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Undeleted > Hematopoiesis > Flashcards

Hematopoiesis Flashcards

0
Q

what produces hematopoietic stem cells (HSCs) and endothelial cells?

A

common embryonic stem cells called hemangioblasts

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1
Q

where do embryonic hematopoietic stem cells (HSCs) originate?

A

in the yolk sac and aorta-gonad-mesenephros (AGM) region of the embryo

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2
Q

what species is the exception when it comes to blood cell types in utero?

A

cats - they produce a wider spectrum of blood cell types

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3
Q

describe the appearance of embryonic cells

A

they are huge and nucleated

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4
Q

when does bone marrow organization begin?

A

during the second trimester

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5
Q

describe bone development in 4 steps

A
  • *
    1. cartilage is calcified
    2. chondroclasts degrade mineralized cartilage
    3. vessels invade marrow space that is created
    4. osteoblasts form bony trabeculae
  • *
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6
Q

what two things form a connective tissue meshwork?

A
  1. vascular sinuses

2. extravascular mesenchymal stromal cells

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7
Q

when do hematopoietic cells from liver form circulating blood cells?

A

once hematopoietic microenvironment forms

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8
Q

what is extravascular space?

A

space between the vascular sinuses in bone marrow

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9
Q

what does extravascular space create?

A

a hematopoietic microenvironment

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10
Q

what does the extravascular space contain?

A
  • stromal elements (cells and extracellular matrix)
  • osteoclasts, plasma cells, mesenchymal stem cells, mast cells (rare)
  • accessory cells for hematopoiesis
  • hematopoietic cells
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11
Q

what cells are produced in the vascular space in birds?

A

erythrocytes and thrombocytes

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12
Q

where are all blood cells created in mammals? where do blood cells then go?

A

in extravascular space. they then have to migrate through the endothelium and into sinus, then circulatory system once its developed

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13
Q

where are quiescent hemaopoietic stem cells (HSCs) concentrated?

A

near endosteal and trabecular bone (osteoblasts)

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14
Q

where are more active HSCs and hematopoietic cells found?

A

near vascular sinuses

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15
Q

where are erythroid cells found?

A

around macrophages

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16
Q

where are megakaryocytic cells found?

A

near sinusoidal endothelial cells

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17
Q

where are granulocytic cells found?

A

near stromal cells located away from vascular sinuses

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18
Q

what cells are found in bone marrow stroma (connective tissue)?

A
  • endothelial cells
  • stromal cells
  • adipocytes
  • autonomic nerves
  • extracellular matrix
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19
Q

what is the function of bone marrow endothelial cells?

A

they synthesize hematopoietic growth factors

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20
Q

what do bone marrow endothelial cells regulate?

A

** they regulate transendothelial movement of cells to and from the extracellular space**

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21
Q

what do bone marrow endothelial cells and stromal cells produce?

A

extracellular matrix components

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22
Q

describe some characteristics of bone marrow stromal cells

A
  • fibroblastic-type or vascular smooth muslce like cells

- extensive branched cytoplasmic processes that provide structural support for the bone marrow

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23
Q

what is the function of bone marrow stromal cells?

A

** they synthesize collagen fibers and other extracellular matrix components **

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24
Q

what is the function of adventitial stromal cells in bone marrow?

A

they support the endothelium of the venous sinuses

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25
Q

** how do bone marrow stromal cells support hematopoiesis? **

A

** through cell-to-cell contacts and synthesis of growth factors **

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26
Q

what do bone marrow adipocytes develop from?

A

stromal cells

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27
Q

** what is the main function of bone marrow adipocytes? **

A

they accumulate increased lipid when the numbers of hematopoietic cells in the marrow decrease (reversible)

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28
Q

what is the main function of nerves in bone marrow?

A

largely vasomotor in function

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29
Q

** what may nerves in bone marrow promote ? **

A

** HSC mobilization **

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30
Q

what might nerves in bone marrow do (we are not sure)?

A

regulate hematopoietic growth factor synthesis by other cells

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31
Q

what is the function of collagen fibers in the extracellular matrix?

A

provide scaffolding

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32
Q

what does the extracellular matrix consist of?

A

collagen fibers
basal laminae of the sinuses
adhesion molecules
proteoglycans

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33
Q

which accessory cells are involved in regulating hematopoiesis that reside in the extravascular space of bone marrow?

A
  • macrophages
  • T-lymphocytes, B-lymphocytes, and NK cells
  • osteoblasts
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34
Q

which accessory cell is most important for erythropoiesis?

A

macrophages

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35
Q

what is the function of the various lymphocytes and NK cells in the extravascular space of bone marrow?

A

some produce positive growth factors

other subsets produce factors that inhibit proliferation of hematopoietic cells

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36
Q

what are osteoblasts important for in the extravascular space of bone marrow?

A

stem cell maintenance

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37
Q

** what are HSCs positive for?**

A

** the CD34 surface antigen **

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38
Q

what is the appearance of HSCs and HPCs? (hematopoietic stem cells and hematopoietic progenitor cells)

A

they are lymphocyte-like in appearance

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39
Q

** what is CD an abbreviation for ? **

A

** clusters of differentiation antigens **

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40
Q

what is the function of hematopoietic stem cells?

A
  • proliferation and sustained self-replication
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41
Q

**what do hematopoietic stem cells (HPCs) have the capacity to do? **

A

** to differentiate into all blood cell types and some tissue cell types (like macrophages, dendritic cells, osteoclasts, mast cells) **

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42
Q

briefly describe the cell cycle (G1, S, G2, M, Go)

A 
G1 = protein synthesis and preparation of DNA replication
S = DNA synthesis
G2 = protein synthesis and preparation for mitosis
M = mitosis
Go = resting phase
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43
Q

what is the function of hematopoietic progenitor cells (HPCs)?

A

proliferation, they replicate more rapidly than HSCs

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44
Q

describe the replication of hematopoietic progenitor cells

A

limited self-replication - not sustained without replenishment from HSCs

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45
Q

describe the differentiation of hematopoietic stem cells

A

more restricted lineage potential than HSCs

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46
Q

describe the amounts of HPCs relative to HSCs

A
  • hamatopoietic progenitor cells are much more common in neonates than adults. HPCs represent about 1% of bone marrow cells in adults *
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47
Q

what do HSCs produce?

A
  • common lymphoid progenitor cells (CLP)

- common myeloid progenitor cells (CMP)

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48
Q

what do CLPs (common lymphoid progenitors) give rise to?

A

B lymphocytes, T lymphocytes and NK cells

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49
Q

what do CMPs (common myeloid progenitors) give rise to?

A

non lymphoid blood cells, macrophages, dendritic cells, osteoclasts and mast cells

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50
Q

what are colony forming units (CFUs)?

A

progenitor cells that are recognized in bone marrow cultures by the types of colonies they form

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51
Q

what are some examples of colony forming units (CFUs)?

A
  • common myeloid progenitor
  • GM progenitor
  • erythroid progenitors
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52
Q

what types of cells do mesenchymal stem cells produce?

A
  • stromal cells and adipocytes
  • endothelial cells
  • fibroblasts and myoblasts
  • osteoblasts and chrondrocytes
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53
Q

what can additional stem cells in marrow grow?

A
  • hepatocytes and cholangiocytes
  • **neural cells **
  • epithelial cells of skin and GI tract
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54
Q

define homing of HSCs and HPCs

A

the process by which circulating HSCs and HPCs bind to luminal surfaces of endothelial cells in the bone marrow

55
Q

what is the process of homing of HSCs and HPCs

A
  1. migrate through endothelial cells
  2. migrate through extravascular space and bind to appropriate microenvironment location
  3. proliferate, self-replicate and differentiate
56
Q

what is the most important adhesion molecule?

A

beta-1-integrin

57
Q

what do adhesion molecules do?

A

they bind to glycoproteins including VCAM-1 in ECM

58
Q

**what type of adhesion molecules do hematopoietic cells express on their surface? **

A

** it varies depending on the hematopoietic cell**

59
Q

what does the binding of hematopoietic cells to ECM glycoproteins play a role in?

A

**activating signal pathways for cell growth, survival and differentiation or modulating responses to growth factors **

60
Q

describe the appearance of proteoglycans

A

they have a protein core with negatively charged repeating charbohydrate glycosaminoglycans (GAGs) such as chondroitin sulfate

61
Q

what is the function of proteoglycans?

A

they bind growth factors and strengthen the bonding of hematopoietic cells through binding with receptors on hematopoietic cells

62
Q

what are hematopoeitic growth factors?

A

they are glycoproteins that promote the proliferation, maturation and survival of hematopoietic cells

63
Q

** where are hematopoietic growth factors produced? **

A

** locally in the marrow (paracrine and autocrine) and/or by cells in peripheral tissues (endocrine) **

64
Q

what do cytokines include?

A

colony stimulating factors (CSFs), interleukins, and poietins

65
Q

what must hematopoietic cells have?

A

**an appropriate surface receptor to respond to a specific hematopoeitic growth factor **

66
Q

what does binding and activation of hematopoietic growth factor receptors do? (4 things)

A
  1. generation of transcription factors
  2. synthesis of molecules that inhibit apoptosis
  3. formation of cell cycle regulators (cyclins)
  4. **synthesis of additional HGF and HGF receptors **
67
Q

what is an identifying characteristic in the cell types or stages stimulated by hematopoietic growth factors (HGFs)?

A

**there is considerable redundancy and overlap in the cell types or stages stimulated by HGFs **

68
Q

what are some examples of early-acting factors within HGFs?

A
  • stem cell factor
  • flt3 ligand (FL)
  • thrmbopoietin (TPO)
69
Q

what do early-acting factors require the presence of?

A

other cytokines including IL3, IL6, IL11 and G-CSF

70
Q

what are some examples of intermediate-acting HGF factors?

A

IL3 (multi-CSF), GM-CSF, and IL-4

71
Q

what are some examples of late acting HGFs?

A

G-CSF, M-CSF, EPO, TPO, and IL5

72
Q

define indirect stimulation

A

TNF and IL1 stimulate stromal and accessory cells to release various HGFs

73
Q

what can CMP give rise to? what can that then differentiate into?

A

CMP can give rise to MkEP which can differentiate into MkP (megakaryocyte progenitors) and EPs (erythroid progenitors)

74
Q

what is the production of EP (erythroid progenitors) stimulated by?

A

SCF, IL-3, GM-CSF, and TPO in presence of EPO

75
Q

where do erythroid cells develop?

A

around macrophages

76
Q

what do macrophages help create?

A

microenvironment

77
Q

in what ways do macrophages help create a microenvironment?

A
  • early intermediate-acting growth factors
  • erythropoietin
  • inflammatory cytokines which can inhibit erythropoiesis
78
Q

what is the function of erythroid islands?

A

** they phagocytize expelled nuclei and damaged or aged erythrocytes **

79
Q

what do erythroid islands store from phagocytized erythrocytes?

A

iron

80
Q

what nutrients are needed for erythropoiesis?

A

amino acids
essential fatty acids
metals
vitamins

81
Q

name some examples of metals needed as nutrients for erythropoiesis

A

iron - for heme synthesis
copper - hephaestin, ceruplasmin
cobalt - component of B12

82
Q

name some examples of vitamins needed for erythropoiesis

A

vitamin B6 - heme synthesis
tetrahydrofolic acid - DNA, RNA synthesis
vitamin B12 - folate metabolism

83
Q

in what step of the maturational divisions is marrow released?

A

during the development of reticulocytes

84
Q

when are reticulocytes formed?

A

when metarubicytes expel their nuclei, usually while still bound to macrophages

85
Q

how many reticulocytes can be formed by one rubiblast?

A

one rubiblast produces about 16 reticulocytes in about 4 days

86
Q

where does reticulocyte maturation occur?

A

in marrow, blood, and spleen

87
Q

what type of reticulocytes do dogs have in blood?

A

aggregate reticulocytes

88
Q

what type of reticuolcytes do cats have in blood?

A

many punctate reticulocytes, sometimes no aggregate reticulocytes

89
Q

what type of reticuolcytes do cattle and goats have in blood?

A

none

90
Q

what type of reticuolcytes do sheep have in blood?

A

small numbers of punctate reticulocytes

91
Q

what type of reticuolcytes do horses have in blood?

A

none, even in response to anemia

92
Q

what are howell-jolly bodies

A

small pieces of nuclei that may be left behind in teh cell after nuclear extrusion

93
Q

how do H-J bodies (howell-jolly) form?

A

either karyorrhexis (fragmentation) of the metaurbricyte nucleus or during abnormal mitosis

94
Q

which organ removes H-J bodies?

A

the spleen

95
Q

what is erythropoietin growth factor?

A

the principal growth factor that promotes the viability, proliferation and differentiation of EPs expressing specific cell surface EPO receptors

96
Q

when do EPO receptors peak?

A

at CFU-E stage and decline

97
Q

what is the main mechanism of erythropoietin?

A

inhibition of apoptosis

98
Q

what is the effect of high concentrations of erythropoietin?

A

shorten marrow transit time and promote early release of large “stress” reticulocytes

99
Q

what are the sites of EPO synthesis?

A

renal interstitial cells

extrarenal production - liver, bone marrow macrophages and erythroid cells

100
Q

what increases the number of cells producing EPO?

A

hypoxia

101
Q

what causes inhibitionof erythropoiesis?

A
  • lack of HGFs

- inhibitors

102
Q

what are some examples of growth factors?

A

IL-3, GM-CSF, G-CSF

they act on CMP, GMP and GP

103
Q

what is the effect of G-CSF? which cells does it effect?

A

increased cell division, decrease marrow transit time

GPs to myeloblasts

104
Q

what cells produce growth factors?

A

T-lymphocytes and mononuclear phagocytes

fibroblasts and endothelial cells

105
Q

how is granulopoiesis inhibited? (3 ways)

A
  1. mature neutrophils in marrow release inhibitory substances like serine proteases
  2. neutrophil clearance of circulating G-CSF by binding to receptors
  3. mature neutrophils in peripheral tissues can remove bacterial stimulus for granulopoiesis
106
Q

how are eosinophils produced (3 ways)?

A
  1. marrow storage pool like neutrophils
  2. IL-3 and GM-CSF for early progenitors
  3. **IL-5 from Th2 lymphocytes for terminal maturation **
107
Q

how are basophils produced? (4 ways)

A
  1. GMP produces bipotential basophil/mast cell progenitor
  2. basophil progenitor for basophils
  3. granules at myelocyte stage
  4. ** specific factor not recognized - growth factors similar to those for eosinophils**
108
Q

how are mast cells produced (3 ways)?

A
  1. mast cell progenitor (MaP)
  2. mast cells develop in tissues
  3. SCF is especially important for mast cell formation, multiple cytokines involved
109
Q

what are examples of growth factors used for the production of monocytes?

A

IL-3, GM-CSF, M-CSF, and IL-34

110
Q

what is an unique characteristic about monocytopoiesis?

A

short generation time and little marrow reserve

111
Q

what may monocytes become?

A

macrophages or inflammatory dendritic cells in tissues, depending on the amounts of various cytokines present

112
Q

what does CDP form?

A

pre-classical dendritic cells and plasmacytoid dendritic cells

113
Q

where are CDP products released?

A

into the blood and enter the tissues

114
Q

what stimulates production of CDP?

A

various cytokines

115
Q

what are osteoclasts?

A

multinucleated cells which degrade bone

116
Q

what do osteoclasts develop from?

A

monocyte progenitors

117
Q

what are SCF and flt3 ligand?

A

early lymphoid progenitor cells in marrow

118
Q

where are most B-cells produced in mammals? birds?

A

in mammals - mostly marrow.
dogs, pigs, ruminants - peyer’s patches
in birds - bursa of fabricius

119
Q

where are T-cells produced?

A

in the thymus
progenitors in the marrow
final development in thymus

120
Q

what is the most important growth factor needed for B-lymphocyte production?

A

Il-7

121
Q

what inhibits B-lymphocyte production

A

certain cytokines including interferons

122
Q

where do activated B-lymphocytes migrate to?

A

cortex of lymph nodes and follicles in peyer’s patches and spleen

123
Q

what may B-lymphocytes developinto?

A

mature plasma cells

124
Q

what growth factors promote development of T-lymphocyte production?

A

Flt3L and IL-7

125
Q

where do T-lymphocytes accumulate?

A

in paracortical areas of lymph nodes
periarteriolar lymphoid sheaths of spleen
interfollicular areas of peyer’s patches

126
Q

where are NK cells primarily produced? are growth factors required?

A

in bone marrow

yes

127
Q

where do subsets of NK cells develop?

A

thymus, lymph nodes, liver and spleen

128
Q

do non-mammals have megakaryocytes?

A

no; the only giant cell in the marrow is the osteoclast

129
Q

where is the megakaryocyte niche located?

A

just outside the vascular sinuses

130
Q

what stimulates thrombopoiesis

A

proliferation and expansion of megakaryocyte progenitor cells

131
Q

what are the 2 main functions of thrombopoietin?

A
  • promotes differentiation of progenitor cells into megakaryocytes
  • stimulates increased endomitosis, results in increased ploidy and size
132
Q

where is the major site of thrombopoietin production?

A

endothelial cells of liver

133
Q

where are TPO (thrmbopoietin) receptors located and what do they do?

A

located on platelets and megakaryocytes, they bind and remove TPO, providing negative feedback

134
Q

what stimulates thrombopoietin (TPO) synthesis by liver during inflammation?

A

IL-6

Undeleted (134 decks)

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