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PHGY 313 > Blood (general) > Flashcards

Blood (general) Flashcards

1
Q

What % of human genome destined for…

a) signalling molecules
b) receptors
c) transcription factors

A

a) 5.6%
b) 6.3%
c) 12%

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2
Q

Name the 6 functions of blood

A
  1. Transport of O2, nutrients (e.g. glucose etc.) and metabolites
  2. Removal of waste products (urea, Co2, lactic acid)
  3. Transport of signalling molecules
  4. Innate and adaptive immune response
  5. Blood clotting and wound repair
  6. Thermoregulation (vasoconstriction/vasodilation)
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3
Q

How many blood cells are produced each day?

What happens to that number in cases of injury or infection?

A
  • > 100 billion blood cells produced each day

- Increases ~ 5-10-fold due to injury or infection

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4
Q

Name the 3 main layers of blood when centrifuged and their % in volume. What changes in cases of pathologies?

A
  1. Plasma (55%)
  2. Buffy coat (< 1%) –> includes leukocytes (WBCs), platelets
    - -> buffy coat increases in some pathologies
  3. Erythrocytes (45%)
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5
Q

Name the 3 main components of plasma and their %

A

Proteins 7%
Water 91%
Other solutes 2%

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6
Q

Name 4 common proteins present in the plasma and their %

A

Albumin 57%
Globulins 38%
Fibrinogen 4%
Prothrombin 1%

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7
Q

Name examples of other solutes present in the plasma

A 
Ions
Nutrients
Waste products
Gases
Regulatory substances
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8
Q

Name 5 types of leukocytes and their %

A 
Neutrophils (50-60%)
Lymphocytes (20-25%)
Monocytes (3-8%)
Eosinophils (2-4%)
Basophils (0.5-1%)
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9
Q

Name the concentration of RBC in blood (# per mm3) and the main function of RBCs

A

5 million per mm3

Oxygen transport

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10
Q

Name the concentration of platelets in blood (# per mm3) and their main function

A
  • ~ 2.5 x 105 / per mm3

- Main function: Blood clotting

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11
Q

Explain the origin of platelets, their diameter and their organelles

A
  • Cell fragment – originating from megakaryocytes
  • 2-3 um in diameter
  • Lack nuclei and most organelles
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12
Q

Name the concentration of leukocytes in blood (# per mm3) and their main function

A
  • ~ 7 x 103 / per mm3

- Main function: Immune and inflammatory response

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13
Q

Lymphocytes:

  • physical appearance
  • lifespan in blood
  • function(s)
A
  • Large round nucleus, no granules, diameter 10um
  • Unknown lifespan
  • T lymphocytes –> Cellular immunity
  • B-Lymphocytes –> Antibody defense (precursor of plasma cells)
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14
Q

Monocytes:

  • physical appearance
  • lifespan in blood
  • function(s)
A
  • Horseshoe-shaped nucleus; cytosolic granules; diameter 10-25 um
  • lifespan 3 days

Functions:

  • Host defense
  • Immune surveillance (precursor of tissue macrophage)
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15
Q

Neutrophils:

  • physical appearance
  • lifespan in blood
  • function(s)
A
  • Multi-lobed nucleus; large number of cytosolic granules; diameter 10 um
  • Lifespan: 5-90 hours (inactive); 24-48 hours (activated)
  • Function: Host defense
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16
Q

Eosinophils:

  • physical appearance
  • lifespan in blood
  • function(s)
A
  • Nucleus with 2 lobes; cytosolic granules; diameter 10 um
  • Lifespan: 8-18 hours
  • Function: Host defense against parasites, allergens
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17
Q

Basophils:

  • physical appearance
  • lifespan in blood
  • function(s)
A
  • Nucleus with 2-3 lobes; cytosolic granules (lower number); cells 10um
  • Lifespan 60-70 hours
    Function: Inflammation and allergy
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18
Q

What is the life span of platelets?

A

7-8 days

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19
Q

What is the minimum time between each blood donation in Canada?

A

males = 56 days; females = 84 days

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20
Q

Name examples of cells that make up the bone marrow

A
  • Osteoblasts, osteoclasts
  • Vascular endothelial cells
  • Mesenchymal stem cells
  • Sympathetic neurons
  • adipocytes
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21
Q

What is the % fat in the bone marrow in an avg 30 year old adult?

A

30%

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22
Q

What does the endoderm layer differentiate into?

A

Gut, liver and lung cells

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23
Q

What does the mesoderm layer differentiate into?

A

Skeleton (bones, cartilage), muscle, kidney, heart, blood cells

24
Q

What does the ectoderm layer differentiate into?

A

Skin, nervous system

25
Q

What is an hemangioblast?

A

mesodermal progenitor that gives rise to blood and vascular endothelium. Develops into either an hematopoietic stem cell or endothelial cell.

26
Q

How many days is a mice gestation and when do blood cells arise from the yolk sac?

A

Mice gestation is ~20 days. Day 7.5 –> all blood cells arise from the yolk sac

27
Q

What are the different sites of blood cell formation in mice

A

Before birth: Yolk sac, AGM, placenta, fetal liver, thymus

After birth: Thymus and bone marrow

28
Q

What are the sites of hematopoiesis in humans

  • As a fetus
  • As infants
  • In adults
A 
Fetus:
- Yolk sac (0-2 months)
- Liver, spleen (2-7 months)
- Bone marrow (5-9 months)
Infants: All bones in bone marrow
Adults: Bone marrow in some bones (vertebra, ribs, sternum, skull, sacrum and pelvis, proximal ends of femur)
29
Q

Explain the hierarchical organization of blood cells (from stem cells to multipotent progenitors)

A

Long-term hematopoietic stem cells (LT-HSC) –> Short-term hematopoietic stem cells (ST-HSC) –> Multipotent progenitor (MPP) –> Either commited myeloid progenitors (CMP) or lymphoid progenitors (CLP)

30
Q

What can committed myeloid progenitors differentiate into?

A
  1. Megakaryocyte - erythroid progenitor (MEP)
  2. Granulocyte-monocyte progenitor (GMP)
  3. Eosinophils
  4. Basophils
31
Q

What can committed lymphoid progenitors differentiate into?

A

Pro-B, Pro-T cells, NK cells

32
Q

What progenitors can give dendritic cells?

A

CMPs and CLPs.

33
Q

What can MEP differentiate into?

A
  1. Erythrocytes

2. megakaryocytes (–> platelets)

34
Q

What can GMP differentiate into?

A
  1. Macrophages

2. Neutrophils

35
Q

What can pro-B differentiate into?

A

Pre-B –> B cell

36
Q

What can pro-T differentiate into?

A

T cell

37
Q

Who are the main characters in the discovery of stem cells

A

Ernest McCulloch and James Till (Evidence of stem cells and hierarchical organization of hematopoiesis)

38
Q

What are the 2 key properties of stem cells?

A
  1. Multipotency: Ability to differentiate into all blood cell types
  2. Self-renewal: Maintain stem cell number and function throughout life
39
Q

How does cell division potential evolute as you go from a stem cell to a differentiated stem cell?

A

It decreases

40
Q

Name 4 types of stain one can use for a blood smear

A

Romanowsky, Wright’s, Giamsa, May-Grunwald (Depend on which cells we want to look at)

41
Q

Name techniques to analyze blood

A
  1. Blood smears
  2. cell count
  3. Polymerase chain reaction, PCR (DNA)
  4. Immunoblot (proteins)
  5. Erythrocyte sedimentation rate (ESR)
  6. Microarrays, next generation sequencing
42
Q

Explain flow cytometry and for what technique it is used

A

Measurement of fluorescence intensity of cells pre-stained with a fluorophore-conjugated antibody against a specific cell-surface protein.

43
Q

Explain fluorescence-activated cell-sorting (FACS)

A

regarde l’image dans les slides

44
Q

In what cases is the ESR low

A

Polycythemia (too many RBCs)
Leukemia
Sickle cell
Abnormal proteins

45
Q

In what cases is the ESR high? Why?

A 
	Inflammation*
	Infections*
	Cancer*
	Autoimmune*
	*Higher amount of fibrinogen --> cells stick together, form clumps and sediment much faster
	Temporal artheritis
	Polymyalgia
	Rheumatica
46
Q

In what year was the first successful transplant using identical twins?

A

1959

47
Q

In what year was the first successful allogenic transplant to treat SCID?

A

1968

48
Q

Who got the 1990 Nobel price in medicine and why?

A

Joseph Murray and Donnall Thomas “for discoveries concerning organ and cell transplantation in treatment of human disease”

49
Q

Name 3 possible sources of donor cells for bone marrow transplantation.

A
  1. Bone marrow: Directly from the bones of the donor
  2. Mobilized peripheral blood: Donor treated with granulocyte colony stimulating factor (G-CSF). Mobilized stem cells are collected from the donor’s blood
  3. Cord blood: Blood from the umbilical cord stored in public and private cord blood banks
50
Q

Name the 3 main types of transplants and their pros/cons

A
  1. Allogenic (from another donor)
    o Risk of graft failure (immune rejection) and graft vs. host disease (GVHD), requires immunosuppression
  2. Autologous (self-donation)
    o Complete immunological compatibility: Low risk of failed engraftment & graft vs host disease (GVHD)
  3. Syngeneic (identical twin)
    o Complete immunological compatibility: Low risk of failed engraftment & graft vs. host disease (GVHD)
51
Q

What is the most common type of transplant and when did it start and peak?

A

Autologous.

Started in 1988 and peaked in 1998.

52
Q

Name the 5 most common diseases for transplants in the US

A
  1. Acute myelogenous leukemia
  2. Chronic myelogenous leukemia
  3. Acute lymphoblastic leukemia
  4. Myelodysplastic disorders
  5. Non-Hodgkin lymphoma
53
Q

Name and explain the 2 types of allogenic bone marrow transplantations.

A
  1. Myeloablative allogenic hematopoietic stem cell transplantation
    - -> 4x high doses of radiation (weeks -7 to -4); then 2x chemo tx (week -3 and -2) Then allogenic stem cell infusion
  2. Non-Myeloablative allogenic hematopoietic stem cell transplantation
    - -> 3x low intensity chemo (weeks -4 to -2) and low intensity radiation on day 0 then stem cell infusion
54
Q

Name the pros/cons of myeloablative allogenic hematopoietic stem cell transplantation and which populations use it

A

a. Risks: Pancytopaenia, infection, organ toxicity
b. Many cells dying
c. GVHD
d. Requires immunosuppression
e. Used in healthy people

55
Q

Name the pros/cons of non-myeloablative allogenic hematopoietic stem cell transplantation and which populations use it

A

a. Less cells dying
b. Risks: Mild pancytopaenia
c. Still GVHD and infection risks (transplant of foreign cells)
d. Still need immunosuppression
e. Used in more vulnerable populations, older people who maybe wouldn’t survive high doses

56
Q

Explain the “berlin” patient case

A 
Had HIV and AML and was cured
To enter cells, one thing that most HIV strains must do is bind to CCR5, a molecule that protrudes from the WBCs surface.
Some people (1-2%) are born with a mutation that prevents CCR5 from appearing on their cells, making them resistant to HIV. Some experimental gene therapy approaches aim to mimic this mutation in AIDS patients
This patient received a hematopoietic stem cell transplant from a donor with this mutation.

PHGY 313 (10 decks)

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