Cytokines and hematopoiesis (Heck) Flashcards

1
Q

Describe the components of blood in a test tube with an anti-coagulant present

A

clear/liquid portion: plasma consisting of proteins (albumin, fibrinogen), hormones, antibodies, vitamins and salts
buffy coat: white blood cells and platelets
cellular: RBCs

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2
Q

Describe the components of blood in a test tube in absence of fibrinogen

A

liquid: Serum

blood clot at base

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3
Q

What percent of the blood is RBCs

A

45

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4
Q

what does thrombopoiesis stand for

A

formation of platelets

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5
Q

What are colony forming units

A

committed precursor cells for hematopoiesis

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6
Q

lymphoid cells

A

will differentiate into B cells and T cells (lymphocytes)

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7
Q

myeloid cells

A

differentiate into every but lymphocytes

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8
Q

When does hematopoiesis begin in development and where?

A

in the yolk sac around 3 weeks. formation on hemangioblasts

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9
Q

What is the big transformation of RBC formation in 7th month of development?

A

Switch to hematopoiesis being done in the bone marrow

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10
Q

general trends in hematopoiesis

A

cell size decrease, cytoplasm becomes less basophilic, changes in nuclear:cytoplasmic ratio,
changes in nuclear condensation rxns (euchromatin and heterochromatin)

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11
Q

2 characteristics of Hematopoietic Stem Cells HSCs

A

pleuripotent–> give rise to many cell types

self renewing–> divide to maintain own population

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12
Q

Stem cell factor/ c-kit ligand is produced where?

A

bone marrow in stromal cells and in fetal tissue during development

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13
Q

C-kit R is expressed by what and what type of R

A

HSCs

tyrosine kinase R–> (MAPK, JAK/STAT, IP-3)

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14
Q

what type of mutation in c kit R leads to cancer

A

gain of function

protooncogene–>oncogene

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15
Q

how is c kit ligand used clinically?

A

used in marrow transplant cases–> to determine which RBS are HSC based on whether they have C-kit ligand (acts as a marker)

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16
Q

Imatinib (drug) does what?

A

Inhibitor of tyrosine kinase activity
reducing differentiation of HSCs
used for chronic myeloid anemia

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17
Q

Linear Restricted Progenitor cells

A

arise from HSCs, multipotent
differentiate into lymphoid or myeloid cells.
These do NOT renew themselves

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18
Q

3 categories of blood elements

A

erthyrocytes RBCs
leukocytes WBCs
platelets

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19
Q

2 types of leukocytes

A

granulocytes and agranulocytes

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20
Q

Anatomy of RBCs

A
biconcave
Anucleate
lack of organelles
PM
unique cytoskeleton
contains hemoglobin
contain glycolytic enzymes
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21
Q

how long do RBCs stay in circulation

A

120 days.

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22
Q

ABO blood groups are what?

A

assemblies on cell surface.. glycoproteins

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23
Q

O antigen

A

lacking functional enzymes
(default)
no sugars

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24
Q

A antigen

A

N- acelylgalactosamine on O structure

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25
B antigen
galactose transferase enzyme to add galactose O antigen
26
What cytokines affect erthyropoiesis?
IL-3 IL-4 and erythropoietin
27
What is the common progenitor type for erythrocytes
myeloid progenitor cells
28
order of erythropoiesis
Megakaryocyte/Erythrocyte progenitor-> Erythrocyte-ommited progenitor->Proerythroblast->Basophilic Erythroblast->Polychromatophilic Erythroblast->Normoblast->Reticulocyte-> Erythrocyte
29
what accounts for blue appearance in early erythrocytes?
synthesis of hemoglobin on ribosomes
30
What state in erythropoiesis does the appearance of nucleus change?
normoblast, nucleus gets more dense | no longer capable of dividing
31
At what stage in erythropoiesis does the RBC no longer have a nucleus
reticulocyte
32
how do we use reticulocytes clinically?
Measured in blood to calculate how much erythropoiesis is going on. Only circulate 1-2 days before they fully mature
33
What GF stimulate erythropoiesis and through what R cascade? Where is it produced?
Erythropoietin, produced in kidnerys. tyrosine-kinase JAK STAT signaling cascade
34
EPO is produced in response to what signal?
Hif-1 (hypoxia)
35
True or false. The activation of EPO R is anti-apoptotic
True! less apoptosis when EPO is circulating and being taken up by those committed erythroid progenitor cells
36
Where is recombinant EPO used?
blood doping Clinically: treat chronic kidney diseases chemotherapy to promote regeneration of RBCs depleted by treatment
37
What method can we detect recomb-EPO in an athlete's blood?
electrophoresis. because isoelectric point of recombinant is different
38
What is the basic structure of platelets
Small, membrane bound cytoplasmic fragments that are anucleate. 2 distinct regions: peripheral hylomere and center granulomere
39
4 zones of platelets
Peripheral zone: PM, glycocalyx Structural zone: cytokeleton Organelle zone: mitochondria, peroxisomes, glycogen, granules for clotting Membrane zone: open canicular system and dense tubular system (store Ca)
40
order of thrombopoiesis
HSC->common myeloid progenitor cell->Megakaryote/Erythrocyte progenitor cell->megakaryote-committed progenitor cell->megakaryoblast->megakaryocyte->platelet formation
41
What cytokines are involved in thrombopoiesis?
Granulo-macrophage colony stimulating factor IL-3 thrombopoietin
42
Endomitosis
replication of chromosomes without cytokinesis-> large cell. seen in megakaryoblast
43
differences between megakaryoblast vs -cyte
megakaryoCYTE has multi-lobed nucleus (karyokinesis) | has scattered azurophilic granules
44
What produces thrombopoietin?
liver primarily. prevents apoptosis | promotes proliferation and thrombopoiesis
45
What and where is the receptor for thrombopoietin
c-Mpl receptor found on platelets megakaryocytes and precursor cells
46
Clinical relevance of thrombopoietin
liver failure patients thrombocythemia patients. (too many platelets because gain of function in R or thrombopoietin) thrombocytosis is the secondary mechanism of thrombocythemia thrombocytopenia- not enough platelets->bleeding disorder
47
types of granules in granulocytes
specific- secretory vesicles with cytotoxic enzymes, release via degranulation non-specific are most common- azurophilic, filled with enzymes that function in phagocytosis
48
All cells from common myeloid progenitor cells have what type of granules
specific granules therefore considered granulocytes.
49
Granulocytes
Neutrophils, Eosinophils and basophils
50
Agranulocytes
Lymphocytes like B and T and NK cells | 1 myeloid cell (monocytes) aka macrophages
51
Describe the developmental characteristics of myeloid granulocytes
myelopoiesis: myeloblasts has nuclei (RNA production) but no granules promyelocytes produces primary granules (azurophilic) myelocyte produces specific granules (differences between eosinophil neutrophil and basophil) metamyelocyte changes in nucleus, post mitosis, each type has characteristic nuclei
52
Neutrophil unique developmental characteristic.
band form- nucleus forms a U shape | nucleus has 2-4 lobes and heterochromatin is at periphery. cytoplasm lacks staining!
53
Neutrophils time spent in circulation vs tissues
hours in circulation, days in tissues
54
Structure unique to eosinophil
stains very dark due to specific granules- degranulation (important in parasitic reactions) bi-lobed nucleus
55
Structure unique to basophil and general function
bi-lobed nucleus- usually cannot see it though because there is so much specific granules(basophilic-very blue) allergy rxns, histamine producing
56
1 meyloid cell type that is an agranulocyte, and unique characteristics and functions
mononuclear phagotcytes. Largest WBC distinct indentation in nucleus circulates about 3 days then moves to a tissue to differentiate into local tissue macrophage and sometimes osteoclasts
57
When are monocytes mobilized into tissues?
they circulate in peripheral circulation until encounter signals on endothelial cells. move through tissue and differentiate into tissue-specific macrophages eg microglia, langerhans etc..
58
Granulopoiesis location
subtype of myelopoiesis | occurs in bone marrow with final differentiation in tissues
59
Order of granulopoiesis
common myeloid progenitor-> granulocyte/monocyte progenitor-> granulocyte progenitors (1 for each type)->myeloblast->promyelocyte->myelocyte->metamyelocyte->mature granulocyte * before mature granulocyte, neutrophils become band cells
60
IL-3
expansion of immature marrow progenitors into all types of mature hematopoietic cells, and mast cells produced by CD4+ T cells
61
GM CSF Granulocyte-macrophage, colonystimulatingfactor
major roles in granulocyte maturation | produced at cell injury or infection.
62
Lymphocytes are distinguishable because?
majority are very small, same size as RBC. nucleus slightly indented. azurophilic staining(normal cell) change in size based on activation increase cytoplasm:nuclear ratio
63
B cells, function and location of maturation
ab producing. live long time. | Mature in bone marrow
64
T cells, function and location of maturation
extremely long lived. Cell-immediated immunity | final differentiation in thymus
65
Natural Killer cell, function and location of maturation
activated lymphocyte with kidney shaped nucleus. more intense staining due to larger granules Mature in peripheral tissues
66
Lymphopoiesis activated by what signal which is produced where
stromal cells in bone marrow and other tissues produce IL-7 to stimulate expansion of immature T and B cells
67
X linked severe combined immunodeficiency
marked dec in T cells. increase in B cells. Lack of IL7 signaling