PCB4233 Immunology Exam 4
What cytokines are required for survival of B cells in secondary lymphoid tissue?
- CORRECT ANSWER-Require CD40/CD40L interactions between B/T
cellsCytokines from FDCs and TFH cells stimulate proliferation further
When are the different Immunoglobulin isotypes produced during an immune
response and how do they differ? - CORRECT ANSWER-Plasma cells are Ig-
producing machines:
Surface Ig is near zero, but secreted Ig values are high
Found within first 5-6 days of immune responses in medullary cord regions of
lymph nodes
What occurs in the germinal center? - CORRECT ANSWER-Somatic
hypermutation (SHM)/affinity selection occur within the germinal center; Class
switch recombination (CSR) occurs within the GC after antigen contact
SHM (Somatic hypermutation) - CORRECT ANSWER--SHM produces individual
point mutations in Ig heavy- and light-chain rearrangements:
Mutations increase over time and with repeated exposures
Followed by affinity selection result in increased affinity for Ag over time
-AID-mediated somatic hypermutation:
Activation-induced cytidine deaminase
Produces opportunity for mutation by altering deoxycytidine bases
-Mutational apparatus targeting:
Mutational hot spots are sequence motifs far more likely to be targeted
Include DGYW/WRCH sequence motif
This prevents mutations in non-Ig areas
-Ag-induced selection of B cells with higher affinity:
B cells that can bind, process, and present more Ag to T cells for cytokine
assistance survive
Higher-affinity B cells may actually steal Ag from lower-affinity B cells, promoting
their own survival signals
class switching mechanism - CORRECT ANSWER--AID initiates CSR processes
(just as in SHM) by deaminating C bases in single-strand DNA dislocated by
germ-line transcripts
-DNA uridine glycosylase removes the U base created by AID
-Endonucleases nick the DNA backbone at the abasic sites at multiple points
-Mismatch repair enzymes convert single-strand breaks into double-strand
breaks
-Double-strand break repair machinery repairs the breaks by cutting out the
intervening DNA
, What is AID; what does it do; what does it convert cytosine into? - CORRECT
ANSWER-Activation-induced cytidine deaminase
Produces opportunity for mutation by altering deoxycytidine bases
What mechanisms of mutagenesis does AID employ (CG-> TA transition; Base
excision repair; Mismatch repair followed by error-prone DNA polymerase fill-in
of the gap created)? - CORRECT ANSWER-
Describe class switching and how it effects Ig Isotype expression and what
possible isotypes can be expressed after class switching occurs. Can B cells
undergo class switching more than once and what possible Ig Isotypes can
result? - CORRECT ANSWER--Recombination occurs between donor and
acceptor switch (S) regions:
Tandem repeats of short, G-rich sequences 20-80 bp long
Contain targeting sites for AID
-B cells must receive costimulatory signals from CD40 to engage in CSR
-Which cytokine signal is received determines which isotype will be produced:
Cytokines stimulate transcription of sterile RNAs from germ-line promoters
This sterile RNA is critical to CSR activity
What are the different types of B-cell responses and what antigens induce them?
- CORRECT ANSWER-For example B cell types (TI-1, TI-2, TD) and antigen
(Soluble Protein antigens, Bacterial Cell wall components, Capsular
polysaccharides). Remember TI (T cell independent), TD (T cell dependent)
T-dependent responses require help from T cells: Are typically generated upon
recognition of protein Ag
T-independent responses do not require T-cell help: Generated upon exposure to
multivalent/polymerized Ag- TI-1 Ag bind to B cells through PRRs and mIgs or TI-
2 Ag cross-link large numbers of BCRs
What receptors on T cells help activate B cells? - CORRECT ANSWER-CD40L on
T cells; CD40 B cells
B-cells bind Ag via BCR
Name the chemokines that B cells follow as they become activated and migrate
through secondary lymphoid tissue. - CORRECT ANSWER-CXCR5 receptor binds
to CXCL13 expressed by FCDs in the B-cell follicles (cortical region of the
secondary lymphoid tissue).
Upon finding antigen CCR7 receptor binds to CCL19 and CCL21 secreted by
stromal cells in the T-cell zones and the B cell moves in the boundary between
the B-cell and T-cell zones.
What transcription factors are essential for plasma cell formation or germinal
center generation? - CORRECT ANSWER-BLIMP-1; Bcl-6; Pax-5
What cytokines are required for survival of B cells in secondary lymphoid tissue?
- CORRECT ANSWER-Require CD40/CD40L interactions between B/T
cellsCytokines from FDCs and TFH cells stimulate proliferation further
When are the different Immunoglobulin isotypes produced during an immune
response and how do they differ? - CORRECT ANSWER-Plasma cells are Ig-
producing machines:
Surface Ig is near zero, but secreted Ig values are high
Found within first 5-6 days of immune responses in medullary cord regions of
lymph nodes
What occurs in the germinal center? - CORRECT ANSWER-Somatic
hypermutation (SHM)/affinity selection occur within the germinal center; Class
switch recombination (CSR) occurs within the GC after antigen contact
SHM (Somatic hypermutation) - CORRECT ANSWER--SHM produces individual
point mutations in Ig heavy- and light-chain rearrangements:
Mutations increase over time and with repeated exposures
Followed by affinity selection result in increased affinity for Ag over time
-AID-mediated somatic hypermutation:
Activation-induced cytidine deaminase
Produces opportunity for mutation by altering deoxycytidine bases
-Mutational apparatus targeting:
Mutational hot spots are sequence motifs far more likely to be targeted
Include DGYW/WRCH sequence motif
This prevents mutations in non-Ig areas
-Ag-induced selection of B cells with higher affinity:
B cells that can bind, process, and present more Ag to T cells for cytokine
assistance survive
Higher-affinity B cells may actually steal Ag from lower-affinity B cells, promoting
their own survival signals
class switching mechanism - CORRECT ANSWER--AID initiates CSR processes
(just as in SHM) by deaminating C bases in single-strand DNA dislocated by
germ-line transcripts
-DNA uridine glycosylase removes the U base created by AID
-Endonucleases nick the DNA backbone at the abasic sites at multiple points
-Mismatch repair enzymes convert single-strand breaks into double-strand
breaks
-Double-strand break repair machinery repairs the breaks by cutting out the
intervening DNA
, What is AID; what does it do; what does it convert cytosine into? - CORRECT
ANSWER-Activation-induced cytidine deaminase
Produces opportunity for mutation by altering deoxycytidine bases
What mechanisms of mutagenesis does AID employ (CG-> TA transition; Base
excision repair; Mismatch repair followed by error-prone DNA polymerase fill-in
of the gap created)? - CORRECT ANSWER-
Describe class switching and how it effects Ig Isotype expression and what
possible isotypes can be expressed after class switching occurs. Can B cells
undergo class switching more than once and what possible Ig Isotypes can
result? - CORRECT ANSWER--Recombination occurs between donor and
acceptor switch (S) regions:
Tandem repeats of short, G-rich sequences 20-80 bp long
Contain targeting sites for AID
-B cells must receive costimulatory signals from CD40 to engage in CSR
-Which cytokine signal is received determines which isotype will be produced:
Cytokines stimulate transcription of sterile RNAs from germ-line promoters
This sterile RNA is critical to CSR activity
What are the different types of B-cell responses and what antigens induce them?
- CORRECT ANSWER-For example B cell types (TI-1, TI-2, TD) and antigen
(Soluble Protein antigens, Bacterial Cell wall components, Capsular
polysaccharides). Remember TI (T cell independent), TD (T cell dependent)
T-dependent responses require help from T cells: Are typically generated upon
recognition of protein Ag
T-independent responses do not require T-cell help: Generated upon exposure to
multivalent/polymerized Ag- TI-1 Ag bind to B cells through PRRs and mIgs or TI-
2 Ag cross-link large numbers of BCRs
What receptors on T cells help activate B cells? - CORRECT ANSWER-CD40L on
T cells; CD40 B cells
B-cells bind Ag via BCR
Name the chemokines that B cells follow as they become activated and migrate
through secondary lymphoid tissue. - CORRECT ANSWER-CXCR5 receptor binds
to CXCL13 expressed by FCDs in the B-cell follicles (cortical region of the
secondary lymphoid tissue).
Upon finding antigen CCR7 receptor binds to CCL19 and CCL21 secreted by
stromal cells in the T-cell zones and the B cell moves in the boundary between
the B-cell and T-cell zones.
What transcription factors are essential for plasma cell formation or germinal
center generation? - CORRECT ANSWER-BLIMP-1; Bcl-6; Pax-5
