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Fundamentals of Pathology > W10 Origin of blood cells > Flashcards

W10 Origin of blood cells Flashcards

1
Q

Steps to mature blood cells

A

Stem cells > progenitors > precursors > mature blood cells

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2
Q

Each day the adult bone marrow produces

A

~2x1011 red blood cells

~5x1010 neutrophils

Plus smaller numbers of other cell types

Requires enormous levels of cell replication

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3
Q

Sites of haematopoiesis in infant

A

Throughout bone marrow

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4
Q

Sites of haematopoiesis in adult

A 
Central skeleton
vertebrae
ribs and sternum
skull
sacrum
pelvis
proximal ends of humerus and femur
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5
Q

Bone marrow

A

Spongy jelly like tissue
Inside the bone
Many blood vessels
- bring nutrients and take away new blood cells

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6
Q

Red marrow

A

Active haematopoiesis

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7
Q

Yellow marrow

A

Filled with fat cells

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8
Q

Bone marrow trephine

A

Trephine biopsy used to examine bone marrow architecture

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9
Q

Bone marrow aspirate

A

Used to examine cellular morphology

See mature cells plus many immature precursor cells

Commonest cells are neutrophil precursors, called myelocytes and myeloblasts

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10
Q

Blast cell

A

Blast- “seed” or “germ” cell

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11
Q

Basophil precursor

A

Basophilic myeloblast

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12
Q

Eosinophil precursor

A

Eosinophilic myeloblast

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13
Q

Erythropoiesis

A

Process which produces RBC

Proerythroblast > basophilic eryhtroblast > polychromatic erythroblast > pyknotic eryhtroblast > reticulocyte > mature RBC

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14
Q

Platelet formation

A

Megakaryoblast undergoes DNA replication but no cell division
Megakaryocyte formed which is a large polyploid cell
Cytoplasmic fragments then forming blood platelets

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15
Q

Lymphopoiesis

A

Stem cell converted into Common lymphoid progenitor

Then into T + B lymhocytes

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16
Q

T-cell formation in thymus

A

Early progenitor migrates to thymus
T-cell receptor gene rearrangement
Positive & negative selection

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17
Q

B-cell formation in bone marrow

A

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

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18
Q

Undifferentiated progenitors

A

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

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19
Q

Committed progenitors

A

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

20
Q

Colony assays process

A

Singe cell suspension of bone marrow which is then incubated for 7-14 days in semi-solid medium (agar, methylcellulose) w/growth factors

21
Q

Colony assays

A

Progenitors grow to form colonies of mature cells
From 32 to hundreds or thousands of cells in a colony
Thus progenitors are called “Colony Forming Units” -CFU

Used to study the proliferation and differentiation pattern of hematopoietic progenitors

22
Q

Colony assays types

A 
CFU-G (neutrophilic) granulocyte progenitor
CFU-GM granulocyte/monocyte progenitor
CFU-E  erythroid progenitor 
CFU-Mk
CFU-bas
CFU-eo
23
Q

Burst forming unit - erythroid

A

Early erythroid progenitors grow to make large colonies that look like they have burst apart
Thus the name BFU-E (burst forming unit- erythroid)

24
Q

CSF

A

Factors which were discovered to stimulate colony growth were named colony stimulating factors (CSF) e.g.
G-CSF granulocyte-CSF
M-CSF monocyte-CSF
GM-CSF

25
Bone marrow transplantation
completely ablate haemopoiesis with radiation and drugs infuse compatible donor bone marrow cells haemopoiesis can be completely restored
26
BMT donor
Donor must be HLA matched sibling or unrelated donor Or autologous BMT (cells or tissues obtained from the same individual) reinfuse patients own bone marrow
27
BMT engraftment
Only haematopoietic stem cells can give long term engraftment NOT progenitors NOT precursors
28
BMT applications
Leukaemia, lymphoma, myeloma Intensified chemotherapy for solid tumours Genetic diseases e.g. thalassaemia, SCID etc
29
BMT risks
significant mortality while waiting for engraftment infection due to neutropenia (low neutrophil count) bleeding due to thrombocytopenia (low platelets) Graft versus Host Disease (GVHD)
30
BMT benefits
For many diseases, this is the only curative treatment
31
Pluripotent
Can give rise to cells of every blood lineage
32
Self maintaining
A stem cell can divide to produce more stem cells
33
Mice (stem cells)
mark stem cells by retrovirus insertion transplant irradiated mice with small number of stem cells same marked stem cell gives rise to neutrophils, lymphocytes etc
34
CML
Human Chronic myeloid leukaemia (CML) is caused by a chromosome translocation in a stem cell disease mostly affects neutrophil lineage but Philadelphia chromosome also found in T-lymphocytes and other lineages.
35
CD34
Stem cells and early progenitors carry the cell surface antigen CD34 Later progenitors = CD34 +ve Immature precursors = CD34 -ve Use to purify stem and progenitor cells
36
HAEMATOPOIETIC GROWTH FACTORS
Polypeptide growth factors (cytokines) Bind to cell surface transmembrane receptors Stimulate growth and survival of progenitors
37
HAEMATOPOIETIC GROWTH FACTORS - specific/stim
some stimulate early progenitors, e.g. Il-3, stem cell factor (SCF) others stimulate late progenitors e.g. M-CSF (monocyte-CSF) some are specific to one lineage e.g. erythropoietin others stimulate several different lineages
38
Erythropoietin
Produced in the kidney In response to hypoxia Increases red blood cell production by increasing survival of erythroid progenitors (CFU-E) Specific to one lineage (erythroid) Acts on late progenitors
39
Clinical applications of recombinant erythropoietin
Treating anaemia of kidney failure | Alternative to blood transfusion in Jehovah’s Witnesses
40
G-CSF
Produced by many cell types In response to inflammation Granulocyte colony stimulating factor
41
G-CSF - acts on mature neutrophils in the periphery
chemoattractant promotes neutrophil maturation promotes neutrophil activation
42
G-CSF - Stimulates neutrophil production in the bone marrow
Stimulates neutrophil progenitors (CFU-G) Helps stimulate progenitors of other lineages, but only in combination with other growth factors
43
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 because G-CSF also helps to stimulate other lineages, it will also (for example) stimulate platelet recovery after bone marrow transplantation
44
Peripheral blood stem cell transplantation
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
45
Peripheral blood stem cell transplantation - advantages
Used an alternative to bone marrow for transplantation | Less traumatic for donor, no general anaesthetic

Fundamentals of Pathology (23 decks)

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