Histology Final-Blood

Front 1

Blood Volume in body?

Back 1

total volume approximately 5 liters, which is about 8% of the total body weight.
cells occupy %50 of that volume

Front 2

Describe Erythrocytes.

Back 2

-RBC
-specialized to transport O2
-biconcave disc, capable of significant distortion
-nucleus not present in mature RBC
-provides significant exchange of materials.

Front 3

Erythrocyte stats?

Back 3

-7.6 um diameter in dried smear
-5 x10^6/uL of blood
-total surface area for all RBCs in human body is about 3500 m^2

Front 4

Describe Rouleaux Formation.

Back 4

RBCs have a tendency to stack up, one on top of the other like coins; this will happen spontaneously in still blood.

Front 5

Describe the RBC membrane.

Back 5

standard lipid bilayer

Front 6

Describe RBC Crenation.

Back 6

if the RBC shrinks osmotically, the membrane becomes wrinkled.

Front 7

Describe RBC Hemolysis.

Back 7

if the RBC swells osmotically, it will round up and eventually lose Hb

Front 8

Describe RBC Anisocytosis.

Back 8

the size of the RBC can vary in pathological conditions.

Front 9

Mirocyte size?

Back 9

<6 um in diameter

Front 10

Describe Sickle Cell Anemia.

Back 10

-Hb molecule of sickle cell anemia has a substitution mutation of valine for glutamic acid.
-under conditions of low O2 tension, this causes thr Hb to polymerize(crystallize) and change the RBC shape.

Front 11

Describe Anemia.

Back 11

-usually a decrease in RBC number
-may also be a decrease in Hb per cell

Front 12

Describe Leukocytes.

Back 12

-WBCs
-1% of total blood volume
-5000 to 9000/uL of blood
-Two main types: Agranular and Granular

Front 13

Approximately 1% of the total blood volume is composed of leukocytes, of this approximately:

Back 13

-50 to 70 % are neutrophils
-20 to 40 % are lymphocytes
-1 to 6 % are monocytes
-1-3 % are eosinophils
- < 1% are basophils

Front 14

Describe Agranular Leukocytes.

Back 14

-have a cytoplasm that appears to be homogeneous and nuclei that are spherical to kidney-shaped.
-two types: Lymphocytes and Monocytes

Front 15

Describe Granular Leukocytes.

Back 15

-contain specific granules in their cytoplasm
-in life, these granules are semi-fluid droplets
-their nuclei show significant variation in shape

Front 16

Two Types of Agranular Leukocytes?

Back 16

1. Lymphocytes
2. Monocytes

Front 17

Describe Lymphocytes.

Back 17

-small cells with little cytoplasm
-6 to 11 um in diameter
-large, round, dark staining nucleus
-size can be variable

Front 18

Lymphocyte Function.

Back 18

function in immune reactions against invading microorganisms, foreign macromolecules, and cancer cells.

Front 19

Describe Monocytes.

Back 19

-larger with more cytoplasm
-12 to 20 um in diameter
-kidney shaped to round nucleus
-differentiate in tissues into macrophages

Front 20

Describe Macrophages.

Back 20

a multiple function cell that internalizes and digests dead or dying cells and foreign materials including invading microorganisms, and participates in immune system function.

Front 21

Three Types of Granular Leukocytes?

Back 21

1. Neutrophils
2. Basinophils
3. Eosinophils/Acidophils

Front 22

Granular Leukocytes are distinguished by what?

Back 22

the affinity of their granules for neutral, basic, and acidic stains

Front 23

Two Types of Granules in Granulocytes?

Back 23

1. specific granules
2. azurophilic granules

Front 24

Describe Specific Granules

Back 24

have specific contents for each cell type

Front 25

Describe Azurophilic Granules

Back 25

stain purple and are lysosomes.

Front 26

Describe Neutrophils.

Back 26

-polymorphonuclear leukocytes (PMNs)
-60 to 70 % of the leukocytes in circulation
-12 to 15 um in diameter (dried smear)
-have multilobed nucleus
-immature PMNs have a horse shoe shaped nucleus
-have glycogen in their cytoplasm in addition to specific and azurophilic granules
-able to survive under anaerobic conditions
-live for a short time
-phagocytes; provide defense against microbes

Front 27

What does the ability to survive in anaerobic conditions enable neutrophils to do?

Back 27

function in inflamed and dying tissues which may have a low O2 supply

Front 28

Neutrophil lifetime?

Back 28

Time in blood= 12 to 14 hours

Time in tissues= 1 to 4 days

Front 29

Describe Neutrophil phagocytosis.

Back 29

-Neutrophils engulf and phagocytose bacteria
-specific granules then fuse with these phagosomes and empty their contents into them; lysozymes, antibacterial proteins, alkaline phosphatase.
-proton pumps in the phagosome membrane lower the pH to 5, optimal for lysozymes
-azurophilic granules, lysosomes, fuse with the phagosomes and empty their contents into them (strong oxidizing agents in the cell also fucntion in the killing process)

Front 30

Describe Eosinophils

Back 30

-2 to 4% of the leukocytes in blood
-12 to 15 um in diameter
-characteristically bilobed nucleus
-specific granules contain major basic protein as 1/2 their total protein content which account for their affinity to eosin
-function in parasitic infection.

Front 31

Eosinophil function.

Back 31

parasitic infection

Front 32

Why are eosiniphils acidophilic?

Back 32

their specific granules contain major basic protein as 1/2 their total protein content which account for their affinity to eosin and acid stains

Front 33

Describe Basophils

Back 33

-less than 1% of blood leukocytes
-12 to 15 um in diameter
-have a partially lobulated (bilobed) nucleus
-basophilic staining is due to heparin; polyanionic metachromatic staining
-basophilic granules also contain histamine
-appear to supplement the function of mast cells and can be triggered by antibodies to release their specific granule contents in response to foreign materials

Front 34

Basophilic Function

Back 34

appear to supplement the function of mast cells and can be triggered by antibodies to release their specific granule contents in response to foreign materials

Front 35

Basophilic Staining is due to?

Back 35

-basophilic staining is due to heparin; polyanionic metachromatic staining
-basophilic granules also contain histamine

Front 36

Describe Monocytes/Macrophages.

Back 36

-part of "mononuclear phagocytic system"
-are produced in bone marrow, circulate in the blood as monocytes and differentiate in the tissues into macrophages
-macrophages engulf and digest microorganisms and particulate matter

Front 37

Two Types of Immune System Receptor Molecules?

Back 37

1. Innate Immune System-encoded by germline genes

2.Adaptive (Acquired) Immune System-expressed by B and T lymphocytes

Front 38

General Receptor Molecule Function?

Back 38

to recognize and bind to foreign materials

Front 39

Describe the Innate Immune System.

Back 39

-receptors are encoded by germline genes that are expressed without modification
-its mechanisms do not require a period of induction or a selection process; they are present in fully functional form and can function immediately
-examples of cells that express these receptors are natural killer cells (a type of lymphocyte) and macrophages

Front 40

Examples of Innate Immune System Cells?

Back 40

examples of cells that express these receptors are natural killer cells (a type of lymphocyte) and macrophages

Front 41

Describe the Adaptive Immune System.

Back 41

-receptors are expressed by B and T lymphocytes and include immunoglobulins (antibodies) produced by B Lymphocytes and the T Cell receptor produced by T Lymphocytes
-genes encoding immunoglobulins and T Cell receptors are not expressed unless they undergo gene rearrangement events during lymphocyte maturation.

Front 42

When are genes encoding immunoglobulins and T Cell receptors expressed?

Back 42

when they undergo gene rearrangement events during lymphocyte maturation.

Front 43

Three classes of Lymphocytes?

Back 43

1. B Cells
2. T Cells
3. Null Cells

Front 44

All three classes of Lymphocytes arise from?

Back 44

precursors produced in the bone marrow and subsequently circulate in the blood.

Front 45

Where are T Cells produced?

Back 45

T Cells are produced in the thymus from precursors that populate the thymus early in fetal development.

Front 46

Describe B Lymphocytes.

Back 46

-mature B Cells produce immunoglobulins (antibodies)
-prior to encounter with an antigen, mature but "naive" B Cells display approximately 10^5 antibody molecules on their surface, all the same.
-following encounter with an antigen and activation, B Cells differentiate into plasma cells

Front 47

Describe B Lymphocytes prior to encounter with an antigen.

Back 47

prior to encounter with an antigen, mature but "naive" B Cells display approximately 10^5 antibody molecules on their surface, all the same.

Front 48

Describe B Lymphocytes after encounter with an antigen.

Back 48

following encounter with an antigen and activation, B Cells differentiate into plasma cells

Front 49

Describe Plasma Cells

Back 49

have no membrane-bound antibody, but instead synthesize and secrete huge quantities of it.

Front 50

Where are T Cells produced?

Back 50

T Cells are produced in the thymus from precursors originating in bone marrow during development

Front 51

Describe T Lymphocytes

Back 51

-produce and display on their cell surfaces the T Cell Receptor (TCR)
-bind to an antigen via the TCR
-has two subclasses, Helper T Cells (Th) and Cytotoxic T Cells (Tc)
-the TCR is never secreted

Front 52

Helper T Cell (Th) Function

Back 52

Th facilitate the activation of other cells in the immune system

Front 53

Cytotoxic T Cell (Tc) Function

Back 53

-upon encounter with an antigen and subsequent activation, Tc differentiate into an effector cell, the Cytotoxic T Lymphocyte, CTL

Front 54

Describe Suppressor T Cell (Ts)

Back 54

-proposed third subtype that suppresses immune system function
-not clear that a separate class of cells mediate this function

Front 55

Describe Null Cells

Back 55

-small group of lymphocytes that do not express the specific antigen receptors or other marker molecules that characterize B and T Lymphocytes
-some may be stem cells that have no markers of differentiation
-others are a population of Natural Killer (NK) cells

Front 56

Describe Natural Killer Cells

Back 56

-NK Cells, type of null cell
-5 to 10% of the lymphocytes in peripheral blood
-provide defense against tumor cells and some virus infected cells

Front 57

Cell types produced in bone marrow but principally residing in tissues?

Back 57

Mast Cells and Dendritic Cells

Front 58

Describe Mast Cells

Back 58

-not a blood cell but are produced in bone marrow
-release from the marrow as undifferentiated cells that travel via blood to their target tissue
-do not differentiate until they leave the blood and enter tissue
-agranular cell containing heparin, histamine, and other active substances such as tumor necrosis factor
-function in inflammatory response

Front 59

When do Mast Cells differentiate?

Back 59

do not differentiate until they leave the blood and enter tissue

Front 60

Mast cell Function?

Back 60

inflammatory response

Front 61

Describe Dendritic Cells

Back 61

-produced in bone marrow and may only be present in the blood in an immature stage as they travel to their target tissue
-those in blood account for 0.1% of total blood leukocytes
-have long extensions of the cell surface membrane giving them dendritic appearance
-function as antigen presenting cells (APC)

Front 62

Describe Antigen Presenting Cells.

Back 62

-APC; internalize, digest, and display pieces of antigens on their surface to T and B Cells as part of their immune repsonse

Front 63

Describe structure of immunoglobulins and T Cell Receptor molecules.

Back 63

Molecules of immunoglobulins and T Cell receptors are each composed of two different polypeptide chains.

Front 64

Describe Polypeptide Chains in Immunoglobulins.

Back 64

the polypeptides are different sizes; one is smaller, the light chain, and one is larger, the heavy chain.

Front 65

Describe Polypeptide Chains in TCR molecules.

Back 65

the polypeptide chains in the TCR are about the same size

Front 66

How many copies of each type of polypeptide chain do immunoglobulins have?

Back 66

Immunoglobulins have two copies of each type of polypeptide.

Front 67

How many copies of each type of polypeptide chain do TCR molecules have?

Back 67

the TCR has one copy of each polypeptide

Front 68

Considering maturation of lymphocytes, B Cells make?

Back 68

immunoglobulins

Front 69

Considering maturation of lymphocytes, T Cells make?

Back 69

T Cell Receptors, TCR

Front 70

B Lymphocyte Mneumonic

Back 70

Bone marrow

Front 71

T Lymphocyte Mneumonic

Back 71

Thymus

Front 72

When are Immunoglobulin and TCR genes expressed?

Back 72

Gene structure is similar for immunoglobulins and TCR molecules; genes are not expressed unless first rearranged to produce a functional unit.

Front 73

Describe Maturation of B Lymphocytes

Back 73

-lymphoid stem cells produce cells that differentiate into Progenitor B Cells (Pro B Cells)
-During Pro B Cell differentiation, heavy chain rearrangement occurs.
-With the production of immunoglobulin heavy chains, the cell becomes a Pre B Cell
-the Pre B Cell undergoes light chain rearrangement
-a productive light chain rearrangement enables the cell to produce immunoglobulin.
-at this stage the cell is an immature B Cell that expresses immunoglobulin with a defined antigenic (ligand binding) specificity

Front 74

What does a productive light chain rearrangement enables the Pre B Cell to do?

Back 74

produce immunoglobulin.

Front 75

What does an immature B Cell express?

Back 75

immunoglobulin with a defined antigenic (ligand binding) specificity

Front 76

General Immunoglobulin and TCR gene organization and expression?

Back 76

These genes consist of multiple units organized in clusters of components

Front 77

Describe human immunoglobulin gene organization.

Back 77

Light chain genes and heavy chain genes are on different chromosomes

Front 78

Describe Light Chain germ-line genes

Back 78

contain V, J, C component
V=variable region
J=joining region; joins variable and constant regions
C=constant region

Front 79

Describe Heavy Chain germ-line genes

Back 79

contain V, J, D, and C component
V=variable region
J=joining region; joins variable and constant regions
D=diversity region
C= constant domain

Front 80

What is each variable region preceded by?

Back 80

a signal sequence (Leader) that directs the synthesized protein into the ER

Front 81

Describe Lymphocyte Gene Rearrangement.

Back 81

-occurs in the immunoglobulin gene sequence during B Lymphocyte maturation
-occurs randomly between components of the variable domain

Front 82

What does Lymphocyte Gene Rearrangement allow?

Back 82

makes it possible for one lymphocyte to produce an antibody molecule that has a unique antigen binding specificity.

Front 83

Describe relationship between immunoglobulins made by one lymphocyte.

Back 83

All immunoglobulins made by one lymphocyte will come from the same rearranged genes and will therefore be the same.

Front 84

How many immunoglobulin light chain rearrangements occur?

Back 84

One immunoglobulin light chain rearrangement occurs between V and J components.

Front 85

What does immunoglobulin light chain rearrangement produce?

Back 85

immunoglobulin light chain rearrangement produces a single functional leader, the VJ Unit.

Front 86

Describe Light Chain Gene Rearrangement.

Back 86

-One immunoglobulin light chain rearrangement occurs between V and J components.
-immunoglobulin light chain rearrangement produces a single functional leader, the VJ Unit.
-a primary RNA transcript is made from the leader sequence through the constant domain sequence
-the primary RNA transcript is processed to produce mature mRNA consisting of a translatable LVJC Unit

Front 87

What is hematopoiesis?

Back 87

the formation of blood cells

Front 88

Describe Myeloid Tissue

Back 88

-bone marrow
-largest organ in the body
-exists as red or yellow marrow

Front 89

Describe Red Marrow Function

Back 89

actively forming blood cells

Front 90

Describe Yellow Marrow

Back 90

red marrow that has been largely replaced by fat

Front 91

Where does most blood cell sysnthesis occur?

Back 91

in the adult, most marrow synthesis of blood cells occurs in the flat bones and short bones

Front 92

Describe the marrow of long bones.

Back 92

the marrow of long bones is yellow (fatty) marrow.

Front 93

Myeloid Tissue Function

Back 93

-production of blood cells
-destruction of worn out RBC
-storage of iron from the breakdown of Hb (in macrophages)

Front 94

Describe bone marrow structure

Back 94

-stroma, a fiber meshwork containing hematopoietic cells and non-hematopoietic cells that support the process
-reticular fibers and associated reticular cells, specialized fibroblasts, are abundant
-the ECM contains collagen type I and III, glycoproteins and proteoglycans.
-laminin, fibronectin, and an additional cell binding molecule hemonectin are bound by cell surface receptors and bind cells to the matrix

Front 95

Describe the bone marrow ECM

Back 95

-the ECM contains collagen type I and III, glycoproteins and proteoglycans.
-laminin, fibronectin, and an additional cell binding molecule hemonectin are bound by cell surface receptors and bind cells to the matrix

Front 96

Describe fat cells in red marrow

Back 96

fat cells are scattered singly within the stroma of red marrow

Front 97

Describe fat cells in yellow marrow

Back 97

in yellow marrow fat cells are abundant and exclude most other marrow components.

Front 98

Describe blood vessels in myeloid tissue

Back 98

-large, tortuous sinusoids are characteristic of myeloid tissue
-sinusoids are lined externally by flattened reticular cells and monocytes
-the internal lining of the sinusoid is endothelium

Front 99

What is the internal lining of sinusoid?

Back 99

endothelium

Front 100

Describe Hemopoiesis

Back 100

-all BC have a shirt lifespan and must be continuously replaced
-all BC originate in the marrow and develop from a pluripotential (hematopoietic) stem cell
-the stem cells give rise to progenitor cells that are committed to a particular lineage

Front 101

Progenitor Cells Differentiate along which two pathways?

Back 101

1. lymphoid lineage
2. myeloid lineage

Front 102

Lymphoid Lineage gives rise to what?

Back 102

lymphocytes

Front 103

Myeloid Lineage give rise to what?

Back 103

granulocytes, monocytes, erythrocytes, and megakaryocytes

Front 104

Describe Hematopoietic Tissue

Back 104

-micorenvironment is very important; various classes of molecules include cell adhesion and signaling molecules to regulate this processes
-cytokine signaling molecules
-programmed cell death, apoptosis, is an important regulatory mechanism in BC populations

Front 105

Describe cytokine signaling molecules

Back 105

soluble molecules defined in cell culture as growth factors required for survival, proliferation, differentiation, and maturation.

Front 106

Describe Immunoglobulin Heavy Chain Rearrangement

Back 106

-two immunoglobulin heavy chain gene rearrangements occur in the variable domain sequence: one between D and J components and then one between V-DJ components
-produce a single functional leader; the VDJ unit
-a primary RNA sequence is made from the leader sequence through the constant domain sequence
-the primary RNA transcript is processed to produce a mature mRNA consisting of a translatable LVDJC unit

Front 107

Describe nucleotide base sequences in heavy chain genes.

Back 107

-nucleotide base sequence can be altered during and after immunoglobulin gene rearrangement
-processes exist that change the nucleotide sequences as the V(D) and J regions are joined during gene rearrangement
-this enhances variation in binding specificity between different antibodies

Front 108

Describe use of gene sequences in a given lymphocyte to produce heavy and light chains.

Back 108

-in one lymphocyte, the gene sequence of only one homologue each is used to produce the heavy and light polypeptide chains
-only one gene sequence in the cell to produce the heavy chain and only one gene sequence in the cell is used to produce the light chain

Front 109

Describe the order and implications of light chain gene rearrangement.

Back 109

-the K light gene sequence is rearranged before the lambda sequence
-productive rearrangement in one allele prevents any further rearrangement

Front 110

Describe implications of non-productive rearrangements events

Back 110

-a lymphocyte will die by apoptosis if all alleles are used without productive rearrangement.
-some rearrangement events are non-productive

Front 111

How can additional immunoglobulin variation be introduced?

Back 111

-additional variation can be introduced into the immunoglobulin gene sequence following gene rearrangement
-in some species, most immunoglobulin gene diversification occurs after gene rearrangement, eg: birds, rabbits, cows, pigs, sheep, and horses