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73 Cards in this Set

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give several properties that distinguish B-1 cells from B-2 cells?
activation?
memory?
other?
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,
Individual B1 cells are?
1) polyspecific for antigen;
2) They produce primarily antibodies of the IgM isotype.
3) B1 cells are unable to switch isotype
polyspecific for antigen?
1) their Ig will bind to a number of different antigens
How are B2 cells activated later in immune responses?
1) owing to the requirement for for Tcell help and antigen processing
individual B2 cells are?
1) monospecificc for antigen. In addition,
2) isotype switching
Isotype switching?
involves?
1) B2 cells
2) can express different isotypes of antibodies through the process of isotype switching,
3) which involves Tcell help
Describe the chemical composition of the antigen recognized by B-1 cells?
1) bacterial polysaccharides and
2) other carbohydrate antigens
what are the antigens recognized by B-1 cells categorized as?
1) T-independent (TI-2) antigens?
explain why these antigens recognized by B-1 cells are categorized as T-independent (TI-2) antigens?
1) Helper tcells recognize protein antigens,
a) not carbohydrates
2) and therefore are unable to provide help for B1 cells
Do you think that B-1 cells should be categorized as participants in innate immune responses or acquired immune responses?
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.
anergic Bcells cannot?
1) Enter secondary lymphoid follicles
role in?
1) eliminating B cells that have antigen receptors specific for soluble self antigen
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?
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
in order to survive, circulating B cells are required to ?
1) enter primary follicles
within primary follicles B cells receive?
1) survival signals delivered by cells in the follicles
Cells within the follicles that deliver survival signals include?
follicular denritic cells
follicular denritic ?
1) which are the stromal cells of primary lymphoid follicles.
circulating B cells that fail to enter follicles in secondary lymphoid tissues ?
1) will die in the peripheral circulation
a) with a half life of about 2 days.
Anergic Bcells that enter secondary lymphoid organs are withheld ?
1) in the Tcell areas adjacent to primary follicle
a) and are thus not permitted to penetrate the primary follicle
Why are Anergic Bcells held within the Tcell area?
1) due to the lack of Tcells that are specific for the same soluble self antigen in the Tcell zone
Why is there a lack of Tcells that are specific for the same soluble self antigen in the Tcell zone?
1) the Tcells would have been deleted in the thymus
What is the result of anergic Bcells being held within the Tcell area?
and instead?
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.
Anergic cells > apoptosis?
1) This is an efficient clensing mechanism and serves to delete potentially autoreactive B cells from the circulation
identify properties that are shared by anergic B cells and plasma cells
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.
what key property is different between anergic B cells and plasma cells?
1) Anergic B cells do not secrete antibody.
2) Plasma cells, in contrast, secrete very large amounts of antibody
Explain why immunological memory is important in acquired immunity
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.
Describe how Ig expressed during a primary immune response differs qualitatively and quantitatively from the Ig expressed during a secondary immune response.
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.
How do Ig expressed during a secondary immune response have higher affinity for its corresponding antigen?
1) through the process of somatic hypermutation
what ensures that only one Hchain locus and one L chain locus produce fnxal gene products
1) allelic exclusion
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
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.
surrogate L-chain
1) VpreB/\5, Iga and IgB
the formation of a complex of a u H-chain complexed with the surrogate L-chain delivers an
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.
cessation of Hchain gene rarrangement and inactivation of surrogate light chain synthesis results in?
1) only one heavy chain locus ends up producing a product.
As surrogate light chain b/c unavailable,
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.
a complete B cell receptor comprising
1) u heavy chains,
2) k or /\light chains,
3) and Iga and IgB chains
cessation of light chain rearrangement.
1) Thus only one light chain locus out of the possible four produces a fnxal produc
TdT
1) terminal deoxynucleotidyl transferase
what would be the consequence if TdT was expressed throughout the whole of small pre-B cell development?
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.
b/c TdT is not expressed until after birth, B1 cells that are generated prenatally
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.
Discuss the importance of the bone marrow stroma for Bcell development?
1) Bone marrow stromal cells provide the necessary environment for B cell development
a) by expressing secreted products and membrane bound adhesion molecules
How do Bone marrow stromal cells provide the necessary environment for B cell development ?
1) by expressing secreted products and membrane bound adhesion molecules.
Give examples of secreted products and membrane bound adhesion molecules?
1) VCAM-1 adhesion molecules
2) Cytokines such as IL-7.
VCAM-1 adhesion molecules?
1) binds to the integrin VLA-4 on early B cell progenitors
Cytokines such as IL-7 play an important role in?
1) later stages of B-cell development,
a) serving to stimulate growth and cell division of late proB and preBcells.
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?
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
In transgenic mice over expressing IL-7?
1) significant increases in pre-B cells are observed in the bone marrow and secondary lymphoid organs
IL-7 knockout mice?
1) where the IL-7 gene locus is interrupted and no IL-7 is produced
while in IL-7 knockout mice?
a) early Bcell expansion is significantly impaired.
These experiments in mice demonstrate clearly?
1) the importance of IL-7 in B cell maturation
B cell tumors originate ?
1) during different developmental stages of B cells
When do B cell tumors originate?
1) during their maturation in the bone marrow or
2) following maturation and export to the periphery
Explain why B cells isolated from a particular B cell tumor all express the same Ig?
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.
the B cell has rearranged the H and L chain genes prior to transformation?
a) then Ig will be expressed at the cell surface.
Because all of the cells in the tumor belong to the same clone, ?
1) the Ig on all of them will be made of the same H and L chains
preB cell leukemia is characterized by?
1) transformation prior to the rearrangement of light chain genes.
How might the Ig expressed on pre-B cell leukemia cells be different from that expressed on immature B cells?
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.
When transformation occurs at the small pre-B cell stage, why is there little or no Ig on the cell surface ?
1) b/c the u H-chains are retained in the ER
multiple myeloma involves?
the unregulated proliferation of an antibody-producing plasma cell (myeloma cell) independent of antigen stimulation or Tcell help,
myeloma cells populate ?
produce?
1) multiple sites in the bone marrow
2) where they produce immense quantities of monoclonal Ig
a) as well as suppressing normal marrow function.
Myeloma cells also synthesize and secrete ?
1) excessive amounts Bence-Jones protein
Bence-Jones protein?
1) free light chains
2) which, are excreted as free light chains in the urine
Why are Bence-Jones proteins secreted as free light chains in the urine?
1) because of their low molecular weight (~25kDa)
in a given patient the free light chains are both monoclonal, and all of either, the k or /\type.?
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.
Normally Lchain specificity is polyclonal b/c ?
1) a diverse array of plasma cells produce different light chains.
In multiple myeloma, the tumor originates ?
1) from a single plasma cell expressing heavy and light chains with specificity for a single antigen (clonotypic Ig).
The tumor in B cells express ?
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.
Why do you think patients with multiple myelomas are more susceptible to pyogenic infections, ?
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
patients will have elevated Ig levels?
1) usually IgG or IgA
Pyogenic infections caused by ?
1) encapsulated bacteria
Pyogenic infections require ___ immune response?
1) require humoral immune responses
a) involving mechanisms that utilize
(i) antibody-mediated complement activation and
(ii) phagocytosis.
Because pyogenic infections require humoral immune response, Insufficient?
1) polyclonal Igs put these patients at risk.
Give examples of pyogneic infections?
1) pneumonia caused by
a) streptococcus pneumoniae or
b) haemophilus influenzae