Blood and Hematopoiesis Flashcards
(91 cards)
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
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%
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
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++
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
6
Q
what are erythrocytes and their major role?
A
= RBCs
- bio-concave cells that carry hemoglobin, which transports oxygen
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
- spectrin
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
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)
10
Q
what is the actin copmlex what are its roles?
A
an erythrocyte cytoskeletal protein
- binds spectrin filaments to glycophorin
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
12
Q
leukocytes
prevalence in the blood stream
A
less prevalent than RBCs
- normal: 5000-9000
- leukocytosis: > 12,000
- leukopenia: < 5000
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
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)
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
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
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)
18
Q
what is diapedesis?
A
= extravasation
the process by which neutrophils migrate through to damaged tissue through endothelium
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
20
Q
what is the major function of neutrophils?
A
phagocytosis of bacteria
(part of cell mediated immunity)
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
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
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
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
25
eosinophils
* what kind of cell
* describe their structure
* describe their characteristics
* are granulocytes (WBCs)
* structure
* have a **bilobed nucleus**
* contain eosinophilic granules, which are made of:
* **cytotoxins:** peroxidases, ribonucleases
* **histaminase**
26
what are the major functions of eosinophils
eosinophils increase in the blood during
* **parasitic infections** (**helminths, protozoa**)
* **allergic reactions**
27
what triggers eosinophil degranulation?
what do the granules to?
* 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
28
basophils
* what kind of cell
* describe their structure
* describe their characteristics
* granulocytes (WBCs)
* structure
* have a **lobed nucleus**
* contain **basophilic granules,** which are made of
* histamine
* heparin
29
what are the main roles of basophils?
* histamine release - main function
* phagocytic (slightly)
30
what triggers basophil degranulation?
what do these granules do?
* 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
31
characterize the granulocytes in terms of
* size
* nuclear shape
* size: neutrophils \> eosinophils \> basophils
* nucleus:
* neutrophil - multilobed
* eisonophil - bilobed
* basophil - lobed
32
discuss the Fc receptors on each granulocyte and
* what they bind
* what this binding leads to
* 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**
33
which granulocyte behaves like mast cells?
how does it do this?
basophils
binding of IgE Fc to Fc receptors induces histamine release → Type I allergic rxn
34
lymphocytes - nuclear shape
large spherical OR slightly indented heterochromatic nucleaus surrounded by a tiny rim of cytoplasm
35
lymphocytes are
* what kind of cell?
* composed of what cell subtypes?
* are agranulocytes (WBCs)
* include
* T-cells
* helper T-cells (CD4)
* killer T-cells (CD8)
* regulatory T-cells
* B-cells
* NK cells
36
T-cells
* are what kind of cells?
* have what distinguishing characteristics?
* have what major role?
* are made of what subtypes?
* 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+
37
helper T-cells
* have what markers
* have what role
* 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
regulatory T-cell
* have what markers
* have what roles
* TCR, CD3, CD4, CD25
* role
* **inhibit autoimmunity**
* inhibit functions of other leukocytes (T-cells, B-cells, NK-cells)
39
cytotoxic T-cells
* have what markers
* have what major roles?
* 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
B-lymphocytes
* are what type of cell?
* have what markers
* include what subsets
* have what main immunological function (s)
* 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
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
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
NK cells
* are what type of immune cell?
* markers
* primary immunological function?
* 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
which immune cells have KIRs? what is their role?
= killer cell immunoglobin receptors
* NK cells
* used to detect & kill **virus infected cells** with **downregulated MHC-I**
44
which immune cells have CD16? what is their role?
* NK cells
* CD16 binds **IgG Fc receptors** on **antibody coated cells** → kills those cells
45
monocytes
* are what kind of immune cells?
* have what structure / characteristics
* have what primary immunological function?
* are agranulocyte WBCs
* structure
* nucleus is **kidney bean shaped**
* cytoplasm = many lysosomes / mitochondria
* function → **become macrophages** once they reach target tissue
46
what are the most common agranulocytes?
lymphocytes
47
platelets - describe their structure / characteristics
* 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
what is the “hyalomere”?
what is its role?
* the **network of cytoskeletal elements** that constitutes the **peripheral zone** of the platelets. made of
* microtubules
* F-actin, G-actin
49
what is the granulomere?
what is its role?
* 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
what are alpha granules & what do they contain?
* vesicles in central zone of platelet
* **contain clotting factors**
* fibrinogen
* platelet thromboplastic factor
* Von Willebrand factor
51
what are dense granules & what do they contain?
* vesicles in the central zone of platelets
* contain
* ADP
* serotonin
52
what is the main role of platelets?
conducting blood clotting
53
outline the steps of the blood clotting cascade
* **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
what is the of ATP & serotonin in the clotting cascade?
= from dense core granules (granulomere)
role = vasoconstriction
55
what is the role of the platelet cytoskeleton in the clotting cascade?
= hyalomere
* **actin & myosin filaments** slide over each-other to
* **contract the clot**
* **pull rupture vessel walls together**
56
* what is the role of platelet thromboplastic factor in the clotting cascade?
from a-granules (granulomere)
* prothrombin → thrombin
* fibrinogen → fibrin
* fibrin → **dense meshwork**: serves as skeleton that “traps” RBCs so clot can form
57
what is the cause of thrombocytopenia?
_type II hypersensitivity_: **auto-antibodies** made against native platelets → phagocytosis/lysis of platelets
58
all blood cells come from
* which precursor cell?
* in response to what stimulus?
* **hematopoietic stem cell (HSC**)
* aka pluripotential stem cell
* in response to **CSF** (colon stimulating factor)
59
the hematopoietic stem cells (HSC) divides into what main populations?
* common myeloid progenitor, which gives off:
* erythrocyte / megakaryocyte progenitor (MEP)
* granulocyte / monocyte progenitor (GMP)
* lymphoid progenitor
60
what immune cells come from the common myeloid progenitor?
* megakaryocyte / erythrocyte progenitor (MEP)
* platelets
* RBCs
* granulocyte / monocyte progenitor
* granulocytes (WBCs)
* neutrophils
* eosinophils
* basophils
* → mast cells
* monocytes → macrophages
61
what immune cells come from the common lymphoid progenitor?
* T-cells
* B-cells
* memory B-cells
* plasma cells
* NK-cells
62
G-CSF - stimulates what immune cell formation?
* granulocytes
* from granulocyte-mast cell progenitor (GMP) from myeloid progenitor
63
M-CSF - stimulates formation of what immune cell?
* macrophages
* from granulocyte/monocyte progenitor (GMP) from common myeloid progenitor
64
GM-CSF - stimulates what immune cell formation?
* granulocytes and macrophages
* from common myeloid progenitor
65
IL-3 stimulates production of what immune cell?
* common myeloid progenitor
* from hematopoietic stem cell (HSC)
66
EPO - stimulates what immune cell formation?
* RBCs (erythrocytes)
* from megakaryocyte / erythrocyte (MEP) from common myeloid progenitor
67
thrombopoietin - stimulates what immune cell production?
* platelets
* from megakaryocyte / erythrocyte (MEP) from common myeloid progenitor
68
IL-II - stimulates what immune cell production?
* platelets
* from megakaryocyte / erythrocyte (MEP) from common myeloid progenitor
69
discuss the stages of erythropoiesis - what characteristics are seen at each stage?
* 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
which erythroblast precursors have mitotic activity?
* pro-erythroblast
* basophilic erythroblast
* polychromatic erythroblast _(last stage with mitosis_)
71
which erythroblast precursor has the largest nucleus?
proerythrocyte
72
which erythrocyte precursors have basophillic cytoplasm?
* pro-erythroblast
* basophilic erythroblast
73
which erythroblast precursor has pink-blue cytoplasm and why is this?
* **the polychromatophilic erythroblast**
* hemoglobin (pink) to basophil (blue) ratio increasing
74
which erythrocyte precursors are post-mitotic?
* ortho-chromatophilic erythroblast (first one)
* reticulocyte
* mature RBC
75
which erythroblast precursor has a nucleus with “checkerboard” chromatin
polychromatic erythroblast
76
which erythroblast precursor is anucleate?
**reticulocyte** (nucleus ingested by macrophages during ortho-chromatophilic erythroblast)
77
which erythroblast precursor is anucleate?
**reticulocyte** (nucleus ingested by macrophages during ortho-chromatophilic erythroblast)
78
poly-chromatophilic erythroblast in terms of
* nucleus / mitotic status
* cytoplasm color
* _last stage of mitotic activity_
* cytoplasm is pink-blue
* **nucleus has checkerboard chromatin**
79
ortho-chromatophilic erythroblast in terms of
* nucleus / mitotic status
* cytoplasm color
* _post-mitotic_
* cytoplasm pink
* **nucleus gets extruded**
80
outline the stages of granulopoiesis - what characteristics are seen at each stage?
* 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
which granulocyte precursor is the largest in the lineage?
pro-myleocyte (second stage)
82
which granulocyte precursors have mitotic activity?
* myeloblast
* pro-myeloblast
* myelocyte (_last one_)
83
which granulocyte precursors are NOT mitotically active?
* metamyelocyte (_first one_)
* band form
84
which is the first granulocyte precursor to contain azurophilic granules?
promyelocyte
85
which granulocyte precursor is the first go contain specific granules?
myelocyte
86
which granulocyte precursor is the first to contain _only one_ specific granule?
band form
87
myelocyte
* nucleus
* granule status
* mitosis
* **smaller nucleus +/- indentation**
* **1st stage of specific granules** (neutrophilic, eosinophilic, basophilic)
* _last stage of mitotic activity_
88
metamyelocyte
* nucleus
* granule status
* mitosis
* **bean shaped nucleus**
* specific granules
* _no mitotic activity_ (first stage)
89
band form granulocyte
* nucleus
* granule status
* mitosis
* **horseshoe shaped nucleus**
* **contains specific granules _of only one type_**
* no mitosis
90
where do NK cells mature?
* bone marrow
* lymph nodes
91
discuss the stages of thrombopoiesis & their characteristics
* megakaryoblast
* DNA replication occurring _without cytokinesis_ (no cytoplasm division)
* megakaryocyte
* _giant, polyploid cell_
* cytoplasm pinched off → platelets
