Chapter 4 Questions

Front 1

X

Back 1

X

Front 2

give several properties that distinguish B-1 cells from B-2 cells?
activation?
memory?
other?

Back 2

1) B1 cells
a) activated early during an immune response,
b) do not produce immunological memory and
c) do not carry out affinity maturation.
2) B2 cells are
a) activated later in immune responses
b) give rise to immunological memory and
c) carry out somatic hypermutation,

Front 3

Individual B1 cells are?

Back 3

1) polyspecific for antigen;
2) They produce primarily antibodies of the IgM isotype.
3) B1 cells are unable to switch isotype

Front 4

polyspecific for antigen?

Back 4

1) their Ig will bind to a number of different antigens

Front 5

How are B2 cells activated later in immune responses?

Back 5

1) owing to the requirement for for Tcell help and antigen processing

Front 6

individual B2 cells are?

Back 6

1) monospecificc for antigen. In addition,
2) isotype switching

Front 7

Isotype switching?
involves?

Back 7

1) B2 cells
2) can express different isotypes of antibodies through the process of isotype switching,
3) which involves Tcell help

Front 8

Describe the chemical composition of the antigen recognized by B-1 cells?

Back 8

1) bacterial polysaccharides and
2) other carbohydrate antigens

Front 9

what are the antigens recognized by B-1 cells categorized as?

Back 9

1) T-independent (TI-2) antigens?

Front 10

explain why these antigens recognized by B-1 cells are categorized as T-independent (TI-2) antigens?

Back 10

1) Helper tcells recognize protein antigens,
a) not carbohydrates
2) and therefore are unable to provide help for B1 cells

Front 11

Do you think that B-1 cells should be categorized as participants in innate immune responses or acquired immune responses?

Back 11

1) B1 cells are probably best associated with innate immune responses
a) because of their
(i) rapid response to antigen,
(ii) limited diversity,
(iii) lack of memory and
(iv) polyspecificity.

Front 12

anergic Bcells cannot?

Back 12

1) Enter secondary lymphoid follicles

Front 13

role in?

Back 13

1) eliminating B cells that have antigen receptors specific for soluble self antigen

Front 14

explain how the inability of anergic B cells to enter secondary lymphoid follicles plays a role in eliminating B cells that have antigen receptors specific for soluble self-antigen?

Back 14

1) circulating B cells are required to enter primary follicles
a) > receive survival signals
2) Failure > death in peripheral circ.
3) Anergic Bcells that enter secondary lymphoid organs > in the Tcell areas
a) Not permitted to penetrate the primary follicle.
(i) fail to receive signal
(a) Cannot proceed to the primary follicle > Apoptosis

Front 15

in order to survive, circulating B cells are required to ?

Back 15

1) enter primary follicles

Front 16

within primary follicles B cells receive?

Back 16

1) survival signals delivered by cells in the follicles

Front 17

Cells within the follicles that deliver survival signals include?

Back 17

follicular denritic cells

Front 18

follicular denritic ?

Back 18

1) which are the stromal cells of primary lymphoid follicles.

Front 19

circulating B cells that fail to enter follicles in secondary lymphoid tissues ?

Back 19

1) will die in the peripheral circulation
a) with a half life of about 2 days.

Front 20

Anergic Bcells that enter secondary lymphoid organs are withheld ?

Back 20

1) in the Tcell areas adjacent to primary follicle
a) and are thus not permitted to penetrate the primary follicle

Front 21

Why are Anergic Bcells held within the Tcell area?

Back 21

1) due to the lack of Tcells that are specific for the same soluble self antigen in the Tcell zone

Front 22

Why is there a lack of Tcells that are specific for the same soluble self antigen in the Tcell zone?

Back 22

1) the Tcells would have been deleted in the thymus

Front 23

What is the result of anergic Bcells being held within the Tcell area?
and instead?

Back 23

1) they fail to receive the necessary stimulatory signal for survival and
a) permission to proceed to the primary follicle is denied,
2) instead, anergic B cells will undergo apop, In the Tcell zone.

Front 24

Anergic cells > apoptosis?

Back 24

1) This is an efficient clensing mechanism and serves to delete potentially autoreactive B cells from the circulation

Front 25

identify properties that are shared by anergic B cells and plasma cells

Back 25

1) they both have limited life spans,
2) express decreased levels of IgM on the cell surface and
3) are nonresponsive to antigen and T-cell help.

Front 26

what key property is different between anergic B cells and plasma cells?

Back 26

1) Anergic B cells do not secrete antibody.
2) Plasma cells, in contrast, secrete very large amounts of antibody

Front 27

Explain why immunological memory is important in acquired immunity

Back 27

1) Memory enables faster, more efficient recall responses when antigen is encountered subsequently.
2) enables the body to get rid a pathogen before it has time to cause disease.

Front 28

Describe how Ig expressed during a primary immune response differs qualitatively and quantitatively from the Ig expressed during a secondary immune response.

Back 28

1) Ig produced during a primary immune response
a) is primarily IgM,
b) in low concentration (titer) and
c) of low affinity for the antigen.
2) Ig expressed during a secondary immune response
a) has undergone isotype switching and
b) often of the IgG isotype.
c) It also has a higher titer and,
d) higher affinity for its corresponding antigen.

Front 29

How do Ig expressed during a secondary immune response have higher affinity for its corresponding antigen?

Back 29

1) through the process of somatic hypermutation

Front 30

what ensures that only one Hchain locus and one L chain locus produce fnxal gene products

Back 30

1) allelic exclusion

Front 31

explain how the two checkpoints in B-cell development correlate with the process of allelic exclusion which ensures that only one H-chain locus and one L-chain locus produce functional gene products

Back 31

1) checkpoint 1 is the formation
a) of a complex of a u H-chain complexed with the surrogate L-chain
b) Thus, only one heavy chain locus ends up producing a product.
2) Checkpoint 2 is when a complete B cell receptor, is expressed on the B cell surface.
a) This signals cessation of light chain rearrangement.

Front 32

surrogate L-chain

Back 32

1) VpreB/\5, Iga and IgB

Front 33

the formation of a complex of a u H-chain complexed with the surrogate L-chain delivers an

Back 33

1) important signal to the cell verifying that a functional H-chain has been made.
a) It triggers cessation of H-chain gene rearrangement
(i) followed by inactivation of surrogate light chain synthesis.

Front 34

cessation of Hchain gene rarrangement and inactivation of surrogate light chain synthesis results in?

Back 34

1) only one heavy chain locus ends up producing a product.

Front 35

As surrogate light chain b/c unavailable,

Back 35

1) u accumulates and is retained in the ER,
a) ready to bind to functional light chain when that is synthesized following successful light chain gene rearrangement.

Front 36

a complete B cell receptor comprising

Back 36

1) u heavy chains,
2) k or /\light chains,
3) and Iga and IgB chains

Front 37

cessation of light chain rearrangement.

Back 37

1) Thus only one light chain locus out of the possible four produces a fnxal produc

Front 38

TdT

Back 38

1) terminal deoxynucleotidyl transferase

Front 39

what would be the consequence if TdT was expressed throughout the whole of small pre-B cell development?

Back 39

1) N nucleotides would be added at the VJ joints of all rearranged light chain genes during gene rearrangement (instead of about half).
a) Resulting in an increase in Ig diversity.

Front 40

b/c TdT is not expressed until after birth, B1 cells that are generated prenatally

Back 40

1) lack N nucleotides in the VD and DJ junctions of their rearranged H chain genes
a) as well as in the VJ junctions of all light chain genes.

Front 41

Discuss the importance of the bone marrow stroma for Bcell development?

Back 41

1) Bone marrow stromal cells provide the necessary environment for B cell development
a) by expressing secreted products and membrane bound adhesion molecules

Front 42

How do Bone marrow stromal cells provide the necessary environment for B cell development ?

Back 42

1) by expressing secreted products and membrane bound adhesion molecules.

Front 43

Give examples of secreted products and membrane bound adhesion molecules?

Back 43

1) VCAM-1 adhesion molecules
2) Cytokines such as IL-7.

Front 44

VCAM-1 adhesion molecules?

Back 44

1) binds to the integrin VLA-4 on early B cell progenitors

Front 45

Cytokines such as IL-7 play an important role in?

Back 45

1) later stages of B-cell development,
a) serving to stimulate growth and cell division of late proB and preBcells.

Front 46

What would be the effect of Anti-IL-7 antibodies on the development of B cells in the bone marrow
and at which stage would development be impaired?

Back 46

1) developing B cells would be arrested
a) at the late pro-B or pre-B cell stage
(i) and would not be able to progress normally to the immature Bcell stage

Front 47

In transgenic mice over expressing IL-7?

Back 47

1) significant increases in pre-B cells are observed in the bone marrow and secondary lymphoid organs

Front 48

IL-7 knockout mice?

Back 48

1) where the IL-7 gene locus is interrupted and no IL-7 is produced

Front 49

while in IL-7 knockout mice?

Back 49

a) early Bcell expansion is significantly impaired.

Front 50

These experiments in mice demonstrate clearly?

Back 50

1) the importance of IL-7 in B cell maturation

Front 51

B cell tumors originate ?

Back 51

1) during different developmental stages of B cells

Front 52

When do B cell tumors originate?

Back 52

1) during their maturation in the bone marrow or
2) following maturation and export to the periphery

Front 53

Explain why B cells isolated from a particular B cell tumor all express the same Ig?

Back 53

a) A B-cell tumor comprises cells that derive from a single cell that has undergone transformation that results in uncontrolled growth.
b) No further maturation of the B cell occurs following transformation.

Front 54

the B cell has rearranged the H and L chain genes prior to transformation?

Back 54

a) then Ig will be expressed at the cell surface.

Front 55

Because all of the cells in the tumor belong to the same clone, ?

Back 55

1) the Ig on all of them will be made of the same H and L chains

Front 56

preB cell leukemia is characterized by?

Back 56

1) transformation prior to the rearrangement of light chain genes.

Front 57

How might the Ig expressed on pre-B cell leukemia cells be different from that expressed on immature B cells?

Back 57

a) If transformation occurs at the large pre-B cell stage,
(i) then the Ig on the cell surface will be composed of u:VpreB5.
b) if transformation occurs at the small pre-B cell stage,
(i) then there would be little or no Ig on the cell surface
c) Normal immature B cells that have not undergone transformation
(i) express IgM containing u plus a k- or /\- L-chain.

Front 58

When transformation occurs at the small pre-B cell stage, why is there little or no Ig on the cell surface ?

Back 58

1) b/c the u H-chains are retained in the ER

Front 59

multiple myeloma involves?

Back 59

the unregulated proliferation of an antibody-producing plasma cell (myeloma cell) independent of antigen stimulation or Tcell help,

Front 60

myeloma cells populate ?
produce?

Back 60

1) multiple sites in the bone marrow
2) where they produce immense quantities of monoclonal Ig
a) as well as suppressing normal marrow function.

Front 61

Myeloma cells also synthesize and secrete ?

Back 61

1) excessive amounts Bence-Jones protein

Front 62

Bence-Jones protein?

Back 62

1) free light chains
2) which, are excreted as free light chains in the urine

Front 63

Why are Bence-Jones proteins secreted as free light chains in the urine?

Back 63

1) because of their low molecular weight (~25kDa)

Front 64

in a given patient the free light chains are both monoclonal, and all of either, the k or /\type.?

Back 64

1) Explain both of these observations
a) Normally Lchain specificity is polyclonal
b) In multiple myeloma,
(i) clonotypic Ig
c) Because B cells the tumor will only kappa or lambda, but not both.
d) Therefore, Bence-Jones protein for a given patient will be of one type or another not both.

Front 65

Normally Lchain specificity is polyclonal b/c ?

Back 65

1) a diverse array of plasma cells produce different light chains.

Front 66

In multiple myeloma, the tumor originates ?

Back 66

1) from a single plasma cell expressing heavy and light chains with specificity for a single antigen (clonotypic Ig).

Front 67

The tumor in B cells express ?

Back 67

1) b/c Bcells only kappa or lambda light chains,
a) the tumor will also express only kappa or lambda, but not both.
b) Therefore, Bence-Jones protein for a given patient will be of one type or another not both.

Front 68

Why do you think patients with multiple myelomas are more susceptible to pyogenic infections, ?

Back 68

1) Although patients will have elevated Ig levels,
2) most will be produced by the myeloma cells and will be monospecific.
3) Hence, normal concentrations of polyclonal Ig will be severely compromised

Front 69

patients will have elevated Ig levels?

Back 69

1) usually IgG or IgA

Front 70

Pyogenic infections caused by ?

Back 70

1) encapsulated bacteria

Front 71

Pyogenic infections require ___ immune response?

Back 71

1) require humoral immune responses
a) involving mechanisms that utilize
(i) antibody-mediated complement activation and
(ii) phagocytosis.

Front 72

Because pyogenic infections require humoral immune response, Insufficient?

Back 72

1) polyclonal Igs put these patients at risk.

Front 73

Give examples of pyogneic infections?

Back 73

1) pneumonia caused by
a) streptococcus pneumoniae or
b) haemophilus influenzae