Chapter 2.1 Acute Inflammation (Part 3) Flashcards
How is material destroyed by neutrophils?
neutrophils form a phagosome, phagosome joins w lysosome =phagolysosome which will destroy the material ingested
What are the mechanisms by which material is destroyed in a phagolysosome?
oxygen dependent and oxygen independent
oxygen dependent is most effective
Describe the mechanism of O2 dependent killing in the phagolysosome.
O2 converted to super oxide O2- by NADPH oxidase
super oxide converted to H2O2 by SOD
H2O2 converted by MPO (myloperoxidase) to HOCl*
(HOCl generated by oxidative burst in phagolysosomse and destroys the phagocytosed microbe)
What happens in chronic granulomous disease (CGD)?
poor O2 dependent killing so patient gets regular infections and develops granulomas
defect due to NADPH oxidase defect (X-linked or autosomal recessive)
problems generating bleach, so get infections
Patients get infections and form granulomas with infections in CGD; what type of organisms cause these infections? Why?
catalase-positive organisms
(can get hydrogen peroxide to convert to bleach with NADPH oxidase pathway; can also get H2O2 because most bacteria produce some H2O2, so take H2O2 from bacteria and then produce bleach that way)
patients with CGD dont have a problem with most organisms because most bacteria have H2O2 which can be converted to bleach
but some bacteria produce catalase along with H2O2 and catalase destroys H2O2 so that pathway is knocked out
so its only with catalase positive bacteria that there is no source of H2O2
What five organisms do patients with CGD get infections with?
catalase-positive organisms
S Aureus P cepacia (REMEMBER!) S marcescens Nocardia Aspergillus
How do you screen for CGD? How does this test work?
Nitroblue tetrazolium test
turns blue if NADPH oxidase can convert O2 to O2-
remains colorless if NADPH oxidase is defective
How do patients with MPO deficiency present? What will NBT test show?
MPO converts H2O2 to HOCl
patients can’t produce bleach (defective conversion of H2O2 to HOCl)
vast majority of patients are asymptomatic … but have increased risk for candida infections
NBT test will be normal with patient with MPO deficiency
Describe O2 independent killing. How does it occur?
(less effective)
occurs via enzymes present in leukocyte secondary granules (e.G. lysozyme in macrophages and major basic protein in eosinophils)
Once infection is destroyed, within 24 hours neutrophils will disappear. How?
neutrophils die in tissue via apoptosis
dissapear within 24 hours after resolution of inflammatory stimulus
(pus=dead neutrophils)
After neutrophils have done their job, what is next phase of acute inflammation?
peak 2-3 days after inflammation begins
Macrophage phase
How do macrophages get into the tissue?
derived from monocytes in blood (when get into tissue we call them macrophages)
come into tissue exact same way as neutrophils
margination, rolling, adhesion, and transmigration
How do macrophages kill off phagocytosed material? What mechanism?
ingest via phagocytosis
destroy phagocytosed material using enzymes in secondary granules (primary mech is oxygen independent, key enzyme is lysozyme)
Macrophages manage the next step of acute inflammatory process. Describe.
manage the next step of the acute inflammatory process
resolution and healing (IL-10 and TGF-beta)-shut down inflammatory process
continued acute inflammation (via IL-8…the cytokine produced by macrophages to call in additional neutrophils)
abscess (organism needs to be walled off to protect rest of host… so call in/create abscess which is a walled off area of fibrosis around area of infection so inflammation trapped in that space, macrophages manage formation of abscess)
chronic inflammation (oh, neutrophils can’t handle, maybe virus, so macrophages ingest antigen and present via MHC-II)
Process has been going on for 8 weeks but patient is still coughing up pus, what is actually happening?
it is still ex of acute inflammation bc of the fact still have neutrophilic response
(neutrophils define acute inflammation)
