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IHL Exam 1 > Cytokines and hematopoiesis (Heck) > Flashcards

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
Q

B antigen

A

galactose transferase enzyme to add galactose O antigen

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26
Q

What cytokines affect erthyropoiesis?

A

IL-3 IL-4 and erythropoietin

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27
Q

What is the common progenitor type for erythrocytes

A

myeloid progenitor cells

28
Q

order of erythropoiesis

A

Megakaryocyte/Erythrocyte progenitor-> Erythrocyte-ommited progenitor->Proerythroblast->Basophilic Erythroblast->Polychromatophilic Erythroblast->Normoblast->Reticulocyte-> Erythrocyte

29
Q

what accounts for blue appearance in early erythrocytes?

A

synthesis of hemoglobin on ribosomes

30
Q

What state in erythropoiesis does the appearance of nucleus change?

A

normoblast, nucleus gets more dense

no longer capable of dividing

31
Q

At what stage in erythropoiesis does the RBC no longer have a nucleus

A

reticulocyte

32
Q

how do we use reticulocytes clinically?

A

Measured in blood to calculate how much erythropoiesis is going on. Only circulate 1-2 days before they fully mature

33
Q

What GF stimulate erythropoiesis and through what R cascade? Where is it produced?

A

Erythropoietin, produced in kidnerys. tyrosine-kinase JAK STAT signaling cascade

34
Q

EPO is produced in response to what signal?

A

Hif-1 (hypoxia)

35
Q

True or false. The activation of EPO R is anti-apoptotic

A

True! less apoptosis when EPO is circulating and being taken up by those committed erythroid progenitor cells

36
Q

Where is recombinant EPO used?

A

blood doping
Clinically: treat chronic kidney diseases
chemotherapy to promote regeneration of RBCs depleted by treatment

37
Q

What method can we detect recomb-EPO in an athlete’s blood?

A

electrophoresis. because isoelectric point of recombinant is different

38
Q

What is the basic structure of platelets

A

Small, membrane bound cytoplasmic fragments that are anucleate.
2 distinct regions: peripheral hylomere and center granulomere

39
Q

4 zones of platelets

A

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
Q

order of thrombopoiesis

A

HSC->common myeloid progenitor cell->Megakaryote/Erythrocyte progenitor cell->megakaryote-committed progenitor cell->megakaryoblast->megakaryocyte->platelet formation

41
Q

What cytokines are involved in thrombopoiesis?

A

Granulo-macrophage colony stimulating factor
IL-3
thrombopoietin

42
Q

Endomitosis

A

replication of chromosomes without cytokinesis-> large cell. seen in megakaryoblast

43
Q

differences between megakaryoblast vs -cyte

A

megakaryoCYTE has multi-lobed nucleus (karyokinesis)

has scattered azurophilic granules

44
Q

What produces thrombopoietin?

A

liver primarily. prevents apoptosis

promotes proliferation and thrombopoiesis

45
Q

What and where is the receptor for thrombopoietin

A

c-Mpl receptor found on platelets megakaryocytes and precursor cells

46
Q

Clinical relevance of thrombopoietin

A

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
Q

types of granules in granulocytes

A

specific- secretory vesicles with cytotoxic enzymes, release via degranulation
non-specific are most common- azurophilic, filled with enzymes that function in phagocytosis

48
Q

All cells from common myeloid progenitor cells have what type of granules

A

specific granules therefore considered granulocytes.

49
Q

Granulocytes

A

Neutrophils, Eosinophils and basophils

50
Q

Agranulocytes

A

Lymphocytes like B and T and NK cells

1 myeloid cell (monocytes) aka macrophages

51
Q

Describe the developmental characteristics of myeloid granulocytes

A

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
Q

Neutrophil unique developmental characteristic.

A

band form- nucleus forms a U shape

nucleus has 2-4 lobes and heterochromatin is at periphery. cytoplasm lacks staining!

53
Q

Neutrophils time spent in circulation vs tissues

A

hours in circulation, days in tissues

54
Q

Structure unique to eosinophil

A

stains very dark due to specific granules- degranulation (important in parasitic reactions)
bi-lobed nucleus

55
Q

Structure unique to basophil and general function

A

bi-lobed nucleus- usually cannot see it though because there is so much specific granules(basophilic-very blue)
allergy rxns, histamine producing

56
Q

1 meyloid cell type that is an agranulocyte, and unique characteristics and functions

A

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
Q

When are monocytes mobilized into tissues?

A

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
Q

Granulopoiesis location

A

subtype of myelopoiesis

occurs in bone marrow with final differentiation in tissues

59
Q

Order of granulopoiesis

A

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
Q

IL-3

A

expansion of immature marrow progenitors into all types of mature hematopoietic cells, and mast cells
produced by CD4+ T cells

61
Q

GM CSF Granulocyte-macrophage, colonystimulatingfactor

A

major roles in granulocyte maturation

produced at cell injury or infection.

62
Q

Lymphocytes are distinguishable because?

A

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
Q

B cells, function and location of maturation

A

ab producing. live long time.

Mature in bone marrow

64
Q

T cells, function and location of maturation

A

extremely long lived. Cell-immediated immunity

final differentiation in thymus

65
Q

Natural Killer cell, function and location of maturation

A

activated lymphocyte with kidney shaped nucleus. more intense staining due to larger granules
Mature in peripheral tissues

66
Q

Lymphopoiesis activated by what signal which is produced where

A

stromal cells in bone marrow and other tissues produce IL-7 to stimulate expansion of immature T and B cells

67
Q

X linked severe combined immunodeficiency

A

marked dec in T cells. increase in B cells. Lack of IL7 signaling

IHL Exam 1 (11 decks)

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