Acute Phase Response Flashcards
The release of pro-inflammatory cytokines during the hsot inflammatory response effects what?
CNS, Bone Marrow equivalent tissues, Liver
How does CNS activation occur?
when pro-inflammatory cytokines bind to respective receptors on parasympathetic neurons and sympathetic neurons
ALSO when circulating pro-inflammatory cytokines diffuse into the brain or are produced in the brain
The activation of the SAM and HPA axis plays key roles in?
controlling inflammatory response and activating other physiological pathways to restore homeostasis
What does the “sickness response” activated by the hypothalamus entail?
fever, anorexia, sleepiness and depression
How does the fever response occur?
Due to unduction of prostaglandins by IL1, IL6 and TNFalpha
Fever enhances?
DC maturation and circulating lymphocyte numbers
Fever inhibits?
T-cell apoptosis
How the poikilotherms (ex. fish) achieve a response similar to fever?
swimming to warm water such as industry outflow
How does the sickness behaviour response occur?
due to pro-inflammatory cytokines
What does IL1 do?
promotes release of sleep-inducing molecules (ex. seretonin) and suppresses hunger signals leading to anorexia (ex. decreased neuropeptide Y)
What do IL1, IL6 and TNFalpha all do?
induce production of HMGB1
What is HMGB1?
an alarmin acting on the HP-axis to induce food aversion
Weight loss is exacerbated by?
pro-inflammatory cytokine induced muscle protein catabolism
What enhances Bone Marrow stem cell activity?
pro-inflammatory cytokines
What activates hepatocytes?
IL1, TNFalpha and ESPECIALLY IL6 and glucocorticoids
Hepatocytes effect synthesis of?
acute phase proteins
What are 7 examples of acute phase proteins?
opsonins, complement proteins, iron binding proteins, free radical scavengers, proteolytic enzyme neutralizers, binding proteins, clotting factors
What is the definition of APPs?
proteins whose serum concentrations change by 25% in response to pro-inflammatory cytokines during a disease process
What are the three groups of positive APPs?
Major, moderate and minor
What are Major APPs?
concentration increases 10-100x, peaking at 24-48 hours and rapidly returning to basal levels
What are examples of Major APPs?
c-reactive protein, serum amyloid A
What are moderate APPs?
concentrations increase 2-10x, peaking at 2-3 days and retunr to basal levels more slowly
What are examples of moderate APPs?
haptoglobin, fibrinogen
What are minor APPs?
concentration increases gradually around 1-2x
What is an exampled of a minor APP?
C3
What does C-reactive protein do?
acts as an opsonin, anti-inflammatory by inhibiting N degranulation and superoxide production and blocking platelet aggregation
What does serum amyloid A do?
pro-inflammatory chemoattractant for N and Mo, also an alarmin via TLR2
What do haptoglobin and transferrin do?
sequester iron
In mammals, transferrin is _______ but is ________ in chickens and zebrafish
negative, positive
In mammals, haptoglobin is _______ but is _______ in chickens
positive, negative
Major APP is a major APP in _____, it is a ______ APP in cattle and it is not found in other species.
pigs, moderate
What are the zebrafish APPs?
transferrin, serum ampyloid A, haptoglobin, hepcidin, leukocytes cell-derived chemotaxin 2 and C-reactive protein-like
