Immuno test 3 (4&6)
μ heavy chains made by late pro-B cells ___________________
are expressed on the cell surface with polypeptides that take the place of the light chain
Identify the correct pairing of recombination signal sequences (RSSs) during somatic recombination at a light-chain locus.
(V) 7-23-9: 9-12-7 (J)
The isotypes of immunoglobulin heavy-chains...
- are gamme, alpha, mu, epsilon, delta - carry out different functions in the immune response
monomeric IgM: monomeric IgA: secreted IgD: pentameric IgM: dimeric IgA: IgG1:
-monomeric IgM: naive B-cell surfaces -monomeric IgA: bloodstream -secreted IgD: upper respiratory tract -pentameric IgM: no hinge region -dimeric IgA: mucosal surfaces IgG1: most abundant antibody in serum
IgA:
-opsonin -complement activation -most abundant in mucosal secretions -more made in body than any other antibody
IgG:
-opsonin -complement activation -most abundant in serum -sensitization of mast cells -sensitization of NK cells -most abundant in body -transport across placenta
IgE:
-sensitization of mast cells -sensitization of basophils
the 6 phases of B cell development in order:
1) repertoire assembly 2) - selection 3) + selection 4) searching for infection 5) finding infection 6) attacking infection
The endosteum is a region of the bone marrow where __________ a) immature B cells are exported to the circulation b) small pre-b cells initiate the rearrangement of light-chain genes c) a high proportion of hematopoietic stem cells reside d) late pro-b cells accumulate while completeing rearrangement of heavy-chain genes
c) a high proportion of hematopoietic stem cells reside
An immunoglobulin domain that exhibits little or no sequence diversity within a given class of antibody is referred to as a(n) _____ domain. a) antigen binding b) variable c) constant d) k
c) constant
The _____ flank the short regions of highly diverse amino acids within the variable region of immunoglobulins. a) HV region b) constant region c) framework regions
c) framework regions
The first checkpoint in B-cell development that tests the quality of the μ chain occurs at the _____ stage. a) large pre-b-cell b) early pro-b-cell c) late pro-b-cell d) small pre-b-cell
c) late pro-b-cell
Once a developing B cell reaches the _____ stage, it is irreversibly committed to the B-cell lineage. a) immature b cell b) pre-b cell c) pro-b cell d) pluripotent hematopoietic stem cells
c) pro-b cell
B cells complete their maturation ______________. a) blood stream b) bone marrow c) 2nd lymphoid tissues
c) secondary lymphoid tissue
What is the name given to the specialized cell type that helps to form the supporting framework required for B-cell development? a) hematopoietic cell b) secondary lymphoid cell c) stromal cell
c) stromal cell
Which of the following does not contribute to generating the diversity of antigen-binding specificities among immuno- globulins? a. somatic hypermutation b. random combination of heavy and light chains c. somatic recombination d. activation-induced cytidine deaminase (AID) e. alternative splicing of heavy-chain RNA transcripts.
e. alternative splicing of heavy-chain RNA transcripts.
SCF:
growth factor made by stromal cells that binds to the Kit receptor on maturing B cells during the pro-B-cell stage
In V(D)J recombination, immediately following cleavage of the DNA at the junctions of gene segments and adjacent recombination signal sequences (RSSs), _____ is (are) formed at the ends of the gene segments, and _____ is (are) formed at the ends of RSSs.
hairpin; double-strand breaks
Which of the following represents the chronological order in which immunoglobulin genes rearrange?
heavy chain -> k chain -> lamda chain
What name is given to a cell that is produced by fusing an antibody-producing B lymphocyte with a tumor cell?
hybridoma
Membrane-associated immunoglobulin has a _____ while secreted antibody has a _____.
hydrophobic anchor sequence; hydrophilic carboxy terminus
What must antibodies undergo in order to acquire effector functions other than those associated with IgM or IgD?
isotype switching
A _____ antigen is one that has many epitopes; the epitopes can be either identical or different.
multivalent
antibody that attaches to a pathogen and prevents its growth or entry into cells
neutralizing antibody
A given B cell expresses _____ of the light-chain loci.
one
molecule that coats a pathogen and stimulates phagocytosis by cells bearing receptors for that molecule
opsonin
cleavage by________ releases 2 Fab fragments and 1 Fc fragment
papain
cleavage by _________ just below the disulfide bonds leaving them intact and releasing one divalent Fab fragment and degrading the Fc into multiple fragments
pepsin
During isotype switching the antigen binding site is ______.
preserved
In the synthesis of a membrane-associated immunoglobulin heavy chain, which of the following sequences of events is correct?
rearranged DNA -> primary RNA transcript -> mRNA -> protein
Assume that an early pro-B cell has productively rearranged D to J segments on both chromosomes. If there is then a nonproductive V-DJ rearrangement of the heavy-chain locus on the first chromosome _______________________.
rearrangement of V-DJ occurs on the 2nd chromosome
_____ is the process that occurs in activated B cells that increases the diversity of V-domain coding sequences.
somatic hypermutation
The DNA recombination process that produces diversity in the antigen-binding sites of immunoglobulins is called ___________.
somatic recombination
Which term refers to the mRNA generated from transcription that initiates at an I-region promoter found upstream of each switch region?
sterile-transcript
Which term refers to the molecule that holds multiple molecules of IgM and IgA together?
the J chain
The hinge region of immunoglobulin G (IgG) ______________________________.
varies between subclasses, is linked by disulfide bonds, helps with antigen binding due to its flexibility.
Following cell division of large pre-B cells _______________.
μ chains are synthesized but are no longer transported to the cell surface
If an individual lacked functional AID:
-The individual's B cells would produce primarily IgM antibodies -The individual's B cells would not be able to mediate isotype switching
IgD:
-sensitization of basophils
identify the mismatched pair 1) secreted antibody: soluble effector molecules 2) IgD: protects respiratory tract and bacterial infections 3) subsequent to antigen encounter; secreted IgM and IgD 4) naive B cell: membrane-bound IgM and IgD 5) plasma cells: production of membrane-bound immunoglobulins and secreted antibodies
5) plasma cells: production membrane-bound immunoglobulins and secreted antibodies
What terms are used to describe the structure on the antigen to which an antibody binds specifically? a) epitope b) HV loop C) CDR D) antigenic determinant
A) epitope D) antigenic determinant
All human hematopoietic stem cells express ____. a) CD19 B) CD34 C) CD10
B) CD34
identify the mismatched pair: a) monomerica IgA: bloodstream b) monomeric IgE: most abundant antibody in serum c) monomeric IgM: naive B-cell surfaces d) pentameric: IgM: no hinge regions e) dimeric IgA: mucosal surfaces f) secreted IgD: upper respiratory tract
B) monomeric IgE: most abundant antibody in serum --- IgG1 is the most abundant
Which of the following C genes resides closest to an assembled VDJ sequence?
C (mew)
Identify the mismatched pair: A) immunoglobulin: cell-surface antigen receptor B) antibody: secreted B-cell receptor C) agammaglobulinemia: inability to produce antibodies D) plasma cell: membrane-bound immunoglobulin E) plasma cell: differentiated B cell
D) plasma cell: membrane-bound immunoglobulin
A. Which of the IgG subclasses is most efficient at activating complement? B. Explain why. C. Which is least efficient and why?
Most: IgG3 Least: IgG4 Hinge region on IgG3 is the longest of all the IgG subclasses. Its length and flexibility make the IgG3 Fc region more accessible for binding C1 compared w/ other IgG molecules IgG4 fails to activate complement because its Fc region binds C1 poorly.
Which of the following is true of Igα and Igβ? a) bind to intracellular cytosolic protein b) enable immunoglobulins to translocate to the cell surface of B cells c) they facilitate signal transduction to ensure B cells divide and differentiate upon antigen encounter d) bind to antigen and transduce cytoplasmic signals e) linked to each other by hydrophobic forces
A/B/C
Which of the following statements regarding the process of differential splicing of primary RNA transcripts encoding immunoglobulins is incorrect? a. It does not require rearrangement of genomic DNA sequences. b. It underlies the production of both membrane-bound IgM and IgD in naive B cells. c. It is the mechanism involved in isotype switching. d. It occurs during B-cell differentiation into plasma cells when antibodies are produced in their secreted form. e. It permits the production of different types of protein originating from the same RNA transcript.
C) It is the mechanism involved in isotype switching.
Rituximab is a chimeric monoclonal antibody used to treat several malignant diseases. It exerts its effect by binding to _____ and targeting malignant cell destruction by _____.
CD20; NK cells
Sequence differences within light-chain V gene segments account for all the variation observed in _____ of the light-chain V domain in different antibodies.
CDR1 and CDR2
Which of the following is not a component of the V(D)J recombinase? A) RAG-1 and RAG-2 B) Ku C) Artemis D) DNA-dependent protein kinase E) a dimer composed of DNA Ligase plus XRCC4 F) all of these are apart of it
F) all of these are apart
T/F Somatic hypermutation results in the random introduction of point mutations in the variable and constant regions of heavy-chain and light-chain genes.
F; immunoglobulins constant regions are not affected by somatic hypermutation
If both D-J rearrangements are nonproductive, the early pro-B cell dies by apoptosis before V-DJ rearrangement occurs.
False
T/F? The purpose of negative selection of developing B cells is to remove useless B cells that express antigen receptors unable to interact with antigen.
False; - selection eliminates/inactivates B cells bearing immunoglobulins that have specificity for self antigens in order to avoid autoreactive immune responses and the attack of health cells and tissues
Allotypic differences
arise due to genetic variation or polymorphisms in the H- and L-chain constant regions between members of the same species
Idiotypic differences
arise when individual antibodies differ in their variable regions
The four subclasses of IgG exhibit considerable germline-encoded variation in the ______________________________. a) light-chain constant region b) hinge region of the heavy chain c) light-chain antigen-binding site d) antigen-binding provided by the heavy chain
b) hinge region of the heavy chains
What are monoclonal antibodies that contain CDR loops of mouse origin but human components elsewhere called?
Humanized monoclonal antibodies
The four IgG subclasses ranked in descending order of their respective proportions of total IgG (highest to lowest %) are ________________.
IgG1; IgG2; IgG3/4
Which of the following are present on the surface of naive B cells? IgG/A/M/E/D
IgM/D
The phenomenon of allelic exclusion ensures that B cells a. use only one V, D, and J segment during somatic recombination b. express only one type of heavy chain and one type of light chain c. do not undergo alternative splicing until cell proliferation commences d. do not secrete antibody until antigen is encountered e. carry out affinity maturation directed at heavy chains and not light chains f. derived from B-cell lymphomas are heterogeneous.
b. express only one type of heavy chain and one type of light chain
What are defects in genes encoding components of V(D)J recombinase other than the RAG complex associated with? - increased DNA damage on exposure to ioninzing radiation -increased numbers of B cells as a results of dysregulated cellular proliferation - retention of immunoglobulins in the ER
Increased DNA damage to exposure to ioninzing radiation
Which term refers to the molecule that holds multiple molecules of IgM and IgA together?
Joining (J) region
Humanized monoclonal antibodies are best described as a. antibodies made in mice in which the mouse antibody genes have been replaced with human equivalents b. human antibodies in which the CDR loops have been replaced by mouse-derived CDRs of the desired specificity c. antibodies made in culture by human hybridomas d. antibodies containing mouse Fab regions of both the heavy and light chain and human Fc regions e. antibodies containing human Fab regions of both the heavy and light chain and mouse Fc regions.
b. human antibodies in which the CDR loops have been replaced by mouse-derived CDRs of the desired specificity
T/F. The antigen-binding properties of immunoglobulins are different as a result of variation in the amino acid sequence of the loops of the V domains.
True
T/F? Isotype switching requires both linked recognition of an activated T follicular helper cell and a B cell (through the engagement of CD40 ligand [T cell] and CD40 [B cell]), and secretion of T-cell cytokines.
True
T/F? The only type of force involved in the binding of antigens to antibodies is noncovalent.
True
T/F? When making monoclonal antibodies, the plasma-cell-derived myeloma cell that is used for the fusion process does not express immunoglobulin heavy or light chains.
True; myeloma cells are tumors of plasma cells that have been purposely selected for their inability to synthesize heavy and light chains.
T/F? In the absence of allelic exclusion, B cells would produce low-avidity immunoglobulins.
Trueeeee
T/F? First-generation monoclonal antibodies were not monospecific.
Trueeeeee
A stage in B-cell development when the quality of the immunoglobulin chains arising from gene rearrangement is tested is called _______.
a checkpoint
A complete and functional immunoglobulin chain is made only if _______________________.
a correct reading frame in the variable region is produced
Which of the following IgG subclasses of antibody is paired correctly with its function? a) IgG3: activates complement the most effectively of all the IgG subclasses b) IgG4: intensifies allergic reactions 3) IgG2: has the longest hinge region of all the IgG subclasses 4) IgG1: circulates in a monovalent form
a) IgG3: activates complement the most effectively of all the IgG subclasses
Medical diagnosis of an immunodeficiency often involves the use of fluorescent antibodies specific for cell-surface proteins in order to distinguish particular cell types in a heterogeneous cell population moving in a stream. What is this technique is called? a) flow cytometry b) cell culture c) cell fusion d) fluorescence microscopy
a) flow cytometry
A gene rearrangement that fails to translate into a useful immunoglobulin is called a(n) _____ rearrangement, whereas a gene rearrangement that preserves a correct reading frame and translates into a functional immunoglobulin is called a _____ rearrangement. a) nonproductive; productive b) immature; mature c) early;late
a) nonproductive;productive
If the antigen used for immunization is multivalent, then the antiserum will contain _____, whereas the cell-culture supernatant of a hybridoma will contain _____. a) polyclonal antibodies; monoclonal antibodies b) purified antigen; unpurified antigen c) antibodies specific for multivalent antigens; antibodies specific for monovalent antigens d) antibodies specific for discontinuous epitopes; antibodies specific for linear epitopes
a) polyclonal antibodies; monoclonal antibodies
Which of the following statements regarding activation-induced cytidine deaminase (AID) is correct? a) somatic hypermutation cannot occur in the absence of AID b) AID is a universal enzyme involved in DNA repair c) AID acts on ssDNA/dsDNA d) AID converts cytidine to thymidine
a) somatic hypermutation cannot occur in the absence of AID
In reference to the production of membrane-bound immunoglobulin, which of the following is mismatched? a) somatic recomb; Iga and Igb b) hydrophobic sequence of immunoglobulin heavy chain; carboxy terminus c) Iga and Igb; transport immunoglobulins to the cell surface d) leader peptide of heavy and light chains: entry into the ER
a) somatic recomb; Iga and Igb
Which of the following descriptions of immunoglobulin domains are correct? a) they are arranged in a linear series b) they contain B sheets stabilized by disulfide bonds c) they are present in heavy chains but not light chains d) they need strong hydrophilic interactions between amino acids side chains to stabilize the domains
a) they are arranged in a linear series b) they contain B sheets stabilized by disulfide bonds
When IgG is cleaved with a protease that targets the hinge region, which of the following is generated? a. two Fab fragments and one Fc fragment b. two Fc fragments and two Fab fragments c. Fc fragments that bind antigen d. Fab fragments that facilitate antibody effector function e. a membrane-bound form of antibody.
a. two Fab fragments and one Fc fragment
Adalimumab is a(n) _____ monoclonal antibody
all human
A B cell expresses only one of its two copies of an immunoglobulin gene. What is this is called?
allelic exclusion
Which term refers to the property that each B cell expresses only one of the two immunoglobulin heavy-chain or light-chain alleles?
allelic exclusion
_____ is the mechanism by which B cells change production of immunoglobulins from a membrane-bound to a secreted form.
alternative mRNA splicing
Each arm of a Y-shaped antibody contains the _____ portion of a heavy chain, and the stem contains _____ portions of the two heavy chains
amino; carboxy
Affinity maturation results in ______________________________. a) conversion of naive B cells to differentiated plasma cells b) increased rates of transcription of immunoglobulin heavy and light chain genes c) production of antibodies that bind more strongly to their target antigen d) generation of additional CDR loops in the antigen binding sites of antibodies
c) the production of antibodies that target bind more strongly to their target antigen
Which of the following recombinations is not permitted during somatic recombination in the heavy-chain and light- chain immunoglobulin loci? (Select all correct answers.) a. DH:JH b. Vλ:Jλ c. Dκ:VH d. VH:JH e. VH:DH.
c. Dκ:VH d. VH:JH
A protein epitope formed as a result of three-dimensional folding of the protein, and which is destroyed if the protein denatures, is called a _______ epitope.
c. conformational
The antigen-binding site of an immunoglobulin is formed from: a. the V regions of light chains only b. the C regions of heavy chains only c. paired V regions of a single heavy chain and a single light chain d. paired V regions of two light chains e. paired C regions of two heavy chains
c. paired V regions of a single heavy chain and a single light chain
P and N nucleotides are introduced into the _____ during the recombination of immunoglobulin genes.
coding joint
The three hypervariable loops of each V domain that form the antigen-binding sites of antibody molecules are also known as ____________. a) framwork b) V domains c) Beta sheets d) CDRs
d) CDRs
In the context of the generation of junctional diversity during gene rearrangement, identify the mismatched pair. a) junctional diversity: P and N nucleotides b) exonuclease: removal of mismatched nucleotides c) CDR3: coding joint d) P nucleotides: TdT
d) P nucleotides: TdT --- adds N not P
Although the pre-B-cell receptor resembles the B-cell receptor, it differs by containing a surrogate light chain that is composed of ___________. a) Iga and Igb b) E2A and E2B c) only the variable region of k light chains d) VpreB and lamda5
d) VpreB and lamda5
Which of the following statements regarding antibodies is incorrect? a) basophils induce localized immune responses in the upper respiratory tract in response to IgD b) the Fabs and Fc of IgG molecules move partly independently of one another c) specialized functions of antibodies are dependent on effector properties restricted to particular isotypes d) different joining chains hold together dimeric IgA and pentameric IgM
d) different joining chains hold together dimeric IgA and pentameric IgM -- J chains are identical for IgA and pentameric IgM
The second checkpoint in B-cell development that tests the quality of the light chain occurs at the _____ stage. a) early pro b cell b) mature b cell c) immature b cell d) small pre b cell
d) small pre b cell
The numbered events listed below participate in the gen- eration of junctional diversity. Put them in chronological order. a. DNA strands pair, and unpaired nucleotides are removed by exonuclease activity. b. P-nucleotides are generated after nicking of one DNA strand. c. DNA polymerase fills in gaps, and DNA ligation forms a coding joint. d. The RAG complex cleaves heptamer RSSs, and DNA hairpins are formed. e. Terminal deoxynucleotidyl transferase adds N-nucleotides to the 3ʹ end of the stretch of P-nucleotides.
d.b.e.a.c
Which of the following is not associated with allelic exclusion of the heavy-chain locus in B cells?
deletion of one of the heavy-chain loci
What is the name given to the process that involves the production of two distinct RNA transcripts from the same primary transcript?
differential splicing
immunoglobulin domains contain beta sheets that are stabilized by
disulfide bonds
An advantage to using IgG4 as a therapeutic monoclonal antibody compared with other IgG subclasses is that it _____. A disadvantage is that it _____.
does not activate complement; is monovalent in circulation
