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HIST Heme-Onc > Blood and Hematopoiesis > Flashcards

Blood and Hematopoiesis Flashcards

1
Q

what are the most common protein in the plasma & what is its role?

A

albumin

most important: regulating osmotic pressure

also, carries:

  • thyroxine
  • bilirubin
  • drugs
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2
Q

what is hematocrit?

clinical relevance?

A

hematocrit: the percentage of blood that is composed of cells relative to the total volume

  • normal: 47-78%
  • anemia: < 30%
  • polycthemia: >60%
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3
Q

what are the m/c clotting factors found in blood? what are their roles?

A
  • prothrombin: becomes thrombin, which
    • facilitates platelet aggregation
    • converts fibrinogen → fibrin in presence of Ca++
  • fibrinogen: becomes fibrin, which polymerizes dense networks at sites of blood vessel damage
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4
Q

what is prothrombin?

what are its roles?

A

a clotting factor

  • becomes thrombin, which:
    • facilitates platelet aggregation
    • converts fibrinogen → fibrin in presence of Ca++
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5
Q

what is fibrin?

what are its roles?

A

a clotting factor

  • becomes fibrin, which polymerizes dense networks at sites of blood vessel damage
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6
Q

what are erythrocytes and their major role?

A

= RBCs

  • bio-concave cells that carry hemoglobin, which transports oxygen
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7
Q

describe the structural elements of erythrocytes

A
  • have a flexible plasma membrane that rests on a skeleton made of 3 main components
    • spectrin
      • a peripheral membrane protein that forms a network of fibers
      • is bound to
        • ankrin
        • actin complex
    • ankyrin
      • binds spectrin filaments to integral membrane proteins (ex: 3 band protein)
    • actin complex
      • binds spectrin filaments to glycophorin
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8
Q

what is spectrin? what are its roles?

A

a erythrocyte cytoskeletal protein

  • a peripheral membrane protein that forms a network of fibers
  • is bound to
    • ankrin
    • actin complex
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9
Q

what is ankryin? what are its roles?

A

an erythrocyte cytoskeletal protein

  • binds spectrin filaments to integral membrane proteins (ex: 3 band protein)
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10
Q

what is the actin copmlex what are its roles?

A

an erythrocyte cytoskeletal protein

  • binds spectrin filaments to glycophorin
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11
Q

what is hereditary spherocytosis?

A
  • a condition where RBCs go from bioconcave → spherical when their cytoskeleton is compromised d/t a spectrin mutation
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12
Q

leukocytes

prevalence in the blood stream

A

less prevalent than RBCs

  • normal: 5000-9000
  • leukocytosis: > 12,000
  • leukopenia: < 5000
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13
Q

categorize leukocytes (WBCs)

A

two main categories

  • granulocytes: contain specific granules + azurophilic granules
    • neutrophils
    • eosinophils
    • basophils
  • agranulocytes: contain azurophilic granules only
    • lymphocytes
    • monocytes
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14
Q

what are the types of granules found in leukocytes (WBCs)? in which leukocytes are each granule type found?

A

two types

  • specific granules
    • found in granulocytes (neutrophils, basophils, eosinophils)
  • azurophilic granules = lysosomes
    • found in granulocytes (neutrophils, basophils, eosinophils) + agranulocytes (monocytes, lymphocytes)
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15
Q

neutrophils

  • what kind of cell
  • describe their structure
  • describe their characteristics
A
  • granulocytes (lymphocytes)
  • structure
    • multilobed nuclei
    • contain 3 types of granules
      • neutrophilic granules (specific granules): that contain bactericidal proteins
      • azurophilic (non-specific): aka lysosomes
      • tertiary granules: gelatinase + glycoproteins
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16
Q

what induces the release of the each neutrophil granule & what does each granule do?

A

chemotactic agents release of:

  • neutrophilic (specific) granules: contain bactericidal agents
  • tertiary granules: contain
    • gelatinase: degrades basal lamina allowing neutrophil migration
    • glycoproteins: aid in phagocytosis
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17
Q

what is neutropenia?

what does it lead to?

what is it most commonly associated with?

A
  • abnormally low neutrophils in the blood
  • leads to bacterial infections
  • often d/t immunodeficiency conditions (AIDS)
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18
Q

what is diapedesis?

A

= extravasation

the process by which neutrophils migrate through to damaged tissue through endothelium

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19
Q

outline the process of diapedesis

A

macrophages trigger neutrophils to travel thru post capillary venules to damage site - extravasation occurs in 3 phases:

  • rolling: neutrophil carbohydrate adhesion molecules (Sialyl Lewis) bind to endothelial cell selectins (E and P selectin) → neutrophil rolls through venules
  • tight adhesion: neutrophil integrins bind to endothelial surface Igs (ICAM-1 and VCAM) → neutrophils adhere to site on vessel wall
  • transmigration: neutrophils squeeze through endothelial cells by extending a pseudopod
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20
Q

what is the major function of neutrophils?

A

phagocytosis of bacteria

(part of cell mediated immunity)

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21
Q

discuss the means by which neutrophils perform selective phagocytosis of bacteria

A

via various surface receptors:

  • Fc receptors: bind Fc portion of IgG
  • Complement receptors: bind to 3Cb complement coating bacteria
  • Scavenger receptors: bind to modified LDLs found on the surface of gram + and gram - bacteria
  • toll like receptors (TLRs): bind PAMPs on bacterial surface, inducing
    • phagocytosis
    • release of IL-1, IL-3 and TNF-a from neutrophils
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22
Q

what are complement receptors and their role?

A

found on neutrophils

facilitate selective phagocytosis

  • bind to bacteria coated by C3b complement, allowing → opsonization of bacteria
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23
Q

what are scavenger receptors and their role?

A

found on neutrophils

facilitate selective phagocytosis

  • bind to modified LDLs found on the surface of gram + and gram - bacteria → phagocytosis
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24
Q

what are toll like receptors (TLRs) and their role?

A

found on neutrophils

facilitate selective phagocytosis

  • bind PAMPs on bacterial surface, inducing
    • phagocytosis
    • release of IL-1, IL-3 and TNF-a from neutrophils → inflammatory response
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25
Q

eosinophils

  • what kind of cell
  • describe their structure
  • describe their characteristics
A
  • are granulocytes (WBCs)
  • structure
    • have a bilobed nucleus
    • contain eosinophilic granules, which are made of:
      • cytotoxins: peroxidases, ribonucleases
      • histaminase
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26
Q

what are the major functions of eosinophils

A

eosinophils increase in the blood during

  • parasitic infections (helminths, protozoa)
  • allergic reactions
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27
Q

what triggers eosinophil degranulation?

what do the granules to?

A
  • triggered by: binding of the Fc portion of antigen bound IgE antibodies to Fc receptors on the eosinophil surface
    • cytotoxic granules (ribonuclease / peroxidase → ROS) destroy protozoan/helminth parasites
    • histaminase: destroys histamine → dec allergic rxn
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28
Q

basophils

  • what kind of cell
  • describe their structure
  • describe their characteristics
A
  • granulocytes (WBCs)
  • structure
    • have a lobed nucleus
    • contain basophilic granules, which are made of
      • histamine
      • heparin
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29
Q

what are the main roles of basophils?

A
  • histamine release - main function
  • phagocytic (slightly)
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30
Q

what triggers basophil degranulation?

what do these granules do?

A
  • triggered by binding of antigen bound anti-IgE antibodies to Fc receptors on basophils
  • basophilic granules cause Type I allergic reaction → vasodilation / bronchoconstriction
    • histamine
    • heparin
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31
Q

characterize the granulocytes in terms of

  • size
  • nuclear shape
A
  • size: neutrophils > eosinophils > basophils
  • nucleus:
    • neutrophil - multilobed
    • eisonophil - bilobed
    • basophil - lobed
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32
Q

discuss the Fc receptors on each granulocyte and

  • what they bind
  • what this binding leads to
A
  • neutrophils - bind IgG Fc
    • these IgG Ab are bound to bacterial antigens, and IgG-neutrophil binding → bacterial phagocytosis
  • eosinophils - bind IgE Fc
    • these antigen bound IgE induce release of eosinophilic granules → cytotoxins, anti-histamines
  • basophils - bind IgE Fc
    • these antigen bound IgE induce release of basophilic granules → histamine
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33
Q

which granulocyte behaves like mast cells?

how does it do this?

A

basophils

binding of IgE Fc to Fc receptors induces histamine release → Type I allergic rxn

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34
Q

lymphocytes - nuclear shape

A

large spherical OR slightly indented heterochromatic nucleaus surrounded by a tiny rim of cytoplasm

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35
Q

lymphocytes are

  • what kind of cell?
  • composed of what cell subtypes?
A
  • are agranulocytes (WBCs)
  • include
    • T-cells
      • helper T-cells (CD4)
      • killer T-cells (CD8)
      • regulatory T-cells
    • B-cells
    • NK cells
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36
Q

T-cells

  • are what kind of cells?
  • have what distinguishing characteristics?
  • have what major role?
  • are made of what subtypes?
A
  • are lymphocytes (agranulocytic WBCs)
  • all produce cytokines
  • have specific markers:
    • all have
      • TCR (T-cell receptor)
      • CD3
    • further distinguished by presence of either CD4, CD8, CD25
      • T-helpers: have CD4+
      • regulatory T-cells: have CD4+, CD25+
      • cytotoxic T-cells: have CD8+
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37
Q

helper T-cells

  • have what markers
  • have what role
A
  • CD3, TCR, CD4
  • major role is to produce various key cytokines:
    • CD4 - binds MHC-II on on APCs (phagocytes, B-cells) cells → inducing phagocytosis of pathogen
    • TH2
      • B-cell development
        • inc B-cell proliferation
        • B-cell differentiation → plasma cells
      • activates
        • mast cells
        • eosinophils
    • Th1 - activate macrophages → phagocytosis
    • Th17 - activate neutrophils
38
Q

regulatory T-cell

  • have what markers
  • have what roles
A
  • TCR, CD3, CD4, CD25
  • role
    • inhibit autoimmunity
    • inhibit functions of other leukocytes (T-cells, B-cells, NK-cells)
39
Q

cytotoxic T-cells

  • have what markers
  • have what major roles?
A
  • TCRs, CD3, CD8
  • major role: to destroy infected host cells
    • CD8 binds MHC-I, which is expressed on host cells carrying the antigen
    • the T-cell then destroy cells carrying the antigen (cell mediated immunity)
40
Q

B-lymphocytes

  • are what type of cell?
  • have what markers
  • include what subsets
  • have what main immunological function (s)
A
  • are lymphocytes (agranulocyte WBC)
  • markers:
    • BCR: made of surface immunoglobin (IgM)
    • MHC-II (since they are an APC that presents to Th cells)
    • CD9, CD19, CD20
  • populations
    • plasma cells
    • memory B-cells → make Ig
  • immunological function
    • plasma B-cells make produce Ig (antibodies)
      • part of humoral immunity
41
Q

compare and contrast T-cell and B-cells in terms of

  • cell population they belong to
  • sites at which where they arise / mature
  • their markers/receptors
  • primary immunological function
A

both

  • are lymphocytes (type of agranulocyte WBC)
  • T-cells
    • arise in the bone marrow & mature in the thymus
    • markers
      • TCR
      • CD3
      • CD4/CD8/CD25
        • CD4 - binds MHC-II on APCs
        • CD8- binds MHC-I on infected cells
    • primary function
      • cell mediated immunity
        • Th: cytokine production
        • Tc: lysis of infected cells
  • B-cells
    • arise in bone marrow, mature in in the bone marrow / lymph tissue
    • markers
      • BRC (IgM)
      • MHC-II - binds CD4 of Th
      • CD9, CD19, CD21
    • primary function
      • humoral immunity
        • antibody production
42
Q

NK cells

  • are what type of immune cell?
  • markers
  • primary immunological function?
A
  • are lymphocytes (agranulocyte WBC)
  • markers
    • KIR (killer cell receptor)
    • CD16, CD56
  • primary immunological functions
    • kill virus infected cells with downregulated MHC-1 (via KIRs)
    • kill antibody coated (IgG coated) cells
43
Q

which immune cells have KIRs? what is their role?

A

= killer cell immunoglobin receptors

  • NK cells
  • used to detect & kill virus infected cells with downregulated MHC-I
44
Q

which immune cells have CD16? what is their role?

A
  • NK cells
  • CD16 binds IgG Fc receptors on antibody coated cells → kills those cells
45
Q

monocytes

  • are what kind of immune cells?
  • have what structure / characteristics
  • have what primary immunological function?
A
  • are agranulocyte WBCs
  • structure
    • nucleus is kidney bean shaped
    • cytoplasm = many lysosomes / mitochondria
  • function → become macrophages once they reach target tissue
46
Q

what are the most common agranulocytes?

A

lymphocytes

47
Q

platelets - describe their structure / characteristics

A
  • structure
    • anucleate
    • biconvex discoid particles
  • characteristics
    • made of two zones:
      • peripheral zone
        • = hyalomere
        • cytoskeletal elements
          • microtubules
          • actin - G-actin, F-actin
      • central zone
        • = granulomere
        • granule filled:
          • lysosomes
          • a granules - clotting factors
          • dense granules - ADP, serotonin
48
Q

what is the “hyalomere”?

what is its role?

A
  • the network of cytoskeletal elements that constitutes the peripheral zone of the platelets. made of
    • microtubules
    • F-actin, G-actin
49
Q

what is the granulomere?

what is its role?

A
  • the group of vesicles that constitute the central zone of platelets. made of
    • lysosomes
    • a-granules
      • clotting factors - fibrinogen, von-willebrand
    • dense granules
      • serotonin
      • ADP
50
Q

what are alpha granules & what do they contain?

A
  • vesicles in central zone of platelet
  • contain clotting factors
    • fibrinogen
    • platelet thromboplastic factor
    • Von Willebrand factor
51
Q

what are dense granules & what do they contain?

A
  • vesicles in the central zone of platelets
  • contain
    • ADP
    • serotonin
52
Q

what is the main role of platelets?

A

conducting blood clotting

53
Q

outline the steps of the blood clotting cascade

A
  • collagen exposed on blood vessel → platelets bind to form sticky surface for clot assembly:
    • platelets release
      • TXA → aggregates platelets
      • serotonin/ADP (dense core granules) → vasoconstriction
      • platelet thromboplastic factor (a-granules)
        • prothrombin → thrombin
          • fibrinogen → fibrin
            • fibrin → dense meshwork
    • platelet cytoskeleton elements (actin & myosin filaments) slide over each-other to
      • contract the clot
      • pull rupture vessel walls together
54
Q

what is the of ATP & serotonin in the clotting cascade?

A

= from dense core granules (granulomere)

role = vasoconstriction

55
Q

what is the role of the platelet cytoskeleton in the clotting cascade?

A

= hyalomere

  • actin & myosin filaments slide over each-other to
    • contract the clot
    • pull rupture vessel walls together
56
Q
  • what is the role of platelet thromboplastic factor in the clotting cascade?
A

from a-granules (granulomere)

  • prothrombin → thrombin
    • fibrinogen → fibrin
      • fibrin → dense meshwork: serves as skeleton that “traps” RBCs so clot can form
57
Q

what is the cause of thrombocytopenia?

A

type II hypersensitivity: auto-antibodies made against native platelets → phagocytosis/lysis of platelets

58
Q

all blood cells come from

  • which precursor cell?
  • in response to what stimulus?
A
  • hematopoietic stem cell (HSC)
    • aka pluripotential stem cell
  • in response to CSF (colon stimulating factor)
59
Q

the hematopoietic stem cells (HSC) divides into what main populations?

A
  • common myeloid progenitor, which gives off:
    • erythrocyte / megakaryocyte progenitor (MEP)
    • granulocyte / monocyte progenitor (GMP)
  • lymphoid progenitor
60
Q

what immune cells come from the common myeloid progenitor?

A
  • megakaryocyte / erythrocyte progenitor (MEP)
    • platelets
    • RBCs
  • granulocyte / monocyte progenitor
    • granulocytes (WBCs)
      • neutrophils
      • eosinophils
      • basophils
        • → mast cells
    • monocytes → macrophages
61
Q

what immune cells come from the common lymphoid progenitor?

A
  • T-cells
  • B-cells
    • memory B-cells
    • plasma cells
  • NK-cells
62
Q

G-CSF - stimulates what immune cell formation?

A
  • granulocytes
    • from granulocyte-mast cell progenitor (GMP) from myeloid progenitor
63
Q

M-CSF - stimulates formation of what immune cell?

A
  • macrophages
    • from granulocyte/monocyte progenitor (GMP) from common myeloid progenitor
64
Q

GM-CSF - stimulates what immune cell formation?

A
  • granulocytes and macrophages
    • from common myeloid progenitor
65
Q

IL-3 stimulates production of what immune cell?

A
  • common myeloid progenitor
    • from hematopoietic stem cell (HSC)
66
Q

EPO - stimulates what immune cell formation?

A
  • RBCs (erythrocytes)
    • from megakaryocyte / erythrocyte (MEP) from common myeloid progenitor
67
Q

thrombopoietin - stimulates what immune cell production?

A
  • platelets
    • from megakaryocyte / erythrocyte (MEP) from common myeloid progenitor
68
Q

IL-II - stimulates what immune cell production?

A
  • platelets
    • from megakaryocyte / erythrocyte (MEP) from common myeloid progenitor
69
Q

discuss the stages of erythropoiesis - what characteristics are seen at each stage?

A
  • pro-erythroblast
    • _Hb first presen_t at this stage
    • cytoplasm deeply basophillic
    • large, spherical nucleus
  • basophilic erythroblast
    • cytoplasm still deeply basophilic
    • nucleus smaller / denser chromatin
  • poly-chromatophilic erythroblast
    • last stage of mitotic activity
    • cytoplasm is pink-blue
    • nucleus has checkerboard chromatin
  • ortho-chromatophilic erythroblast
    • post-mitotic
    • cytoplasm pink
    • nucleus gets extruded
  • reticulocyte
    • anucleate
70
Q

which erythroblast precursors have mitotic activity?

A
  • pro-erythroblast
  • basophilic erythroblast
  • polychromatic erythroblast (last stage with mitosis)
71
Q

which erythroblast precursor has the largest nucleus?

A

proerythrocyte

72
Q

which erythrocyte precursors have basophillic cytoplasm?

A
  • pro-erythroblast
  • basophilic erythroblast
73
Q

which erythroblast precursor has pink-blue cytoplasm and why is this?

A
  • the polychromatophilic erythroblast
    • hemoglobin (pink) to basophil (blue) ratio increasing
74
Q

which erythrocyte precursors are post-mitotic?

A
  • ortho-chromatophilic erythroblast (first one)
  • reticulocyte
  • mature RBC
75
Q

which erythroblast precursor has a nucleus with “checkerboard” chromatin

A

polychromatic erythroblast

76
Q

which erythroblast precursor is anucleate?

A

reticulocyte (nucleus ingested by macrophages during ortho-chromatophilic erythroblast)

77
Q

which erythroblast precursor is anucleate?

A

reticulocyte (nucleus ingested by macrophages during ortho-chromatophilic erythroblast)

78
Q

poly-chromatophilic erythroblast in terms of

  • nucleus / mitotic status
  • cytoplasm color
A
  • last stage of mitotic activity
  • cytoplasm is pink-blue
  • nucleus has checkerboard chromatin
79
Q

ortho-chromatophilic erythroblast in terms of

  • nucleus / mitotic status
  • cytoplasm color
A
  • post-mitotic
  • cytoplasm pink
  • nucleus gets extruded
80
Q

outline the stages of granulopoiesis - what characteristics are seen at each stage?

A
  • myeloblast
    • large nucleus - oval shaped
  • promyelocyte
    • largest nucleus - oval shaped
    • 1st stage of azurophilic granules
  • myelocyte
    • smaller nucleus +/- indentation
    • 1st stage of specific granules (neutrophilic, eosinophilic, basophilic)
    • last stage of mitotic activity
  • metamyelocyte
    • bean shaped nucleus
    • no mitotic activity
  • band form
    • horseshoe shaped nucleus
    • contains specific granules of only one type
81
Q

which granulocyte precursor is the largest in the lineage?

A

pro-myleocyte (second stage)

82
Q

which granulocyte precursors have mitotic activity?

A
  • myeloblast
  • pro-myeloblast
  • myelocyte (last one)
83
Q

which granulocyte precursors are NOT mitotically active?

A
  • metamyelocyte (first one)
  • band form
84
Q

which is the first granulocyte precursor to contain azurophilic granules?

A

promyelocyte

85
Q

which granulocyte precursor is the first go contain specific granules?

86
Q

which granulocyte precursor is the first to contain only one specific granule?

87
Q

myelocyte

  • nucleus
  • granule status
  • mitosis
A
  • smaller nucleus +/- indentation
  • 1st stage of specific granules (neutrophilic, eosinophilic, basophilic)
  • last stage of mitotic activity
88
Q

metamyelocyte

  • nucleus
  • granule status
  • mitosis
A
  • bean shaped nucleus
  • specific granules
  • no mitotic activity (first stage)
89
Q

band form granulocyte

  • nucleus
  • granule status
  • mitosis
A
  • horseshoe shaped nucleus
  • contains specific granules of only one type
  • no mitosis
90
Q

where do NK cells mature?

A
  • bone marrow
  • lymph nodes
91
Q

discuss the stages of thrombopoiesis & their characteristics

A
  • megakaryoblast
    • DNA replication occurring without cytokinesis (no cytoplasm division)
  • megakaryocyte
    • giant, polyploid cell
    • cytoplasm pinched off → platelets

HIST Heme-Onc (2 decks)

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