Week 5

Question 1

Red Blood Cells (erythrocytes)

Answer 1

– Main function: transport O2, also CO2 transport
– Lifetime: about 120 days
– Did you know? No nucleus or DNA, no other
organelles. About 2 million die every second (this
turnover rate is like the world’s population
changing every hour!)

Question 2

Platelets: not technically cells, but fragments
of megakaryocytes

Answer 2

– Main function: clotting (aka coagulation,
thrombosis) and hemostasis
– Lifetime: 5-12 days
– Did you know? They seal small openings routinely
without the need for clotting cascade

Question 3

Monocytes

Answer 3

– Main function: develop into macrophages at tissues –
phagocytosis of pathogens & cell debris
– Lifetime: about 1-3 days in the bloodstream
– Did you know? They squeeze and crawl out of blood
vessels by a process called extravasation or diapedesis

Question 4

Neutrophils; a granulocyte

Answer 4

– Main function: phagocytosis of bacteria at sites of
infection
– Lifetime: 1-6 days
– Did you know? Dead neutrophils are main
component of pus

Question 5

Basophils; a granulocyte

Answer 5

– Main function: release histamine & many other
powerful triggers of inflammation
– Lifetime: 1-2 days
– Did you know? Rarest of the blood cell types

Question 6

Eosinophils; a granulocyte

Answer 6

– Main function: fighting parasitic worms
– Lifetime: 1 day
– Did you know? Implicated in many allergic or
immune hypersensitivity reactions

Question 7

B-cells; a type of lymphocyte

Answer 7

– Main function: make antibodies (aka: g-globulins,
immunoglobulins)
– Lifetime: up to years!
– Did you know? Named derived from description
of their origin in Bursa of Fabricius – an immune
system organ in birds

Question 8

T-cells; a type of lymphocyte

Answer 8

– Main functions: cell-mediated immune response,
help B-cells, kill virus-infected cells
– Lifetime: up to years!
– Did you know? Named for development and
maturation in the thymus

Question 9

NK-cells; a type of lymphocyte

Answer 9

– Main function: natural killer of cancer and virusinfected cells
– Lifetime: weeks
– Did you know? First called null cells since they
were lymphocytes lacking B- or T-cell receptors

Question 10

Origin of blood

Answer 10

• Earliest form of blood was not distributed via a
  circulatory system, but was simply expanded
  interstitial or extracellular fluid
  – Invertebrates (e.g. worms, molluscs, insects)
• Coelemic fluid, hemolymph in open system
• Worms appear to have originated a vascular system
• Many use hemocyanin as oxygen-binding protein with
  copper (Cu) atom instead of iron (Fe) in porphyrin group
  – Vertebrates
• Cardiovascular/Hematopoietic as a closed system
• First version may have been a ‘distributed spleen’ adjacent
  to or within the GI tract

Question 11

Cold blooded vs. Warm blooded

Answer 11

• Ectothermy vs. Endothermy (humans)
  – heat from environment vs. heat generation from metabolism
  – one hypothesis is that endothermy was elaborated with separation of systemic and pulmonary circulatory systems and the origin of the 4-chambered heart
  – high blood pressure and increased skeletal muscle and
  metabolic demands generated new circulatory and heating mechanism
  – this is true for mammals and birds

Question 12

Embryonic stage of development: the creation of the 3
primary germ layers (ectoderm, mesoderm, endoderm)

Answer 12

Question 13

Yolk origin

Answer 13

– This extraembryonic tissue is initial site of blood cell manufacture
– ‘primitive’ phase in or near the yolk, in so called ‘blood islands’

Question 14

Mesoderm origin

Answer 14

– One of three primary germ layers that develop during embryogenesis: endoderm, mesoderm, ectoderm
– Begins ‘adult’ or definitive phase
– An early aorta is formed and pluripotential hematopoietic stem cells (HSC) are
found within
* n.b. Saving umbilical cord blood also captures some of these stem cells

Question 15

Hemangioblasts

Answer 15

– Embryonic precursor cell that gives rise to
* Angioblasts destined to become endothelial cells of the vessels
* Hematopoeitic stem cells in the blood itself
* Exist post-natally and into adult stage

Question 16

Embryonic Switching

Answer 16

1st = blood islands w/ hemangioblasts (or EMP) in yolk
2nd = early vasculature of embryo (AGM)
3rd = early liver of embryo
4th = bone marrow

Question 17

Erythropoiesis Switching

Answer 17

Question 18

Subunit switching

Answer 18

Question 19

Switch at birth

Answer 19

Question 20

Blood synthesis flowchart

Answer 20

Question 21

Stem cells

Answer 21

self-renewing cells and give rise
to other cells in tissues

Question 22

Two types of mechanisms that can
influence cell fate: nature & nurture

Answer 22

Question 23

Totipotent

Answer 23

can make all descendent cell types, including
extraembryonic cell and tissue types

Question 24

Pluripotent

Answer 24

can make all embryonic cell types and
tissue types

Question 25

Multipotent

Answer 25

can make all cell types of a particular tissue

Question 26

Oligopotent

Answer 26

can make some, but not all cell types of a tissue

Question 27

Bipotent

Answer 27

can make two cell types

Question 28

Unipotent

Answer 28

can make only one cell type

Question 29

Many cells and signals make a stem cell neighborhood or niche

Answer 29

Question 30

What do blood stem cells make? (make >200 billion cells each day!)

Answer 30

Question 31

Signals and Receptors

Answer 31

* Some factors control cell differentiation pathways and are often secreted and diffusible molecules (signals or ‘senders’) – e.g. interleukins (IL-7), colony stimulating factors (GM-CSF), erythropoietin (EPO) * Some other factors are molecules that receive such signals and because they are typically on the cell surface, they also distinguish cells (receptors or ‘markers’) – e.g. interleukin receptors (IL7R), cell determinants (CD4), ABO antigens

Question 32

Hematopoiesis: Map 1

Answer 32

Question 33

Hematopoiesis: Map 2

Answer 33

Question 34

Hematopoiesis: Map 3

Answer 34

Question 35

Hematopoiesis: Map 4

Answer 35

Question 36

Hematopoeitic Stem Cell or bone marrow transplant

Answer 36

* Replacing HSC from a donor * To treat malignant and non-malignant diseases or conditions – e.g. leukemias, hemoglobinopathies * May need to ablate existing HSC in BM (typically by radiation or chemotherapy) * Transfer by donor (aka graft) – Allogeneic: donor to another person and matched by HLA alleles (cell surface markers or receptors, much like matching blood types) – Typical matches will come from family members, though this is not guaranteed and is why there are drives to sign up more stem cell donors

Question 37

HSCs from umbilical cord blood

Answer 37

* Hematopoietic stem cells are present in the vasculature of umbilical cords * Can be frozen and used for transplant – Some efforts to expand such cells ex vivo * Advantage: less graft vs. host disease (i.e. the attack of recipient or host by the transplant) * Disadvantage: few HSCs, costly to store * Starting to outnumber BM transplants

Question 38

Human RBC development

Answer 38

Question 39

Human RBC death

Answer 39

* Death can occur by a number of mechanisms * Turnover of cell components – Phagocytosis * RBC mostly recycled by macrophages at spleen and liver – Red pulp of spleen – Hemoglobin turnover is major job in the liver * Free hemoglobin binds haptoglobin in bloodstream * Digest globins to amino acids and reuse * Heme porphyrin → Bilirubin (bile component) * Recycle the iron (Fe) – ferritin or hemosiderin are protein-bound and transported/stored forms of Fe

Question 40

Human RBC death

Answer 40

Question 41

Vasculogenesis - Angiogenesis

Answer 41

Question 42

Vasculature can itself shape development - reciprocity

Answer 42

Tissue needs drive angiogenesis ↔ angiogenesis supports tissue development

Question 43

Relationship between Qi and Blood

Answer 43

Question 44

ABO blood type alleles: A, B, o

Answer 44

A allele is codominant B allele is codominant O allele is recessive (null or non-functional allele)

Question 45

possible genotypes/phenotypes:

Answer 45

AA, Ao Type A blood BB, Bo Type B blood AB Type AB blood oo Type O blood

Question 46

* 3 different I alleles

Answer 46

* the ABO or I gene encodes a glycosylation enzyme that creates glycoproteins and glycolipids expressed on the surface of red blood cells

Question 47

4 major (ABO) blood types

Answer 47

Question 48

What the major ABO blood type antigens look like

Answer 48