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What are cytokines?
Cytokines are low-molecular weight proteins produced by inflammatory (and other) cells during inflammation
Which experiments found the active agent TNF (tumour necrosis factor)
- bacterial products were injected to mice elicited the production of a protein which caused some tumours to become necrotic
- People with cancer undergo wasting (cachexia). Shown in mice infected with sleeping sickness parasite Trypanosoma. Mediator of cachexia was called cachextin-same protein as TNF
Why is TNF only have limited use as a anti cancer agent?
- induces unpleasant flu-like symptoms
- is not effective against most common cancers
At low concentration cytokines lead to what?
- induce protein synthesis
- expression of EC adhesion molecules that recruit inflammatory cells
At high concentrations of cytokines induce?
- the coagulation casase
- progressive development of scar tissue, fibrosis
- (over time) cachexia
Neutrophils contributef __ % of granulocytes, their function is to ________________________ and their harmful effect is _______.
- phagocytosis of tissue debris, microbes
- tissue injury
Eosinophil contribute ____% of granulocytes, their function is to_________ and their harmful effect is _____
Mast cell/ basophil contribe < ___% of granulocytes. Their function is ________ and their harmful effect is _____
- regulation of inflammation
Injury without infection generate_____?
ECM fragments can be DAMPS, what is an example of this type of DAMP? and what is its receptor?
- toll-like receptors, TLRs
HMGB1 from chromatin is an example of DAMP, what type of DAMP is it and what is its receptor
- intracellur proteins
DNA and RNA is a type of DAMP, what is its receptor
P2X7 purinergic is a receptor for what type of DAMP?
Crystal is a type of DAMP, what is a couple examples of this type of DAMP? What is its receptor?
- MSU, cholesterol
- components of inflammasomes
signalling from what two receptors activates inflammasomes
TLR & P2X7Rs
When caspase-1 becomes activated what does it cleave into an active form? What other cytokine is released
what is the function of IL-1β and IL-1α?
Induce ECs to become adhesive for leukocytes
What is margination?
Recruitment of circulating neutrophils requires adherence to the endothelium
When do neutrophils leave the axial stream and move to the plasmatic zone?
When blood flow rate decreases with loss of plasma and increased viscosity
How do neutrophils contact the epithelium? How is this mediated?
- by rolling across the surface
- P- and E- selections on stimulated ECs and glycoproteins and sugar residues
When does firm adhesion with flattening occur?
Occurs when inflamma