Hematopoiesis

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What is the micoenvironment necessary for hematopoiesis?

Bone marrow (primarily)

What are the general functions of growth factors in hematopoiesis?

- Stimulate proliferation
- Support differentiation of maturing cells
- Enhance function of mature cells

During the early months of gestation, where does hematopoiesis take place?

In the yolk sac

Where does hematopoiesis take place after the yolk sac but before the bone marrow?

Mainly the liver, but also the spleen in small amounts

What are the two types of bone marrow?

1. Red bone marrow
2. Yellow bone marrow

What makes red bone marrow red?

The color is produced by blood and blood forming cells

What makes yellow bone marrow yellow?

The color is produced by adipocytes

Adults have mainly which type of bone marrow?

Yellow bone marrow

What are the components of red bone marrow?

Stroma, hematopoietic cords, and sinusoidal capillaries

Stroma of red bone marrow

3D network of reticular cells and reticular fibers containing collagen type 3, fibronection, laminin, and proteoglycans

What forms the hematopoietic cords?

Hematopoietic cells and macrophages interacting with the stroma

What supports sinusoidal capillaries?

Reticular cells and reticular fibers

What are the main functions of red bone marrow?

- Production of blood cells
- Destruction of senescent red blood cells
- Storage of iron

Where in red bone marrow is iron stored?

In the macrophages - the hemoglobin molecules

Where do all blood cells arise?

From a single pluripotential stem cell in the bone marrow

What forms colony-forming units (CFUs)?

Pluripotential stem cells give rise to CFUs

What are the two groups of cells found in CFUs?

1. Multipotential lymphoid stem cells (CFU-L)
2. Multipotential myeloid stem cell (CFU-GEMM)

What lineage specific progenitors does CFU-GEMM differentiate into?

- CFU-E
- CFU-GM
- CFU-Eo
- CFU-Ba
- CFU-Meg

CFU-E

Gives rise to erythroid lineage

CFU-GM

Gives rise to the neutrophil and monocyte lineage

What does CFU-GM further differentiate into?

- CFU-G = neutrophils
- CFU-M = monocytes

CFU-Eo

Gives rise to the eosinophil lineage

CFU-Ba

Gives rise to the basophil lineage

CFU-Meg

Gives rise to the megakaryocytes

What are the first cells morphologically distinguishable as to which cell type they will become?

Precursor cells (from the lineage specific progenitor cells)

What influences the development of erythrocytes from CFU-GEMM?

- Erythropoietin (most important!)
- Granulocyte-macrophage colony stimulating factor (GM-CSF)
- Interleukin-3 (IL-3)
- Interleukin-4 (IL-4)

What is the first recognizable erythroid precursor?

Proerythroblast

What gives rise to a Proerythroblast?

The erythropoietin-senstive progenitor cell (CFU-E)

Erythropoiesis

The maturation of erythrocytes

What occurs during erythropoiesis?

- Cell volume decreases
- Nucleus diameter decreases, chromatin condenses, nucleus is extruded
- Cytoplasm has a decreased number of polyribosomes, increased hemoglobin, and mitochondria and other organelles disappear

In what cells of erythropoiesis does mitosis occur?

It occurs in proerythroblasts, basophilic erythroblasts, and polychromatic erythroblasts

When are erythrocytes released into circulation?

As soon as they are formed

What regulates erythrocyte formation and release?

Erythropoietin

What is the lifespan of erythrocytes?

about 120 days

What induces CFU-GEMM to differentiate into CFU-GM and then CFU-G?

- GM-CSF
- Granulocyte colony stimulating factor (G-CSF)
- IL-3

What induces the development of Eosinophils from CFU-GEMM, and CFU-Eo?

- GM-CSF
- IL-3
- IL-5

What induces the development of basophils from CFU-GEMM, and CFU-Ba?

- GM-CSF
- IL-3

What happens during the maturation of neutrophils, eosinophils, and basophils?

- Nucleus becomes more condensed and lobulated
- Cytoplasm undergoes granule synthesis

What is the first stage of granule synthesis in granulopoiesis?

The development of azurophilic granules (lysosomes)

What is the second stage of granule synthesis in granulopoiesis?

The development of specific granules (and tertiary granules in neutrophils)

What is the distinguishing factor for a Myeloblast?

There are no granules present

What is the distinguishing factor for a Promyelocyte?

Azurophilic granules are present in the cell

What is the distinguishing factor for a Myelocyte?

Cell has developed by azurophilic and specific granules

What is the distinguishing factor for a Metamyelocyte?

Cell has more specific granules than azurophilic granules and nucleus has undergone some changes

How long do neutrophils stay in circulation? How long do they live in tissue?

- Circulatory half life of 6-8 hours
- Live about 2 days in connective tissue before undergoing apoptosis

What are the two main compartments that neutrophils pass through?

- Bone Marrow Compartments
- Vascular Compartment

Bone marrow consists of what compartments for neutrophils?

- The medullary formation compartment
- The medullary storage compartment

The medullary formation compartment

- Consists of Mitotic and Maturation Compartments
- Where cells are forming

Medullary Storage Compartment

Capable of releasing large numbers of neutrophils on demand

What cell types are found in the Mitotic compartment?

Stem cells
Myeloblasts
Promyelocytes
Myelocytes

What cell types are found in the Maturation compartment?

Metamyelocytes
Band cells
Mature granulocytes

The Vascular Compartment

- Circulating compartment
- Marginating compartment

Circulating Compartment

Consists of actively circulating neutrophils

Marginating Compartment

- Neutrophils in vessels, but not circulating
- Sequestered by vasoconstriction or endothelial adhesion
- Same size as neutrophils in circulation and can exchange with them

What induces monocytes to development from CFU-GEMM, then CFU-GM, and then CFU-M?

- GM-CSF
- IL-3
- Monocyte colony stimulating factor (M-CSF)

What are the monocyte precursors in bone marrow?

Monoblasts and promonocytes

How long do monocytes circulate before entering the tissues?

about 16 hours

What happens to monocytes when they are in tissue?

They differentiate into macrophages

A monoblast is almost identical morphologically to what cell?

A myeloblast

What are platelets produced by?

Megakaryocytes

What induces platelets to develop from CFU-GEMM, and then CFU-Meg?

- GM-CSF
- IL-3
- Thrombopoietin

Megakaryoblasts

- Nucleus becomes polypoid due to endomitoses as the cell develops
- cytoplasm is homogeneous and intensely basophilic

Demarcation Membranes

Invaginations of plasma membrane that shed platelets as cytoplasmic fragments

What are the only two recognizable precursor stages of Lymphopoiesis?

1. Lymphoblast
2. Prolymphocyte

Where do lymphocytes proliferate?

Outside the bone marrow

Where do circulating lymphocytes originate?

Mainly in the thymus and peripheral lymphoid organs

Where do all the progenitor cells originate?

In the bone marrow

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