Lecture 6 Flashcards
What is hematopoiesis?
The formation of blood cellular components
What is primitive hematopoiesis?
- HSC-like cells emerge from yolk sac and migrate to the liver
- cannot self-renew
- makes nucleated erythrocytes and primitive MPs (to get rid of apoptotic cells)
What is definitive hematopoiesis?
- @30 days post-fertilization
- multipotent (can make ALL the blood cell types) hematopoietic stem cell adheres to aortic endothelium
- fetal liver gets HSCs and becomes principle site
- erythrocytes are anucleated and produce adult hemoglobin
What is the role of the adult liver in the immune system?
producing complement proteins and acute phase reactants that participate in innate responses
Which organs/bones are hematopoietic in a fetus, child and adult?
fetus: yolk sac, then liver/spleen, then bone marrow
child: all of the bones
after puberty: sternum, vertebrae, pelvis and ribs
What is the purpose of yellow bone marrow?
stores fats and provides sustenance
What is a bone marrow niche?
cellular/molecular micro-environments that provide signals to regulate the activities of HSCs
What is asymmetric cell division?
specific cell fate determinants are not distributed equally before the onset of division (eg mRNA, proteins)
- cleavage plane in mitosis is oriented so one daughter cell gets more and starts differentiation
What is environmental asymmetry?
one daughter cell receives from a distinct microenvironment that intiates differentiation, and goes through many rounds of cell division before process is complete
What is CXCL12?
chemokine that retains HSC in the endosteum niche
Why might someone need bone marrow/HSC transplant?
- inherited immunodeficiency
- bone marrow failures that cause deficiency
- cancer treatments that damage bone marrow
What are the three main sources of HSCs?
- umbilical cord blood
- cytokine mobilized peripheral blood
- bone marrow
what are the advantages/disadvantages of harvesting HSCs via bone marrow?
good: Can isolate large numbers of HSCs for one procedure, can be done on emergency basis
bad: invasive, recovery for donor
How does cytokine mobilized peripheral blood harvesting work?
- small number of HSCs leave the bone marrow and come back
- G-CSF increased, causes proteolytic enzyme secretion and breaks down cell adhesion molecules between HSC and stromal cells
- increase in HSC emigration
- collected by aphresis (HSCs are skimmed off and blood is returned)
what are the advantages/disadvantages of harvesting HSCs via peripheral blood?
good: less invasive
bad: G-CSF injection, may require 2-3 procedures to collect enough, cannot be done on emergency basis
