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BMS2.28 Hematopoeisis (RUBIN) > Hematopoeisis > Flashcards

Hematopoeisis Flashcards

1
Q

Aplasia:

A
  • lack of growth
  • the failure of an organ or tissue to develop or to function normally.
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2
Q

The “buffy coat” in centrifuged blood consists of:

A
  • white blood cells
  • platelets
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3
Q

Red Blood Cell function:

A
  • transport oxygen and carbon dioxide
  • acid-base balance
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4
Q

Platelet function:

A
  • initiate blood clotting
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5
Q

Natural killer cell function:

A
  • kill virus-infected cells and some tumor cells
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6
Q

Monocyte function:

A
  • become macrophages
  • phagocytose and digest invading microorganisms, foreign bodies, and damaged cells.
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7
Q

Basophil function:

A
  • release histamine
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8
Q

Eosinophil function:

A
  • destroy large parasites
  • modulate allergic inflammatory response
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9
Q

Neutrophil function:

A
  • phagocytose and destroy bacteria
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10
Q

B-cell function:

A
  • make antibodies
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11
Q

T-cell function:

A
  • kill virus-infected cells
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12
Q

All blood cells are produced from:

A
  • hematopoeitic stem cells in the bone marrow.
  • continuous production
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13
Q

What is this an image of?

A
  • normal bone marrow biopsy.
    • red material = bony trabeculae.
    • large multi-nucleated cells in the blood producing areas are megakaryocytes, the platelet producing cells.
    • white areas = fat globules.
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14
Q

Megakaryocytes are:

A
  • platelet producing cells in the bone marrow.
  • multi-nucleated.
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15
Q

What is this an image of?

A
  • aplastic anemia bone marrow biopsy
    • no megakaryocytes (leads to bleeding)
    • no RBCs (leads to shortness of breath)
    • no WBCs (leads to infection)
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16
Q

Aplastic anemia is due to:

A
  • the destruction of uncommitted hematopoeitic stem cells in the bone marrow
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17
Q

The three fates of stem cells:

A
  • replicate itself to produce more stem cells
  • differentiate (eventual apoptosis)
  • mutate (failure to differentiate or apoptose)
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18
Q

Hematopoeitic stem cells are recognized by what cell surface marker?

A
  • CD34+
  • c-Kit+
  • lin- (no lineage markers)
    • Lineage negative refers to any marker associated with any degree of maturity.
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19
Q

CD34 cell surface marker in true stem cells versus multipotent progenitors:

A
  • true stem cells: CD34- or CD34low
  • multipotent stem cells: CD34+
    • hematopoeitic stems cells are multipotent.
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20
Q

Lineage negative (lin-) cell marker refers to:

A
  • any marker associated with any degree of maturity.
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21
Q

A committed stem cell can only differentiate into one type of cell called a:

A
  • progenitor
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22
Q

Pluripotent stem cells can differentiate into:

A
  • more than one type of cell, but not all types of cells
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23
Q

Totipotent stem cells can differentiate into:

A
  • any type of cell; i.e. embryonic stem cells
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24
Q

The two models of stem cell development:

A
  • hierarchical
  • stochastic
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25
Q

Hierarchic Stem Cell Development:

A
  • stem cells differentiate into progenitor cells and then more mature cells that eventually apoptose with age.
  • ordered development.
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26
Q

Stochastic Stem Cell Development:

A
  • random replication, differentiation, and maturation of stem cells.
  • No order.
  • Leads to cancer.
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27
Q

Hematopoeitic Stem Cells can differentiate into:

A
  1. myeloid stem cells
    • give rise to RBCs, platelets, monocytes, neutrophils, eosinophils, basinophils
  2. lymphoid stem cells
    • give rise to lymphocytes
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28
Q

Pure red blood cell aplasia is due to:

A
  • absence of RBCs in the bone marrow
  • a failure of RBC progenitors to mature
29
Q

Agranulocytosis is due to:

A
  • absence of granulocytes in the bone marrow
  • a failure of granulocyte progenitors to mature
30
Q

Sites of blood cell development in the embryo from fertilization to birth:

A
  1. yolk sac (0-12 weeks)
  2. liver (12-32 weeks)
  3. bone marrow (32 weeks to birth)
31
Q

What two vascular factors direct the migration of hematopoeitic stem cells to the bone marrow?

A
  • vegf
  • tel
32
Q

In what types of bone is blood primarily produced in adults?

A
  • flat bones
    • pelvis
    • vertebrae
    • sternum
    • ribs
33
Q

Hematopoeitic stem cells are in close vicinity to what cells in the bone marrow (i.e. where is their niche)?

A
  • osteoblasts lining bony trabeculae (periosteum)
    • high calcium concentration
    • low oxygen concentration
    • chemokine CXCL4
34
Q

What is the environment of the stem cell niche in adult bone marrow?

A
  • high calcium concentration
  • low oxygen concentration
  • chemokine CXCL4
  • near osteoblasts lining trabeculae (periosteum)
35
Q

Bone Niche Function:

A
  • Maintains inactive hemopoietic stem cells in appropriate numbers for blood cell homeostasis.
    • a reserve of hemopoietic stem cells
  • Niche is near osteoblasts in the bone marrow.
36
Q

CXCL4 is:

A
  • a chemokine found in the bone marrow stem cell niche that attracts hematopoeitic stem cells and keeps them localized to the bone marrow stem cell niche.
37
Q

Inhibition of chemokine CXCL4 in the bone marrow stem cell niche will lead to:

A
  • liberation of hematopoietic stem cells from the stem cell niche into general circulation.
38
Q

What is necessary for maintaining the “stemness” of hematopoeitic stem cell in the bone marrow stem cell niche?

A
  • osteoblasts
  • low oxygen
  • high calcium
  • c-Kit/SCF-steel factor interaction
  • CXCL4 chemokine
39
Q

RUNX gene is neccessary for:

A
  • osteoblast formation
40
Q

Where does hemopoiesis occur in RUNX mutants?

A
  • yolk sac or liver
    • Runx mutants never develop osteoblasts and hemopoiesis therefore never migrates/occurs in the bone marrow
41
Q

RUNX and CBFβ genes encode for:

A
  • transcription factors that that activate and repress key regulators of stem cell growth, survival, and differentiation pathway.
  • important in osteogenesis and hematopoeisis differentiation.
42
Q

Downstream elements of RUNX and CBFβ genes include:

A
  • p53
  • TGFβ
  • hematopoeitic stem cell differentiation
  • cell cycle regulation
  • osteogenesis
43
Q

How do hematopoietic stem cells enter the circulation from the stem cell niche?

A
  1. hematopoeitic stem cells located in stem cell niche near osteoblasts.
  2. hematopoietic stem cells mature into progenitors and migrate away from osteoblasts.
  3. progenitors mature into mature blood cells, enter circulation via sinusoids running through the bone marrow.
44
Q

RBC turnover:

A

every 120 days

45
Q

WBC turnover:

A

every few days except for lymphocytes

46
Q

Platelet turnover:

A

rapid

47
Q

What type of blood cells are allowed to enter circulation from the bone marrow (through the sinusoids)?

A
  • only mature blood cells
48
Q

How do hematopoeitic stem cells properly migrate to the hematopoeitic stem cell niche in the osteoblast lining of the bone marrow?

A
  • hematopoeitic stem cells express a c-Kit receptor, which binds to the stem cell/steel factor ligand expressed by osteoblasts.
49
Q
  1. _____ expresses c-Kit receptors.
  2. ______ expresses SCF/steel factor ligands.
A
  1. hematopoeitic stem cells express c-Kit.
  2. osteoblasts express SCF/stee factor ligand.
50
Q

All hematopoietic growth factors are:

A

cytokines

51
Q

Cytokines are:

A
  • small proteins released by cells that affect the behavior of other cells.
  • all hematopoietic growth factors are cytokines
52
Q

Hematopoietins are:

A
  • hormone-like substances that influence the development of blood cells.
    • cytokines
    • interleukins
53
Q

The two broad classes of hematopoietins:

A
  1. bind to Hemopoeitin Receptor Superfamily
  2. bind to Kinase Receptor Superfamily
54
Q

Interleukins are:

A
  • cytokines produced by leukocytes/lymphocytes that influence leukocytes and some hemopoeitins.
55
Q

What do cytokines and interleukins do?

A
  • promote proliferation/growth of blood cells
  • regulate progenitor cell divisions
  • influence function of some WBCs
  • commit stem cell to a specific cell line
56
Q

Regulation of blood cell proliferation and differentiation is controlled by:

A
  • a network of cytokines
57
Q

Colony forming units (CFUs) are:

A
  • The colonies produced when progenitor cells are stimulated by a CSF to produce colonies of specific differentiated cells.

ONLY FOUND ON AGAR PLATES IN VITRO

CFUS ARE NOT FOUND IN VIVO

58
Q

Colony stimulating factors (CSFs) are:

A
  • cytokines/interleukins that induce progenitor cells to proliferate and differentiate into a specific kind of blood cell.
59
Q

Burst forming units (BFU) are promoted to erythrocyte (RBC) maturation via:

A
  • erythropoeitin
60
Q

Interleukin-3 (Il-3) promotes the formation of what colony forming unit (CFU)?

A
  • CFU-GEMM:
    • granulocytes
    • erythrocytes
    • monocytes
    • megakaryocytes
61
Q

Erythropoietin promotes the formation of what colony forming unit (CFU)?

A
  • Burst forming units (BFUs)
    • leads to erythrocyte (RBC) maturation
62
Q

Steps in in erythropoeisis (RBC maturation):

A
  1. Cells get smaller
  2. Cytoplasm changes (blue to pink)
  3. Nucleus/cytoplasm ratio falls
  4. Nucleus extruded prior to reticulocyte phase
63
Q

What signaling pathway is used by erythropoeitin to induce maturation of BFU-Es and CFU-Es into RBCs?

A

JAK-STAT

  • Enhances growth
  • Suppress apoptosis
64
Q

Mutations in the JAK gene or EPO secretion can lead to:

A
  • blood cancers
  • renal insufficiency
65
Q

What is the largest cell in the bone marrow?

A

megakaryocytes

  • can hav eup to 16 nuclei
66
Q

Steps in platelet production:

A
  • thrombopoeitin stimulates megakaryocytes to shed cytoplasmic buds that develop into platelets.
67
Q

CFU-GEMM is induced by _____ and gives rise to ______.

A
  • IL-3
    • granulocytes
    • erythrocytes (EPO)
    • monocytes
    • megakaryocytes (TPO)
68
Q

CFU-L gives rise to ______.

L = Lymphoid Stem Cell.

A
  • B-Cells
  • T-Cells
  • NK-Cells

BMS2.28 Hematopoeisis (RUBIN) (1 decks)

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