What is the FUNCTIONAL consequence of acute inflammation?
Allows inflammatory cells, plasma proteins, and fluid to exit blood vessels and enter interstitial space
What is the GOAL of acute inflammation?
To eliminate dead cells/microorganisms so as to make way for wound healing
What is more likely to trigger acute phase inflammatory response, necrosis (e.g. due to infarct) or or apoptosis?
What are the three phases of acute inflammation, in order or onset?
Necrosis - rupturing of cells is fastest trigger of acute inflammatory response.
Phase 1 - liquid phase
Phase 2 - neutrophil phase
Phase 3 - macrophage phase
What cell types are the initiators of acute inflammatory response - first responders to necrotic cell death?
Mast cells (first) and later neutrophils then macrophages
Where are mast cells found?
Widely distributed through connective tissue.
What cell type is rapidly activated by trauma and Compliment (C3A, C5A)?
What cell type involved in Phase 1 of the acute inflammatory response expresses IgE? What happens when antigen cross-links these surface receptors (Does this cell type get activated or inactivated)?
Mast cells - activated by antigen crosslinking IgE receptors
(1) What is the rapid response of a mast cell to IgE crosslinking by antigen, trauma, or compliment binding (C3A, C5A)? (2) What is the main function of all of these responses?
Release of PREFORMED histamine granules - vasodilation of smooth muscle (arteriolar) and increased vascular permeability (post capillary venules)
(1) 24 hours after necrotic tissue damage, what cell type has reached it’s peak concentrations in injured tissue? (2) What cell type reaches it’s peak at 2-3 days?
1) polymorphic leukocytes …. AKA…neurtrophils
(1) What cell type exhibits a both a rapid and a delayed response to trauma, C3A, C5A, or IgE antigen crosslinking? (2) In the delayed response, what important immunogenic molecule is cleaved from the cell membrane and what enzyme is responsible for it’s cleavage? (Hint: the molecule in question is big and fat ).
1) Mast cells 2)Arachodonic acid - the great grand-daddy of all the lipid signalling molecules. 3) Cleaved from plasma membrane by phospholipase A2 (PLA2).
What metabolite of arachidonic acid causes fever and pain?
PGE2 “fEEEEver” (and pain)
(1) What enzyme produces prostoglandins? (2) What is precursor molecule (of the prostoglandin, not the enzyme)? (3) What are the products of the precursors enzymatic cleavage? (4) What do they all have in common, (5) which one does somethings that are unique during acute inflammation? (Hint: 3 we should know about)
1) In acute inflammatory phase, cyclocoxiginase cleaves 2) arachidonic acid into prostaglandins 3) PGI2, PGD2, and PGE2. 4) Once AracAcid is released from cell membranes of mast cells via PLA2 and cleaved by COX, all prostoglandins triggeer vasodilation and increase vascular permiability. (5) PGE2 cases pain and fever.
What are the three pathways of compliment?
Clasical - antipbody (IgM/IgG) binds microbe/antigen then C1/C2 comlex binds anitibody - activates antibody cascade leading to C3BbBbbbbbbbbs some this where it get’s opsonized
Alternative pathway - more straight-forward C3 is clearved, binds, causes cascade making more and more C3b until packman eats the cherries.
Manose-binding lectin pathways - pokes holes in cells via creation of “memory attack complex” utilizes C5 and C9 to make pore in membrane and then pop goes the weasel.
Cleavage byproducts of C3 convertase pathways (common route of all three compliment pathways) lead to production of C3A and C5A which further degranulate mast cells and more make histomine and more vasodilation/vascular permeability (swelling)
What other enzymatic pathway acts on the grand-daddy of all lipids (arachidonic acid)? What are the byproducts? What do the byproducts do? Which employ largely counter-regulatory functiosn to PGI2 and PGD2? What is the exception that we should know for sure?
5 - lipogenase cleaves Arachacid to produces leukotrines!
Leukotrine B4 (LESBIAN TRANSEXUAL BISEXUAL 4) or LTB4 is a chemoattractant for neurtrophils
LTC4, LTD4, LTE4 all mediate vascoCONSTRICTION and slow the reacting substances of anaphylaxis (e.g HISTAMINE!) but also mediate brochospasm and increase vascular permeability
What substance plays an important role in the acute inflammatory response by ultimately activating compliment, the coagulation and fybrolytic systems, and the kinin systemis, but is formed and rleased as an inactivated proinflammatory molecule by the liver? What ultimately activates it? What does it ultimately do? what systemic condition can it contribute to that leads to anemea? what is another name for it?
Hageman factor (Factor XIII), Activates kinin system by cleaving high molecular weight kininogen (HMWK), which leads to bradykinin (vasodilation, increased vascular permeability, and pain) and can give you painful DIC that leaves you with with anemia. Hageman factor is activated by expose ure subendothlelial or tissue collagen.
What cell type are integrins expresed on? what is their function? what happens when you have a defficiency of integrins (specifically the CD18 subunit?)
Integrins are upregulated on leukocytes by action of C5a and LTB4 (byproducts of the delayed
What is NF-kB? What’s it’s function, what receptor activates it and under what conditions?
Transcription factor for acute immunre response mediators, activated/upregulated by binding of bacterial products (e.g. LPS) to TLR4. Key step for intitating the actute inflamatory response.
What is a PAMP? Where are they found? What happens when they’re detected? Are they pro-inflammatory or anti-inflammatory, involved in acute or chronic immunre reponse?
Pathagen associated molecular patters (PAMPs) are non-specific regcognition sequences that bind to the non-specific toll like receptor 4, which then intiates upregulation of transcription factor NF-kB to trigger acute immune response. Found on surface of microbes