Week 5 Flashcards
Red Blood Cells (erythrocytes)
– 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!)
Platelets: not technically cells, but fragments
of megakaryocytes
– 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
Monocytes
– 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
Neutrophils; a granulocyte
– Main function: phagocytosis of bacteria at sites of
infection
– Lifetime: 1-6 days
– Did you know? Dead neutrophils are main
component of pus
Basophils; a granulocyte
– Main function: release histamine & many other
powerful triggers of inflammation
– Lifetime: 1-2 days
– Did you know? Rarest of the blood cell types
Eosinophils; a granulocyte
– Main function: fighting parasitic worms
– Lifetime: 1 day
– Did you know? Implicated in many allergic or
immune hypersensitivity reactions
B-cells; a type of lymphocyte
– 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
T-cells; a type of lymphocyte
– 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
NK-cells; a type of lymphocyte
– 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
Origin of blood
- 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
Cold blooded vs. Warm blooded
- 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
Embryonic stage of development: the creation of the 3
primary germ layers (ectoderm, mesoderm, endoderm)
Yolk origin
– This extraembryonic tissue is initial site of blood cell manufacture
– ‘primitive’ phase in or near the yolk, in so called ‘blood islands’
Mesoderm origin
– 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
Hemangioblasts
– 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
Embryonic Switching
1st = blood islands w/ hemangioblasts (or EMP) in yolk
2nd = early vasculature of embryo (AGM)
3rd = early liver of embryo
4th = bone marrow
Erythropoiesis Switching
Subunit switching
Switch at birth
Blood synthesis flowchart
Stem cells
self-renewing cells and give rise
to other cells in tissues
Two types of mechanisms that can
influence cell fate: nature & nurture
Totipotent
can make all descendent cell types, including
extraembryonic cell and tissue types
Pluripotent
can make all embryonic cell types and
tissue types
Multipotent
can make all cell types of a particular
tissue
Oligopotent
can make some, but not all cell types of a
tissue
Bipotent
can make two cell types
Unipotent
can make only one cell type
Many cells and signals
make a stem cell neighborhood or niche
What do blood stem cells make?
(make >200 billion cells each day!)
Signals and Receptors
- 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
Hematopoiesis:
Map 1
Hematopoiesis:
Map 2
Hematopoiesis:
Map 3
Hematopoiesis:
Map 4
Hematopoeitic Stem Cell or
bone marrow transplant
- 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
HSCs from umbilical cord blood
- 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
Human RBC development
Human RBC death
- 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
Human RBC death
Vasculogenesis - Angiogenesis
Vasculature can itself shape development -
reciprocity
Tissue needs drive angiogenesis ↔ angiogenesis supports tissue development
Relationship between Qi and Blood
ABO blood type alleles: A, B, o
A allele is codominant
B allele is codominant
O allele is recessive (null or non-functional allele)
possible genotypes/phenotypes:
AA, Ao Type A blood
BB, Bo Type B blood
AB Type AB blood
oo Type O blood
- 3 different I alleles
- the ABO or I gene
encodes a
glycosylation enzyme
that creates
glycoproteins and
glycolipids expressed
on the surface of red
blood cells
4 major (ABO) blood types
What the major ABO blood type antigens
look like
