IHL I - Cytokines and Hematopoeisis Flashcards
difference between serum and plasma
serum lacks fibrinogen
plasma is collected in the presence of an anticoagulant
-heparin or sodium citrate
two components of blood
plasma and cells
plasma is liquid
hematopoiesis
formation of new blood cells
erythropoiesis
formation of red blood cells
leukopoiesis
formation of white blood cells
thrombopoiesis
formation of platelets
where does hematopoiesis occur?
different stages of development
- yolk-sac phase (main source until third week of gestation) - hepatic phase (begins early, major source during 2nd trimester) - bone marrow phase (only location in adulthood)
general trends in hematopoiesis
cell diameter decrease
cytoplasm less basophilic
hemoglobin pink color
nuclear to cytoplasm ration decreases (nuclear diameter decrease)
nuclear color change from purple to dark blue
nuclear chromatin condenses
hemopoeitic stem cells
pluripotent (can give rise to all three germ layers)
-can also differentate into non-blood cell lineages
self renewing
stem cell factor
c-kit ligand that is expressed by bone marrow stromal cells
binds the c-kit receptor
c-kit receptor
tyrosine kinase that activates a number of pathways
-MAPK, PI3-K, Jak/STAT
proto-oncogene
-signaling induces differentiated and self-renewal
gain of function leads to over-synthesis of blood cells
imatinib
tyrosine kinase receptor inhibitor
targets the c-kit receptor
treats chronic myeloid leukemia
lineage restricted progenitor cells
multipotent
two categories
-myeloid and lymphoid
leukocyte categories
granulocytes and agranulocytes
granulocytes - all myeloid
agranulocytes - one myeloid and lymphoid
erythrocytes
RBC
- anucleate - biconcave - lack organelles - have plasma membrane, cytoskeleton, hemoglobin, glycolytic enzymes
life 120 days
ABO blood groups
glycoproteins on the blood cells
A and B
-O is lack of enzyme and no extra sugar
n-acetylgalactosamine
enzyme that adds A antigen to RBCs
adds N-acetylgalactosamine
galactose tranferase
enzyme that adds B antigen to RBCs
adds galactose to the blood antigen
AB blood group
has both enzymes and has both sugars added
what sugar on the O antigen
has glucose, galactose, and N-acetylglucosamine
-A and B add additional sugars to this structure
erythropoiesis
red blood cell development
- in the bone marrow - last step maturation in the blood stream
what three cytokines are important in erythropoiesis
erythropoietin (EPO), IL-3, and IL-4
what is the first cell of erythropoiesis
common myeloid cell
What are the cells in erythropoiesis pathway
Megakaryocyte/Erythrocyte Progenitor (MEP) Erythrocyte-commited Progenitor (ErP) Proerythroblast Basophilic Erythroblast Polychromatophilic Erythroblast Normoblast Reticulocyte Erythrocyte
Proerythroblast
large nucleus
stains basophilic - bc lots of free ribosomes synthesizing hemoglobin
can see the nucleolus - ribosome production
basophilic erythroblast
large nucleus and basophilic staining
no nucleoli present
polychromatophilic erythroblast
large nucleus, lots or ribosomes
stains both basophilic (ribosomes) and acidophilic (hemoglobin)
normoblast
changes in nucleus
- dense nucleus - no longer capable of dividing - acidophilic - hemoglobin staining
reticulocyte
anucleate
eosiniphilic - hemoglobin
basophilic - some ribosomes present
released into the blood stream and then becomes mature erythrocyte
secreted to be blood stream
-will mature to erythrocyte in the blood stream
erythropoietin
stimulates erythrocyte production
tyrosine kinase receptor
-JAK-STAT signaling
its synthesis is triggered by Hif1
produced by the kidneys, in the response to Hif-1
EPO receptor
expressed by committed erythroid progenitors
activation of EPO receptor?
activation leads to antiapoptotic events
EPO receptor on proerythroblasts and normoblasts
-induces their proliferation
recombinant EPO
used in the clinic and on the streets!
chronic kidney disease and EPO?
kidney damage leads to reduced EPO > anemia
given to patients to increase erythropoiesis
also, used in chemotherapy (which depletes RBCs)
blood doping and EPO?
increases the number of RBCs to increase muscle tissue oxygenation
- detected by isoelectric point different isoforms
- to find it in athletes
thrombocytes
platelets
small, membrane bound, cytoplasmic fragments, anucleate
divided into peripheral hyalomere and central granulomere
-book divides further