Cytokines and hematopoiesis (Heck) Flashcards
Test tube with anticoagulant
Plasma (albumin, fibrinogen, lipids, salts, vit., hormones, etc.)
Buffy coat (leukocytes)
Hematocrit (RBC’s ~45 percent)
Test tube without anticoagulant
Serum (no fibrinogen, but containing albumin Blood clot (fibrin containing network)
Erythropoiesis
Formation of red blood cells
leukopoiesis
formation of white blood cells
thrombopoiesis
formation of platelets
hematopoietic stem cells
pluripotent (can give rise to all three germ layers) capable of self-renewal
located in bone marrow
Phases of hematopoiesis
Yolk sac phase (hemangioblasts)
Hepatic phase (involves liver and spleen)
Bone marrow phase (at 7 months, bone marrow phase)
General trends of hematopoiesis
Decrease cell diameter Cytoplasm less basophilic Hemoglobin deposition--> pink color Nuclear diameter decrease Nuclear color from purplish red to dark blue nuclear chromatin condensed
Stem cell factor
AKA--> C-Kit ligand Receptor is C-kit Hematopoietic cytokine produced in bone marrow stromal cells signal stimulates self-renewal and differentiation
What expresses C-Kit ligand receptor
Expressed by Hematopoietic stem cells
C-kit receptor
Tyrosine kinase receptor (activates MAPK, PI3-K, JAK/STAT)
located on HSC
proto-oncogene (mutation causes gain of function, induces proliferation of cells)
C-kit ligand in therapy
Given to pt’s after chemotherapy to repopulate stem cells
can tell which cells are stem cells b/c they have the C-kit receptor
Imatinib
Tyrosine Kinase Inhibitor
Binds to and inhibits C-Kit receptor
good results in treatment of chronic myeloid leukemia because it reduces the amount of HSC’s that are differentiating
Lineage restricted progenitor cells
aka colony forming units (CFU) Descendants of HSC's multipotent non-renewing includes Common Myeloid and Common Lymphoid progenitor cells
Erythrocytes
Type of Myeloid Anucleate Biconcave Lacks organelles 120 day lifespan Contains (plasma mem, cytoskeleton, hemoglobin, glycolytic enzymes)
O Antigen
Present when individual lacks functional enzymes (no extra sugar added)
default blood type
A Antigen
When individual has the enzyme N-acelylgalactosamine that adds extra N-Acelylgalactosamine
ABO blood groups
glycoprotein markers on surface of RBC’s
products of glycosylation
includes A, B, O and AB antigens
B antigen
have galactose transferase which adds additional galactose
AB blood group
Have both N-acelylgalactosamine and glucose transferase to add both additional sugars
Erythropoiesis
Starts in bone marrow
Erythrocytes mature in blood stream
10 step process
10 steps in Erythropoiesis
HSC CMP MEP ErP Proerythroblast Basophilic Erythroblast Polychromatophilic erythroblast Normoblast Reticulocyte Erythrocyte
Proerythroblast
can see nucleolus (so means making tRNA and mRNA for ribosomes)
large nucleus
cytoplasm stains blue (positive) b/c free ribosomes synthesizing hemoglobin
Basophilic erythroblast
more basophilic
lots of ribosomes so still blue
polychromatophilic erythroblast
stains both pink and blue because now have accumulation of hemoglobin
Normoblast
dense nucleus because of condensed chromatin
can no longer divide
nucleus is seen at the edge of the cell to be extruded
Reticulocyte
Anucleate stains pink (eosinophilic) looks pretty indistinguishable from mature RBC's this is released into the bloodstream (matures in 1-2 days) and used clinically to determine how much erythropoiesis is happening
Erythropoietin (EPO)
Cytokine (growth factor) that stimulates erythrocyte production
produced by kidneys
binds to erythroid cell lineage in bone marrow
prevents apoptosis
induced by hypoxia
Hif-1
induces expression of erythropoietin in hypoxic conditions
erythropoietin receptor
Located on erythroctye progenitor cells (also can be on proerythroblasts and normoblasts)
tyrosine kinase receptor
induces JAK/STAT pathway–> STAT induces expression of genomic sequences required for erythrocyte differentiation
Recombinant EPO clinical uses
chronic kidney disease: reduced EPO production leads to decreased RBC’s
chemotherapy: repopulate cells lost during chemotherapy
Recombinant EPO use in blood doping
Given to athletes to increase RBC, more muscle tissue oxygenation
Detected by using electrophoresis–> isoelectric point of recomb. EPO different than human produced EPO
Platelets
very small compared to RBC’s
anucleate
little membrane bound cytoplasm
4 zones
Peripheral zone and Structural Zone (platelet)
Cell membrane
Glycocalyx (integral membrane of glycoproteins)
Cytoskeleton
Organelle Zone (platelets)
Mitochondria
Peroxisomes
Glycogen
Granules (contain clotting factors and activators, etc.)
Membrane Zone (of platelets)
Open canalicular system (OCS)
these are remnants of membrane channels that subdivided the precursor megakaryocytic into platelets
Dense tubular system -storage for calcium ions, originates from rER of precursor
Thromboeisis
6 step process
located in bone marrow
Megakaryoblast
large
non lobed
Undergoes endomitosis
under influence of thrombopoietin
Megakaryocyte
Final step before platelet formation larger than megakaryoblast multi lobed nucleus undergoes Karyokinesis (nucleus) Cytokinesis (division of cytoplasm)
Thrombopoietin
Growth factor
regulates platelet function
targets and prevents apoptosis of megakaryocytic
promotes maturation of megakaryocytic
produced by liver mainly
c-Mpl receptor
Receptor for thrombopoietin
expressed on platelets, megakaryocytes
Liver failure
Insufficient in producing thrombopoietin
Thrombocythemia
Pt having too many platelets due to primary mechanism (So activating mutation in receptor or in thrombopoietin)
results in clotting abnormally
thrombocytosis
too many platelets due to secondary mechanism
thrombocytopenia
not enough platelets
Leukopoiesis
Development of white blood cells
myeloid
lymphoid
Granulocytes (have granules)
Agranulocytes (no granules)
Specific granules
Secretory vesicles filled with cytotoxic enzymes and peptides that are released from cell during degranulation
Special or specific (not present in most cells)
only myeloid type white blood cells contain specific granules
Azurophilic granules
Non-specific to cells that degranulate (primary)
filled with enzymes that function in phagocytosis (killing a microbe)
Lymphoid type white blood cells
T lymphocyte
B lymphocyte
Natural killer cells
Myeloid type white blood cells
Neutrophils
Monocytes
Basophils
Eosinophil
Myelopoiesis (cell types)
Myeloblast Promyelocyte Myelocyte Metamyelocyte Mature cell
Myeloblast (myeloid type white blood cells)
Contains nucleoli (producing RNA) no granules
Promyelocyte (myeloid type white blood cells)
producing primary (azurophilic) granules
Myelocyte
starts to produce specific granules (secondary)
can begin to determine differences in cell type
nucleus no longer round (no nucleoli
Metamyelocyte
Changes in nucleus occur (shape)
post-mitotic so no longer dividing
nucleus begins to indent
Neutrophil
Nucleus has 2-4 lobes
cytoplasm lacks staining b/c it’s specific granules are not highly staining
Band cells (unique stage of development) "u-shaped nucleus"
most common
eliminate bacteria or parasites
Eosinophil
granulocyte of myeloid cell descent
Bilobed nucleus
stains darkly b/c of its specific granules
not usually in high conc.
Basophil
Bilobed nucleus- but can’t see it b/c of it’s specific granules
intense basophilic staining (blue)
present in very low conc.
histamine producing cell type (allergies)
Monocyte
Only agranulocyte of the myeloid cell descent
cytoplasm doesn’t stain b/c just has azurophilic granules
in blood 3 days
Differentiate in local tissue
Macrophages (tissue specific)
Osteoclasts (bone)
Microglia (brain)
IL-3
cytokine produced by lymphocytes
expansion of immature marrow progenitors into all types of mature hematopoeitic cells
and mast cells
used after chemotherapy to replenish cell types
GM-CSF
Granulocyte-Macrophage Colony stimulating factor
targets neutrophils, eosinophils, basophils, monocytes, and dendritic cells
source–> endothelial cells, T cells, fibroblasts, monocytes
used after chemotherapy to replenish cell types
B cell
Lymphocyte of Lymphoid type cell descent
Antibody production
located in bone marrow
T Cells
Lymphocyte of lymphoid type cell descent
cell-mediated immunity
produced in bone marrow but undergo differentiation in the thymus
Natural killer cell
Large Lymphocyte
Kidney shaped nucleus
more intense staining
mature in peripheral tissues
Lymphophoiesis
Lymphocyte production
IL-7
IL-7
Cytokine
stimulates expansion of immature B and T cells
produced by stromal cells (CT type cell) of many tissues
X-linked severe combined immunodeficiency
Lack of IL-7 signaling causes decrease in T cells
