Chapter 9 Leukocyte Development, Kinetics, and Functions

Question 1

(also known as white blood cells, or WBCs) are so
named because they are relatively colorless compared to red blood cells

Answer 1

Leukocytes

Question 2

The number of different types of leukocytes varies depending on whether they are being viewed with a light microscope after staining with a

Answer 2

Romanowsky stain

Question 3

group of leukocytes whose cytoplasm is filled with granules with differing staining characteristics and whose nuclei are segmented or lobulated

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Granulocytes

Question 4

granules containing basic proteins that stain with acid stains such as eosin

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eosinophils

Question 5

granules that are acidic and stain with basic stains such as methylene blue

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basophils

Question 6

granules that react with both acid and basic stains, which gives them a pink to lavender color

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neutrophils

Question 7

nuclear segmentation is quite prominent in mature neutrophils, they have also been called

Answer 7

polymorphonuclear cells, or PMNs

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categorized into monocytes and lymphocytes

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Mononuclear cells

Question 9

These cells have nuclei that are not segmented but are round, oval, indented, or folded

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monocytes and lymphocytes

Question 10

The number of circulating leukocytes varies with

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sex, age, activity, time of day, and ethnicity;

Question 11

leukocytes also differs according to whether or not the leukocytes are reacting to

Answer 11

stress, being consumed, or being destroyed

Question 12

overall function of leukocytes is in mediating immunity, either

Answer 12

innate (nonspecific) or specific (adaptive)

Question 13

phagocytosis by neutrophils

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innate (nonspecific)

Question 14

production of antibodies by lymphocytes and plasma cells

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specific (adaptive)

Question 15

movement of cells through developmental stages, into the circulation, and from the circulation to the tissues and includes the time spent in each phase of the cell’s life

Answer 15

kinetics

Question 16

make up the vast majority of circulating leukocytes

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Segmented neutrophils

Question 17

Neutrophil development occurs in the bone marrow. Neutrophils share a common progenitor with monocytes and distinct from eosinophils and basophils, known as the

Answer 17

granulocytemonocyte progenitor (GMP)

Question 18

major cytokine responsible for the stimulation of neutrophil production is

Answer 18

granulocyte colony-stimulating factor, or G-CSF

Question 19

There are three pools of developing neutrophils in the bone marrow

Answer 19

stem cell pool, the proliferation pool, and the maturation pool

Question 20

consists of HSCs that are capable of self-renewal and differentiation

Answer 20

stem cell pool

Question 21

consists of cells that are dividing and includes (listed in the order of maturation) common myeloid progenitors (CMPs), also known as colony-forming units granulocyte, erythrocyte, monocyte, and megakaryocyte (CFUGEMMs)

Answer 21

proliferation (mitotic) pool

Question 22

consisting of cells undergoing nuclear maturation that form the marrow reserve and are available for release: metamyelocytes, band neutrophils, and segmented neutrophils

Answer 22

maturation (storage) pool

Question 23

not distinguishable with the light microscope and Romanowsky staining and may resemble early type I myeloblasts or lymphoid cells

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HSCs, CMPs, and GMPs

Question 24

make up 0% to 3% of the nucleated cells in the bone marrow and measure 14 to 20 “m in diameter

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Myeloblasts

Question 25

high nucleus-to-cytoplasm (N:C) ratio of 8:1 to 4:1

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type I myeloblast

Question 26

slightly basophilic cytoplasm, fine nuclear chromatin, and two to four visible nucleoli no visible granules when observed under light microscopy with Romanowsky stains

Answer 26

Type I blasts

Question 27

presence of dispersed primary (azurophilic) granules in the cytoplasm; the number of granules does not exceed 20 per cell

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type II myeloblast

Question 28

have a darker chromatin and a more purple cytoplasm, and they contain more than 20 granules that do not obscure the nucleus.

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Type III myeloblasts

Question 29

Type III myeloblasts are rare in normal bone marrows, but they can be seen in certain types of

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acute myeloid leukemias

Question 30

Mufti and colleagues10 proposed combining type II and type III blasts into a single category of

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“granular blasts”

Question 31

comprise 1% to 5% of the nucleated cells in the bone marrow

Answer 31

Promyelocytes

Question 32

Promyelocytes are relatively larger than the myeloblast cells and measure

Answer 32

16 to 25 "m in diameter

Question 33

Promyelocytes nucleus is round to oval and is often eccentric. A paranuclear halo or “hof ” is usually seen in normal promyelocytes but not in the

Answer 33

malignant promyelocytes of acute promyelocytic leukemia

Question 34

make up 6% to 17% of the nucleated cells in the bone marrow and are the final stage in which cell division (mitosis) occurs

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Myelocytes

Question 35

Myelocytes production of primary granules ceases and the cell begins to manufacture secondary (specific)

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neutrophil granules

Question 36

may look very similar to the promyelocytes (described earlier) in size and nuclear characteristics except that patches of grainy pale pink cytoplasm representing secondary granules begin to be evident in the area of the Golgi apparatus

Answer 36

Early myelocytes

Question 37

patches of grainy pale pink cytoplasm representing secondary granules begin to be evident in the area of the Golgi apparatus. This has been referred to as the

Answer 37

dawn of neutrophilia

Question 38

somewhat smaller than promyelocytes (15 to 18 "m), and the nucleus has considerably more heterochromatin

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Late myelocytes

Question 39

constitute 3% to 20% of nucleated marrow cells. From this stage forward, the cells are no longer capable of division and the major morphologic change is in the shape of the nucleus.

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Metamyelocytes

Question 40

Nucleoli are absent. Synthesis of tertiary granules (also known as

Answer 40

gelatinase granules

Question 41

The size of the metamyelocyte is slightly smaller than that of the myelocyte

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14 to 16 "m

Question 42

The cytoplasm of metamyelocyte contains very little residual ribonucleic acid (RNA) and therefore little or no

Answer 42

basophilia

Question 43

make up 9% to 32% of nucleated marrow cells and 0% to 5% of the nucleated peripheral blood cells

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Bands

Question 44

(also known as secretory vesicles) may begin to be formed during this stage

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Secretory granules

Question 45

nucleus is highly clumped, and the nuclear indentation that began in the metamyelocyte stage he cell should be called a

Answer 45

segmented neutrophil

Question 46

recommends that bands should be included within the neutrophil count and not reported as a separate category because of the difficulty in reliably distinguishing bands from segmented neutrophils

Answer 46

Clinical and Laboratory Standards Institute (CLSI)

Question 47

make up 7% to 30% of nucleated cells in the bone marrow. Secretory granules continue to be formed during this stage.

Answer 47

Segmented neutrophils

Question 48

The only morphologic difference between segmented neutrophils and bands is the

Answer 48

presence of between two and five nuclear lobes connected by thread-like filaments

Question 49

present in the highest numbers in the peripheral blood of adults

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Segmented neutrophils

Question 50

pediatric values are quite different; relative percentages can be as low as 18% of leukocytes in the first few months of life and do not begin to climb to adult values until after

Answer 50

4 to 7 years of age

Question 51

Neutrophil production has been calculated to be on the order of between

Answer 51

0.9 and 1.0 X 10 to the power 9 cells/kg per day

Question 52

proliferative pool contains approximately

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2.1 X 10 to the power of 9 cells/kg

Question 53

maturation pool contains roughly

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5.6 X 10 to the power of 9 cells/kg, or a 5-day supply

Question 54

transit time from myeloblast through myelocyte has been estimated to be roughly

Answer 54

6 days

Question 55

transit time through the maturation pool is approximately

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4 to 6 days

Question 56

Granulocyte release from the bone marrow is stimulated by

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G-CSF

Question 57

loosely localized to the walls of capillaries in tissues such as the liver, spleen, and lung

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neutrophils in the MNP

Question 58

ratio of neutrophils of either the CNP or the MNP, two pools is roughly equal overall; however, marginated neutrophils in the capillaries of the lungs make up a considerably larger portion of

Answer 58

peripheral neutrophils

Question 59

The half-life of neutrophils in the blood is relatively short at approximately

Answer 59

7 hours.

Question 60

significant importance in allowing neutrophils to marginate as well as exit the blood and enter the tissues by a process

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Integrins and selectins

Question 61

Integrins and selectins are of significant importance in allowing neutrophils to marginate as well as exit the blood and enter the tissues by a process known as

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diapedesis

Question 62

Those neutrophils that do not migrate into the tissues eventually undergo programmed cell death or apoptosis and are removed by macrophages in the

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spleen, bone marrow, and liver

Question 63

the neutrophil’s life span is measured in hours

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absence of infectious or inflammatory agents

Question 64

regulated by pro- and antiapoptotic members of the Bcl-2 family

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Spontaneous neutrophil apoptosis

Question 65

inflammation and infection such as Mcl-1 and myeloperoxidase (MPO) tend to prolong the neutrophil’s life span through antiapoptotic signals, whereas others such as

Answer 65

MAC-1 trigger the death and phagocytosis of neutrophils

Question 66

Neutrophils are part of the

Answer 66

innate immune system

Question 67

Characteristics of innate immunity include

Answer 67

destruction of foreign organisms that is not antigen specific; no protection against re-exposure to the same pathogen; reliance on the barriers provided by skin and mucous membranes phagocytes such as neutrophils and monocytes inclusion of a humoral component known as the complement system

Question 68

major function of neutrophils is

Answer 68

phagocytosis and destruction of foreign material and microorganisms

Question 69

The process involves seeking and destruction

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seeking (chemotaxis, motility, and diapedesis) and destruction (phagocytosis and digestion)

Question 70

The first neutrophil response is to roll along endothelial cells of the blood vessels using stronger adhesive molecules than those used by

Answer 70

nonstimulated marginated neutrophils

Question 71

Rolling consists of transient adhesive contacts between neutrophil selectins and adhesive molecules on the surface of endothelial cells

Answer 71

(P selectins and E selectins)

Question 72

Activation is facilitated by the rolling of neutrophils on endothelium surfaces by

Answer 72

chemokines

Question 73

neutrophil scans the region while tightly attached and does not always transmigrate at the location of adhesion

Answer 73

adhesion occurs

Question 74

Surface cell receptors are primed when neutrophils are exposed to

Answer 74

lipopolysaccharide, tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor (GM-CSF)

Question 75

Surface cell receptors are primed when neutrophils are exposed to lipopolysaccharide, tumor necrosis factor-alpha or granulocyte-macrophage colony stimulating factor (GM-CSF), which are recognized by

Answer 75

Toll-like receptors

Question 76

Pseudopodia are extended around the foreign particle and enclose it within a

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“phagosome” (engulfment)

Question 77

Respiratory burst through the activation of NADPH oxidase.

Answer 77

H2O2 and hypochlorite are produced.

Question 78

Formation of the phagosome allows the reduced

Answer 78

nicotinamide adenine dinucleotide (NADH) oxidase complex, NOX2, within the phagosome membrane to assemble

Question 79

second function of neutrophils is the generation of

Answer 79

neutrophil extracellular traps, or NETs

Question 80

extracellular thread-like structures believed to represent chains of nucleosomes from unfolded nuclear chromatin material (DNA)

Answer 80

NETs

Question 81

NETs are generated at the time that neutrophils die as a result of

Answer 81

antibacterial activity

Question 82

has been used to describe this unique form of neutrophil cell death that results in the release of NETs

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NETosis

Question 83

third and final function of neutrophils is their

Answer 83

secretory function

Question 84

Neutrophils are a source of

Answer 84

transcobalamin I or R binder protein

Question 85

Neutrophils are a source of transcobalamin I or R binder protein, which is necessary for the proper absorption of

Answer 85

vitamin B12

Question 86

make up 1% to 3% of nucleated cells in the bone marrow

Answer 86

Eosinophils

Question 87

Eosinophil development is similar to that described earlier for neutrophils, and evidence indicates that eosinophils arise from the

Answer 87

CMP

Question 88

Eosinophil lineage is established through the interaction between the cytokines

Answer 88

interleukin-3 (IL-3), IL-5 (induced by IL-33), and GM-CSF and three transcription factors (GATA-1 (hematopoietic transcription factor), PU.1, and c/EBP)

Question 89

critical for eosinophil growth and survival

Answer 89

IL-5 and IL-33

Question 90

can be identified cytochemically because of the presence of Charcot-Leyden crystal protein in their primary granules

Answer 90

Eosinophilic promyelocytes

Question 91

presence of large (resolvable at the light microscope level), pale, reddishorange secondary granules, along with azure granules in blue cytoplasm

Answer 91

Eosinophil myelocytes

Question 92

Transmission electron micrographs of eosinophils reveal that many secondary eosinophil granules contain an

Answer 92

electron-dense crystalline core

Question 93

resemble their neutrophil counterparts with respect to their nuclear shape.

Answer 93

Eosinophil metamyelocytes and bands

Question 94

Secondary granules increase in number, and a third type of granule is generated called the

Answer 94

secretory granule or secretory vesicle

Question 95

The secondary granules become more distinct and refractory. Electron microscopy indicates the presence of two other organelles:

Answer 95

lipid bodies and small granules

Question 96

display a bilobed nucleus. Their cytoplasm contains characteristic refractile, orange-red secondary granules

Answer 96

Mature eosinophils

Question 97

last myelocyte mitotic division to the emergence of mature eosinophils from the marrow is about

Answer 97

3.5 days

Question 98

large storage pool of eosinophils in the marrow consisting of between

Answer 98

9 and 14 X 10 to the power 8 cells/kg