Exam 3 CH 4, 6, 9
If a breastfed baby is receiving IgA from its mother in breast milk, why are serum IgA levels low during the first year of life?
Maternal IgA remains in the digestive tract
What is the term for the three hypervariable regions of each V domain that form the antigen-binding sites of antibody molecules?
complementary demining regions
Which of the following are correct statements regarding bone marrow stroma?
-Cytokines facilitate growth and proliferation of B cells at late stages of development. -Adhesion molecules promote binding of the ligands on B-cell progenitors. -Growth factors provide stimulation of cell division of B cells at early stages of development.
An advantage to using IgG4 as a therapeutic monoclonal antibody compared with other IgG subclasses is that it does not activate complement. A disadvantage is that it is monovalent in the circulation. The advantage here means that IgG4 is less likely to promote/drive inflammation. The disadvantage means that either more of it must be used to achieve the desired effect, or it must be mutated in a particular way to overcome the disadvantage.
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An immunoglobulin domain that exhibits little or no sequence diversity within a given class of antibody is referred to as a(n) constant domain. Conversely, an immunoglobulin domain that exhibits a high degree of sequence diversity is referred to as a(n) variable domain. Even within these regions, though, there are specific areas that contain the most extreme diversity of amino acid sequences in antibody subunits—these areas are known as the hypervariable regions. Variable regions from the heavy and light chains must come together to form the antigen-binding site of an antibody molecule.
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Analyze the figure and then enter the maximum theoretical number of times immunoglobulin gene rearrangement can occur on chromosome 14, the heavy-chain locus.
1
Individuals with complete DiGeorge syndrome make limited immune responses involving which subpopulation of lymphocytes?
B-1
Which of the following are correct statements regarding antibodies?
Basophils induce localized immune responses in the upper respiratory tract in response to IgD. Specialized functions of antibodies are dependent on effector properties restricted to particular isotypes. The Fabs and Fc of IgG molecules move partly independently of one another.
Order the steps of how B cells circulate through a lymph node.
Blood -> High endothelial venue -> T-cell area -> primary lymphoid follicle -> T-cell area to medullary cords -> efferent lymphatic vessel
Hypervariable regions are found in both antibody heavy and light chains, in the variable region of each. Which hypervariable regions contribute to the antigen-binding specificity of an antibody?
Both VH and VL hypervariable regions, interacting together, contribute to the antigen-binding specificity of an antibody.
A common complication of the autoimmune disease systemic lupus erythematosus (SLE) is kidney damage due to immune-complex deposition on renal podocytes. What is expected to decrease in the serum when individuals are experiencing a flare-up of SLE?
C3
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 _____. As a chimeric monoclonal antibody, it possesses _________ V domains, but ________ C domains.
CD20, NK cells, mouse, human
Which of the following are correct statements regarding flow cytometry?
Individual cells in suspension are analyzed in a single-file line when interrogated by the laser. Fluorescent dyes emit light of different wavelengths.
What is true of μ heavy chains made by late pro-B cells?They are expressed on the cell surface with κ or λ light chains.They are expressed on the cell surface with polypeptides that take the place of the light chain.They receive a survival signal through their heavy chain.They are retained inside the cell because light chains are not yet available.They are transported to the cell surface with Igα/Igβ without any other molecules bound to the complex.
Correct/Applicable to late pro-B-cells:They are expressed on the cell surface with polypeptides that take the place of the light chain.They receive a survival signal through their heavy chain.Incorrect/ Not applicable to late-pro-B-cells:They are expressed on the cell surface with κ or λ light chains.They are retained inside the cell because light chains are not yet available.They are transported to the cell surface with Igα/Igβ without any other molecules bound to the complex.
Match each stromal cell molecule to the stage in the B-cell development pathway where it first interacts. IL-7 SCF VCAM-1
Early pro-b-cell: SCF Immature B cell Late pro-b-cell:IL-7 Stem Cell: VCAM-1
Isotype switching changes the variable regions of one antibody isotype to those of another isotype. T or F
F If the variable regions were changed, the antibody would bind a different antigen, but still be of the same isotype. Isotype is determined by the constant region segments, not the variable region segments.
Cytokines influencing isotype switching by mouse B cells have been well characterized. There are some similarities with the human system. For example, IL-4 switches human and mouse B cells to make which antibodies?
IgE
Forcible ejection of multicellular parasites by violent reactions, including sneezing, coughing, vomiting, and diarrhea, relies on the function of which of the following?
IgE
A group of immunologists are developing a human monoclonal antibody for the treatment of B-cell lymphoma. A requirement is that the antibody facilitate destruction of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC). For which reason are they not interested in IgG2 antibodies?
IgG2 does not bind efficiently to FcyRIII
Which of the following are correct statements regarding the tyrosine kinase Syk?
It binds to phosphorylated Igβ. It activates other Syk molecules by transphosphorylation
Which of the following statements regarding the V(D)J recombinase is true?
It contains multiple components needed to recombine V, D, and J segments.It facilitates the cleavage of RSSs at the ends of the two heptamer sequences.It forms both coding and signal joints.
Identify the property of FcRn that makes it distinct from other Fc receptors.
It has an MHC class I-like structure.
Which are correct statements regarding FcγRIII?
It induces target-cell killing by antibody-dependent cell-mediated cytotoxicity (ADCC). It has a low affinity for IgG Fc regions.
Which statements are true of the deposition of C3b on the surface of a pathogen?
It targets the pathogen for opsonization,It is amplified by C3bBb,It is carried out by C4bC2a
Which of the following are components of the V(D)J recombinase?
Ku DNA-dependent protein kinase RAG-1 and RAG-2
Which of the following are true statements regarding the mutations in antibodies during somatic hypermutation followed by affinity maturation?
Mutations are present at a much greater frequency than would be generated by the typical spontaneous mutation rate. Mutations are concentrated at nucleotide positions encoding CDR loops that make up antigen-binding sites.
Match each term with the correct description.
Opsonin: molecule that coats a pathogen and stimulates phagocytosis by cells bearing receptors for that moleculeFc receptor: phagocyte cell-surface component that binds to antibodiesaffinity: the strength with which a single antigen-binding site of an antibody binds to antigenneutralizing antibody : antibody that attaches to a pathogen and prevents its growth or entry into cellsavidity : overall strength of binding of an antibody at multiple sites on an antigen
Homozygosity for the R131 variant of FcγRIIA increases an individual's susceptibility to infections with Neisseria meningitidis compared with the H131 variant. What is the reason for this?
The R131 variant is ineffective at phagocytosing IgG2-coated N. meningitidis.
What happens if the B-cell receptor of an immature B cell does not interact with multivalent self antigens present in the bone marrow?
The cell is exported to the peripheral circulation as an immature B cell.
A patient with mutations in both alleles of the gene for λ5 was the subject of a case study. The maternal allele carried a stop codon in exon 1 of the gene causing premature termination of translation. The paternal allele, believed to have originated from a gene-conversion event, contained three base-pair substitutions in exon 3 that corresponded with the sequence in the nonfunctional λ5 pseudogene. Flow-cytometric analysis of bone marrow B-cell precursors showed only 6% of cells were CD19+ (compared with 46% in the control) and only 0.7% were positive for surface immunoglobulin (compared with 29% in the control). In addition, only 85% of the CD19+ cells expressed CD34, indicative of a block in transition between the pro-B-cell and pre-B-cell stages of development. The long-term management regimen for this patient included intravenous immunoglobulin replacement and prophylactic and therapeutic antibiotics with careful monitoring of antibiotic efficacy at times of infection. Which of the following best explains the underlying cause of the profound B-cell immunodeficiency detected in this patient?
The developing B cells die by apoptosis at the pro-B-cell stage
Which of the following are correct statements about the immunoglobulin chain gene loci?
The heavy-chain variable region is encoded by three different types of gene segments called variable (V), diversity (D), and joining (J) segments. The light-chain variable region is encoded by two different types of gene segments called variable (V) and joining (J) segments. The light and heavy chains contain a leader peptide (L), variable region (V), and constant region (C).
What is not associated with the formation of a B-cell and T-cell cognate pair? -CD40 ligand is expressed by the T cell, which binds to CD40 on the B cell. -Reorganization of the T cell's cytoskeleton and Golgi apparatus ensures localized delivery of cytokines onto the B-cell surface. -The lymphocytes become activated after their interaction as a cognate pair. -The T cell involved is a TFH cell.LFA-1 on the T cell binds to ICAM-1 on the B cell. -The B cell presents antigen using MHC class II molecules.
The lymphocytes become activated after their interaction as a cognate pair.
What are the characteristics of B-1 cells that are unique from B-2 cells?
They are located in the peritoneal and pleural cavities. They contain few N-regions in VDJ junctions. They have polyspecificity for antigen.
Indicate whether each of the following statements regarding the RAG-1 and RAG-2 proteins is true or false.
They are regulated to permit allelic exclusion to occur. They are expressed only at certain times during the multiple stages of B-cell development.
Which of the following are true statements regarding Igα and Igβ?
They bind to intracellular cytosolic proteins. They enable immunoglobulins to translocate to the cell surface of B cells. They facilitate signal transduction to ensure B cells divide and differentiate upon antigen encounter.
Which of the following are correct statements regarding immunoglobulin domains?
They contain β sheets stabilized by disulfide bonds. They are arranged in a linear series.
Drag the cell to the appropriate location on the image based on the following descriptions:B Cell Charlie—one functional self-reactive rearranged κ-chain gene, a germline-encoded κ-chain gene, and two germline-encoded λ-chain genesB Cell Echo—two nonfunctional λ-chain genes and two self-reactive κ-chain genesB Cell Sierra—one functional, self-tolerant κ-chain gene; one germline-encoded κ gene; and two germline-encoded λ genes
This B cell has generated a functional self-tolerant antigen receptor. This B cell can migrate into the periphery as an immature naive B cell. When it encounters its antigen, it will be able to respond with effector functions.Receptor editing allows self-reactive B cells that have gone through the majority of their development another chance to develop a self-tolerant antigen receptor. Each B cell can rearrange a total of four light-chain genes before it is condemned to die—two λ genes and two κ genes. About 85% of pre-B cells are able to generate a self-tolerant antigen receptor and migrate into the periphery.
Which of the following statements regarding the construction of V-region sequences is correct? (Select all that apply.)
True: Somatic recombination of heavy and light chain loci is a random process that generates diversity in the variable regions of immunoglobulins, light-chain V regions result from a single somatic recombination between V and J segmentsFalse: reversible alterations in the immunoglobulin genes occur during the development of B cells, heavy-chain V regions result from two somatic recombination of V, D, and J segments; the first joins V to D and the second joins VD to J
If an individual lacked functional AID ______________________________.
True: the individuals B cells would produce primarily IgM antibodies, the individuals B cells would not be able to mediate isotype switchingFalse: the individuals B cells would not be able to isotype switch from IgM to IgD, there would be a deficiency of B cells and the individual would require a bone marrow transplant to survive
In contrast to peripheral tolerance, central tolerance _____________.a) signals continuation of light-chain gene rearrangmentb) causes death of self-reactive B cells by apoptosisc) induces a stage of anergy in self-reactive B cellsd) occurs in the circulation
a) signals continuation of light chain gene rearrangement
Which of the following is not associated with allelic exclusion of the heavy-chain locus in B cells?a. Deletion of one of the heavy-chain loci.b. Termination of RAG gene transcription.c. Production of identical heavy chainsd. Degradation of RAG proteinse. Modification of the heavy-chain locus by chromatin remodeling.
a. Deletion of one of the heavy-chain loci
Following pinocytosis on the luminal side of endothelial cells, IgG associates with FcRn inside endosomes at a(n) _____ pH, and dissociates at the basolateral face of the cell at a(n) _____ pH.
acidic;basic
What is the mechanism by which B cells change production of immunoglobulins from a membrane-bound to a secreted form?
alternative RNA processing
Immediately after activated B cells have migrated to primary follicles, they do what?
become proliferating centroblasts
RNA tumor viruses that directly mediate the development of cancer in their vertebrate hosts contain oncogenes originating from _________________. a. A virus that have accumulated multiple mutations in viral genes that affect in viral genes that affect host-cell growth. b. A reciprocal chromosomal translocation between host and viral genomes. c. The genome of the host d. Rearrangement events in the viral genome involving a mechanism similar to somatic recombination.
c. The genome of the host
What is the name given to the B cell that goes through the process of affinity maturation?
centrocyte
A humanized monoclonal antibody has had the gene segments coding for constant region segments replaced by human versions, while the gene segments encoding the variable region segments are nonhuman.
false
In what location do the four subclasses of IgG exhibit considerable germline-encoded variation
hinge region of the heavy chain
What is the name given to a cell that is produced by fusing an antibody-producing B lymphocyte with a tumor cell?`
hybridoma
Degranulation of mast cells results in the release of which of the following that is (are) packaged in storage granules.
inflammatory mediators
What happens if an immature B cell binds to a multivalent self antigen after the cell has emerged from the bone marrow?
it dies by apoptosis or becomes inactivated
Although secreted IgM has 10 antigen-binding sites, more than any other antibody, it does have important limitations. Which of the following are limitations of secreted IgM?
low-affinity antigen-binding sites bulkiness due to its high molecular weight less flexibility than other antibodies
C3b-coated immune complexes in the circulation are taken up and degraded by which of the following?
macrophages in the liver and spleen
You are a researcher interested in learning more about B-cell anergy. You would like to obtain a B-cell line from a tumor that has a single receptor specificity and resembles a naive B cell. Which tumor type would most likely serve your needs?
mantle cell lymphoma
Which statement correctly describes IgG and its ability to activate the classical pathway of complement?
only 3/4 subclasses of IgG are able to fix complement
What is true regarding FcγRI?
only myeloid cells express FcyRI
During isotype switching the antigen binding site is ______.
preserved
Order the sequence of events in the synthesis of a membrane-associated immunoglobulin heavy chain.
rearranged DNA ----> primary RNA transcript ----> mRNA --->primary protein structure ----->post-translational modifications to protein
Naive B cells enter lymph nodes at which component if they are delivered in the lymph?
subcapsular sinuses
Match each antibody type with the correct anatomical location.
surface of naive B cells : monomeric IgM.bound to mast cells in the absence of antigen: IgEbloodstream : monomeric IgAupper respiratory tract: secreted IgDmucosal surfaces: dimeric IgA
Which ability is of key importance to the function of follicular dendritic cells (FDCs)?
the expression of the complement receptor CR2
What drives changes in the expression of proteins that facilitate gene rearrangement of immunoglobulin loci during B-cell development?
transcription factors
Antibody molecules have a number of regions, portions, and accessory proteins. Each plays a crucial role in the overall expression of the antibody molecule on the surface of a naive B cell. Match each protein or region of the protein with the correct location or function.
transport immunoglobulins to the cell surfaceIgα and Igβ Correct label:Igα and Igβ carboxy terminushydrophobic sequence of immunoglobulin heavy chain Correct label:hydrophobic sequence of immunoglobulin heavy chain entry into endoplasmic reticulumleader peptide of heavy and light chains Correct label:leader peptide of heavy and light chains
Somatic recombination is an essential process for the generation of immunoglobulins and T-cell receptors, and requires V(D)J recombinase. Individuals homozygous for missense mutations in either of the recombinase-activating genes RAG1 or RAG2 have an immunodeficiency called Omenn syndrome, a rapidly fatal condition treatable only by bone marrow transplantation. Which of the following would be consistent with a diagnosis of Omenn syndrome?
undetectable serum IgM
