Origin of blood cells Flashcards
What is haematopoiesis?
Formation of red blood cells
How many red blood cells and neutrophils does each bone marrow produce?
○ 2x10^11 red blood cells
○ 5x10^10 neutrophils
What is required in haematopoiesis?
• Enormous levels of cell replication required
What is the pathway of haematopoiesis?
○ Stem cells–>Progenitors–>Precursors–>Mature red blood cells
Where are the sites where haematopoiesis occurs?
• Sites:
○ Early embryo
○ Foetus
○ Infant:
§ Throughout bone marrow
○ Adult:
§ Central skeletonWhat is the bone marrow and where is it located?
- Spongy jelly like tissue
* Inside the bone
What does bone marrow have many of?
Many blood vessels to bring nutrients
What are the two types of bone marrow and what are there roles?
• Red marrow:
○ Active haematopoiesis
• Yellow marrow:
○ Filled with fat cells
What can be used to examine bone marrow architecture?
• Trephine biopsy used to examine bone marrow architecture
What can aspirate be used for?
○ Used to examine cellular morphology
What can you see in aspirate?
○ Can See mature cells plus many immature precursor cells
What are the commenest cells in aspirate?
○ Commonest cells are neutrophil precursors
§ Called myelocytes and myeloblasts
What is erythropoiesis?
• Formation of red blood cells when low levels of O2 detected
Platelet formation mechanism
- Megakaryoblast undergo DNA replication however no cell division forming megakaryocyte
- Megakaryocyte are large polypoid cells which remodel to form platelets
- Platelets are formed and they’re cytoplasmic fragments
What is the pathway of lymphopoiesis?
○ Stem cell–>Common lymphoid progenitor–>T or B lymphocytes
Where does T cell formation occur?
Occurs in Thymus
Formation of T cell
○ Early progenitor migrates to thymus
○ T-cell receptor gene arrangement
○ Positive and negative selection
How are B cells formed?
○ Immunoglobulin rearrangement
○ Expression of surface IgM
○ Immature B-cell migrates to 2 degree lymphoid organs for maturation and antigen selection
Undifferentiated progenitors?
○ Cannot tell difference morphologically as they do not show characteristics of mature cells
Committed progenitors
○ Already committed as to what they’ll become when they generate mature cells
What do progenitors do in colony assays and thus what are they called?
○ Progenitors grow to form colonies of mature cells
○ From 32 to hundreds or thousands of cells in a colony
○ Thus progenitors called colony forming units(CFU)
What do early progenitors do?
• Early erythroid progenitors grow to make large colonies that look like they have burst apart
What do colony stimulating factors do?
• Colony stimulating factors stimulate colony growth
Bone marrow transplantation steps
- Completely ablate haemopoiesis with radiation and drugs
- Infuse compatible donor marrow cells
- Haemopoiesis can be completely restored
What must the donor be in BMT?
• Donor must be HLA matched
Sibling or unrelated donor
What is autologous BMT?
Where the patients own bone marrow is reinfused
What can only give long term engraftment?
• Only Haematopoietic stem cells can give long term engraftment, not progenitors and precursors
Risks of BMT
○ Significant mortality while waiting for engraftment
○ Infection due to neutropenia
○ Bleeding due to thrombocytopenia
○ Graft versus host disease
Benefits of BMT
○ Only curative treatment for many diseases
Pluripotent haematopoietic stem cells
Can give rise to cells of every blood lineage
what are haematopoietic stem cells able to do?
• Self-maintaining:
○ Stem cell can divide to produce more stem cells
Haematopoietic stem cells in mice
○ Mark stem cells by retrovirus insertion
○ Transplant irradiated mice with small number of stem cells
Same marked stem cells give rise to neutrophils, lymphocytes etc
What is Chronic myeloid leukemia caused by and what does it affect?
○ Chronic myeloid leukaemia caused by a chromosome translocation in a stem cell
§ Mostly affects neutrophil lineage
§ Philadelphia chromosome also found in T-lymphocytes and other lineages
What do stem cells and early progenitors carry?
• Stem cells and early progenitors carry cell surface antigen, CD34
What do haematopoietic growth factors do?
• Polypeptide growth factors bind to cell surface transmembrane receptors
Stimulate growth and survival of progenitors
Where are erythropoietin produced?
• Produced in kidney in response to hypoxia
What do erythropoietin do?
• This increases red blood cell production by increasing survival of erythroid progenitors
What are eryhtropoietin specific to?
• Specific to one lineage(erythroid)
What do erythropoietin act on?
Acts on late progenitors
What are the clinical applications of recombinant erythropoietin?
• Clinical applications of recombinant erythropoietin:
○ Treating anaemia of kidney failure
○ Alternative to blood transfusion for religious purposes
What is G-CSF produced by?
G-CSF Produced by many cell types in response to inflammation
What does G-CSF act on and promote?
• Acts on mature neutrophils in the periphery:
○ Chemoattractant
○ Promotes neutrophil maturation
Promotes neutrophil activation
What does G-CSF stimulate?
• Stimulates neutrophil production in bone marrow
○ Stimulates neutrophil progenitors
○ Helps stimulate progenitors of other lineages, but only in combination with other growth factors
Clinical applications of G-CSF
• Clinical applications:
○ Stimulate neutrophil recovery after bone marrow transplantation
○ Stimulate neutrophil recovery after chemotherapy
○ Treatment of hereditary neutropenia and other causes of neutropenia
What other lineages does G-CSF stimulate?
• Stimulates other lineages like platelet recovery
Peripheral blood stem cell transplantation?
- G-CSF treatment causes stem cells to be released from the bone marrow into circulation
- Seen by appearance of CD34+ cells in the circulation
- Collected by leukapherisis
- Used as an alternative to bone marrow for transplantation
- Less traumatic for donor as anaesthetic not required.
