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
zones of platelet
peripheral - cell membrane, glycocalyx, coag factors
structural - cytoskeleton actin and microtubules
organelles - mitochondria, peroxisomes, glycogen, granules
membrane - open canalicular system
peripheral zone
cell membrane and glycocalyx
- integral membrane glycoproteins - glycosaminoglycans - coagulation factors
structural zone
cytoskeleton
organelle zone
mitochondria, peroxisome, glycogen, granules
membrane zone
open canalicular system and dense tubular system
open to external environment
-remnants of breaking down large cell to smaller platelets
thrombopoeisis
6 step process
occurs from the CMP
in the bone marrow
cytokines that regulate thrombopoiesis
granulocyte-macrophage colony stimulating factor (GM-CSF)
IL-3
megakaryoblast
very large
non-lobed nucleus
undergoes endomitosis - replicates but no cytokinesis
forms the megakaryocyte
megakaryocyte
very large cell
- complex multi-lobed nucleus - scattered granules - karyokinesis and cytokinesis to divide into the platelets
karyokinesis
division of nucleus
thrombopoietin
produced by the liver (also, kidney and bone marrow)
prevents apoptosis of megakaryocytes
-stimulates their proliferation
c-MPL receptor
receptor on platelets, megakaryocytes, and precursors
ligand is thrombopoietein (TPO)
liver failure and TPO?
liver failure leads to decrease in TPO
-patient needs it for platelet formation
thrombocythemia
too many platelets, abnormal clotting
-due to mutations in these components (inherited)
thrombocytosis
too many platelets due to secondary mechanism
thrombocytopenia
not enough platelets
leukopoiesis
development of leukocytes (white blood cells)
granulocyte vs. agranulocyte
specific - secretory with cytotoxic enzymes released from cell
- degranulation - not present in most cells
azurophilic (non-specific) - filled with enzymes involved in phagocytosis
-not specific to cells that degranulate (also found in other cells)
what contains specific granules?
myeloid leukocytes
what cells are granulocytes
neutrophils, eosinophils, and basophils
what cells are agranulocytes
lymphocytes, and monocytes
lymphocytes - T cells, B cells, and NK cells
myeloid development
all similar
band form nucleus
u-shaped nucleus
neutrophils
nucleus with multiple lobes
cell that stains the least
most common leukocyte in the blood (circulate for hours in blood and are in tissues for days)
function to eliminate bacteria or parasites
what cells are derived from the myeloid progenitor?
erythrocytes, platelets, granulocytes, and monocytes
what are the cells derived from the lymphoid progenitor?
T cells, B cells, and NK cells
monocytes
give rise to the macrophages
neutrophil development
myeloblast, promyelocyte, myelocyte, metamyelocyte, band form
myelopoiesis
myeloblast
has nucleoli
no granules
cannot different granulocytes early in development
promyelocyte
beginning to produce primary granules (azurophilic granules)
myelocyte
produce specific granules (this stage is when you can determine change in the cell types)
metamyelocyte
postmitotic cell
make characteristic changes to nuclei
- neutrophil has stage others (band form) - banded nucleus (u-shaped)
neutrophil
aka polymurphonuclear nucleophlie
larger than erythrocytes
2-4 lobes in nucleus (heterochromatin at the periphery)
no cytoplasm staining**
function in eliminating bacteria
eosinophils
larger than erythrocyte
always has bilobed nucleus ***
stains darkly eosinophilic - its specific granules
-contain lots of crystalline proteins that stain
function in parasite defense
basophil
larger than erythrocytes
nucleus is lobed (but you can’t see it normally)
will stain basophilic due to specific granules and azurophilic granules
histamine producing cell type
monocyte
agranulocyte
largest white blood cell
distinct indentation in the nucleus
cytoplasm stains azurophilic granules
smooth and rough ER and mitochondria
short life span: 3,4 days
organ specific and differentiate into osteoclasts
monocyte signaling
will be secreted into blood stream
- differentiate in tissues - microglia, langerhans, kupffer, osteoclasts
azurophilic granules
primary granules
specific granules
produced during myelocyte stage
these are what are characteristic of granulocytes
IL-3
interleukin 3
produced by leukocytes
involved in stimulating formation of lots of different cells
band cell
only in neutrophil generation
GM-CSF
granulocyte-macrophage colony stimulating factor
important cytokine
promotes maturation into dendritic cells and macrophages
lymphocytes
separated into small and large
small lymphocytes
slightly indented nucleus
-intensely staining
large lymphocyte
activated lymphocytes and NK cells
B cell
antibody production
T cell
cell-mediated immunity
develop in thymus
natural killer cell
kidney shaped nucleus
larger than T and B cells
large cytoplasmic granules
lymphopoiesis
synthesis of lymphocytes
involves IL-7**
- stimulates B and T cell production - produced by stromal cells of many tissues
IL-7
stimulates expansion of B and T cells
X-linked severe combined immunodeficiency
-missing IL-7
what cells are from lymphoid progenitor?
B lymphocytes, T lymphocytes, NK cells
stimulated by IL-7
what cells are derived from myeloid progenitor
erythrocytes, platelets, granulocytes, and monocytes
erythropoietin
synthesized in kidney (hypoxia > Hif-1 response)
cause the formation of RBCs
granulocyte colony-stimulating factor (G-CSF)
induced by inflammatory cytokines
causes the synthesis of neutrophils
granulocyte-macrophage colony-stimulating factor
does something
