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BMS 2 Week 3 > Hematopoiesis > Flashcards

Flashcards in Hematopoiesis Deck (17):
1

Aplastic Anemia 

  1. Patient’s own lymphocytes attack bone marrow cells

    1. Evidence is that suppression of immune system reverses this process.

  2. Patients who do not respond to immunosuppresants can have bone marrow function restored by translatation from a compatible marrow donor

    1. Transplantation success requires patients to take immunosuppressants

  3. Characterized by failure of bone marrow to produce blood components due to distruction of uncommitted hematopoietic stem cells

    1. ​Lack of megakaryocytes= low platelets = bleeding

    2. Lack of RBCs= weakness and shortness of breath on exertion

    3. Lack of WBCs= results in infections without abscess 

    4. Lymphocytes are still present due to having slow turnover 

2

Bone Marrow Section vs. Aspiration 

  1. Bone Marrow Section- allows us to view histology of tissue
  2. Aspiration- allows us to see cytology of individual cells within the tissue 

3

Hematopoietic Stem Cells characterization

  1. Small round cells of the same density as lymphocytes 
  2. Congregate near the periosteum
  3. Recognized by CD34 surface markers
  4. There is absence of lineage markers (lin-) 

4

Hierarchal Model of Stem Cell Division 

  1. Rare divisions my stem cells generate rapidly dividing transit amplifying cells 
  2. Transit amplifying cells then give rise to differentiated cells 

 

5

Stochastic Model 

Each division of the stem cell can yield 3 different outcomes

  1. One differentaited daughter and one progenitor made 
  2. Two progenitors made
  3. Two differentiated cells made

6

Agranulocytosis 

-Characterized by low WBC count and infections

-Caused by mutations in granulocyte progenitor 

 

7

RBC Anemia 

-Characterized by low RBC count 

-Caused by mutation in RBC progenitor 

 

8

Evolution of Blood Production

  1. Yolk Sac
  2. Liver
  3. Bone marrow- flat bones
  4. Bone marrow- long bones 

9

Stem Cell Niche in Bones 

Stem cell niche is in bone marrow osteoblast lining 

10

Culture of Clonogenic Progenitors 

  1. This experimental system demonstrates that hemopoietic progenitors can be stimulated to grow and mature in vitro along specific lineage and does not require the highly complex in vivo niche which we saw with stem cell maintenance.
    1. CSF-GM: Colony stimulating factor for Granulocytes and Macrophages
    2. CFU-GM: Colony Forming Units for Granulocytes and Macrophages 
    3. CSF-G: Colony Forming Units for Granulocytes
    4. Interleukin 3: promotes CFU-GEMM
    5. CFU-GEMM: promotes granulocytes, erythrocytes, monocytes, and megakaryotes 
    6. Erythropoietin: promotes BFU which promote RBC maturation 
    7. CFU-L: Colony Forming Units for B-cell, T-cell, and NK-cell precursor. 

11

Two classes of Hematopoietic Growth Factors 

  1. Hematopoietins that bind to Hemopoeitin Receptor Superfamily
  2. Hematopoietins that bind to the Kinase Receptor Superfamily 
    1. C-kit ligand 

12

Mechanism of action of cytokine growth factors 

  1. Growth factor binds to a cell membrane receptor with low affinity
  2. It recruits and binds to high affinity receptor generating a growth signal 

13

Erythropoiesis

  1. Cells get smaller
  2. Cytoplasm changes
  3. Nucleus/cytoplasm ratio falls
  4. Nucleus extruded prior to reticulocyte phase 
  5. Stages: 
    1. HSC
    2. Proerythroblast
    3. Early erythroblast  (from this point onwards, can be recognized morphologically)
    4. Late erythroblast
    5. Pronormoblast 
    6. Normoblast (last stage where division is possible) 
    7. Reticulocyte (no nucleus but residual ribosomes making hemoglobbin)
    8. Erythrocyte (no DNA or RNA) 

14

Erythropoietin 

  1. EPO is produced in kidney in response to anemia and hypoxemia
  2. BFU-E and CFU-E are RBC precursors that have EPO receptors 
  3. Process
    1. EPO binds to EPOR and induces JAK activation
    2. EPOR dimerizes 
    3. EPOR dimer autophosphorylates
    4. STAT5 binds and is phosporylated 
    5. STAT5 dimerization occurs
    6. Transcriptional events that enhance growth and suppress apoptosis are stimuated. 
  4. As a result, BFU-E and CFU-E go to normoblast and eventually mature erythrocyte 

15

Monocytes 

  1. Stages of development
    1. HSC --> CFU-GEMM --> CFU-GM
    2. Monoblast
    3. Promonocyte
    4. Monocyte
    5. Macrophage 
  2. Involved in phagocytosis of bacteria, fungus, parasites, tumor cells, foreign material
  3. Release cytokines
  4. Release mediators of inflammation
  5. Professional antigen presentation to lymphs
  6. In tissue, they flatten to become macrophages 

16

Thrombopoiesis 

  1. Thrombopoietin stimulates megakaryocyte to produce platelets
  2. Platelets form from cytoplasmic budding 
  3. Stages of development
    1. HSC
    2. Megakaryoblast
    3. Promegakaryocyte
    4. Megakaryocyte --> Thrombopoietin 
    5. Platelets

17

Granulopoiesis 

Note: granulocyte precursors are recognizable in bone marrow smears and biopsies. 

Stages of development

  1. HSC
  2. Myeloblast 
  3. Promyelocyte
  4. Myelocyte
  5. Metamyelocyte 
  6. Band
  7. Poly