2.1 - Acute inflammation Flashcards
which CD located on macrophages is a coreceptor for TLR4?
CD14
CD14 on macrophages recognizes what bacterial component?
LPS
which CD on macrophages is responsible for recognition of LPS?
CD14
TLR activation results in upregulation of ______, a nuclear transcription factor
NFkB
PGE2 is responsible for mediating ______ and _______
pain and fever
5-lipoxygenase produces ______________
leukotrienes
what are the neutrophil chemoattractants? (4)
- LTB4
- C5a
- IL-8
- bacterial products
mast cells are activated by what 3 factors?
- tissue trauma
- C3a and C5a
- cross linking of cell surface IgE by antigen
the second phase of the mast cell response is mediated by ____________
leukotrienes
what are the 3 main complement pathways, and activators?
- classical: C1 binds IgG or IgM
- alternative: microbial products
- mannose-binding lectin: MBL binds mannose on microorganisms
all complement pathways converge in production of:
C3 convertase
what are the complement anaphylatoxins?
C3a and C5a
hageman factor is responsible for activation of what 3 systems?
- coagulation / fibrinolytic
- complement
- kinin
in inflammation, vascular permeability occurs in what vessel type, specifically?
post-capillary venules
in inflammation, what two molecules are responsible for sensitization of nerve endings?
- bradykinin
- PGE2
what is the pathophysiology behind fever?
- pyrogens cause macrophages to release IL-1 and TNF, which increase cyclooxygenase activity in perivascular cells of the hypothalamus
- increased PGE2 raises temperature set point
in fever production, macrophages release what compounds? what do they act on? where?
- IL-1 and TNF
- increase cyclooxygenase activity in perivascular cells of hypothalamus
what PG is responsible for raising the temperature set point in fever?
PGE2
weibel palade bodies contain what mediators?
- von willebrand factor (“W”)
- P-selectin (“P”)
in the rolling phase of neutrophil chemotaxis, P-selectin is mediated by ______________
histamine
in the rolling phase of neutrophil chemotaxis, E-selectin is induced by what two compounds?
- TNF
- IL-1
in the rolling phase of neutrophil chemotaxis, where are selectins located?
endothelial cells
in the adhesion phase of neutrophil chemotaxis, where are CAMs located?
endothelium
what 2 molecules are responsible for upregulation of ICAM and VCAM in the adhesion phase of neutrophil chemotaxis?
TNF and IL-1
in the adhesion phase of neutrophil chemotaxis, where are integrins located?
leukocytes
in the adhesion phase of neutrophil chemotaxis, leukocytes are upregulated by what two molecules?
C5a and LTB4
what is the inheritance of leukocyte adhesion deficiency?
AR
leukocytes adhesion deficiency is a defect of what molecule type, and on what cell type? what is the result?
- integrins (CD18 subunit) on leukocytes
- delayed separation of umbilical cord, lack of pus
leukocytes transmigrate across endothelium of what vessel type, specifically?
postcapillary venules
chediak higashi syndrome is a defect in what process? what is the underlying cause?
impaired phagolysosome formation due to protein trafficking defect
what is the inheritance of chediak higashi syndrome?
AR
the following sequelae correspond to what syndrome?
- increased risk of pyogenic infections
- neutropenia
- giant granules in leukocytes
- defective primary hemostasis
- albinism
- peripheral neuropathy
chediak higashi syndrome
the neutropenia seen in chediak higashi syndrome is due to________________
intramedullary death of neutrophils
the giant granules in leukocytes seen in chediak higashi syndrome is due to________________
fusion of granules arising from golgi apparatus
the defective primary hemostasis seen in chediak higashi syndrome is due to________________
abnormal dense granules in platelets
chronic granulomatous disease is characterized by a defect in what process?
poor oxygen dependent killing
chronic granulomatous disease is due to a defect in what ENZYME?
NADPH oxidase
what are the main catalase positive organisms responsible for infections in chronic granulomatous disease?
- pseudomonas cepacia**
- s. aureus
- serratia marcescens
- nocardia
- aspergillus
what is the test used to diagnose chronic granulomatous disease? how does it work?
- nitroblue tetrazolium
- leukocytes are incubated with NBT dye, which turns blue if NADPH oxidase can convert oxygen to superoxide radical but remains colorless if NADPH oxidase is defective
NBT test returns with a colorless result - what is the interpretation? why?
- defect in NADPH oxidase
- NADPH oxidase cannot convert oxygen to superoxide radical
myeloperoxidase is responsible for what step in oxygen dependent killing?
conversion of H2O2 to HOCl
MPO deficiency predisposes to infection by what organism?
candida
in MPO deficiency is the NBT test normal or abnormal? why or why not?
- normal
- conversion from oxygen to superoxide radical is intact (NADPH oxidase function is normal, which is what NBT tests)
during the resolution phase of neutrophil arrival and function, neutrophils regress via what mechanism?
apoptosis
do macrophages typically use oxygen dependent or independent killing?
independent (with lysozyme, eg)
in inflammation, macrophages are responsible for what main processes / pathways?
- resolution and healing
- continued acute inflammation
- abscess
- chronic inflammation
macrophages are the “managers” of inflammation - they dictate if a good job has been done and resolution can occur, or if more work needs to be done and more mediators need to be recruited
during the resolution and healing phase of acute inflammation, macrophages secrete what 2 cytokines? what is their general purpose?
- IL-10 and TGFB
- anti-inflammatory
