Ppt Part 2 Flashcards
STEM CELL THEORY
•YEAR- Till and McCulloch:
1961
Stem cell theory by
Till and McCulloh
= COLONIES of HSCs
Aplastic Mice + Intravenous injection of marrows
(CFU-S)
COLONY-FORMING UNITS-SPLEEN
• Capable of self-renewal and production of differentiated progeny
COLONY-FORMING UNITS-SPLEEN (CFU-S)
• NOW: committed myeloid progenitors or colony-forming unit-granulocyte, erythrocyte, monocyte, and megakaryocyte (CFU-GEMM)
COLONY-FORMING UNITS-SPLEEN (CFU-S)
Unrecognizable hematopoietic progenitor
• 2 Major Types:
Non committed or Undifferentiated HSCs
Committed Progenitor cells
: can differentiate into progenitor cells committed to either lymphoid or myeloid lineages
Undifferentiated HSC
Undifferentiated HSC: can differentiate into progenitor cells committed to either
lymphoid or myeloid lineages
2 Theories
Monophyletic theory (widely accepted theory)
Polyphyletic theory
•HSCs 3 Possible fates:
Self renewal
Differentiation
Apoptosis
• HSC: 2 divides to…
2 identical daughter cells
(symmetric division/asymmetric division/ apoptosis)
• A group of specific glycoproteins
CYTOKINES & GROWTH FACTORS
CYTOKINES & GROWTH FACTORS
• A group of specific_______
glycoproteins
• Regulate the proliferation, differentiation, and maturation of hematopoietic precursor cells
CYTOKINES & GROWTH FACTORS
• Responsible for stimulation or inhibition of production, differentiation and trafficking of mature blood cells and their precursors
CYTOKINES
• Diverse group of soluble proteins that have direct & indirect effects on HSC
CYTOKINES
CYTOKINES
• Responsible for stimulation or inhibition of…
production, differentiation and trafficking of mature blood cells and their precursors
Examples of CYTOKINES
Interleukins (IL)
lymphokine
monokines
interferons
chemokines
CSFs
: Kit ligand, FLT3 ligand, GM-CSFIL1,IL3,IL6,IL11
POSITIVE INFLUENCE
: Transforming factor B, TNF a, interferons
NEGATIVE INFLUENCE
POSITIVE INFLUENCE:
Kit ligand
FLT3 ligand
GM-CSF
IL1
IL3
IL6
IL11
NEGATIVE INFLUENCE
Transforming factor B
TNF a
interferons
CYTOKINES
• Prevent precursor cells from dying by…
inhibiting apoptosis
• Prevent precursor cells from dying by inhibiting apoptosis, decreasing the transit time (cell cycle), they regulate cell differentiation into the various cell lineages.
CYTOKINES
• Programmed cell death
• Normal physiologic process that eliminates unwanted abnormal, or harmful cells.
APOPTOSIS
= APOPTOSIS IS INITIATED WHEN
NO APPROPRIATE CYTOKINE
• Produced by many different cells
• High specificity for their target cells
• Active at low concentrations
Colony-Stimulating Factors
” Names of indicate the predominant cells lines that respond to their presence
Colony stimulating factor
CSF FOR - granulocytic cell line
• G-CSF
Granulocyte colony stimulating factor
CSF FOR- targets the granulocyte-monocytic cell
• GM- CSF
Granulocyte monocyte colony stimulating factor
CSF
Works synergistically with ______to enhance_______ colony formation
IL-3
megakaryocyte
… described early acting growth factors (multilineage)
intermediate-acting growth factors (multilineage)
late-acting growth factors(lineage restricted)
Ogawa
KIT ligand (aka:_______)
Stem CellFactor (SCF)
Stem CellFactor (SCF) aka
KIT ligand
• Early-acting growth factor
KIT ligand (aka: Stem Cel Factor (SCF))
receptor of KIT ligand
transmembrane KIT
: receptor type tyrosine-protein kinase that is expressed on HSC is down regulated with differentation
KIT
= STIMULATE cell to proliferate = essential in the early stages of hematopoiesis
• KIT LIGAND + KIT
Early-Acting Multilineage Growth Factors
KIT Ligand
Interleukin 3
FLT3 - Fms-like tyrosine kinase-3
-Is also a receptor-type tyrosine-protein kinase.
Fms-like tyrosine kinase-3
FLT3
•_____ and ______ works synergistically with IL3, GM-CSF, and other cytokines = Promote early HSC proliferation and differentiation
KIT ligand and FLT3 ligand
• Regulates blood cell production by controlling the production, differentiation, and function of granulocyte ad macrophages
IL 3
Interleukins
Characteristics:
- Protein that exhibit multiple biologic activities
- They have synergistic interactions with other cytokines
- They are part of interacting systems amplification potential
- They are effective at very low concentration
ERYTHROPOIESIS
• Occurs in the
bone marrow
ERYTHROPOIESIS
: gives rise to earliest identifiable colony of RBC (burst-forming unit-erythroid (BFU-E))
• CFU-GEMM
colony forming unit – granulocyte, erythrocyte, monocyte, megakaryocyte
ERYTHROPOIESIS
: produces a large multi-clustered colony resembles a cluster of grapes containing brightly colored hemoglobin
• Contain few receptor for EPO
• BFU-E
(burst-forming unit-erythroid (BFU-E))
• Many EPO receptor & has an absolute requirement for EPO
• Responsive to low levels of EPO
CFU-E:
colony-forming unit-erythroid
ERYTHROPOIESIS
glycoprotein produced in the renal peritubular interstitial cells
EPO
Erythropoietin
• EPO: glycoprotein produced in the
renal peritubular interstitial cells
LEUKOPOIESIS
• 2 MAJOR CATEGORIES:
MYELOPOIESIS & LYMPHOPOIESIS
LEUKOPOIESIS
: stimulates the proliferation and differentiation of neutrophil and macrophage colonies from CFU-GM
• GM-CSF
Granulocyte-macrophage colony-stimulating factor (GM-CSF)
LEUKOPOIESIS
: stimulate the neutrophil & monocyte from CFU-G & CFU-M
G-CSF & M-CSF
LEUKOPOIESIS
multi-lineage stimulating factor
IL3
LEUKOPOIESIS
EOSINOPHIL: require
GM-CSF
IL5
IL3
LEUKOPOIESIS
BASOPHIL:
IL3
KIT ligand
LEUKOPOIESIS
• Promoting lymphoid differentiation:
IL2,IL7,IL12 & IL5, IL4, IL10,IL13, IL14,IL16
• Influences megakryopoiesis
• GM-CSF, IL-3, IL6,IL11, KIT Ligand and TPO
Megakaryopoiesis: stimulating hormonal factor (aka MPL Ligand)
TPO
Thrombopoieitin
Megakaryopoiesis
•______: controls the production and release of platelets
IL 11
Megakaryopoiesis
•_____: major site of TPO
LIVER