exercise and inflammation Flashcards
functions of inflammatory response
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
acute inflammation
common cold
immune cells destroy affected cells/ tissue
inflammatory proteins stimulate tissue repair
rapid, short lasting response
chronic inflammation
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
cardinal signs
calor- heat
rubor- redness
tumor- swelling
dolor- pain
function laesa- loss of function - as result of the other 4 signs
basis of cardinal signs
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
step 1 of inflammatory response
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)
step 2
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
PAF
platelet activating factor
mediator of inflammation
prostaglandins and bradykinin stimulate nerve endings which cause pain
vascular dilation and vascular permeability
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
step 3
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
step 4
neutrophils arrive rapidly to inflammatory event
any inflamed area will have large number of neutrophils in it
step 5
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
step 6
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
summary inflammatory
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
biomarkers of chronic inflammation
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
inflammatory cytokines
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
study- IL6
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
study- inflammatory pathways
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
study- obesity
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
study- inflammatory markers
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
summary- inflammatory response
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
