Origin of blood cells

Question 1

What is haematopoiesis

Answer 1

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

Question 2

What is the stem cell lineage

Answer 2

1. Stem cells
2. Early progenitors
3. Late progenitors
4. Immature precursors
5. Mature cells

Question 3

What are key rules when it comes to stem cell lineage

Answer 3

The mature cells cannot go back to being stem cells
Only stem cells can divide to produce more stem cells
Progenitor cells are differentiated from stem cells but this cannot be seen through a microscope

Question 4

Where does haematopoiesis occur in an early embryo

Answer 4

The yolk sac

Question 5

Where does haematopoiesis occur in a foetus

Answer 5

The foetal liver

Question 6

Where does haematopoiesis occur in an infant

Answer 6

Through the bone marrow

Question 7

Where does haematopoiesis occur in an adult

Answer 7

The central skeleton (vertebrae, ribs and sternum, skull, sacrum, pelvis and the proximal end of the humerus and femur)

Question 8

Whats red marrow

Answer 8

Active haematopoiesis

Question 9

What yellow marrow

Answer 9

Filled with fat cells

Question 10

What does a blood marrow trephine do and how is it performed

Answer 10

Its used to examine bone marrow architecture

remove a 1 or 2cm core of bone marrow in one piece

Question 11

What is a bone marrow aspiration

Answer 11

sucks some bone marrow cells up into a syringe

Question 12

What is the neutrophil lineage - myelopoiesis

Answer 12

1. Myeloblast
2. Promyelocyte
3. Myelocyte
4. Metamyelocyte
5. Band
6. Segmented neutrophil

Question 13

What is the red blood cell lineage - erythropoiesis

Answer 13

1. Pro-erythroblast
2. Basophilic erythroblast
3. Polychromatic erythroblast
4. Pyknotic erythroblast
5. Reticulocyte
6. Mature red blood cell

Question 14

Platelet formation

Answer 14

1. Megakaryoblast - DNA replication but no cell division
2. Megakaryocyte - Large, polypoid cell
3. Blood platelets - cytoplasmic fragments

Question 15

Lymphopoiesis

Answer 15

1. Stem cell
2. Common lymphoid progenitor
3. T-lymphocytes and B-lymphocytes

Question 16

T-cell formation in thymus

Answer 16

1. Early progenitor migrates to thymus
2. T-cell receptor gene rearrangement to get necessary antibodies
3. Positive and negative selection to prevent auto immunity

Question 17

B-cell formation in bone marrow

Answer 17

1. immunoglobin gene rearrangment
2. Expression of surface IgM
3. Immature B-cell migrates to secondary lymphoid organs for maturation and antigen selection

Question 18

How are progenitors undifferentiated

Answer 18

You cannot tell the difference between them morphologically because they do not show the characteristics of mature cells

Question 19

How are progenitors committed

Answer 19

They are already committed as to what they will become when they generate mature cells

Question 20

How do you form colonies

Answer 20

• Semi-solid medium
• Plus growth factors
• Single cell suspension of bone marrow
• Will form colonies

Question 21

What colonies will progenitors form

Answer 21

Colonies of mature cells

Thus progenitors are called ‘colony forming units’ (CFU)

Question 22

What colonies will early erythroid progenitors form

Answer 22

They will form ‘burst forming unit - erythroid’ (BFU-E)

Question 23

What are CSF

Answer 23

Colony stimulating factors

Question 24

How is a bone marrow transplant done

Answer 24

1. Completely ablate haemopoiesis with radiation and drugs
2. Infuse compatible donor bone marrow cells
3. Haemopoiesis can be completely restored

Question 25

What must bone marrow donors be

Answer 25

Must be HLA matched; sibling or unrelated donor | Or autologous BMT; Re-infuse patients own bone marrow

Question 26

What are the applications of bone marrow transplant

Answer 26

1. Leukaemia, lymphoma and myeloma 2. Intensified chemotherapy 3. Genetic diseases e.g. SCID, thalassaemia

Question 27

What are the risks of a bone marrow transplant

Answer 27

- Significant mortality whilst waiting for engraftment - Infection due to neutropenia (low neutrophil count) - Bleeding - Graft versus host disease (GVHD)

Question 28

What are the benefits of of a bone marrow transplant

Answer 28

For many diseases this is the only curative treatment

Question 29

How can stem cells be studied through mice

Answer 29

1. Mark stem cells by retrovirus insertion 2. Transplant irradiated mice with small number of stem cells 3. Same marked stem cells gives rise to neutrophils and lymphocytes

Question 30

How can stem cells be studied through humans

Answer 30

1. Chronic myeloid leukaemia (CML) is caused by a chromosome translocation in stem cells 2. provides a natural marker within cells 3. The disease mostly effects neutrophil lineage, but Philadelphia chromosome also found in T-lymphocytes and other lineages

Question 31

What are growth factors and how do they work

Answer 31

Polypeptide growth factors Bind to cell surface transmembrane receptors Stimulates growth and survival of progenitors

Question 32

Where and why is erythropoietin produced and what does it do

Answer 32

Produced in the kidney is response to hypoxia | Increases red blood cell production by increasing survival of erythroid progenitors (CFU-E)

Question 33

What is the clinical application of recombinant erythropoietin

Answer 33

Treating anaemia of kidney failure, alternative to blood transfusion in Jehovahs witnesses

Question 34

Where is granulocyte colony stimulating factor (G-CSF) produced, why and what does it do

Answer 34

Produced by many cell types in response to inflammation Its a glycoprotein that stimulates the bone marrow to produce neutrophils and neutrophil progenitors and release them into the bloodstream

Question 35

What are the clinical applications of G-CSF

Answer 35

Stimulate neutrophil recovery after bone marrow transplantation and chemotherapy Treatment of neutropenia Treatment is seemed to be working after appearance of CD34