an increased susceptibility to upper respiratory tract functions.
2-3 hours after exercise, diet can modulate the physiological response.

Question 5

Why might athletes want to delay the recovery period?

Answer 5

Some may want to increase stress levels and delay recovery period for a few hours/ days, as it can push the body more to enhance some physiological adaptations
If not consuming food after exercise, it encourages mitochondria to metabolise more fatty acids, which can enhance mitochondrial function.
However there are risks of compromising immune function and increasing risk of infection.

Question 6

What happens to immune cells during the acute response to exercise?

Answer 6

Exercise at 55% VO2 max
- 1 hour after exercises causes neutrophils to increase quite significantly which continues well into recovery
- Lymphocytes also increase, but not as much as neutrophils, increases up until 2.5 hours after exercise

Exercise at 80% VO2 max
- Both neutrophils and lymphocytes fall below baseline for around 5 hours
- Lymphocytes increase slightly at beginning of exercise before falling

Question 7

What is demargination?
Immune cells response to acute exercise

Answer 7

The initial rise in neutrophil count is due to demargination.
Marginated neutrophil are attached to the blood vessel wall and are not circulating.
During exercise these neutrophil come away from the blood vessel wall and circulate –> mechanism that explain the rapid increase of immune cells.

Higher cardiac output is a large stimulus to remove neutrophils from the wall.
Adrenaline, epinephrine, nitric oxdie acts to increase neutrophil numbers through a few mechanisms: increases cardiac output, increased lung and muscle blood flow and by reducing the adherence of neutrophils to the endothelium

Question 8

What is cardiac output
Affect during exercise

Answer 8

Stroke volume X Heart rate
70 70

= 4900ml/ min
Normal cardiac output is around 5 litres in resting conditions

During exercise
- Heart rate rapidly increase –> 180bpm
- Stroke volume –> 140ml/min
- Cardiac output = 25litres per minute

In the recovery period, as cardiac output and adrenaline begin to return to resting levels, the stress hormone cortisol begins to get involved

Question 9

Why do lymphocyte levels drop below baseline 1 hour after exercise?

Answer 9

This pattern is seen in all lymphocytes subsets, with the largest response seen in natural killer and t helper cells.
Being below baseline gives an opportunity for minor infections

Apoptosis
- Depends on stress cells
- Can induce apoptosis of older cells
- Exercise can replace older cells with new cells, but with a period of time where the level is below baseline

Mobilisation of lymphocytes to secondary lymphoid organs
- Some lymphocytes sent to lymphoid organs such as spleen or thymus where there is a reservoir of lymphocytes

Question 10

What are some other immune changes after acute exercise?

Answer 10

A decrease in the oxidative burst of neutrophils
- Lower capacity to produce free radicals for a few hours –> free radicals can help to kill potential pathogens
- M1 can shift metabolic pathway and are more likely to use glucose in anaerobic respiration producing lactate –> low levels of glucose after exercise can effect amount of neutrophils
- Glycogen is the main energy source used at high intensity exercise –> can compromise M1 usage which then influence immune cells after exercise. When glycogen stores run out immune cells run out of their main fuel, which can impair oxidative burst

An initial rise in natural killer cells cytotoxic activity
- With a subsequent decrease around 2 hours into the recovery period
- Lower activity during recovery, due to low levels of glycogen

Question 11

How can carbohydrate consumption improve recovery after exercise?

Answer 11

Eating CHO before exercise increases amount of glycogen in muscles which can improve immune response after exercise and exercise capacity during.
Consuming CHO during can also enhance this, can help modulate the impact of exercise on body, can keep plasma cortisol/ stress levels from increasing
As well as after –> muscle very susceptible to taking glucose

Question 12

How does low carbohydrate intake affect immune function?

Answer 12

Direct immunosuppression due to the depletion of glucose
- Low glycogen levels can compromise immune response for a few hours –> depends on the work load

Indirectly via increased concentration of stress hormone
- Cortisol (catabolic hormone that increases during exercise) –> can modulate levels of cortisol with diet
- Higher levels of cortisol in those with a low CHO (<10%) diet after exercise, indicating higher levels of stress
- Higher CHO diet before exercise can decrease cortisol/ stress levels

Question 13

What happens to insulin levels during exercise?

Answer 13

They stay the same

Question 14

What is the non-insulin pathway?

Answer 14

When insulin can enter the muscle without requiring insulin
- occurs during exercise and in the recovery period
- can take more glucose into the muscle
- no change in insulin levels
- especially in open window period, ability to take glucose from circulation to muscle is greatly increased

Question 15

Recommended amount of CHO to be consuming during exercise?

Answer 15

Used to be 30-60g
Now 90-100g per hour is beneficial
However depends on the activity/ sport as for some this may not be possible

Question 16

Does glutamine enhance immune response?

Answer 16

In the 1990, it was discovered that lymphocytes, macrophages and immune cells utilise the amino acid, glutamine, as an energy source.
Glutamine can be used to produce ATP.

Some evidence suggests that supplementation with glutamine is not that effective to enhance immune response after exercise.
Better to increase CHO intake

Question 17

Can protein help immune response after exercise?

Answer 17

Protein deficiency can lead to reduced ability to the innate system to destroy pathogens or virally infected cells. With the adaptive system can decrease the proliferative response of T cells and daughter cells.

Insufficient dietary protein intake can lead to a reduction in immune function

A study of people doing 2 week of HIIT training whilst consuming a high protein diet of 3g/kg/day
- The circulatory levels of CD8 during exercise didn’t change between the focus group and the control group that didn’t do exercise
- The control group that did not follow a high energy diet, CD8 levels went down
- Same results for post-exercise
- Control group that did exercise, had a much higher incidence of URTI than the focus group

During open window period, 10-15g of protein can be useful to enhance the immune response

Probably a combination of adequate protein and CHO would help with immune response

Question 18

Can fatty acids have any impact on immune response after exercise?

Answer 18

It has been suggested that athletes can benefit from an increase in the consumption of the n-3 PUFAs found in fish oil
n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid found in the fish oil displace arachidonic acid from the cell membranes and are used a precursors for eicosanoid synthesis

Consumption of omega-3 or monounsaturated fatty acids can be quite influential during the recovery period to enhance immune response.
Omega-3 –> fatty fish, nuts, flaxseeds

Question 19

How can exercise modulate low-grade chronic inflammation?

Answer 19

• Reduction of visceral fat mass
• Inhibition of macrophage infiltration
• Release of myokines
• Increased levels of circulating cortisol and adrenaline
• Down-regulation of TLR expression
• Reduced number of circulatory monocytes
• Increased circulatory levels of Treg cells

Question 20

How can exercise influence macrophage infiltration in the CRE?

Answer 20

• Less adipose tissue
• Lower recruitment of M1 macrophages and CD8 T lymphocytes
• TLR4 expansion and activation
• Lower lipid accumulation in liver and muscle

Methylation makes expression of genes more unlikely to happen as they block the expression in that part of the DNA
Exercise induces hypomethylation in muscles, DNA
Whereas, there is hypermethylation in adipose tissue, which decreases ability to store fat

Frequent exercise can down-regulate amount of fatty acids in adipose tissue

Question 21

How does exercise affect methylation?

Answer 21

Induces hypomethylation in muscles –> have high ability to express muscle genes that can be related to muscle protein synthesis and can enhance proteins related to glycogen storage

Induces hypermethylated in adipose tissue –> lower capacity to store fat –> an acute response to exercise, depending on stimulus

Frequent exercise can down-regulate the amount of fatty acids in the adipose tissue due to the hypermethylation blocking gene expression

Question 22

What is the affect of exercise on cytokine production?

Answer 22

Muscle can produce and release cytokines in response to exercise/ stimulation

Active muscle was found to be the major source of IL-6 during exercise (in a study)
Was thought to be due to muscle damage, increasing immune response, however not confirmed by other studies.
Lengthening muscle exercises –> promotes more muscle damage –> increases creatine kinase levels more than others –> but no a major increase in IL-6 which explains that cytokine release is not solely down to muscle damage

Release of IL-6 appears to be a key mechanism to induce some of the physiological adaptations to exercise
- Glycogen storage in muscle and liver
- Angiogenesis –> increase the number of capillaries in the muscle, increase the size of blood vessels
- Improve size of skeletal muscle

IL-6 release from muscle is a key mechanism in cell signalling, improving the adaptation to all the different physiological response.
Nutrition is a key factor in modulating the synthesis and release of IL-6 in the muscle.
Depending on glycogen levels –> lower glycogen, higher IL-6 production and visa versa

Low glycogen can also increase expression in mRNA in muscle,

Question 23

What is the role of IL-6 in exercise?

Answer 23

Release of IL-6 appears to be a key mechanism to induce some of the physiological adaptations to exercise
- Glycogen storage in muscle and liver
- Angiogenesis –> increase the number of capillaries in the muscle, increase the size of blood vessels
- Improve size of skeletal muscle

IL-6 release from muscle is a key mechanism in cell signalling, improving the adaptation to all the different physiological response.
Nutrition is a key factor in modulating the synthesis and release of IL-6 in the muscle.
Depending on glycogen levels –> lower glycogen, higher IL-6 production and visa versa
Related to improving mitochondrial function

However, can increase risk of infections that compromise training, and increase risk of injury.

In an animal study, where one mouse had IL-6 knockout. They expressed a phenotype of obesity despite being active, lower ability to control body weight, lower improvement to endurance capacity and metabolic regulation after the exercise intervention.

Question 24

How is cortisol secretion related to IL-6?

Answer 24

Cortisol is known to have potent anti-inflammatory effects
Cortisol secretion is also linked to IL-6 from working skeletal muscle
Higher cortisol = higher IL-6
Also related to diet, cortisol synthesis can be altered due to CHO intake.
IL-6 expression can be modulated by CHO intake
Hormones, myokines and cytokines all contribute to the anti-inflammatory affect of exercise

Question 25

What is the Intramuscular Lipid Athlete’s Paradox?

Answer 25

Expected - The amount of fatty acids in muscle in obese and type 2 diabetics is higher than in trained individuals

Results - Trained individuals had higher levels of intramuscular lipids than obese and T2D

IL-6 enhances mitochondrial function
One of the main affects of exercise is the body wanting to try and promote aerobic respiration as much as it can. Ability to use oxygen is better after exercise. Higher ability to use mitochondria and transport to muscle due to improve angiogenesis. 9 molecules of energy from 1g of fat, so muscle will try and be as efficient as possible and promote oxidation of fatty acids in mitochondria.

Question 26

How does exercise influence T regulatory cells?

Answer 26

Exercise can increase the expression of T regulatory cells
Treg cells
- Inhibition of antigen-presentation
- B cell modulation
- Tissue remodeling
- Down-regulation of T effector cells
- Inhibition of cells from innate immunity

Not enough Treg cells can compromise activation of B cells and antibody synthesis.
Chronic exercise can help improve immune response and function by increasing treg cells.

A combination of high intensity aerobic plus resistance exercise training, in addition to daily physical activity, is required to achieve a significant anti-inflammatory effect
This suggests that high intensity exercise might be more beneficial than moderate-intensity in reducing the risk of chronic cardiovascular and metabolic diseases, as a result of its anti-inflammatory effects

Question 27

How can exercise affect gut microbiota?

Answer 27

Exercise can increase the diversity of bacteria in the gut. It can also increase the functionality of bacteria.
During exercise, large amounts of lactate are passed to the bloodstream where it travels to the liver where it is converted into glucose which can be used again, e.g. in muscle
Small amounts of lactate can also be passed to circulation where it is taken to the gut (across gut barrier) and different bacteria species can use lactate to produce SCFA which can be used by GI cells or can pass through circulation to be used by muscle. SCFA is linked to improving insulin sensitivity.

Question 28

What environment does skeletal muscle promote?

Answer 28

Anti-inflammatory
Modulated by frequency, intensity and duration of exercise