Granulocytes Flashcards

1
Q

Granulocyte colony stimulating factor (GCSF)

A
  • Stimulates granulocyte production
  • Releases them from BM (loss of CXCR4)
  • Is anti-apoptotic
  • CXCR4 induces adhesion in BM and granulocyte retention, GCSF causes loss of CXCR4
  • Re-expression of CXCR4 brings granulocytes back to BM
  • 3-5% of granulocytes are in blood, the rest in BM
  • Release of granulocytes from BM controlled in part by sympathetic NS
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2
Q

Isolated neutropenia

A
  • Tested w/ absolute neutrophil count (ANC)
  • ANC = WBC x (SEGS + bands)
  • Bands= immature PMNs, SEGS= mature PMNs
  • Normal ANC is ≥1500, significant risk of infection <300 if due to marrow reserve pool depletion
  • Almost never due to malignancy
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3
Q

Propensity to infection in neutropenia

A
  • Related to adequacy of marrow reserve pool and not to ANC
  • ANC reflect propensity to infection only in the case of marrow failure (depleted reserve pool)
  • If there is neutropenia (low ANC) but BM has reserves, there will not be infection
  • If there is neutropenia and BM doesn’t have reserves, there will be infection
  • In immune or destructive neutropenia, there is no relation btwn ANC and propensity to infection
  • Must determine if neutropenia is causing infection of if its a secondary result of another global inflammatory process (AID such as RA or lupus)
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4
Q

Margination and diapedesis

A
  • Rolling along endothelium induced by selectins (weak interaction), adhesion induced by integrins (strong interaction)
  • Diapedesis induced by actin cytoskeleton reorganization to squeeze btwn endothelium
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5
Q

Chemotaxis

A
  • Based on chemokine/cytokine gradient
  • Actin polymerization and degradation responsible for movement
  • Actin polymerizes in 8 second cycles and drives PMN shape change
  • Actin extends pseudopod and pulls the cell forward
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6
Q

Phagocytosis

A
  • Fc receptor binds to Fc region on Ab (which is bound to Ag)
  • Could also be complement opsonization
  • Binding of the receptor leads to actin polymerization around the Ag
  • Once Ag is engulfed in the phagosome killing will commence
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7
Q

Bacterial killing

A
  • Through O2 independent and O2 dependent mechanisms
  • O2 independent: proteases and hydrolases in granules, antimicrobial peptides (defensins, cathelicidins)
  • O2 dependent: respiratory burst
  • Using NADPH + O2 to give superoxide (O2-), which will dismutate into H2O2 (NADPH oxidase)
  • Respiratory burst is critical in killing bacteria and fungi (defects in it cause CGD- lack of NADPH oxidase)
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8
Q

Myeloperoxidase (MPO)

A
  • Nz synthesized by promyelocytes and packaged in the primary granules
  • MPO used to combine Cl- w/ H2O2 to make HOCl (hypochloric acid, bleach)
  • HOCl is the agent which kills bacteria and fungi
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9
Q

Defects in superoxide generation of MPO

A
  • CGD: deficient in Phox gene which is required for generation of superoxide radicals (leads to recurrent infections at epithelial surfaces)
  • Dx w/ NBT test
  • MPO deficiency leads to impairment in host defense to candida, but not staph aureus
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10
Q

Clinical manifestations of neutropenia

A
  • Gingivitis
  • Mucosal ulcers
  • Ab pain
  • Abscesses
  • Fevers
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