exercise and inflammation

Question 1

functions of inflammatory response

Answer 1

protect against injury and infection
physical damage
infections- viruses, bacteria, fungal and parasitic
exposure to toxins, pollutants or industrial chemicals + radiation
stimulate repair of damaged tissue- cytokines and other mediators released from immune cells and damaged tissue

Question 2

acute inflammation

Answer 2

common cold
immune cells destroy affected cells/ tissue
inflammatory proteins stimulate tissue repair
rapid, short lasting response

Question 3

chronic inflammation

Answer 3

occurs when a stimulus remains from acute inflammation
immune cells keep trying to repair
low level, continuous release of inflammatory proteins- is a risk to health as cytokines can cause damage to other tissues
major cause of cardiometabolic disease
common causes- unhealthy lifestyle, autoimmune disease
long lasting- weeks/months/ years

Question 4

cardinal signs

Answer 4

calor- heat
rubor- redness
tumor- swelling
dolor- pain
function laesa- loss of function - as result of the other 4 signs

Question 5

basis of cardinal signs

Answer 5

increased blood flow due to vascular dilation gives redness and heat
increased vascular permeability allows fluid and immune cells to move into damaged area casuing swelling
certain chemical mediators stimulate sensory nerve endings giving pain- nerves are also stimulated via stretch receptors due to swelling
pain and swelling result in loss of function

Question 6

step 1 of inflammatory response

Answer 6

initiation of the acute inflammatory response- injured tissue releases complement eg C5A and LPS is released by pathogens
injury or the prescence of pathogens
recognised by resident phagocytic immune cells - neutrophils and macrophages
once activated will secrete soluble mediators eg cytokines, prostaglandins, leukotrienes, platelet activating (PAF), nitric oxide (macrophages)

Question 7

step 2

Answer 7

vascular dilation and increased vascular permeability
activated neutrophils and macrophages will release:
- prostglandins- nitric oxide casuse vascular dilation
- leukotrienes- PAF- cause increased vascular permeability
- cytokines- TNF, iL6- activate mast cells which produce mediators such as histamine, bradykinin, leukotrines, PAF, prostaglandins, cytokines also activate increased vasvular permeability

Question 8

PAF

Answer 8

platelet activating factor
mediator of inflammation
prostaglandins and bradykinin stimulate nerve endings which cause pain

Question 9

vascular dilation and vascular permeability

Answer 9

vascular permeability increases + vascular dilation
impact:
- blood flow increases to area
- leakage of fluid into interstitial space (oedema)
- blood gets thicker (more viscous)
- slows down blood flow
- clotting leukocyte margination

Question 10

step 3

Answer 10

margination- process of leukocyte migrating from blood vessel to tissue- need to slow down blood so WBCs can leave
neutrophils will stick to blood vessel wall via adhesion molecules - first step is loose binding which slows down the cell slightly, allows higher affinity protein to bind which causes tight binding and the neutrophil stops
once the neutrophil is bound, can move between endothelial cells, tight junctions pull apart and can move into tissue
macrophages- release cytokines ensures the endothelial cells produce protein for neutrophils to adhere to
chemokines- magnets that help pull neutrophil through
helped my chemotaxis - movement from low to high chemokine concentration
chemically induced movement directed migration of cells in response to conc gradients of secreted cytokines known as chemokines

Question 11

step 4

Answer 11

neutrophils arrive rapidly to inflammatory event
any inflamed area will have large number of neutrophils in it

Question 12

step 5

Answer 12

damaged tissue is removed by phagocytosis
macrophages are phagocytic
engulf the bacteria/ target cells and take it into a phagosome
lysosomes will bind with phagosome and enzymes will be released, killing the target cell

Question 13

step 6

Answer 13

resolution- termination of the acute inflammatory response- only want damaged tissue to be removed
neutrophils self destruct- mediators are released which stimulate apoptosis
switch from releasing pro inflammatory mediators to pro resolving mediators- eg resolvins- which are anti inflammatory
these stop neutrophil recruitment and signal clearance of apoptopic neutrophils by macrophages

Question 14

summary inflammatory

Answer 14

resident macrophages, neutrophils and mast cells release mediators leading to vasodilation and increased vascular permeability
fluid and neutrophils- attracted by chemokines- leave the blood
neutrophils destroy the microbe/ damaged tissue

Question 15

biomarkers of chronic inflammation

Answer 15

stimulus- injury, infection, high blood lipid, toxins, tissue hypoxia
activates endothelial cells and activated immune cells
pro inflammatory cytokines- TNF-a, IL-6, IL1B
to liver which activate acute phase protein

Question 16

inflammatory cytokines

Answer 16

eg TNF, IL-6
play active roles in different systems as well as acting as indicators of inflammation
bone- remodelling and osteoporosis
skeletal muscle- sarcopneia (loss of muscle mass) + insulin resistance
endothial cells- endothelial dysfunction, arteriosclerosis
brain- build up of amyloidogenic proteins - inflammatory cytokines go through blood brain barrier
adipose tissue- adipokine production, immune cell filtration
liver- insulin resistance, sustained acute phase protein release

Question 17

study- IL6

Answer 17

circulating IL-6 increases with risk factors for CVD in apparently healthy women
risk factors - age > 60 years, current smoker, sedentary lifestyle, BMI > 27, diabetes
IL-6 conc increases with age
number of risk factors - 0 to 3- linked with an increase in circulating il-6

Question 18

study- inflammatory pathways

Answer 18

tagetting inflammatory pathways reduces incidence of atheroslerotic disease
10,00 patients with previous myocardial infaction and CRP >2mg/l
targeted IL-1B inflammatory pathways leads to IL-6 production
stops prod of IL-6
therapy lowered CRP and reduced incidence of HA, stroke or CV death after 4 years

Question 19

study- obesity

Answer 19

inactivity and positive energy balance results in subcutaneous and visceral fat accumlation- leading to chronic inflammation and risk of cardiometabolic
increased pro inflammatory cytokines (IL6 + TNFa) increased triglycerides, increased FFA
chronic low-grade inflammation, increased risk for atherosclerosis , t2d and tumour growth
inflammatory immune cells are higher in circulation in obesity and there is more chemokines in the blood causing this

Question 20

study- inflammatory markers

Answer 20

markers are lower in more active people + circulating markers decreasd with increased amounts of moderate- vigorous activity
relationship between moderate physical activity and IL-6 can be indepdentof body fat area
for more active people, IL6 is still lower than in less active people, even taking into account the amount of body fat each person has

exercise= anti inflammatory

Question 21

summary- inflammatory response

Answer 21

1-acute response, recognised by neutrophils and macrophages
2- vascular dilation + increased vascular permebaility- cytokines, leukotrienes and prostaglandins relased bt neutrophils and macrophages
3- margination- migration of leukocytes (neutrophils) from blood vessel to tissue by adhesion, using chemokines
4- neutrophils arrive rapidly at inflammatrory event
5- phagocytosis removes damaged tissue
6- resolution-termination of acute infalmmatory response- swtich from pro inflam mediators to pro resolving mediators to stop further neutrophil recruitment