13) Granulocytes & monocytes Flashcards

1
Q

normal diff ranges for an adult

A
  • 40-80% segs
  • 0-5% bands
  • 25-35% lymphs
  • 2-10% monos
  • 0-5% eos
  • 0-1% basos
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2
Q

general changes that occur as grans mature

A

Nucleus
- chromatin condenses
- nucleoli lost
- indentation

Cytoplasm
- loses RNA (less blue)
- no granules → primary granules → secondary granules

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3
Q

6 morphologically identifiable gran stages

A
  1. myeloblast
  2. promyelocte
  3. myelocyte
  4. metamyelocyte
  5. band neutrophil
  6. segmented neutrophil
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4
Q
  • high N:C ratio
  • nucleus round or oval, smooth
  • 1-5 nucleoli visible
  • small blue cytoplasm
  • no granules
  • larger than a lymph
A

blast

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5
Q

auer rods

A

pink/red splinters made of fused primary granules
found in myeloblasts, monoblasts, pros

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6
Q
  • high N:C ratio
  • smooth chromatin, slightly coarse
  • several nucleoli
  • nucleus frequently eccentric
  • blue cytoplasm with prominent primary granules
  • granules often overlay nucleus
A

pro

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7
Q

last gran stage capable of mitosis
goes through 2-3 divisions

A

myelocyte

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8
Q

first gran stage committed to one of the 3 lines

A

myelocyte

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9
Q
  • nucleus round, oval or flattened on one side
  • chromatin beginning to clump
  • nucleoli usually not visible
  • pale area visible next to nucleus
  • secondary granules appear, cytoplasm less blue
A

myelo

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10
Q

dawn of neutrophilia

A

secondary granules made by the Golgi, which appears as a pale area next to the nucleus of a myelo

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11
Q

peroxidase = granules

A

secondary

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12
Q

peroxidase + granules

A

primary

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13
Q

vesicles formed by endocytosis
fuse with plasma membrane upon activation, allowing expression of adhesion and chemotactic receptors

A

secretory vesicles

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14
Q

secretory vesicle first appear in…

A

myelos

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15
Q
  • coarse and clumping chromatin
  • no nucleoli visible
  • nuclear indentation <1/2 diameter
  • pinkish tan cytoplasm
  • predominance of secondary granules
A

meta

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16
Q
  • clumped chromatin
  • indentation >1/2 diameter
  • no filaments
  • pinkish tan cytoplasm
A

band

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17
Q

hyposegmented neutro

A

1-2 lobes in most

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18
Q

hypersegmented neutro

A

5 or more lobes in 5 or more cells

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19
Q

barr body

A

inactive X chromosome
extension of nucleus on a seg
only in women
clinically insignificant

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20
Q

3 compartments where neutros spend their life

A

BM
PB
tissues

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21
Q

2 pools of BM neutros and characteristics

A
  • mitotic pool/proliferating pool—3-6 days—capable of DNA synth—blasts, pros, myelos
  • postmitotic pool—5-7 days—metas, bands, segs—3x size of mitotic pool
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22
Q

2 pools of PB neutros

A
  • circulating pool—drawn in CBC
  • marginal pool—rolling along vessel walls

freely exchange
50:50 ratio

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23
Q

neutros spend —– hours in PB before diapedesing

A

7.5

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24
Q

blast:pro:myelo:meta:band:seg ratio in BM

A

1:3:12:16:12:7

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25
Q

neutros usually live for ——– days in tissue, but GM-CSF and C-CSF can increase this to ——- days

A

1-2
3-5

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26
Q

neutros time spent in BM

A

1-2 weeks

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27
Q

stem cell → blast

A

stem cell
CMP
CFU-GEMM
CFU-GM
CFU-G
blast

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28
Q

4 steps of neutro function

A
  • adherence
  • migration/chemotaxis
  • phagocytosis
  • bacterial killing
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29
Q

interaction between neutro and vascular endothelial cells (VECs)

A

adhesion

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30
Q

VEC

A

vascular endothelial cells

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31
Q

types of cell adhesion molecules that facilitate adherence

A
  • selectins
  • integrins
  • ICAMs
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32
Q

on activated VECs and inactivated neutros
bind loosely

A

selectins

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33
Q

selectins on VEC and neutro

A

VEC: E-selectin, P-selectin
neutro: L-selectin

34
Q

———- is always present on the neutro in absence of cytokines, but cytokines cause upregulation

A

L-selectin

35
Q

β2 family are ———-

A

integrins

36
Q

on activated neutros
bind tightly to VECs

A

integrins

37
Q

on activated VEC
bind tightly to neutros

A

ICAMs

38
Q

ICAM

A

intercellular adhesion molecules

39
Q

bind tightly, causing arrest of neutro

A

β2 integrin on neutro and ICAM on VEC

40
Q

stages of neutrophil adherence and diapedesis

A
  1. Loose attachment—selectins on VEC activated; transiently associated with L-selectin; allow rolling adhesion
  2. Activation of neutros—chemokines & chemoattractants activate neutrophil to express integrins; L-selectin downregulated
  3. Arrest of neutrophil—neutro β2 integrin + VEC ICAM allows tight binding; cytoskeleton of neutro changes shape and NADPH oxidase membrane complexes are assembled to prepare for bacterial killing
  4. Diapedesis—neutrophils follow chemoattractants into tissue; neutro enzymes like gelatinase B help dissolve basement membranes
41
Q

neutrophils move toward targets with ——– motion

A

ameboid

42
Q

stages of neutro phagocytosis

A
  • recognition and binding
  • engulfment
  • formation of phagosome
  • phagolysosome fusion
  • killing and digestion
  • exocytosis
43
Q

2 ligands that neutros use to phagocytize

A

PAMPs (pathogen associated molecular patterns)
Opsonins (IgG, C3)

44
Q

2 types of neutro microbicidal mechanisms

A
  • oxygen-dependent/oxidative
  • oxygen-indepentent
45
Q

oxidative microbicidal mechanisms in neutro

A
  • respiratory burst
  • myeloperoxidase (MPO)
46
Q

respiratory burst

A

NADPH oxidase generates and pours reactive oxygen species into phagosome

47
Q

MPO action

A

catalyzes interaction of H2O2 produced during resp burst with halides

oxidized halogens increase bacterial killing

48
Q

examples of oxygen-independent mechanisms in neutro

A
  • acid pH
  • lysozyme
  • lactoferrin
  • defensins
  • collagenase
  • hydrolases
49
Q

a normal left shift does not include ——– or ———

A

pros or blasts

50
Q

causes of neutrophilia

A
  • bacterial infection
  • metabolic intoxication
  • drug intoxication
  • tissue necrosis
  • shift from marginating pool to circulating pool (no net increase)
  • reduced egress of neutros from blood to tissues
51
Q

normal neutrophilia during infection

A

10-25

52
Q

changes to neutros during infection

A
  • left shift
  • toxic gran
  • dohle bodies
  • vacuolization
53
Q

pseudoneutrophilia/shift neutrophilia

A

result of redistribution from marginating to circulating pool

54
Q

causes of pseudoneutrophilia

A
  • active exercise
  • epinephrine
  • anesthesia
  • stress
55
Q

leukemoid reaction

A

extreme benign neutrophilia
due to severe infection or necrotizing tissue

56
Q

how to tell CML apart from leukemoid reaction

A

In leukemoid rxn…
- WBC count <50 usually
- inclusions: toxic gran, dohle bodies, vacuoles
- usually no blasts
- transient
- normal karyotype (no Philadelphia chromosome)
- ↑ LAP in 90-95% pts
- rare to have ↑ basos or eos
- no blue histiocytes, pseudo-gaucher, or pseudo-PH
- normal platelet morphology, may be ↑

57
Q

ANC defining neutropenia

A

<1.8

58
Q

major cytokines affecting eosinophil differentiation

A
  • IL-5 released by TH2 cells
  • GM-CSF
  • IL-3
59
Q

3 types of eo granules

A
  1. primary granules
  2. small granules
  3. specific/secondary granules
60
Q

eo’s specific granules contents

A
  • major basic protein
  • eosinophil cationic protein
  • eosinophil peroxidase
  • eosinophil derived neurotoxin
61
Q

eos are influenced by the ———- part of the immune system

A

cellular/T cell

62
Q

host defense against helminths

A

eos

63
Q

eosinophilia

A

> 0.45

64
Q

when is eosinophilia seen?

A
  • allergic diseases
  • parasitic infections
  • toxic reactions
  • GI diseases
  • resp tract disorders
  • certain neoplastic disorders
65
Q

how long do eos spend in PB before migrating to tissues?

A

18 hours

66
Q

basophilic granules contain…

A
  • histamine
  • heparin
  • cathepsin G
  • major basic protein
  • lysophospholipase
67
Q

how are basos different from masts?

A

Basos
- found in PB, not tissues
- mature in BM
- do not proliferate
- live for days
- segmented nucleus
- varying amt of granules

Masts
- found in BM and tissues, not PB
- mature in tissues
- proliferative potential
- live weeks to months
- round nucleus
- cytoplasm completely full of dense granules

68
Q

mediators of inflammatory response
asthma, urticaria, allergic rhinitis, anaphylaxis

A

basos

69
Q

have receptors for IgE

A

basos

70
Q

baso enzymes cause…

A

vasodilation
bronchoconstriction
chemotaxis

71
Q

basos express ——— ligand to induce IgE class switching in B cells

A

CD40

72
Q

monocyte precursors

A
  • monoblasts
  • promonocyte
73
Q
  • ovoid or round nucleus, folded or indented
  • pale purple fine chromatin
  • several nucleoli
  • abundant agranular blue-gray cytoplasm
A

monoblast

74
Q

nonspecific esterase activity, inhibited by Na fluoride

A

monoblast

75
Q
  • irregular, indented nucleus with fine chromatin
  • may have nucleoli
  • abundant blue-gray cytoplasm
  • fine azurophilic granules
A

promonocyte

76
Q

2 types of monocyte granules

A
  • contains peroxidase, acid phosphatase, arylsulfatase
  • not much known about the other
77
Q

histiocytes

A

tissue macrophages

78
Q

no significant storage pool in BM

A

monos

79
Q

monos time in BM

A

54 hours

80
Q

monos spend —— hours in PB before they diapedese

A

8