Hematopoiesis Part 2 Flashcards

1
Q

All blood cells are derived from single Pluripotent Hematopoietic Stem Cells

Most widely accepted

A

Monophyletic Theory

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2
Q

Pluripotent means

A

capable of self renewal, proliferation and differentiation

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3
Q

Each of the blood cell lineages is derived from its own unique stem cell

A

Polyphyletic Theory

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4
Q

 capable of self-renewal
 have a high-degree of proliferative capability
 pluripotent
 morphologically unrecognizable cells
 give rise to differentiated progenitor cells

A

Noncommitted or Undifferentiated Hematopoietic Stem Cells

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5
Q

 descendants of stem cells that can differentiate further into a specific cell lineage
 morphologically unrecognizable cells

A

Committed or Differentiated Progenitor Cells

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6
Q

Two types of Multilineage-specific Progenitor Cells

A
  1. Commo Myeloid Progenitor
  2. Common Lymphoid Progenitor
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7
Q

Committed or Differentiated Progenitor Cells lineage

A

Multilineage progenitors → Unilineage progenitors → give rise to precursor cells

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8
Q

CFU-GEMM

A

Granulocyte, erythrocyte, megakaryocyte, monocyte

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9
Q

CFU-E

A

Erythrocyte

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10
Q

CFU-Meg

A

Megakaryocyte

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11
Q

CFU-M

A

Monocyte

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12
Q

CFU-GM

A

Granulocyte, Monocyte

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13
Q

CFU-Baso

A

Myeloid to basophil

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14
Q

CFU-Eo

A

Myeloid to eosinophil

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15
Q

CFU-G

A

Myeloid to neutrophil

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16
Q

CFU-pre-T

A

T lymphocyte

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17
Q

CFU-pre-B

A

B Lymphocyte

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18
Q

 committed to forming a particular type of blood cell
 morphologically recognizable cells
 lineage-specific

A

Precursor Cells

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19
Q

MODEL OF HEMATOPOIESIS (Myeloid)

A

Pluripotent HSCs → Common Myeloid Progenitor → Granulocytic, Monocytic, Erythrocytic, Megakaryocytic Lineage

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20
Q

MODEL OF HEMATOPOIESIS (Lymphoid)

A

Pluripotent HSCs → Common Lymphoid Progenitor → T, B, NK-Lymphocytes, Dendritic Lineages

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21
Q

Stem Cell Marker - Lymphoid & Myeloid Precursors

A

CD 34

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22
Q

Stem Cell Marker - Committed Myeloid Progenitor

A

CD 33 & CD 38

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23
Q

Stem Cell Marker - Committed Lymphoid Progenitor

A

CD 10 & CD 38

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24
Q

Stem Cell Marker - T-lymphoid Progenitor cells

A

CD 7

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25
Q

Stem Cell Marker - B-lymphoid Progenitor Cells

A

CD 19

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26
Q

3 possible fates of Hematopoietic Stem Cells

A

 Self-renewal
 Differentiation
 Apoptosis

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27
Q

Symmetric Division Lineage

A

HSCs divide → 2 identical daughter cells → both daughter cells leave the stem cell pool → undergo differentiation

28
Q

Asymmetric Division Lineage

A

HSCs divide → 2 identical daughter cells → 1 daughter cell remains in the stem cell pool | 1 daughter cell leaves the stem cell pool → undergo differentiation or apoptosis

29
Q

HSC randomly commits to self-renewal or differentiation

A

Stochastic Model (Till and McCulloch)

30
Q

Microenvironment in the BM determines whether the HSC will self-renew or differentiate

A

Instructive Model

31
Q

Initial decision: (THEORY)

A

HSC randomly commits to self-renewal or differentiation (Stochastic) → decision to proceed with lineage differentiation in the presence of various signals from the hematopoietic inductive microenvironment of the BM (Instructive) → cell differentiation and maturation occur

32
Q

MORPHOLOGIC CHANGES THAT OCCUR AS CELL DIFFERENTIATES AND MATURES

A

 Overall decrease in cell volume and decrease in the ratio of nucleus and cytoplasm (N:C ratio)
 Changes in the nucleus
 Changes in the cytoplasm

33
Q

Changes in the NUCLEUS as cells DIFFERENTIATES and MATURES

A

 Loss of nucleoli
 ↓ diameter of nucleus
 Condensation of nuclear chromatin
 Shape of nucleus
 Loss of nucleus

34
Q

Changes in the CYTOPLASM as cells DIFFERENTIATES and MATURES

A

 ↓ in basophilia
 ↑ proportion of cytoplasm
 Possible appearance of granules in the cytoplasm

35
Q

SIGNALS FROM THE HEMATOPOIETIC INDUCTIVE MICROENVIRONMENT

A
  • Intrinsic Factors
  • Extrinsic Factors
  • Regulatory Signaling Factors
36
Q

 Intrinsic regulation involves ______

A

genes

37
Q

 TAL1 and GATA2 are essential for ____________

A

primitive and definitive hematopoiesis

38
Q

(FACTORS)
expressed in the cells in the hemangioblast (bipotential progenitor cell of mesodermal origin)

A

TAL1

39
Q

(FACTORS)
expressed in late-appearing HSCs

A

GATA2

40
Q

Extrinsic regulation involves _______________

A

growth factors/cytokines

41
Q

Allows HSCs to respond to hematopoietic inductive microenvironment
 Notch-1
 Notch-2

A

Regulatory Signaling Factors

42
Q

group of specific glycoproteins that regulate the proliferation, differentiation and maturation of hematopoietic precursor cells

have stimulatory or inhibitory effects

A

Hematopoietic Growth Factors or Cytokines

43
Q

Cytokines include:

A

interleukins (ILs), lymphokines, monokines, interferons, chemokines, and colony-stimulating factors (CSFs)

44
Q

Cytokines that exert positive influence (stimulatory)

A

 KIT ligand
 FLT3 ligand
 GM-CSF
 IL-1
 IL-3
 IL-6
 IL-11

45
Q

Cytokines that exert negative influence (inhibitory)

A

 Growth factor-β
 Tumor necrosis factor-a
 Interferons (gamma)

46
Q

Roles of Cytokines

A
  1. Inhibits apoptosis
  2. Stimulate cells to divide by decreasing the transit time from G0 to G1 phase
  3. Regulate cell differentiation into various cell lineages
47
Q

 Programmed cell death
 Natural physiologic process
 Eliminates unwanted, abnormal or harmful cells

A

Apoptosis

48
Q

 When cells do not receive the appropriate cytokines necessary to prevent cell death,
__________ is initiated

A

apoptosis

49
Q

they have the ability to induce hematopoietic colony formation

A

Colony-Stimulating Factors

50
Q

stimulates formation of CFU-GM (colony-forming unit for granulocyte & monocyte/macrophage also known as Granulocyte-Monocyte Progenitor)

A

GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor)

51
Q

stimulates formation of CFU-M (colony-forming unit-monocyte)

A

M-CSF (Macrophage-Stimulating Factor)

52
Q

stimulates formation of CFU-G (colony-forming unit-granulocyte)

A

 G-CSF (Granulocyte-Stimulating Factor)

53
Q

Receptor: KIT

A

KIT Ligand (Stem Cell Factor)

54
Q

Receptor: FLT3

A

FLT3 Ligand

55
Q

EARLY-ACTING MULTILINEAGE GROWTH FACTORS

A

 KIT Ligand (Stem Cell Factor)
 FLT3 Ligand

56
Q

 Protein molecules that have synergistic interactions with other cytokine to stimulate proliferation and differentiation of specific cell lines
 Effective at very low concentrations

A

Interleukins

57
Q

Erythropoiesis Lineage

A

Pluripotent HSC → Common Myeloid Progenitor/CFU-GEMM → BFU-E → CFU-E → Erythroid Precursor Cells → Mature erythrocytes

58
Q

contains few receptors for EPO

A

Burst-Forming Unit – Erythroid (BFU-E)

59
Q

contains many receptors for EPO

A

Colony-Forming Unit – Erythroid (CFU-E)

60
Q

 Lineage-specific glycoprotein hormone produced specifically by the peritubular interstitial cells of the kidney
 A small amount of it is produced in the liver

A

Erythropoietin (EPO)

61
Q

Stimulus for production and secretion of EPO: oxygen availability in the kidneys

A

↓ oxygen → ↑ EPO production

62
Q

EPO Stimulates RBC production by:

A
  1. Recruitment of CFU-E from BFU-E
  2. Preventing apoptosis of erythroid progenitors
  3. Inducing hemoglobin synthesis
63
Q

Two Major Categories of LEUKOPOIESIS

A

Myelopoiesis
Lymphopoiesis

64
Q

production of monocytes and granulocytes (neutrophils, basophil, eosinophil)

A

Myelopoiesis

65
Q

production of lymphocytes

A

Lymphopoiesis

66
Q

MEGAKARYOPOIESIS Lineage

A

Pluripotent HSC → CMP/CFU-GEMM → Megakaryocyte progenitors (Burst-Forming Unit-Meg/BFU-Meg → CFU-Meg → Light Density-CFU-Meg/LD-CFU-Meg) → Precursor cells → Platelets