Inflammation Flashcards
What causes heat and what are its benefits during infection?
The pyrogens Il-6 and IL-1B. They increase the metabolism of immune cells and decrease microbial growth.
PGE2 also acts on neurones to increase body temperature.
What causes redness and swelling? Benefits?
Extravasation from capillaries and post capillaires causes swelling, and increases leukoctye infiltration as well as infiltration of collections, pentraxins, complement, natural antibodies and ficolins.
Pain?
Caused by nociceptive stimuli, e.g. bradykinin and alarmins.
How might inflammation contribute to loss of function?
increased infiltration of lymphocytes, smooth muscel contractin and over secretino of mucus. Inflammation break down of tight junctions (MCLK?0)
What 3 detrimental effects can inflammation lead to if not resolved?
Autoimmune disease and inflammatory tissue damage, sepsis.
Lack of tissue repair can cause fibrosis.
Adaption to stress- shift in homoestatic balance, Autoinflammatory disease.
What causes acute inflammatory responses? And what cells contribute?
Pathogens and tissue damage.
innate cells essentially, especially neutrophils NK cells, monocytes and other granuloctyes.
Maybe other innate like cells?
Primary mecahnisms of actue infections?
vasoactive amines and eicosanoids.
Why might eicosanoids take longer to react?
Synthesised through the arachindonic pathway.
Examples of eicosanoids?
PGE2 and leukotrienes.
Functions of PGE2? And Luekotrienes?
Increase vasodilation and acts on neurones to act as a pyrogen. Very chemotactic for Th2 and eosinophils for the lungs.
Leukoctrienes also cause vasodilation and recruit neturophils.
How does C3a and C5a contribute to acute inflammation?
C3a and C5a can bind to mast cells and stimulate histamine release- vasodilation and extravastion.
They can both also act as chemoattractant e.g, forneutrophils and macrophages.
plsamin in actue inflammation?
breaks down fibrin clots, and cleaves complemet C3.
Also activates Factor XII.
What can factor XII do?
Factor XII can stimulate coagulation and fibrinolysis.
More importantly, factor XII activates the kinin system.
what can bradykinin do?
pain, vasodilation and permeability and causes smooth muscle contraction.
Can PGE2 cause phenotypic changes to immune cells?
Yes, can act on DCs to increase their IL-23production, to favour Th17 cell differentiation.
What are the two precursors and the products of the kinin system?
tissue kallikren and plasma kallikrin. Producees kalldin and bradykinin.
Proteases in the kinin system
amino peptidases.
Where is tissue and plasma kallikrein mostly found?
In the muscles and adipsoe.
Plasma kallikrein is in the liver mostly
what two pathways are involved in the arachidonic system?
pathways that makes prostaglandin and the other lipoxygenase pathway that make leukotrienes and other anti inflammatory molecules.
what enzymes are targeted by NSAIDs in the arachidonic pathway?
COX1 and COX2.
What chemokines attract neutrophils? What receptors do neutrophils have?
CXCL1-7.
CXCR1 and CXCR2 important for neutrohpil migration.
What chemokines attract lymphoctyes and monocytes? And what are the receptors for them?
CCL3,4 and 5.
Receptors are CCR5.
What chemokines attrct B cells with receptors CXCR4 and CXCR5?
CXCL12 and CXCL13.
What chemokines attract cell (T cells) with receptors CCR7?
CXCL19 and CXCL21.
What is the ligand for CX3CR1?
CX3CL1.
receptors in the IL-2 receptor family.
IL-2,4 IL-7,9 and Il-15 and Il-21. TSLP.
What are HSP, ATP, uric acid have in commno?
They are all DAMPs.
What components of the ECM can act as DAMPs? What TLR do they bind?
heparin sulfate, fibrinogen and tapasin C.
What are two inhibitory compleemnt receptors?
CD55 and CD59.
What does TLR9 recognise?
unmethylated CpG motfis on DNA.
What can TLR5 bind?
TLR5 can bind flagellin.
What does TLR 3 bind?
dsRNA
What can TLR 7 and 8 detect?
ssRNA.
What can TLR2 bind?
lipoproteins and glucans along with TLR6.
What do NLRs like NALP signal through?
When bound to HSP90 in steady state has PyCARD domain that maintains pro capsapse 1.
K+ efflux in inflammation and procaspase 1 becomes activated and cleaves inactive forms of IL-1B and IL-18.
What can NODs and NLPs and Rig like helciases sends?
bacterial peptidoglycans and RNA.
What does NOD signal through?
RIP2
how is NK-KB released?
IKKa and IKKB complex activated and phosphorylates IKB. IKB which was matinaing NF-KB is then degraded and NF-KB goes to nucleus.
