H&M chp 1 Flashcards
Site of haemopoiesis for fetus 0-2 monthes
yolk sac
Site of haemopoiesis for fetus 2-7 monthes
liver, spleen
Site of haemopoiesis for fetus 5-9 monthes
bone marrow
Site of haemopoiesis for infants
bone marrow of practically all bones
Site of haemopoiesis for adults
vertebrae, ribs, sternum, skull, sacrum, pelvis, proximal ends of femur
What is extramedullary haemopoiesis?
ability of liver and spleen to resume their fetal haemopoietic role
What are haemangioblasts?
these stem cells are the common precursors to endothelial and haemopoietic cells. They are found in the AGM region and are believed to seed the liver and spleen.
Where are haemopietic stem cells found?
bone marrow
phenotype of haemopoietic stem cells?
CD34+ CD38-, neg for lineage markers, small lymphocyte
CFU-GEMM
the earliest detectable mixed myeloid precursor which gibes rise to granulocytes, erythrocytes, monocytes, and megakaryocytes
The bone marrow is composed of ____ and ____.
stromal cells, microvascular network
The stromal cells include
adipocytes, fibroblasts, osteoblasts, endothelial cells, macrophages
Function of stromal cells
secrete extracellular molecules including collagen, glycoproteins (fibronectin, thrombospondin), glycosaminoglycan (hyaluronic acid, chondroitin derivatives) to form the matrix. Secrete growth factors for stem cells.
What stem cell is critical in stromal cell formation?
mesenchymal stem cell
What do mesenchymal stem cells do?
with osteoblasts, they form niches, provide growth factors, adhesion molecules, and cytokines to support stem cells
What process allows stem cells to traffic around the body? What cytokine is involved?
Mobilization, G-CSF
What chemokine gradient is critical for homing?
SDF-1
What interactions are critical for maintaining stem cell viability and production?
SCF and jagged proteins on stroma and their receptors KIT and NOTCH (respectively)
What is SCF?
stem cell factor which is expressed on stromal cells. It binds to receptor KIT, which is a critical interaction for maintaining stem cell viability and production
What are jagged proteins?
They are expressed on stromal cells and bind receptor NOTCH on stem cells. This interaction is crucial in stem cell viability and production
What is SDF-1?
stromal-derived factor 1, its chemokine gradient is critical to stem cell homing
What is self -renewal?
Haemopoiesis starts with stem cell division in which one cell replaces the stem cell and the other is commited to differentiation
Why do early committed progenitors express low levels of transcription factors?
they may commit them to discrete cell lineages
What are haemopoietic growth factors?
glycoprotein hormones that regulate proliferation and differentiation of haemopoietic progenitor cells and the function of mature blood cells
____ are the major source of growth factors.
Stromal cells
Where is erythropoietin made?
kidney
Where is thrombopoietin made?
liver
_____ and _____ have a negative effect on haemopoieses and may have a role in the development of aplastic anemia.
TNF and TGF-B
Dimerization of a receptor leads to activation of a complex series of intracellular signal transduction pathways of which the 3 major ones are:
JAK/STAT, mitogen activated protein (MAP), and the phosphatidylinositol 3 (PI3) kinase pathways
Transcription factors typically contain what 2 domains?
DNA binding and activation
Haemopoetic tissue occupies about ___% of the marrow space in adults
50
How common is the haemopoetic stem cell?
1 in every 20 million nucleated cells in bone marrow
Are haemopoietic stem cells effectively transferred during transplant?
yes
What are the functions of growth factors in the bone marrow?
stimulate proliferation of early bone marrow cells, direct differentiation, stimulate maturation, suppress apopotsis, affect function of non-dividing cells
What cytokine has an important role in early haemopoiesis?
IL-3
What is the function of TPO?
BFUemeg–> CFU meg
What is the function of EPO?
BFUe–> CFUe
What is the function of M-CSF?
CFUgm–> CFUm
What is the function of G-CSF?
CFUgm–> CFUg
What is the function of IL-5?
CFUeo–> eosinophil
Granulocyte and monocyte formation can be stimulated by infection or inflammation through release of ___.
IL-1 and TNF
____ phosphorylate downstream proteins targets and are regulated by cyclins.
Cdk
___ are synthesized and degrarded in the cell cycle and regulate Cdk
cyclins
Apoptosis results from the action of ____.
incracellular cysteine proteases called caspases which are activated following cleavage and lead to endonuclease digestion of DNA and disintegration of the cell skeleton
FAS and TNF-R receptor have a _________ domain.
intracellular death
What are DNA-binding domains?
leucine zipper or helix-loop-helix
____ regulate migration of white cells
chemokines
____ are involved in cell adhesion to ECM
integrins
____ are involved in leukocyte and platelet adhesion to endothelium during inflammation and coagulation
selectin
Does p53 have a role in the transduction pathway of growth factors?
NO- it has an important role in sensing DNA damage
