Lecture 15: Hematopoesis Flashcards Preview

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Flashcards in Lecture 15: Hematopoesis Deck (18):
1

Give some basic characteristics of stem cells

- May proliferate extremely well
- Self-renewing
- May differentiate into several (at least 2) different cell-types
- May reconstitute tissues after injury

2

Describe the 3 hierarchies of stem cells pertaining to developmental capacity

- Totipotent: Totipotent cells give rise to all cells of an organism, including embryonic and extraembryonic tissues (cells which support embryonic development). A zygote is totipotent.
- Pluripotent: Pluripotent cells give rise to all cells of the embryo and subsequently adult tissues. (embryonic stem cells).
- Multipotent: Multipotent cells give rise to different cell types of a given lineage. (adult stem cells).

3

What are the two types of stem cells

* Embryonic Stem Cells
- Derived from Inner-Cell Mass of blastocyst
- Pluripotent, differentiate to all cell lineages
- Technical and ethical limitations
- May be induced from adult tissues
* Adult Stem Cells
- Harvested from mature organs/tissues (bone marrow)
- Multipotent
- More restricted ability to produce different cell types and to self-renew

4

Describe the hematopoetic sites pertaining to gestation times

* 2-8 weeks of gestation:
- Islands of hematopoiesis (blood islands) are found in the yolk sac wall.
- Give rise to nucleated erythrocytes from 2-8 weeks of gestation.
- No leukocytes form during this phase.
* 8-28 weeks of gestation:
- Hematopoiesis first occurs in the liver and then the spleen.
- Normally ceases around the time of birth.
* 6 months gestation to birth and beyond:
- Hematopoiesis occurs in red bone marrow.
- See Slide 6

5

Describe the characteristics of bone marrow

- At birth, all the marrow is red marrow.
- Red marrow is the source of all blood cells.
-- Prior to puberty: Skull, ribs, sternum, vertebrae, clavicles, pelvis, long bones
--After puberty: As above except for long bones
- Extramedullary hematopoiesis: In certain disease states, blood cell formation may occur in liver and spleen.
- In time, most marrow is converted to yellow marrow, and red marrow is usually restricted to sternum and iliac crests (see text).

6

Give the histology of bone marrow

* Stroma:
- Contains fibroblasts, reticular cells, adipose cells, and endothelial cells.
- Synthesizes and secretes hematopoietic growth factors. •
* Parenchyma:
- Consists of various lineages of hematopoietic cells in different stages of differentiation.
* Sinusoids:
- Endothelial-lined spaces that connect arterial and venous vessels.
- Provides access for mature blood cells to move into the circulation.
* Hematopoietic cords:
- Bands of parenchyma and stroma lying between the sinusoids.

7

Describe the distribution of hematopoietic cells

* Total number of cells:
- 60% in granulocytopoiesis
- 30% in erythrocytopoiesis
- 10% in thrombocytopoiesis, monocytopoiesis, and lymphocytopoiesis
* Myeloid/erythroid ratio: Total volume of cells in granulocytopoiesis/Total volume of cells in erythrocytopoiesis

3:1 is normal
8:1 suggests leukemia
1:5 suggests polycythemia

8

Describe transendothelial migration

- Mature blood cells migrate from the hematopoietic cords through the sinusoidal endothelial walls into the sinusoids.
- Megakaryocytes (site of platelet production) are too large to translocate and must remain in the stroma.
- See slides 10-16

9

Describe hematopoietic stem cells

- Are pluripotential: Committed to either myeloid or lymphoid stem cell lines
- Can self-renew
- Produce two kinds of multipotential precursor cells:
-- Myeloid stem cell: Give rise to all blood cell lines except lymphocytes
-- Lymphoid stem cell: Give rise to lymphocytes
- Cannot be identified by morphology but can be recognized by cell surface markers

10

List everything leukocytes can break down into (or at least what's listed on slide 18)

1. Granulocytes: Neutrophils, eosinophils, basophils

2. Agranulocytes: Monocytes, Lymphocytes

11

Describe Myeloid Stem Cells:

Gives rise to five kinds of colony-forming units:

- Erythroid CFU: Derived from myeloid stem cell but produces red blood cells, not white blood cells
- Megakaryocyte CFU: Derived from myeloid stem cell but produces platelet-forming cells, not white blood cells
- Basophil CFU*
- Eosinophil CFU*
- Granulocyte-Macrophage CFU*
* = White Blood Cell
- See Slides 20-24

12

What two classes do lymphoid stem cells break down into

Give rise to two kinds of cell lines:
- T-cell progenitor: Matures in thymus
- B-cell progenitor Matures in bone marrow

T = Thymus, B = Bone Marrow, (But remember it says MATURE)

13

What is the maturation phases of a macrophage?
For a neutrophil?

Of an erythrocyte

- Monoblast*, Promonocyte, Monocyte**, Macrophage

- Myeloblast*, Promyelocyte*, Myelocyte*, Metamyelocyte, Band cell**, Neutrophil**

- Proerythroblast*, Basophilic erythroblast*, Polychromatophilic erythroblast*, Orthochromatic erythroblast, Reticulocyte**, Erythrocyte** (See Slide 36-41)

* Cells which can divide
** Cells normally found in circulation

14

What are the characteristics of hematopoietic growth factors?

- Hematopoietic growth factors and cytokines are produced by endothelial cells in the marrow, fibroblasts, and stromal cells.
- Glycoproteins
- Three major groups:
-- Colony –stimulating factors
-- Erythropoietin and thrombopoietin
-- Cytokines (primarily interleukins)

15

Describe colony-stimulating hematopoietic growth factors

* Granulocyte/monocyte colony-stimulating factor: (GM-CSF)
- Produced by endothelial cells, T cells, fibroblasts, and monocytes
- Stimulates granulocytopoiesis and monocytopoiesis
- Ameliorates neutropenia associated with chemotherapy or radiation therapy (synthetic form: sargramostim or melgramostim).
* Granulocyte colony stimulating factor (G-CSF):
- Produced by endothelial cells, fibroblasts, and macrophages
- Directs CFU-G to proliferate and differentiate into myeloblasts
- May be used following chemotherapy or radiation therapy to treat neutropenia
* Monocyte colony stimulating factor:
- Commits CFU-GM to monocytic pathway

16

Describe the hematopoietic growth factor categories: erythropoietin and thrombopoietin

* Erythropoietin:
- Directs CFU-E to proliferate and differentiate into proerythroblasts
- Produced in kidney in response to decrease in oxygen saturation
- Secondary polycythemia is any abnormal increase in total RBC mass resulting from hypoxia and stimulating release of erythropoietin.
-- Possible causes include Tetralogy of Fallot and cigarette smoke.
* Thrombopoietin:
- Directs formation of megakaryoblasts
- Produced in proximal convoluted tubules of kidney
- Produced in parenchymal cells and sinusoidal endothelial cells of liver
- No therapeutic use
- See Slide 47

17

Describe the hematopoietic growth factor, cytokines

* Cytokines (primarily interleukins):
- Mediate positive and negative effects on cellular quiescence, apoptosis, proliferation, and differentiation.
- Engage specific receptors and activate a variety of signaling pathways.
- Examples:
-- Interleukin-3
-- GM-CSF
-- Fit-3 ligand
-- Kit ligand
- See Slide 49

18

What are the 2 other smaller categories of hemtopoietic growth factor regulators and describe each.

* ECM components:
- Heparin sulfates
- Collagens
- Laminin
- Fibronectin
* Chemokines:
- Regulate blood cell trafficking and homing to sites of need.
- May serve as positive and negative growth regulators.
- Bind to guanine protein-coupled transmembrane receptors.
- Example: Sdf-1