Hematopoesis Flashcards
aplastic anemia
difflymphocytes attack bone marrow stem cells
only fat and storm left
blood/components
bottom to top
- rbc
- buffycoat-wbc/platelets
difference between appearance of myeoblast cells
bsopihl-all dark
neutrophil-several uncle
esoinopihl-darker but not as dark as basophil
neutrophil function
phago cytose invading bacteria
eosinophil
destroy large parasite
-allergic respinse
basohpil
release histamine
monocyte
become macropages-digets micros and foregone bodies and old cells
which cells are continuously made
bone marrow-as long as have stem cells will be good-can even inject if don’t have (as long as no immune incompatibility)
-get around by using synergistic litter mate
syngenic
genetially indetical
blood production
bony trabecular-large red material-glowing blood precursor
multinucleate cells-megakaryocte-platelet producing cells
CD34
on surface of blood stem cells
neoplasia
failure to differentiate or undergo pop
senescne
deterioration with age
progeinitor
committed stem cells can only differentiate into this
what kind of stem cells are bone marrow
polurpotent or committed progenitor-takes more time to become pluripotent?
Stochastic vs hierarchicial
sot-cells are same and each division yields either 2 fully differentiated cells, 2 progenitorsrs, or one of each
heriarchical-stem makes progenitors which then become differentiated
-with each step in maturation-less ability to replicate until nucleus becomes incapable
blood stem cell surface characteristics
cd34
- got by flow cyto/immunocyto
- ckit positve and lin negative (lineage)
- lin has to do wit maturity
flow cyto
measures na danlyzes multiple charactersitcs of particles
-add floruest dyte to antibody-identify patroller cell (that has that antibody)
diseases of hemopoietic progenitor cell
either granulates or rbis not maturing
-show stem cells ar real
hemapoesis throughout life
early occur in gold sac, then move to liver, then to bone marrow
occurs in niche
Long bones make slightly les than flat
-less made in adult then young-but not alot
medularry areas of bones
nurturing environemnt to support growth and proliferation-this is niche
bone niche
maintenance of long term quiescence of hemopoietic stem cells in appropriate numbers for blood cell homeostasis
-site for receptor ligand combos between stem and supporting stream cells to support bone niche
vascular niche
proliferation of hemopoietic stem cells-their differ nation into mature blood cells and delivery to circulation
cxcl4
when inhibited by antibody-litertes stem cell into general circulation
chimokine-substance elaborated by local cells attracting specific other cells
bone structure
near endostium and around sinusoids-swhere stem cells formed
inner bone-osteobalsts, macrophages
stem cell state
quiescent-divdies enough to maintain population but not mature
-the more claim the more stem cell maintenence
why does hemopoiesis only occur in niche
cell cell signals
factors secreted here help-chemical interactions
cells here promote HSC maintencen by regulating function of third party cells-other proteins
really just bone marrow micro environment
runx gene + what would mutant be lie
allows for osteobast formation
-mutant-no hemopoesis inbone marrow-only in yolk sac
CBF bta
allows hemopoiesis in fetal liver
Runx and CBF complexes
activates and repspresses trx of key regulatory of growth, survival, differentiation pathways
absence in these genes cause blood production failure or leukemia
Formed elements in blood production
formed elects-rbc/wbc/platelets
constant turnover-must react to rapid changes in environment
Kit interaction (3 things it does) and mechanism
ligand for kit is on stromal cell
involved with hemopoietic stem cell maintenance
allows for stem cells to go to correct place
allows for mature stem cells to be i nporper number
ensure that cd34 positive stem cels are
insufficient to restore bone marrow (need kit in addition to cd34 stem cells)
sl locus
w losuc
where ckit ligand is encoded
where ckit is encoded
what does homeless require reading cell and stormal cells
need direct cell contact
-need both or else will not have hemopoiesis
stratgetic reserve
strategic reserve of stem cell in niche-make sure don’t rn out because when begin maturation they will lose ability to proliferate
maturation of progenitors (not stem cells)
do not require tight niche contact like stem cells do
growth of cells in suspensin
- what is required
- what determines what grows
require presence of growth promoting factors-need cytokines and interleukins
factors introduced-appropoirate cytokines or interleukins
interleukin 3 creates
eryhtocytes, mono, mega, granulo
CSF creates
colonies of macro and granulocytes
colony stimulating factor
eryhthropoietin
produced by vascular endothelium in kineys
-example of cytosine
how does each colony arise
from a single progenitor cell
how do blood cells exist in tissue
semisolid agar
remain in suspension
slow down movement-but still in suspension
-allows to see CFUs/progenitors
Hematopoietic growth factors 3
defineition
bind to hemoatopoeitin recepotrs
-cytokines-substances that induce growth
bind to kinase receptors
- c-kit
- keep cells in niche
- surface recognizeing receptors
interleukins-produced by leukocyytes- affect function of leukocytes
hematopoietns-hormone like substances which act in endocrine (one organ affecting other), paracrine (one cell affecting other), or autocrine manner
cytokine binding
TF (usually for growth) binds to cell membrane recptor with low affinity, then becomes attracted and binds to high affinity receptor-gnerates growth signal
4 erythropoiesis steps
and what stimulates this
cells get smaller
cyto changes
nucleous/cyto ratio falls
nucelus removed
eryothropoiten
erythropoiten
incdueces JAK/STAT dimerization
- epo is ligand
- results in events that enhance growth/suppress apop
monocytes
macrophages in tissue
phagocytose baceria, fungus, turmor etc.
- release cytokines-mediators of inflammation, presents antigen to lymph
- may become macrophage
thrombopoeises
platelet fomration
megakaryocyte (large and 16 nuclei)
- platelets form by budding
- stimulated by prothrombin-stim production/activation of platelets
granulopoiesis
each stage allows cell to become less able to proliferate-more capable of effector function
-precursors are able to be seen in biopsy/bone marrow
-CSFGM and CSF G-important growth factors
cd34
context critical-on myelomonocyte progenitor
-can result in monocle or promyeloyte
cd14
associated with monocytes
pathway of hieracrcy
myelooid stem cell
- myloblast>basophil, eosinophil, neutrophil
- monocyte
- megakaryocyte>platelets
- pronomoblast-erythrocyte
lymphoid stem cell-lymphocyte
colony forming unit
CSF and colonies produced are measured as BFU
-measured when progenitor cells are stimulated in system to produce colonies of granulocytes or macrophages
shows that progenitors can grow in vitro with specific factors instead of in niche
