1. Self-renewal 2. Differentiation 3. Apoptosis

[DISCUSSION] MODULE 2: QUIZ 2 COVERAGE Flashcards by Arriane Camacho

1961: Till and McCulloch

- irradiated [?] and [?] of mice = aplasia

spleens and BM

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1961: Till and McCulloch

- Aplastic mice given IV injection of

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1961: Till and McCulloch

- Colonies of HSCs were seen [?] later in the spleens

7-8 days

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1961: Till and McCulloch

- Colonies =

Colony Forming Unit-Spleen (CFU-S)

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Capable of self renewal and production of differentiated progeny

Colony Forming Unit-Spleen (CFU-S)

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“committed myeloid progenitors”

colony forming unit granulocyte, erythrocyte, monocyte, megakaryocyte “CFU-GEMM

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capable of giving rise to multiple lineages of blood cells

Colony Forming Unit-Spleen (CFU-S)

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HEMATOPOIETIC PROGENITOR CELLS

2 Major types

I. Noncommitted/Undifferentiated hematpoietic stem cells (HSCs)
II. Committed projenitor cells

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HEMATOPOIETIC PROGENITOR CELLS (committed and noncommitted) give rise to

all of the mature blood cells

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2 Theories of Hematopoietic Progenitor cell origin

Monophyletic theory

2. Polyphyletic theory

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Pluripotent hematopoietic stem cell

Monophyletic theory

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Most widely accepted theory

Monophyletic theory

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vCapable of self-renewal

HEMATOPOIETIC STEM CELLS

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vAre pluripotent

HEMATOPOIETIC STEM CELLS

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vGive rise to diff progeny

HEMATOPOIETIC STEM CELLS

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vAble to reconstitute the hematopoietic system of a lethally irradiated host

HEMATOPOIETIC STEM CELLS

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Can differentiate into progenitor cells committed to either lymphoid or myeloid lineages

UNDIFFERENTIATED HSCS

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Proliferates and Differentiates into: T, B, natural killer lymphocyte, dendritic cells

Common lymphoid progenitor

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Proliferates and differentiates into: individual granulocytic, erythrocytic, monocytic and megakaryocytic lineages

Common myeloid progenitor

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FATES OF HSCS

Self-renewal
Differentiation
Apoptosis

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When the HSC divide, it gives rise to two identical daughter cells

a. Symmetric division

b. Asymmetric division

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**Till and Mculloch: Proposed that hematopoiesis is a random process whereby the JSC randomly commits to self-renewal or differentiation

STOCHASTIC model of hematopoiesis

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Later studies suggest that the microenvironment in the BM determines whether the HSC will sef-renew or differentiate

INSTRUCTIVE model of hematopoiesis

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Current thinking suggests that the ultimate decision made by the HSC can be describes by both

stochastic and instructive

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Initial decision to self renew is probably

stochastic

which occurs later is determined by various signals from the HIM in response to spp requirements of the body

Lineage differentiation

parent cell produces identical cells with identical chromosomes; chromosomes are visible with light microscope

Mitotic phase

-Cytoplasm and nucleus mature at the same rate

1. Synchronous

-Cytoplasm or nucleus mature first before the other Can lead to abnormality in shape and size

2. Asynchronous

1. Blast cells do not have

granules

2. Blast cells contain a (?) ([?] to [?] of cell area) and a (?)

large nucleus - 3/3 to 7/8 | small amount of cytoplasm

3. As cells mature, the cytoplasm becomes

less basophilic

``` 4. As cells mature, the (?) of the nucleus becomes heavier, and the darker the (?) stains, the heavier the chromatin is ```

chromatin | nucleus

5. As the cells mature, they become

smaller

6. (?) tend to disappear in mature cells

Nucleoli

7. As cells mature, specific granules become

less prominent and smaller

8. There are 4 different types of granules:

neutrophilic, basophilic, eosinophilic, azurophilic (primary)

-Group of specific glycoproteins secreted by cells

Cytokine

-in Hematopoiesis, they regulate the proliferation, differentiation, and maturation of hematopoietic precursor cells (include: IL, lymphokines, monokines, interferons, chemokines, colony stimulating factors)

Cytokine

•Have direct and indirect effects on hematopoietic cells

CYTOKINES OR GROWTH FACTORS

•Cytokines with a positive influence on hematopoietic stem cells and progenitor cells with multilineage potential

KIT ligand, FLT3 ligand, GM-CSF, IL-1, 6, 11

KIT ligand, FLT3 ligand, GM-CSF, IL-1, IL-6, IL-11

Cytokines with a positive influence on hematopoiesis

Cytokines with a negative influence on hematopoiesis

Transforming growth factor-B, Tumor necrosis factor-a, interferons

Cytokines with multiple actions

Interleukins

a. Proteins exhibiting

multiple biologic activities

b. Have [?] with other cytokines

synergistic interactions

c. Part of interacting systems with [?]

amplification potential

d. effective at

very low concentrations

-have high specificity for their target cells

Colony Stimulating Factors (CSF)

-active at low concentrations

Colony Stimulating Factors (CSF)

Can be classified accdg to the part of the development process that they influence

Growth Factors

Multilineage in action

Early acting growth factors

Ex: KIT ligand, FLT3 Ligand, GM-CSF, IL-3

Early acting growth factors

formerly erythrocytes

RBCs

Erythroblasts

nucleated red cell precursors

Normoblasts

developing nucleated cells with normal appearance

Megaloblast

abnormal appearance of developing nucleated cells in megaloblastic anemia

Three nomenclatures are used in naming for the erythroid precursors

NORMOBLASTIC RUBRIBLASTIC ERYTHROBLASTIC

-The glycoprotein hormone produced by the kidneys (renal peritubular interstitial cells)

ERYTHROPOIETIN

-ERYTHROPOIETIN Main effect:

Place more erythrocytes into the circulation at a faster rate

Main effect: Place more erythrocytes into the circulation at a faster rate. HOW?

1. Early release of reticulocytes 2. Prevent apoptotic cell death 3. Reduces maturation time inside the bone marrow

MATURATION SEQUENCE

I. Erythroid progenitors | II. Erythroid Precursors

I. Erythroid progenitors

a. Pluripotential hematopoietic stem cells b. CFU-GEMM/CFU-S c. CFU-MegE d. BFU-E d. CFU-E

II. Erythroid Precursors

a. Pronormoblast b. Basophilic normoblast c. Polychromatic normoblast d. Orthochromic normoblast e. Reticulocyte/Polychromatic (polychromatophilic) erythrocyte f. Erythrocyte

is a process encompassing replication (division) to increase cell numbers and development from immature to mature cell stages.

Normoblastic proliferation

Period between cell divisions; chromosomes not visible under the light microscope

Interphase

Limbo phase; Cells that are not dividing and possibly never to divide again

G0 phase

Metabolically active cell duplicates most of its organelles and cytosolic components

G1 phase (8-10 hours)

Replication of chromosome begins

G1 phase (8-10 hours)

Replication of DNA and chromosomes

S phase (8 hours)

Cell growth, enzyme and protein synthesis continue

G2 phase (4-6 hours)

Replication of centrosome complete

G2 phase (4-6 hours)

Parent cell produces identical cells with identical chromosomes; chromosomes visible under the light microscope

Mitotic Phase

▪ Nuclear division

Mitosis

▪ Distribution of two sets of chromosomes into separate nuclei

Mitosis

Chromatin fibers condense into paired chromatids

Prophase

Nucleolus and nuclear envelope disappear

Prophase

Each centrosome moves to an opposite pole of the cell

Prophase

Centromeres of chromatid pairs line up at the metaphase plate

Metaphase

Centromeres split

Anaphase

Identical sets of chromosomes move to opposite poles of cell

Anaphase

Nuclear envelopes and nucleoli reappear

Telophase

Chromosome resume chromatin form

Telophase

Mitotic spindle disappears

Telophase

▪ Cytoplasmic division

Cytokinesis

▪ Usually begins in late anaphase with the formation of a cleavage furrow & is completed after the telophase

Cytokinesis