Lecture 4 – Origin of blood cells

Question 1

Haematopoiesis

Answer 1

The commitment and differentiation processes that lead to the formation of all blood cells from haematopoietic stem cells.

Question 2

Bone marrow produces (3)

Answer 2

o 2x1011 RBCs
o 5x1010 neutrophils
o Plus smaller numbers of other cell types
• Requires enormous levels of cell replication

Question 3

Sites of haematopoiesis (3)

Answer 3

•	Infant 
	Throughout bone marrow
•	Adult
	Central skeleton 
•	Vertebrae / Ribs and sternum /
Skull / Sacrum / Pelvis /
Proximal ends of humerus and femur.

Question 4

Bone marrow (7)

Answer 4

• Spongy jelly like tissue
• Inside the bone
• Many blood vessels - bring nutrients and take away new blood cells
• Red marrow - active haematopoiesis.
• Yellow marrow - filled with fat cells.
• Bone marrow trephine - Trephine biopsy used to examine bone marrow architecture.
• Bone marrow aspirate

Question 5

Bone marrow aspirate (3)

Answer 5

o Used to examine cellular morphology
o See mature cells plus many immature precursor cells
o Commonest cells are neutrophil precursors, called myelocytes and myeloblasts

Question 6

Myelopoiesis

Answer 6

The regulated formation of myeloid cells, including eosinophilic granulocytes, basophilic granulocytes, neutrophilic granulocytes, and monocytes. In hematology, myelopoiesis is the production of blood cells in the bone marrow.

Question 7

Platelet formation (5)

Answer 7

Megakaryoblast –> DNA replication but no cell division –> Megakaryocyte –> Cytoplasmic fragments –> Blood platelets

Question 8

Lymphopoiesis

Answer 8

Is the generation of lymphocytes, one of the five types of white blood cell (WBC). It is more formally known as lymphoid haematopoiesis.

Question 9

T-cell formation in thymus (3)

Answer 9

T-cell formation in thymus:
• Early progenitor migrates to thymus
• T-cell receptor gene rearrangement
• positive & negative selection

Question 10

B- cell formation in bone marrow (3)

Answer 10

• Immunoglobulin gene rearrangement
• expression of surface IgM
• Immature B-cell migrates to 2o lymphoid organs for maturation and antigen selection

Question 11

Progenitors (4)

Answer 11

• A biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its “target” cell.
• Undifferentiated
You cannot tell the difference between them morphologically because they do not show the characteristics of mature cells
• Committed
They are already committed as to what they will become when they generate mature cells

Question 12

Colony Assays

Answer 12

On sheet

Question 13

Bone marrow transplantation -

Overview (8)

Answer 13

• Completely ablate haemopoiesis with radiation and drugs.
• Infuse compatible donor bone marrow cells.
• Haemopoiesis can be completely restored.
• Donor must be HLA matched - sibling or unrelated donor.
• Or an Autologous BMT- reinfuse patients own bone marrow.
• Only haematopoietic stem cells can give long term engraftment.
• NOT progenitors.
• NOT precursors.

Question 14

Bone marrow transplantation -

Applications (3)

Answer 14

o Leukaemia, lymphoma, myeloma.
o Intensified chemotherapy for solid tumours.
o Genetic diseases e.g. thalassaemia, SCID etc.

Question 15

Bone marrow transplantation -

Benefits (1)

Answer 15

 For many diseases, this is the only curative treatment.

Question 16

Bone marrow transplantation -

Risks (4)

Answer 16

 Significant mortality while waiting for engraftment.
 Infection due to neutropenia (low neutrophil count).
 Bleeding due to thrombocytopenia (low platelets).
 Graft versus Host Disease (GVHD).

Question 17

Haematopoietic stem cells:

Answer 17

On sheet

Question 18

Haematopoietic growth factors:

Answer 18

On sheet

Question 19

Erythropoietin (6)

Answer 19

• Produced in the kidney.
• In response to hypoxia.
• Increases RBC production by increasing survival of erythroid progenitors (CFU-E).
• Specific to one lineage (erythroid).
• Acts on late progenitors.
• Clinical applications of recombinant erythropoietin.
o Treating anaemia of kidney failure.
o Alternative to blood transfusion in Jehovah’s Witnesses.

Question 20

G-CSF (granulocyte colony stimulating factor) (5)

Answer 20

• Produced by many cell types.
• In response to inflammation.
• Acts on mature neutrophils in the periphery.
• Stimulates neutrophil production in the bone marrow.
• Clinical applications.

Question 21

G-CSF (granulocyte colony stimulating factor) - Mature neutrophils (3)

Answer 21

o Chemoattractant.
o Promotes neutrophil maturation.
o Promotes neutrophil activation.

Question 22

G-CSF (granulocyte colony stimulating factor) - Neutrophil production in bone marrow (2)

Answer 22

o Stimulates neutrophil progenitors (CFU-G).

o Helps stimulate progenitors of other lineages, but only in combination with other growth factors.

Question 23

G-CSF (granulocyte colony stimulating factor) - Clinical applications (4)

Answer 23

o Stimulate neutrophil recovery after bone marrow transplantation.
o Stimulate neutrophil recovery after chemotherapy.
o Treatment of hereditary neutropenia and other causes of neutropenia.
o Because G-CSF also helps to stimulate other lineages, it will also (for example) stimulate platelet recovery after bone marrow transplantation.

Question 24

Peripheral blood stem cell transplantation (PBCST) (5)

Answer 24

• G-CSF treatment causes stem cells to be released from the bone marrow into the circulation.
• Seen by appearance of CD34 + cells in the circulation.
• Collect by leukapheresis.
• Used an alternative to bone marrow for transplantation.
• Less traumatic for donor, no general anaesthetic.