10.1 - Bone Marrow + Hematopoeisis Flashcards
Stem Cell
= 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)
Progenitor Cell
- 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
Precursor Cell
- cannot renew itself
- generates daughter cells that are more differentiated than the parent cell
- more fully committed than both stem and progenitor cells
What are the two lineages directly stemming from the pluripotential hematopoietic stem cells (PHSC)
- common lymphoid progenitor (CLP)
- common myeloid progenitor (CMP)
What progenitor cells come from the CLP and what are the corresponding adult cells from those?
1) CFU-LyT –> T-lymphocytes
2) CFU-LyB –> B-lymphocytes
What progenitor cells come from the CMP and what are the corresponding adult cells from those?
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
CD markers
= 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
Give five examples of CD markers from the video that have functional significance to the cell and what that function is
- 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
What two general developmental lineages collaborate to form the bone marrow and what cells do they generate
1) Mesenchymal stem cells –> generates the CT cells of bone marrow
2) PHSC –> generates the hematopoietic cells of the bone marrow
Describe the 2 Types Bone Marrow
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
What are megakaryocytes
= 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)
What are the first two steps to examining a bone marrow smear
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
Yolk Sac Phase of development
- when the first blood and vasculature occurs at the margins of the embryonic disc
Hepatic phase of development
- once the organs are formed
- hemopoiesis moves to the liver and spleen during this phase
Bone marrow phase of development
- begins around time of birth
- hemopoiesis moves to its adult location within the CT spaces of the marrow
Red marrow
- contains mostly hemopoietic cells
Yellow Marrow
- contains mostly adipocytes
Marrow stromal cells
- fibroblasts
- reticular cells
- stromal cells are crucial to the FXN of hemopoiesis
Marrow sinusoid capillaries
- location where cells leave the marrow by entering systemic circulation
Pluripotential hematopoietic stem cell (PHSC)
- the stem cell for blood
what are the first two progenitor cells for blood
- Common myeloid progenitor (CMP)
- Common lymphoid progenitor (CLP)
What ar CD molecules
- antibody staining for leukocyte surface antigens
- often used to create distinction between progenitor cells that have morphologic similarity
Describe the progenitors for erythrocytes
1) Erythrocyte burst-forming Unit (BFU-E)
2) Erythrocte Colony-Forming Unit (CFU-E)
- both are sensitive to Erythropoietin
What are the erythrocyte precursor cells in order of development
1) Proerythroblasts
2) Basophilic Erythroblasts
3) Orthochromatic Erythroblasts
4) Poly chromatic erythroblasts
5) Reticulocytes
What are the granulocyte precursor cells in order of development
1) Myeloblasts
2) Promyelocytes
3) Myelocytes
4) Metamyelocytes
5) Band (stab) cells - for neutrophils only
Describe the granules of leukocytes
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
Marrow serves as a reserve pool for blood, what other peripheral pools exist and what is stored there
- 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.)
Chemokines
- hemopoiesis is control by various chemokines
- many that act on progenitor population are termed colony stimulating factors (CSF)
What is the easiest- to-recognize hematopoietic cell in the marrow and what is its FXN
= megakaryocyte - produces platelets (thrombocytes) out of pro platelet strings = extensions of the megakaryocyte cytoplasm into the sinus lumen
What are proplatelet strings
= extensions of the megakaryocyte cytoplasm into the sinus lumen
What are platelet demarcation channels
= recognizable EM features of megakaryocytes
what are Megakaryoblast and Promegakaryocytes and what are the recognizable differences between them
- Megakaryocytes = early megakaryocyte precursor cells
- Promegakaryocytes = late megakaryocyte Precursor cells
- distingushable chiefly by the appearance of the nucleus
Stem Cells
- generate all cell types in a particular system through mitosis and subsequent differentiation
- also can renew themselves through mitosis
Progenitor cells
- generate a restricted set of lineages through mitosis and subsequent differentiation
- can also renew themselves through mitosis
Precursor Cells
- 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
