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Pathology 1 > Haematopoiesis > Flashcards

Haematopoiesis Flashcards

(54 cards)

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1
Q

What are growth factors?

A

Polypeptides that control replication and survival vs. death throughout the various stages of blood cell formation

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2
Q

Name the neutrophil precursors

A 
Myeloblasts 
Promyelocyte 
Myelocyte 
Metamyelocyte 
Band
Segmented neutrophil
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3
Q

What is myelopoiesis?

A

Formation of bone marrow

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4
Q

What are myeloblasts?

A

Bone marrow progenitor cells

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5
Q

Outline the stages of platelet formation

A
  1. DNA replication occurs in megakaryoblasts
    • but no cell division
  2. Megakaryocytes formed
    • large polypoid cells
  3. Cytoplasmic fragments bud off to form platelets
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6
Q

What is lymphopoiesis?

A

Generation of lymphocytes

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7
Q

Describe the cells needed for initiating blood cell formation

A

Blood cell formation starts from a small no. of stem cells in bone marrow
–> pluripotent stem cells
–> specific to blood cells and can give rise to early
progenitors

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8
Q

What are the requirements of a bone marrow transplant donor?

A 
Must be (human lymhocyte antigen) HLA matched 
Can be un/related or autologous (reinfuse patients own bone marrow)
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9
Q

Daily, how many blood cells are produced?

A

RBCs ~ 2x10¹¹
Neutrophils ~ 5x10¹⁰
Smaller no. of other cell types

There’s a constant high level of blood cells production requiring a lot of cell replication

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10
Q

Describe how a bone marrow transplant works

A
  • Completely ablate haemopoiesis with radiation and
    drugs
  • Infuse compatible donor bone marrow
  • Haemopoiesis completely restored

Only haematopoietic stem cells give permanent engraftment - not progenitors or precursors

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11
Q

What are the different types of myeloblasts?

A

Basophilic myeloblasts

Eosinophilic myeloblasts

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12
Q

What are CSFs?

A

Colony stimulating factors that stimulate colony growth

e.g. G-CSF (granulocyte-CSF)

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13
Q

Outline the stages of haematopoiesis

A

early progenitors –> late progenitors –> immature precursors –> mature blood cells

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14
Q

How are lymphocytes formed from stem cells?

A

Stem cells decide whether to differentiate into lymphocytes or myeloid cells
Once committed to becoming a lymphocyte, stem cells form either:
T- Lymphocytes (in Thymus)
B- Lymphocytes (in Bone marrow)
involving positive feedback loops with the correct transcription factors present

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15
Q

What is erythropoiesis?

A

Eryhtrocyte formation

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16
Q

Name the different types of CFUs

A
  • CFU-G (neutrophilic granulocyte progenitor)
  • CFU-GM (granulocyte/monoprogenitor)
  • CFU-E (erythroid progenitor)
  • CFU-MK
  • CFU-bas
  • CFU-eo
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17
Q

How is Haematopoiesis regulated?

A

Haematopoiesis is regulated by growth factors

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18
Q

Name the precursors of platelet formation

A

megakaryoblasts –> megakaryocyte –> blood platelets

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19
Q

What are BFU-Es?

A

Early erythroid progenitors produce colonies that look as though they’ve been burst apart
AKA BFU-E (burst forming unit - erythroid)

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20
Q

How can we examine bone marrow structure?

A

Using Trephine Biopsy
Aspirate for more detail
- used to examine cellular morphology
- can see both precursors and mature cells

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21
Q

Describe the devlopment of erythrocyte precursors in the bone marrow

A

As erythrocytes develop, cytoplasm becomes pinker in colour as Hb produced and nucleus becomes smaller
Erythroblasts leave bone marrow, leaving nucleus behind forming RBC

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22
Q

How are T cells formed?

Study These Flashcards
A
  1. Early progenitor migrates to thymus once committed to
    T cell lineage
  2. T cell receptor gene arrangement
  3. Positive and negative selection occurs
23
Q

Where does haematopoiesis occur in the early embryonic state?

Study These Flashcards
A

Haematopoiesis takes place in the yolk sac

(yolk sac - embryonic structure outside the main embryo) in placenta

24
Q

What type of process is haematpoiesis?

Study These Flashcards
A

Irreversible, one way process

25
What are the risks of Bone marrow transplants?
Mortality while waiting for engraftment Infection due to neutropenia Bleeding due to thrombocytopenia Graft vs Host Disease
26
Why is it important to measure reticulocyte production in bone marrow?
Increased amount of reticulocytes in marrow means cells are working overtime to produce RBCs - diagnostic of haemolytic anaemia
27
What are the applications of Bone Marrow Transplant?
- leukaemia, lymphoma, myeloma - intensified chemotherapy for solid tmours - genetic diseases (thalassemia, SCIID etc.)
28
What is the benefit of stem cells' individual ability to initiate their own replication?
Acts as an anticancer mechanism - prevents cells undergoing genetic damage when replicating including the activation of oncogenes Ensures most cells that replicate are committed to terminal differentiation
29
What are the important features of progenitors?
Undifferentiated - unidentifiable morphologically as no mature cell characteristics present yet Committed - Already committed to which mature cells they'll generate
30
How does B cell formation occur?
1. Immunoglobulin gene rearrangement occurs 2. Expression of surface immunoglobulin (IgM) on membrane 3. Immature B cells migrates to secondary lymphoid organs for maturation & antigen selection
31
What are immature red blood cells called?
Reticulocytes
32
Describe how colony assays can be used to grow a colony of mature cells
1. Growth factors in semi solid medium (agar) 2. A progenitor cell with correct growth factor will grow into a colony of one lineage 3. Progenitors grow to form mature cell colonies from 32- 1000's of cells ``` - progenitors are therefore also known as Colony Forming Units (CFUs) ```
33
What is the role of stem cells in mice?
- Mark cells via retrovirus insertion - Transplant irradiated mice with small no. of stem cells - Same marked stem cells give rise to neutrophils, lymphocytes etc.
34
In a foetus, where does haematopoiesis occur?
In the foetal liver - very red haematical vital organ
35
How can stem cells cause leukaemia in humans?
Can cause chronic myeloid leukaemia (CML) caused by a chromosome translocation on small chromosome 22 and large 23 found in T cell lineages most produce excess neutrophils Stimulates myeloid cell production
36
What are the advantages of Bone marrow transplant?
Only curative treatment available for many diseases
37
During infancy where does haematopoiesis happen?
Occurs throughout the bone marrow
38
What type of stem cells are haematopoietic cells?
Pluripotent and self maintaining
39
Outline how blood cells are formed
Stem cells -> progenitors -> precursors -> mature blood cells
40
List some G-CSF applications
- neutrophil recovery after BMT/chemo - hereditary neutropenia - stimulates platelet recovery as stimulates other lineages (only in combination with other growth factors)
41
When do blood cells become differentiable?
Stem cells & progenitors can't be distinguished morphologically as there is no real difference between them Precursors begin looking like mature cells Mature cells are easily identifiable via their morphology
42
How do haematopoietic growth factors work?
Cytokines (polypeptides) bind to cell surface membrane receptors Stimulating growth and progenitor survival
43
What is erythropoietin?
EPO is a hormone produced in the kidney, in response to hypoxia
44
How are stem and progenitor cells purified?
Stem cells and early progenitors carry cell surface antigen CD34 used to purify them
45
Where does blood cell formtaion occur in adults?
Haematopoiesis is limited to the central skeleton under normal conditions which includes: - vertebrae - ribs & sternum - skull - sacrum - pelvis - proximal ends of humerus & femur
46
What is the advantage of Peripheral blood stem cell transplantation?
Less traumatic alternative to bone marrow transplantation , no general anaesthetic needed
47
What is the role of eryhtropoietin?
Increases RBC production via increase of progenitor survivor using CFU-E Speciifc to lineage; acts on late progenitors
48
When are G-CSF produced?
Granulocyte colony stiumlating factors are produced by many cell types in response to inflammation
49
What are the different types of blood vessels?
Red marrow - Active haematopoiesis - contains lots of eyrhtrocytes Yellow marrow - filled with fat cells
50
What is haematopoiesis?
Formation of blood cells
51
How is G-CSF used in peripheral blood stem cell transplantation?
G-CSF causes stem cells to be released from the bone marrow into circulation Seen by appearnce of CD34 and cells in circulation Collected by leukapheresis
52
What are the clinical applications of recombinant erythropoietin?
- Treatment of anaemia kidney failure | - Alternative to blood transfusion
53
What is bone marrow?
A spongy jelly like tissue inside the bone that is highly metabolically active Contains many blood vessels to bring nutrients in and take away new blood vessels
54
How do G-CSFs work?
Acts on mature neutrophils in periphery as a chemoattractant promoting neutrophil activation and maturation. Also stimulates neutrophil production in bone marrow by stimulating neutrophil progenitors CFU-G

Pathology 1 (20 decks)

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