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
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
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)
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
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
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
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)
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
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
10
Q
Clinical manifestations of neutropenia
A
- Gingivitis
- Mucosal ulcers
- Ab pain
- Abscesses
- Fevers