W7 - Exercise & Inflammation

Question 1

What are the functions of the inflammatory response?

Answer 1

• Protect against injury and infection
• Initiated when there is physical damage (external objects, unaccustomed exercise)
• Infections (viruses, bacteria, fungal, parasitic)
• Exposure to toxins, pollutants or industrial chemicals, radiation, high levels of FFA
• Stimulate repair of damaged tissues
• Cytokines(signalling molecules, like the hormones of the immune system) and other mediators released from immune cells and damaged

Question 2

What are the features of acute inflammation?

Answer 2

• immune cells destroy affected cells
• inflammatory proteins stimulate tissue repair
• rapid, short-lived response (mins, days. hours)
  Without acute inflammation: would end up with sepsis
  
  • Acute = short lasting

Question 3

What are the features of chronic inflammation?

Answer 3

• Immune cells keep trying to repair
• low level, continuous release of inflammatory proteins
• common causes: unhealthy lifestyle, autoimmune disease
• long-lasting (months, years)
  Chronic - is stimulated when the stimulus remains in the blood e.g.: high levels of alcohol
  
  • Immune system turns on its own tissues
    Low level of pro-inflammatory mediators into the blood, lasts months & years

Question 4

Provide some examples of acute and chronic inflammatory illnesses

Answer 4

Acute:
* Common cold
* A splinter
* Muscle damage - does not lead to any long term health issues
* Radiation exposure
Chronic:
* Obesity
* Autoimmune disease
* Long-term smoking

Question 5

What are the 5 cardinal signs of acute inflammation?

Answer 5

Heat –> Redness –> Swelling –> Pain –> Loss of Function

Heat happens particularly in the extremities
Redness - from scratching
- Start of 20th century(vechal) - loss of function

Question 6

Describe each of the cardinal signs:

Answer 6

• Heat & Redness - Increased blood flow due to vascular dilatation gives redness and heat - first 2 to appear
• Swelling - Increased vascular permeability allows fluid and immune cells to move into the damaged area, causing swelling - endothelial cells retract, the cells shrink and this makes the gaps bigger
• Pain - Certain chemical mediators stimulate sensory nerve endings giving pain
• Nerves are also stimulated via stretch receptors due to swelling - can also cause pain
  
  • Pain and swelling result in loss of function
  • Protects, to stop further damage being caused

Question 7

What is the difference between monocytes and macrophages?

Answer 7

• Monocytes will respond the same way no matter the infection
  Monocytes - in the blood
• Macrophages - in the interstitial fluid and out of the blood(mature tissue version
  Of monocytes)

Question 8

What are granulocytes?

Answer 8

Granulocytes - cytoplasm had granules in it, granules are cytotoxic(killing) enzymes
* Both these cell types are phagocytic (wrap themselves around it to engulf it)

Question 9

What happens in the acute inflammatory response?

Answer 9

1) Initiation of acute inflammatory response
2) Vascular dilation and increased vascular permeability
3) Margination
4) Neutrophils arrive rapidly
5) phagocytosis of damaged tissue
6) Termination of acute inflammatory response

Question 10

Describe the first step of: initiation of acute inflammatory response

Answer 10

1) Injury/presence of pathogen
2) LPS & complement proteins
3) recognised by the resident phagocytic immune cells (macrophages & neutrophils)
4) These secrete soluble mediators
e.g.: cytokines, prostaglandins, nitric oxide

Question 11

Describe step 2: vascular dilation and increased vascular permeability

What is the impact of vascular dilation & increased vascular permeability?

Answer 11

1) activated neutrophils and macrophages
2) These release IL-6 and TNF-a cytokines
3) These cytokines along with Csa activate mast cells
4) the mast cells release: histamine, bradykinin, leukotrienes, PAF, prostaglandins, cytokines
5) bradykinin along with leukotrienes & PAF increase vascular permeability
6) Activated neutrophils and macrophages release prostaglandins, this along with nitric oxide causes vascular dilation

Question 12

Explain step 3: margination - the process of leukocytes migrating from the blood vessel to tissue

Answer 12

1) Rolling - the neutrophils with adhesion molecules on its surface rolls slowly
2) Tight Binding - These adhesion molecules then stick to the adhesion molecules on the surface of the blood vessel
3) Diapedesis - neutrophils move through the vessel wall via diapedesis into the interstitial space

Question 13

What is the impact of increased vascular permeability and vascular dilation

Answer 13

1) blood flow increases to the area
2) leakage of fluid into the interstitial space(oedema/swelling)
3) Blood gets thicker - more viscous
4) slow down blood flow
5) clotting leukocyte- margination

Question 14

What is margination helped by?
explain it

Answer 14

Chemotaxis
* chemically induced movement
* directed migration of cells in response to concentration gradients of secreted cytokines known as ‘chemokines’
* e.g. interleukin‐8 (IL‐8), (potent neutrophil chemokine released by macrophages and mast cells
- Like magnets to move neutrophils into tissues from the blood

Question 15

Describe step 4: neutrophils arrive rapidly

Answer 15

Main cell recruited in acute inflammation
are neutrophils
- swelling in the local area

Question 16

Explain step 5: time to remove the damaged tissue, phagocytosis

Answer 16

Once engulfed becomes a phagosome
- Lysosome fuses with phagosome
- combining killing enzymes with target(phagolysosome)
- Neutrophils have extracellular material that create nets for the debris that prevents it from infecting more cells

Question 17

Explain step 6: the resolution, termination of the acute inflammatory response

Answer 17

• neutrophils self-destruct
• switch from releasing pro-inflammatory mediators to pro-resolving mediators (e.g.: resolvers)
• these stop further neutrophil recruitment and signal to apoptotic neutrophils and macrophages

Question 18

How do inflammatory cytokines effect the liver?

Answer 18

insulin resistance, sustained acute phase, protein release

Question 19

How do inflammatory cytokines effect adipose tissue?

Answer 19

adipokine production, immune cell infiltration
- In adipose tissue - stimulates - leptin(inflammatory)

Question 20

How do inflammatory cytokines effect endothelial cells?

Answer 20

endothelial dysfunction, atherosclerosis

Question 21

How do inflammatory cytokines effect skeletal muscle?

Answer 21

sarcopenia, insulin resistance

Question 22

How do inflammatory cytokines effect bone?

Answer 22

bone remodelling, osteoporosis

Question 23

how does weight loss impact inflammation?

Answer 23

Q1 - least active
Q4 - most active, these had the lowest biomarkers
If adipose tissue is large reservoir, losing the source of inflammatory cells (cytokines) been lost through weight loss

• Some activity is better than no activity

Question 24

What is the result of physical inactivity and positive energy balance?

What cell increases cause this?

Answer 24

subcutaneous and visceral fat accumulation
‐ leading to chronic
inflammation and risk of
cardiometabolic disease, type 2 diabetes
- reduced longevity
- reduced functional capacity

• Pro-inflammatory cytokines
• Triglycerides
• LDL
• free fatty acids
• TLR expression