10.1 - Bone Marrow + Hematopoeisis

Question 1

Stem Cell

Answer 1

= can renew itself without further differentiation

• is totipotent (potential to produce all of cells and can divide and produce a daughter cells that has the same potential as its self)
• truly totipotent stem cells are found in embryo (inner cell mass - zygote before that - make all body cells and placenta)

Question 2

Progenitor Cell

Answer 2

• ability to renew itself (w/o further differentiation)
• can give rise to a restricted number of cell lines (less than the stem cell)
• -> generates a subset of lineages

Question 3

Precursor Cell

Answer 3

• cannot renew itself
• generates daughter cells that are more differentiated than the parent cell
• more fully committed than both stem and progenitor cells

Question 4

What are the two lineages directly stemming from the pluripotential hematopoietic stem cells (PHSC)

Answer 4

• common lymphoid progenitor (CLP)

- common myeloid progenitor (CMP)

Question 5

What progenitor cells come from the CLP and what are the corresponding adult cells from those?

Answer 5

1) CFU-LyT –> T-lymphocytes

2) CFU-LyB –> B-lymphocytes

Question 6

What progenitor cells come from the CMP and what are the corresponding adult cells from those?

Answer 6

1) BFU-E –> CFU-E–> Erythrocyte
2) CFU-GM –> CFU-M (Monocyte) and CFU-G (mature neutrophil)
3) CFU-Eos –> Mature eosinophil
4) CFU-Basophil –> Mature basophil

Question 7

CD markers

Answer 7

= cluster of differentiation
= cell-surface molecules
- are able to bind antibodies (each CD is known to bind at least 2 monoclonal antibodies)
- CD is not just for blood
- presence or absence of CD molecules –> can be used in identifying a cell
- expression of certain markers can be dependent on stage of differentiation

Question 8

Give five examples of CD markers from the video that have functional significance to the cell and what that function is

Answer 8

• CD34 = cell adhesion molecule
• CD14 = receptor for molecules found on bacteria
• CD3 = part of t-cell receptor complex
• CD4 = part of immunoglobin superfamily - specific for MHCII
• CD8 = t-cell receptor molecule - specific for MHC I

Question 9

What two general developmental lineages collaborate to form the bone marrow and what cells do they generate

Answer 9

1) Mesenchymal stem cells –> generates the CT cells of bone marrow
2) PHSC –> generates the hematopoietic cells of the bone marrow

Question 10

Describe the 2 Types Bone Marrow

Answer 10

1) Red Marrow - large number of hematopoietic cells and very few adipocytes
2) Yellow Marrow - mostly see in adult/young adults –> significant quantities of hematopoietic spaces are taken over by adipocytes - occurs relative to age, need, which bone is being examined

Question 11

What are megakaryocytes

Answer 11

= very large cells, often appear multinucleate due to endomitotic divisions

• are almost always next to the sinus
• probably only recognizable cell on cut section of marrow (need a marrow smear to separate others)

Question 12

What are the first two steps to examining a bone marrow smear

Answer 12

1) don’t try to identify cells that are not round or are damaged - need to see a clear nucleus and clear, well-preserved cytoplasm
2) Triage into 3 categories
I. Small cells with round nuclei = erythrocitic lineage
II. Small cells with non-round nuclei = granulocyte lineage
III. large cells - look for presence of nucleoli and azurophilic granules

Question 13

Yolk Sac Phase of development

Answer 13

• when the first blood and vasculature occurs at the margins of the embryonic disc

Question 14

Hepatic phase of development

Answer 14

• once the organs are formed

- hemopoiesis moves to the liver and spleen during this phase

Question 15

Bone marrow phase of development

Answer 15

• begins around time of birth

- hemopoiesis moves to its adult location within the CT spaces of the marrow

Question 16

Red marrow

Answer 16

• contains mostly hemopoietic cells

Question 17

Yellow Marrow

Answer 17

• contains mostly adipocytes

Question 18

Marrow stromal cells

Answer 18

• fibroblasts
• reticular cells
• stromal cells are crucial to the FXN of hemopoiesis

Question 19

Marrow sinusoid capillaries

Answer 19

• location where cells leave the marrow by entering systemic circulation

Question 20

Pluripotential hematopoietic stem cell (PHSC)

Answer 20

• the stem cell for blood

Question 21

what are the first two progenitor cells for blood

Answer 21

• Common myeloid progenitor (CMP)

- Common lymphoid progenitor (CLP)

Question 22

What ar CD molecules

Answer 22

• antibody staining for leukocyte surface antigens

- often used to create distinction between progenitor cells that have morphologic similarity

Question 23

Describe the progenitors for erythrocytes

Answer 23

1) Erythrocyte burst-forming Unit (BFU-E)
2) Erythrocte Colony-Forming Unit (CFU-E)
- both are sensitive to Erythropoietin

Question 24

What are the erythrocyte precursor cells in order of development

Answer 24

1) Proerythroblasts
2) Basophilic Erythroblasts
3) Orthochromatic Erythroblasts
4) Poly chromatic erythroblasts
5) Reticulocytes

Question 25

What are the granulocyte precursor cells in order of development

Answer 25

1) Myeloblasts 2) Promyelocytes 3) Myelocytes 4) Metamyelocytes 5) Band (stab) cells - for neutrophils only

Question 26

Describe the granules of leukocytes

Answer 26

1) Primary, lysosomal granules --> azurophilic granules contained by all leukocytes 2) Specific granules (secondary) 3) Particularly neutrophils - also have tertiary granules - contain cathespins and gelatinizes --> breakdown CT elements to facilitate cell migration - Terms primary, secondary, tertiary refer to the order of synthesis within the precursor cells

Question 27

Marrow serves as a reserve pool for blood, what other peripheral pools exist and what is stored there

Answer 27

- macrophages are sequestered in the spleen - neutraphils are sequestered in peripheral capillaries (especially in the lung) called the marginal pool? - lymphocytes are sequestered in various lymphatic organs and peripheral tissues (MALT, BALT, etc.)

Question 28

Chemokines

Answer 28

- hemopoiesis is control by various chemokines | - many that act on progenitor population are termed colony stimulating factors (CSF)

Question 29

What is the easiest- to-recognize hematopoietic cell in the marrow and what is its FXN

Answer 29

``` = megakaryocyte - produces platelets (thrombocytes) out of pro platelet strings = extensions of the megakaryocyte cytoplasm into the sinus lumen ```

Question 30

What are proplatelet strings

Answer 30

= extensions of the megakaryocyte cytoplasm into the sinus lumen

Question 31

What are platelet demarcation channels

Answer 31

= recognizable EM features of megakaryocytes

Question 32

what are Megakaryoblast and Promegakaryocytes and what are the recognizable differences between them

Answer 32

- Megakaryocytes = early megakaryocyte precursor cells - Promegakaryocytes = late megakaryocyte Precursor cells - distingushable chiefly by the appearance of the nucleus

Question 33

Stem Cells

Answer 33

- generate all cell types in a particular system through mitosis and subsequent differentiation - also can renew themselves through mitosis

Question 34

Progenitor cells

Answer 34

- generate a restricted set of lineages through mitosis and subsequent differentiation - can also renew themselves through mitosis

Question 35

Precursor Cells

Answer 35

- are restricted to a single lineage of cells - may still undergo mitosis - only to produce a further differentiated cell - in hematopoiesis, percursor differentiation is visible through changes in cell morphology - are not capable of renewing themselves