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What are cytokines?
Cytokines are low-molecular weight proteins produced by inflammatory (and other) cells during inflammation
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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
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Why is TNF only have limited use as a anti cancer agent?
- induces unpleasant flu-like symptoms
- is not effective against most common cancers
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At low concentration cytokines lead to what?
- induce protein synthesis
- vasodilation
- vasopermability
- expression of EC adhesion molecules that recruit inflammatory cells
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At high concentrations of cytokines induce?
- fever
- the coagulation casase
- progressive development of scar tissue, fibrosis
- (over time) cachexia
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Neutrophils contributef __ % of granulocytes, their function is to ________________________ and their harmful effect is _______.
- 75%
- phagocytosis of tissue debris, microbes
- tissue injury
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Eosinophil contribute ____% of granulocytes, their function is to_________ and their harmful effect is _____
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Mast cell/ basophil contribe < ___% of granulocytes. Their function is ________ and their harmful effect is _____
- 1%
- regulation of inflammation
- allergy
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Injury without infection generate_____?
Sterile inflammation
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ECM fragments can be DAMPS, what is an example of this type of DAMP? and what is its receptor?
- hyaluronan
- toll-like receptors, TLRs
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HMGB1 from chromatin is an example of DAMP, what type of DAMP is it and what is its receptor
- intracellur proteins
- TLRs,RAGE
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DNA and RNA is a type of DAMP, what is its receptor
TLRs
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P2X7 purinergic is a receptor for what type of DAMP?
ATP
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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
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signalling from what two receptors activates inflammasomes
TLR & P2X7Rs
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When caspase-1 becomes activated what does it cleave into an active form? What other cytokine is released
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what is the function of IL-1β and IL-1α?
Induce ECs to become adhesive for leukocytes
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What is margination?
Recruitment of circulating neutrophils requires adherence to the endothelium
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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
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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
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When does firm adhesion with flattening occur?
Occurs when inflamma
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