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ANSC 411 - Veterinary Immunology > 4. Hematopoiesis > Flashcards

4. Hematopoiesis Flashcards

1
Q

What is hematopoiesis?

A

The formation of BLOOD CELLS (exclusively, which include immune cells

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2
Q

Animal hematopoietic diseases can involve what?

A

Acquired or congenital defects in any steps required for blood cell formation and can affect leukocyte numbers and/or fxn

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3
Q

Stem cell: what is it, what does it have the capacity to do, what does it provide?

A
  • Early progenitor cell with the capacity to differentiate into mature cells
  • Potential to mature into a number of different cell types
  • Provides “raw material” to repopulate cells that die (normal turnover), are killed (through infections or die fighting), or are removed because of errors/injuries
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4
Q

What is the stem cell hierarchy?

A

Totipotent
- The ability of stem cells to give rise to all embryonic and extra-embryonic tissues
- Ex. the zygote that forms by the fusion of an egg and sperm

Pluripotent
- The ability to give rise to all embryonic, but NOT extra-embryonic tissues
- Ex. stem cells in the inner cell mass of the blastocyst

Multipotent
- The ability to give rise to the diverse cell types of one or a few tissues
- Ex. the hematopoietic stem cell that gives rise to all blood lineages

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5
Q

Where do all of the cells of the immune system derive from?

A

A common hematopoietic stem cell (HSC) in the bone marrow

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6
Q

What do hematopoietic stem cells supply?

A

Supply ENTIRE repertoire of mature blood cells for the LIFETIME of an organism

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7
Q

How do hematopoietic stem cells (HSC) supply the entire repertoire of mature blood cells for the lifetime of an organism?

A
  1. SELF-RENEWAL CAPACITY: maintains and expands stem cell pool
    - in theory, ONE cell should be sufficient to replenish the whole blood cell repertoire of an irradiated animal
  2. MULTI-LINEAGE DIFFERENTIATION POTENTIAL: produces the diverse blood cell types of the mature hematopoietic system
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8
Q

In addition to immune cells, what else do hematopoietic stem cells yield?

A
  1. Erythrocytes (RBC)
  2. Megakaryocytes/platelets (responsible for blood clotting)
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9
Q

In general terms, on each division what does a stem cell give rise to?

A

Another stem cell and a progenitor cell
- Progenitor cell committed to producing related cells
- The greater the level of differentiation, the greater the level of commitment to a particular lineage and lower capacity to self-renew
- Under homeostatic conditions the number of HSC in a particular organ remains fairly constant

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10
Q

How can you distinguish between the various leukocyte population? Why would you want to?

A

HOW
1. Can do it at protein level
- Ex. flow cytometry
2. Or the gene (mRNA expression) level
- Ex. Q-PCR and Microarrays
- looking at if the cellular population is expressing the genes we expect or if the tissue has high levels of a leukocyte-specific gene

WHY
- For research studies
- To identify and characterize diseases
- To assess animal health status

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11
Q

Flow cytometry

A
  1. Start with a basis which is a mixture of cells, all of which are expressing different antigens
  2. Add fluorescent antibodies that bind specific antigens
  3. Send the “bag of cells” single file through a laser that based on the antibodies, tells you how “red” or how “green” the cell is and gets plotted on a table
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12
Q

What does bone marrow provide?

A

An important STEM CELL NICHE
- occupies the centre portion of bones
- 2 types: yellow and red
- only red marrow actively generates blood cells
- yellow marrow is dormant
- at birth all marrow is red; in adults it remains through the axial skeleton and epiphysis of the humerus and femur

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13
Q

What is the importance of interaction between stem cells and the microenvironment (stem cell niche) for differentiation?

A
  • Bone marrow stem cell niche helps maintain stem cell properties, including self-renewing capacity and ability to differentiate into multiple lineages
  • For example, critical component for sustaining slow-cycling/dormant (quiescent) stem cells
  • Quiescent state is an essential mechanism to protect stem cells from stress and sustain long-term hematopoiesis
  • Both stem cells and microenvironment are important!
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14
Q

How do stromal and other cells provide a nurturing hematopoietic microenvironment for stem cells?

A
  1. Cell-derived components
    - soluble growth factors, cell adhesion molecules, extracellular matrix molecules
  2. Systemic control factors
    - injury and neurohormones
  3. Physiological conditions
    - O2 tension
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15
Q

There are many hematopoietic organs, what does this depend on?

A
  1. Depends on species
  2. Depends on developmental stage
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16
Q

Ontogeny of hematopoiesis

A

*organ that produces WBC is not the same throughout the organism’s life

  1. Primitive
    a. Outside embryo
    - Yolk sac
  2. Definitive
    a. Inside embryo
    - AGM
    - Fetal liver

b. Adult hematopoietic tissues
- Bone marrow

17
Q

Overall regulation of hematopoiesis

A
  • Hematopoietic proliferation, commitment, differentiation, and survival events are coordinated through interactions with cells and extracellular matrix components of the surrounding microenvironment, through interactions with SOLUBLE FACTORS that are produced LOCALLY or ARRIVE FROM THE CIRCULATION, as well as through INTRINSIC MECHANISMS in part regulated by stochastic events
  • Integration of extracellular and intracellular stimuli culminates in an overall response and the expression of specific genes
18
Q

Where does integration of extracellular and intracellular stimuli regulating hematopoiesis occur?

A
  • Ultimately, all signal transduction pathways converge at the level of gene expression where positive and negative regulators of transcription delineate the pattern of gene expression and overall cellular response
  • Transcription factors represent a nodal point of hematopoietic control, through integration of all incoming signaling pathways, and subsequent modulation of the transcriptional machinery
  • The expression of these genes is dependent on the complex interactions between transcription factors, co-regulatory molecules, and specific binding sequences in the DNA
19
Q

Convergence of regulatory signals occurs at the level of…

A

Gene expression

20
Q

Are all stem cells equal?

A

No

21
Q

Link to animal disease

A
  • Hematopoietic stem cells yield blood
  • Several diseases are associated with changes in numbers and/or fxns of these cells
22
Q

Ontogeny significantly affects…

A

Hematopoiesis!
- dramatic changes from embryo, young, adult, old
- location and efficiency
- relevance to immune fxns and competence as animals age

23
Q

Integration of all signals occur at the level of _________. _________ are critical to this control.

A

a. Gene expression
b. Transcription factors

ANSC 411 - Veterinary Immunology (8 decks)

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