Cytokines and Hematopoiesis Flashcards
compare/contrast blood collected with/without anticoagulant
uncoagulated: consists of plasma with fibrinogen, buffy coat (leukocytes and platelets, 1%) and RBCs (42-47%)
coagulated: consists of serum and clotted blood with fibrin
describe process of erythropoiesis
occurs in bone marrow
maturation within blood stream
1) HSC
2) CMP - induced by EPO, IL-3 and IL-4
3) Megakaryocyte/Erythrocyte Progenitor (MEP)
4) Erythrocyte-Committed Progenitor (ErP)
5) Proerythroblast - immature but fully committed to pathway; basophilic staining
6) Basophilic Erythroblast - basophilic staining
7) Polychromatophilic Erythroblast - basophilic (ribosomes) and acidophilic (hemoglobin) staining
8) Orthochromatophilic Erythroblast/Normoblast - acidophilic staining; dense nucleus ready to be extruded
9) Reticulocyte - anucleate, polychromatophilic, 1-2% of circulating RBCs; level can tell us how much erythropoiesis is occurring
10) Erythrocyte
describe locations of hematopoiesis during development
week 3 - 2T: yolk sac
2T: liver; WBCs begin forming
2T - adulthood: bone marrow; becomes primary site in 3T
general trends of hematopoiesis
1) cell diameter decreases
2) cytoplasm becomes less basophilic
3) hemoglobin deposition imparts pink color
4) nucleus:cytoplasm decreases
5) nuclear color changes: purplish red -> dark blue
6) nuclear chromatin condenses
stem cell factor (C-Kit ligand)
produced by bone marrow stromal cells
induces self-renewal and differentiation
c-kit receptor
expressed by hematopoietic stem cell (HSC)
tyrosine kinase receptor (MAPK, PI3-K, Jak/STAT)
proto-oncogene
common myeloid progenitor cells (CMP) produce?
give rise to RBCs, leukocytes, and platelets
common lymphoid progenitor cells (CLP) produce?
give rise to B cells, T cells, and natural killer cells
erythrocytes - properties
anucleate
biconcave
contain plasma membrane, cytoskeleton, hemoglobin and glycolytic enzymes
live for ~120 days
compare/contrast ABO blood types
type O: standard glycosylation, lacks functional enzyme -> no extra chain, anti-A and anti-B antibodies
type A: standard glycosylation, N-acetylgalactosamine, anti-B antibodies
type B: standard glycosylation, galactose, anti-A antibodies
type AB: both A and B antigens, no antibodies
properties of erythropoietin (EPO)
produced by kidneys
response to hypoxia (HIF-1)
stimulates erythrocyte production
properties of EPO receptor
binds EPO
expressed by proerythroblasts and normoblasts
uses Jak/STAT pathway
action: antiapoptotic, proliferation
clinical relevance of recombinant EPO (rHuEPO)
chronic kidney disease: kidneys cannot produce enough EPO -> anemia
chemotherapy: RBCs depleted by treatment -> use to promote regeneration
blood doping: detectable by isoelectric point of different isoforms
thrombocytes - properties
anucleate
membrane-bound cytoplasmic fragments
contain granules with clotting factors/activators, adhesion and vasoconstriction signals, hydrolytic enzymes and clot resorption signals
describe process of thrombopoiesis
occurs in bone marrow
1) HSC
2) CMP - induced by GM-CSF and IL-3
3) MEP
4) Megakaryocyte-Committed Progenitor Cell (MKP)
5) Megakaryoblast - undergoes endomitosis (chromosomes replicate but cell does not divide), induced by TPO
6) Megakaryocyte - multi-lobed nucleus, basophilic granules, undergoes karyokinesis (division of nucleus) and cytokinesis (division of cytoplasm)
properties of thrombopoietin (TPO)
produced primarily by liver (kidneys, bone marrow)
regulator of platelet production
prevents apoptosis, promotes maturation/proliferation
synergistic with platelet agonists -> promotes thrombosis
properties of c-Mpl receptor
binds TPO
expressed on platelets, megakaryocytes and precursors
clinical relevance of TPO
liver failure: no TPO -> no platelets -> thrombocytopenia
thrombocythemia: inherited activating mutation; abnormal clotting due to increased platelets
thrombocytosis: secondary increase of platelets
describe process of granulopoiesis
occurs in bone marrow
maturation in connective tissue
1) CMP
2) Granulocyte/Monocyte Progenitor (GMP) - N, E, or B progenitors
3) Myeloblast - spherical nucleus w/ 3-5 nucleoli
4) Promyelocyte - all azurophilic granules produced here
5) Myelocyte - production of specific granules begins
6) Metamyelocyte - can no longer divide, specific granule production differentiates subtypes
7) Band Cell (N only) - nucleus elongates, horseshoe appearance
8) Mature Granulocyte - nuclear lobes appear
9) differentiation in connective tissue
neutrophils - properties
induced by G-CSF, IL-3, and GM-CSF 3-5 lobed nucleus no cytoplasmic staining 50-70% of circulating leukocytes primary defenders
eosinophils - properties
induced by IL-5, IL-3, and GM-CSF bilobed nucleus eosinophilic (red) staining (due to specific and azurophilic granules) 1-5% of circulating leukocytes primarily react to parasites
when is eosinophilia detected?
parasitic infxn (uncommon in developed countries)
allergic rxns
iatrogenic
basophils - properties
induced by SCF, IL-3, and GM-CSF
lobed nucleus obscured by dense granules
intense basophilic (blue) staining (due to specific and azurophilic granules)
<1% of circulating leukocytes
when is basophilia detected?
lymphoproliferative syndromes often produce basophilia
monocytes - properties
largest of WBCs nucleus w/ indentation site at center small, dense, azurophilic granules circulate for 3 days differentiate in local tissues, can persist peripherally for years
IL-3 - properties
produced by CD4+ T cells
general hematopoietic cytokine
promotes expansion of immature marrow progenitors into all types of mature hematopoietic cells
GM-CSF - properties
granulocyte-macrophage colony stimulating factor
promotes maturation of bone marrow cells into dendritic cells and monocytes
produced at infection sites to mobilize neutrophils
used to recover from cancer chemo and bone marrow transplantation
lymphocytes - properties
histologically distinguishable by size
small: dormant, inactivated; slightly indented nucleus, intense staining, thin pale blue rim; 90% of circulating lymphocytes
large: activated
B cell - properties
produce antibodies (humoral immunity) variable lifespan
T cell - properties
cell-mediated immunity
undergo differentiation in thymus
long life span
natural killer cell - properties
induce apoptosis in infected or “non-self” identified cells
larger than T and B cells
kidney-shaped nucleus
large cytoplasmic granules
IL-7 - properties
produced by stomal cells of many tissues
stimulates expansion of immature B and T cells
X-linked severe combined immunodeficiency (SCID)
mutated T cell-specific IL-7R
decreased T cells, normal or increased B cells
