Acute Inflammation Flashcards
What is the main role of the selectin family of proteins?
Mediates the rolling interactions of leukocytes on the vessel wall.
What do selectin molecules bind to on leukocytes?
The ligands for selectins are the Sialyl-Lewis X oligosaccharides that are on leukocytes. This is how they mediate the rolling effect of leukocytes along the vessel wall.
What induces release of P-selectin, and from what cell? What induces the release of E-selectin, and from what cell?
P-selectin release is induced by histamine from Weibel-Palade bodies on endothelial cell granules.
E-selectin release is induced by TNF and IL-1 and is from endothelial cells
What family of proteins mediates the adhesion of leukocytes (specifically neutrophils) to the endothelium?
The integrins
What two molecules upregulate the expression of integrins on the vessel wall?
TNF and IL-1 upregulate integrins
What are the two main integrin proteins that are upregulated on the vessel wall?
VCAM-1 and ICAM-1
What upregulates the expression of integrins on leukocytes?
C5a and LTB4
What is the most likely cause of leukocyte adhesion deficiency?
Most commonly due to autosomal recessive defect of integrins (CD18 subunit)
What is the physiologic process that produces exudate? Transudate?
Exudate is produced by an increase in permeability of small blood vessels due to ongoing inflammatory response. Transudate is produced as a result of osmotic or hydrostatic imbalances.
What cell type contains the most histamine that is released in acute inflammation?
Mast cells
What are the activator of mast cells?
- trauma
- complement proteins C3a or C5a
- Antigen binding to IgE and cross linking (allergies happen via this mechanism)
Where are mast cells located?
In the connective tissue surrounding endothelial cells
What two lipid mediators of the acute inflammation are produced from arachidonic acid?
Prostaglandins and leukotrienes
What acts on the phospholipid cell membrane to release arachidonic acid?
phospholipase A2
What two enzymes act on arachidonic acid to create (1) prostaglandins and (2) leukotrienes?
(1) cyclooxygenase and (2) 5-lipoxygenase
Which prostaglandin are major players in vasodilation (at the level of the arteriole) and vascular permeability (at the post-capillary venule)?
PGI2, PGD2, and PGE2.
What prostaglandin mediates pain and fever?
PGE2 (feeever)
Which leukotriene is a key attractant for neutrophils during an acute inflammatory response?
LTB4
Which leukotrienes are involved in vasoconstriction, bronchospasm, and increased vascular permeability of the venules?
LTC4, LTD4, and LTE4
By what mechanism do NSAIDS reduce pain?
Pain is mediated by the prostaglandin PGE2. NSAIDS block the COX enzymes which create prostaglandins including PGE2.
Which eicosanoids are involved in vasodilation?
PGI2, PGE1, PGE2, and PGD2
Which eicosanoids are involved in vasoconstriction?
TXA2, LTC4, LTD4, LTE4
Which eicosanoids are involved in increased vascular permeability?
LTC4, LTD4, and LTE4 (the leukotrienes)
Which eicosanoids are involved in chemotaxis and leukocyte adhesion?
LTB4
What receptor is present on cells of the innate immune system and are activated by pathogen-associated molecular patterns?
Toll-like receptors
What is the mechanism by which toll-like receptors are activated and how they produce multiple immune mediators?
TLRs are activated when pathogen-associated molecular patterns are recognized by CD14 (a coreceptor for TLR4) on the outside of gram negative bacteria.
They function by upregulation NF-kB which activates immune response genes leading to production of many mediators.
What are the key roles of TNF and IL-1?
Key role in induction of the systemic acute-phase response.
- in endothelial activation (allowing for neutrophil arrival and function; via E selection induction and cell adhesion molecules)
- for induction of fever
- for production of leukocytes
How is fever induced in an inflammatory response?
Pyrogens (eg from bacteria) cause macrophages to release IL-1 and TNF which increase COX activity in the perivascular cells of the hypothalamus.
fever is also induced
What 3 factors attract neutrophils to the site of injury?
IL-8, C5a, LTB4, and bacterial products
What is the pathway by which HOCl is generated?
O2 -> O2- via NADPH oxidase
O2- -> H2O2 via superoxide dismutase
H2O2 -> HOCL by myeloperoxidase (MPO)
What are NETs?
Neutrophil extracellular traps which provide a high concentration of antimicrobial substance sat site of infection and prevent the spread of microbes by trapping them.
What type of proteins enhances phagocytosis of neutrophils?
Opsonins (IgG and C3b)
What are the 3 ways that the complement protein C3 can become cleaved?
Classical: C1 binding to IgM or IgG bound to antigen
Alternative: microbial products activate complement
Lectin: mannose-binding lectin in plasma binds to carbohydrates on microbes and directly activates C1
Which complement protein acts as a C5 convertase to make C5a and C5b?
C3b (cleaved from C3 to make C3a and C3b)
How is the MAC formed?
C5b binds C6-C9 to make the MAC and lyse cells
Which complement proteins stimulate histamine release?
C3a, C5a and C4a
Which complement proteins are chemotaxic for neutrophils, eosinophils, and basophils?
C5a
Which complement proteins are opsins?
C3b
What is a factor of the coagulation cascade that is also an inactive proinflammatory protein? How does it become active?
factor XII. Activated when XII leaks out of vessels and comes in contact with extracellular components. Activates kinin and coagulation cascades
What does factor XIIa do that connects it to the inflammatory response?
Cleaves C3 in the complement protein system
What are the 3 morphological patterns of acute inflammation?
Serous inflammation
Fibrinous inflammation
Purulent (suppurative) inflammation
What characterizes serous inflammation?
Marked by the exudation of cell-poor fluid into spaces created by cell injury or into body cavities.
What characterizes fibrinous inflammation?
Fibrinous exudate develops when the vascular leaks are large (happens with a more pronounced increase in vascular permeability.
What characterizes purulent inflammation?
Characterized by production of pus, especially as in an abscess
