Chapter 1: Haemopoiesis Flashcards

1
Q

What is the main site of haemopoiesis in the first few weeks of gestation?

A

The yolk sac

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2
Q

From where is definitive haemopoiesis derived?

A

Definitive Haemopoiesis is derived from stem cells from the AGM region (aorta-gonads-mesonephros) called haemangioblasts seed the liver, spleen, bone marrow.

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3
Q

What are the major sites of haemopoiesis from 6 weeks to 7 months in utero?

A

The liver and the spleen.

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4
Q

When to the liver and spleen stop making blood cells?

A

About two weeks after birth.

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5
Q

What is the major site of haemopoiesis throughout most of life?

A

The bone marrow

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6
Q

How much of the bone marrow is haemopoietic during infancy?

A

All of the bone marrow is haemopoietic.

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7
Q

Where does haemopoiesis occur in the adult?

A

Mostly in the central skeleton. The peripheral marrow and up to 50% of the central skeletal marrow is converted to fat.

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8
Q

What is term for reactivation of haemopoiesis in the liver and spleen?

A

extramedullary haemopoiesis.

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9
Q

With what cell does haemopoiesis start?

A

The hematopoietic stem cell.

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10
Q

How common are hematopoietic stem cells?

A

1 in 20 million nucleated cells in the blood.

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11
Q

What is the known phenotypic characteristics of hematopoietic stem cells?

A

CD34+, CD38-, and they look like small or medium sized lymphocytes.

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12
Q

What cells do the hematopoietic stem cells give rise to?

A

Mixed myeloid progenitor (colony forming unit) and the lymphoid stem cell.

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13
Q

What is the importance of stromal cells in the bone marrow?

A

They provide a suitable environment for the survival of stem cells.

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14
Q

What are the stromal cells?

A

Adipocytes, fibroblasts, endothelial cells, and macrophages

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15
Q

What do stromal cells do?

A

They provide adhesion, growth factors, and ECM necessary for stem cells.

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16
Q

Can stem cells exit the bone marrow?

A

Yes they are found in the peripheral blood in low numbers

17
Q

What is necessary for the mobilization of stem cells?

A

They must cross the endothelium in the marrow. This process is aided by G-CSF, and GM-CSF.

18
Q

How is stem cell homing to particular tissues achieved?

A

Stem cell homing is achieved by chemokine gradients. Stromal derived factor-1 (SDF-1) is critical to this process.

19
Q

Which transcription factor commits cells to the myeloid lineage?

A

PU.1 is a transcription factor that commits cells to the myeloid lineage.

20
Q

What is GATA-1?

A

GATA-1 is a transcription factor that is important in erythropoietic and megakaryocytic differentiation.

21
Q

What are the functions of haematopoietic growth factors?

A

Haematopoietic growth factors can stimulate (1) differentiation, (2) maturation (3) prevent apoptosis, (4)affect function of mature cells.

22
Q

What is the major source of haemopoietic growth factors?

A

Stromal cells are the major source of haemopoietic growth factors. However, 90% of erythropoietin is produced by the kidneys, and thrombopoietin is produced mostly in the liver.

23
Q

What are the growth factors that act on stromal cells?

A

IL-1 and TNF

24
Q

What are the growth factors that act on pluripotential stem cells?

A

SCF and Flt-L

25
What growth factors act on multipotential progenitor cells?
(1) IL-3 (2) GM-CSF (3) IL-6 (4) G-CSF (5) Thrombopoietin
26
What growth factors act on committed progenitor cells?
(1) G-CSF (2) M-CSF (3) IL-5 (eosinophil csf) (4) Erythropoietin (5) Thrombopoietin
27
What mediators inhibit haematopoiesis?
TGF-beta, and INF-gamma
28
What three pathways are responsible for haematopoietic growth factor signal transduction?
(1) JAK/STAT (2) MAP kinase (3) Phosphatidylinositol 3
29
What does erythropoietin stimulate?
stem cell production of erythrocytes
30
What does thrombopoietin stimulate?
Stem cell production of platelets
31
What does M-CSF stimulate?
M-CSF stimulates the differentiation of CFU-GM stem cells into monocytes.
32
What does G-CSF stimulate?
G-CSF stimulates the conversion of CFU-GM stem cells into Neutrophils.
33
What does IL-5 stimulate in Haematopoiesis?
IL-5 stimulates the production of eosinophils by stem cells.
34
What are the principle families of adhesion molecules?
(1) Immunoglobulin superfamily (bind to antigens or surface) (2) Selectins (leukocyte and platelet adhesion to endothelium) (3) Integrins (involved in adhesion to ECM)