Immunology Exam 2

True/False: Several small GTPases play critical roles in antigen receptor signaling pathways. When activated by binding to GTP, these mediators induce changes in cytoskeletal organization, adhesion, and metabolism, but have no role in transcription factor activation.

False

True/False: The generation of a complete coding sequence for an antibody heavy chain involves a lymphocyte-restricted process of DNA rearrangement that links V, D, and J gene segments together to form the exon that encodes the heavy chain V region. A similar type of DNA rearrangement is also utilized for the simultaneous expression of IgM and IgD antibodies by the same B cell.

False

True/False: The invariant chain protein, Ii, has only one function in MHC class II antigenpresentation. This function entails Ii protein occupying the peptide-binding site of each newly synthesized class II protein, thereby preventing nascent MHC class II proteins from binding peptides or misfolded proteins in the endoplasmic reticulum.

False

True/False: The mechanism by which CTLA-4 inhibits T cell activation is by recruiting inhibitory phosphatases

False

True/False: The only mechanism by which CD28 co-stimulation enhances T cell activation is by recruiting and activating PI 3-kinase, leading to Akt activation

False

True/False: The repertoire of T-cell receptors, like that of antibodies, is formed by the random rearrangement of multiple gene segments that combine to generate the variable domain of each receptor subunit. The bias of T-cell receptors for binding to peptide:MHCcomplexes, rather than to all possible antigenic structures like antibodies, is simply the result of positive selection in the thymus.

False

True/False: Unlike TCR signaling, B cell receptor (BCR) signaling is not initiated by a Src-family kinase phosphorylating tyrosine resides in ITAM motifs of BCR signaling subunits.

False

Matching: BCR stimulation and TCR stimulation generally activate similar downstream signaling modules, but do so using related, but not identical, signaling proteins. From the list below, match each B cell protein to its T cell counterpart.

1. d 2. J 3. B 4. E 5. G 6. a

Approximately one in every three : T cells expresses two different rearranged TCR chain proteins. Yet T cells are still considered to have 'clonal specificity' for recognizing antigen. The reason for asserting that each T cell has a singlefunctional specificity for recognizing antigen is that: A. Only one of the two TCR chains expressed by a T cell will pair with its TCRchain. B. T cells expressing two different TCR chains will die by apoptosis when they are activated .C. Only one T-cell receptor expressed by each T cell will recognize peptide presented by self-MHC molecules. D. The majority of T cells in an individual will never encounter their specific peptide-MHC ligand and so will not be part of an immune response. E. The majority of T cells are self-reactive and therefore eliminated during their development in the thymus

.C. Only one T-cell receptor expressed by each T cell will recognize peptide presented by self-MHC molecules.

Using an antibody that recognizes the phosphorylated, but not the non-phosphorylated form of the transcription factor, NFAT, T cells are permeabilized, stainedwith this antibody, and analyzed by flow cytometry. Which of the data in Figure Q7.15represent the expected pattern of staining from wild-type T cells before and after TCR stimulation.

B

MHC class II molecules expressed on the surface of thymic cortical epithelial cells normally have a wide repertoire of different peptides bound to them. By engineering a construct that fuses the MHC class II protein to a single peptide sequence,and expressing this construct in thymic cortical epithelial cells that have their endogenous MHC class II genes knocked out, it is possible to generate a mouse line where all MHC class II proteins expressed on all thymic cortical epithelial cells are boundto the same peptide. These mice are often referred to as 'single-peptide' mice. Examination of the T cell developing in these single peptide mice would likely show: A. A significant reduction in the numbers of mature CD4 T cells B. No change in the numbers of mature CD4 T cells C. A block in T cell development at the CD4 CD8 double-positive stage D. A repertoire of T-cell receptors on mature CD4 T cells restricted to a single VB #. A block in T cell development at the CD4 CD8 double-negative stage

A. A significant reduction in the numbers of mature CD4 T cells

The adaptive immune system developed a strategy for monitoring the proteins synthesized in virtually any cell in the body, thereby preventing pathogens from 'hiding out' by adopting an intracellular lifestyle. To accomplish this, the immune system: A. Co-opted the ubiquitin-proteasome system used by cell for protein turnover B. Created a novel pathway using the immunoproteasome for generating peptides C. Created a novel pathway to express foreign proteins on the cell surface D. Took advantage of proteolytic enzymes present in endocytic vesicles E. Engineered an immune-specific ubiquitin molecule for tagging foreign proteins

A. Co-opted the ubiquitin-proteasome system used by cell for protein turnover

The TCR signaling module leading to transcription factor activation is dependent on the enzyme phospholipase-C- (PLC-). The mechanism by which PLC-activates multiple transcription factors is by: A. Generating two small second messengers that act on multiple target proteins in the T cell B. Directly cleaving inhibitory subunits of multiple transcription factors, thereby releasing the active transcription factors C. Generating two small second messengers that diffuse to the nucleus and activate transcription factors present there D. Generating two small second messengers that act as chaperones to promote nuclear localization of transcription factors E. Directly cleaving the lipid binding domain from membrane-tethered transcription factors, allowing them to migrate to the nucleus

A. Generating two small second messengers that act on multiple target proteins in the T cell

Several types of pathogens encode proteins that function as superantigens, which activate massive numbers of T cells in an individual. One example is the staphylococcal enterotoxins that cause food poisoning. These superantigens are the exception to the general rule that T cells only recognize specific peptide:MHC complexes, because they: A. Induce activation of any T cell whose T-cell receptor uses a particular Vβ region bound by that superantigen B. Simultaneously stimulate all of the T-cell receptors on a given T cell C. Cover up the peptide-binding site, preventing MHC molecules from binding peptides D. Activate a large number of T cells that are specifically recognizing peptides derived from the superantigen protein E. Induce anti-microbial cytokine production that aids the immune system in clearingthe pathogen

A. Induce activation of any T cell whose T-cell receptor uses a particular Vβ region bound by that superantigen

The pre-B-cell receptor provides an important signal that induces transition of pro-B cells to pre-B cells. An important characteristic of this receptor is that: A. It signals without binding to an extracellular ligand. B. It is composed of immunoglobulin heavy chains and the VJ region of a rearranged light chain .C. It is expressed at very high levels on the surface of the pro-B cell. D. It signals without requiring association with B-cell receptor signaling subunits, Igand Ig. E. It signals without requiring the B-cell receptor signaling kinase, BTK

A. It signals without binding to an extracellular ligand.

TNF-receptor signaling commonly includes several steps that are regulated by ubiquitination. One important step following TNF-receptor stimulation is the: A. K48-linked ubiquitination and degradation of a TRAF protein, itself a ubiquitin-ligase B. K48-linked ubiquitination of the TNF-receptor cytoplasmic tail, leading to its degradation C. K63-linked ubiquitination of the TNF-receptor, providing a docking site for TRAF protein binding D. K48-linked ubiquitination of NIK, the NFB-inducing kinase E. K63-linked ubiquitination of cIAP, leading to its binding to NIK, the NFB-inducingkinase

A. K48-linked ubiquitination and degradation of a TRAF protein, itself a ubiquitin-ligase

Peptide editing is an important component of antigen presentation for both MHC class I and MHC class II pathways, as it drives the preferential presentation ofhigh-affinity binding peptides. For MHC class II peptide editing, HLA-DM plays a key role. In the absence of HLA-DM: A. MHC class II molecules traffic to the cell surface with CLIP in their binding sites. B. No MHC class II molecules are released to traffic to the cell surface. C. MHC class II molecules bind to HLA-DO and are inhibited from binding peptides. D. Pathogens can evade the immune system by blocking peptide exchange on MHC class II. E. HLA-DO competes for high-affinity binding peptides with MHC class II molecules and blocks antigen presentation.

A. MHC class II molecules traffic to the cell surface with CLIP in their binding sites.

Self-reactive B cells can be eliminated from the repertoire at several stages of B cell maturation, including immature B cells that have already emigrated from the bone marrow into the circulation. This latter stage of tolerance induction is critical because: A. Not all self-antigens are expressed or present in the bone marrow during B cell development. B. Immature circulating B cells are more sensitive to antigen stimulation than the developing B cells in the bone marrow. C. Receptor editing is not a perfect process and some self-reactive B cells may fail to be eliminated in the bone marrow. D. Circulating immature B cells do not encounter tissue-specific antigens in peripheral organs and tissues. E. Immature B cells are trapped in the bone marrow by strong B-cell receptor cross-linking

A. Not all self-antigens are expressed or present in the bone marrow during B cell development.

Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by: A. Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes B. Blocking the binding of anti-microbial antibodies to the pathogen surface C. Cleaving the antibody into fragments that separate the antigen-binding region from the effector function D. Inducing aggregation of the anti-microbial antibodies by multivalent binding to thepathogen-derived protein E. Preventing the antibody from neutralizing the pathogen

A. Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes

The immunosuppressive drug rapamycin acts by inhibiting mTOR. When activated T cells are treated with rapamycin in a cell culture assay, they show greatly diminished proliferation, and accumulate to much lower numbers than control-treated cells. This is because: A. Rapamycin inhibits cells from increasing their synthesis of lipids and proteins. B. Rapamycin inhibits cells from activating the pro-survival protein, Bcl-2. C. Rapamycin inhibits DNA synthesis in activated T cells. D. Rapamycin inhibits cell cycle progression in activated T cells. E. Rapamycin inhibits the T cell's production of the growth factor, IL-2.25.

A. Rapamycin inhibits cells from increasing their synthesis of lipids and proteins.

Unlike : T cells, : T cells are considered to be components of the innate immune system. One feature of : T cells that leads to their classification as innate cells is: A. That they migrate from the thymus directly to barrier surfaces such as mucosa and epithelia B. Their ability to produce pro-inflammatory cytokines C. That their T-cell receptors are germline encoded rather than a product of VD-J recombination D. Their rapid turnover in the tissue, with an average survival time of 3-4 days E. Their ability to make growth factors that act on epithelial cells rather than other hematopoietic cells

A. That they migrate from the thymus directly to barrier surfaces such as mucosa and epithelia

Antibody diversity is generated by multiple mechanisms, each of whichcontributes to the generation of antibodies with up to 1011 different amino acid sequences in their antigen-binding sites. Several of these mechanisms involve changes in the DNA sequences encoding the antibody heavy and light chain proteins. One mechanism that does not rely on changes to the DNA within the immunoglobulin heavy and light chain gene loci is, instead, dependent on: A. The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site B. The random usage of V, D, and J gene segments to form the heavy chain V region sequence C. The random usage of light chains versus light chains to pair with the heavy chain D. The activity of TdT to add random nucleotides at the junctions between the V, J, and D region sequences E. The fact that heavy chain V regions contain an extra gene segment encoded by the D region compared to light chain V regions

A. The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site

Second messengers, such as calcium ions (Ca2+), are chemical mediators commonly used in intracellular signaling pathways. Despite its common usagein many different cell types in the body, Ca2+ has specific effects in lymphocytes following antigen receptor stimulation. The specific responses of lymphocytes to increased concentrations of intracellular Ca2+ are determined by: A. The expression of a specific subset of Ca2+-responsive enzymes in lymphocytes compared to other cell types B. The increased expression of calmodulin in lymphocytes compared to other cell types C. The presence of enzymes that bind calmodulin in lymphocytes but not other cell types D. The high levels of Ca2+ in the endoplasmic reticulum of lymphocytes compared to other cell types E. The ability of Ca2+ to amplify signaling pathways in lymphocytes but not other cell types

A. The expression of a specific subset of Ca2+-responsive enzymes in lymphocytes compared to other cell types

Some T cells express : T-cell receptors rather than : T-cell receptors. The organization of the locus and the locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that: A. The rearrangement of a T-cell receptor gene deletes the locus on that allele. B. The rearrangement of a T-cell receptor gene deletes the locus on that allele. C. The RAG recombinase enzymes are down-regulated immediately after the first T-cell receptor genes rearrange. D. The : T-cell receptor signals the T cell to delete the locus. E. The : T-cell receptor signals the T cell to delete the locus.

A. The rearrangement of a T-cell receptor gene deletes the locus on that allele.

Some CD1 molecules bind to glycosphingolipids, and are recognized by a subset of T cells known as invariant NKT (iNKT) cells. The ability of these T cells to recognize different glycolipid constituents from microorganisms when they are bound to CD1d places these cells in the 'innate immune' category. While iNKT cells do express a fully rearranged : T-cell receptor, one key feature of the T-cell receptors expressed oniNKT cells also places them in the 'innate immune' category. This feature is: A. iNKT cells have a highly restricted T-cell receptor repertoire, with the majority of cells utilizing the same V and J rearrangement. B. iNKT cells express receptors that are also expressed on NK cells. C. iNKT cells express T-cell receptors that induce inhibitory, rather than activating signals. D. iNKT cells do not generally express CD4 or CD8. E. The T-cell receptors expressed on iNKT cells recognize both MHC class I and MHC class II molecules.

A. iNKT cells have a highly restricted T-cell receptor repertoire, with the majority of cells utilizing the same V and J rearrangement.

True/False: Immature B cells expressing sIgM receptor emigrate from the bone marrow into the circulation. This is a passive process of cell diffusion, requiring no active signaling by the B cell

False

Two distinct lineages of T cells can be identified based on their expression of : versus : T-cell receptors. A deficiency in the signaling receptor Notch1 would result in :A. A loss of : but not : T cells B. A loss of both of : and : T cells C. A loss of : T cells and a massive expansion of : T cells D. An increased number of both of : and : T cells E. A normal number of both of : and : T cells

B. A loss of both of : and : T cells

The MARCH-1 E3-ubiquitin ligase is expressed in B cells, dendritic cells, and macrophages. The pathway regulated by MARCH-1 is targeted by some pathogens in an immune evasion strategy. In this strategy, the pathogens encode: A. A protein that induces degradation of MARCH-1 B. A protein that mimics MARCH-1 and functions similarly C. A protein that binds to MARCH-1 and inhibits its function D. A protein that is induced by IL-10 in macrophages and dendritic cells E. A protein that induces degradation of CD86

B. A protein that mimics MARCH-1 and functions similarly

Human patients with genetic defects that result in a failure to produce the calcium channel protein ORAI1, or the ER calcium sensor protein STIM1, have severe immunodeficiency diseases. An immunosuppressive drug that would most closely mimic these primary immunodeficiencies is: A. Rituximab, a drug that depletes B cells B. Cyclosporin A, a calcineurin inhibitor C. Rapamycin, an mTOR inhibitor D. Tysabri, an inhibitor of integrin binding E. Enbrel or Humira that inhibit TNF

B. Cyclosporin A, a calcineurin inhibitor

In patients with 'CD40 ligand deficiency', T cell-dependent B cell activation is impaired, leading to poor antibody responses to protein antigens. The signaling pathway missing in these patients' B cells is important for: A. Inducing integrin activation to promote adhesion B. Inducing NFB activation by the noncanonical pathway C. Inducing WASp activation and actin polymerization D. Inducing Ca2+ influx leading to NFAT activation E. Inducing Ras activation and Erk Map-kinase signaling

B. Inducing NFB activation by the noncanonical pathway

A potential candidate molecule for the gene that is defective in Mutant-1 is: A. CD4 B. MHC class II C. Th-POK D. MHC class I E. Runx3

B. MHC class II

In spite of their low affinity for binding to their antigen, IgM antibodies can be quite effective at promoting the elimination of extracellular bacterial infections. This is due to: A. The ability of IgM antibodies to traffic across epithelial surfaces B. Multivalent binding of IgM pentamers to repetitive epitopes on bacterial surfaces C. The high concentration of IgM antibodies in the serum and in all tissues D. The early production of IgM antibodies during an immune response E. The high rate of somatic hypermutation in the genes encoding IgM antibodies

B. Multivalent binding of IgM pentamers to repetitive epitopes on bacterial surfaces

Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells? A. Yes, because no viral peptide:MHC class I complexes would form to activate CD8 T cells. B. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells. C. No, because some presentation of MHC class I complexes with viral peptides would occur before the virus could down-regulate all the surface MHC class I protein. D. Yes, because this immune evasion strategy would also function in dendritic cells,even if the virus doesn't replicate in dendritic cells. E. No, because the type I interferon response induced by the virus infection will up-regulate MHC class I expression and override the immune evasion mechanism.

B. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells.

In rare instances, B cells can be found that have two immunoglobulin light chain alleles, both of which are rearranged in frame, and can encode functional lightchain proteins. Yet, on the surface of the B cell, only one of the two light chain proteins isdetected in the membrane-bound immunoglobulin receptor. The reason these rare cells have two functional light chain rearrangements but only express one of the two light chains as part of the B-cell receptor is: A. One of the two light chains is formed from rearrangement of a V gene segment that is a pseudogene. B. One of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell. C. One of the two light chain alleles is not transcribed efficiently, and produces only low levels of protein. D. One of the two light chain alleles uses a V gene segment that is not targeted veryoften by the RAG recombinase.

B. One of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell.

T cells expressing : T-cell receptors have been found to recognize a diversity of ligands, including pathogen-derived proteins, self-peptides, and stress-induced molecules. This pattern of antigen recognition shows similarity to that of iNKT cells and MAIT cells, suggesting that : T cells: A. Do not play an important role in immunity, but likely have a non-immune function B. Share features of both innate and adaptive immune cells C. Are only able to respond when the host is infected with a virus such as herpes simplex virus D. Are involved in maintaining the integrity of endothelial cells in the host E. Are most important in responses to tumor cells that show stress responses

B. Share features of both innate and adaptive immune cells

Immunoreceptor signaling proteins, such as the TCR chain and CD3 subunits, have conserved ITAM motifs in their cytoplasmic tails. When fully phosphorylated, the ITAM recruits a tyrosine kinase with a tandem SH2 domain structureat the amino-terminal end of the protein. Tandem SH2 domain-containing kinases do notbind to sequences in other proteins, even if they contain a phosphorylated tyrosine because: A. The amino acid sequence adjacent to the phosphorylated tyrosines in the ITAM motif is unique, and not found in any other proteins. B. The affinity of a single SH2 domain within these kinases for a tyrosine phosphorylated sequence is too low for efficient binding. C. The amino-terminal SH2 domain of the kinase has very high affinity for both of the phosphorylated tyrosines in the ITAM motif, so will not bind to other proteins. D. The amino-terminal SH2 domain of the kinase is in an autoinhibited conformationand can only bind to a phosphorylated ITAM. E. The tandem SH2 domain-containing kinase phosphorylates the tyrosines in the ITAM itself, so can only bind to these sequences.

B. The affinity of a single SH2 domain within these kinases for a tyrosine phosphorylated sequence is too low for efficient binding.

Lymphocyte activation leads to robust proliferation and effector cell differentiation. The metabolic demands of these processes are met, in part, by up-regulation of glycolytic enzymes and nutrient transporters on the activated cell membrane. A key intermediate in the signaling pathway leading to enhanced glucose metabolism following antigen receptor stimulation is: A. The lipid mediator diacyl-glycerol (DAG) B. The phosphoinositide, PIP3 C. Increases in cytoplasmic Ca2+ D. Cleavage of the membrane phospholipid, PIP2 E. The mitochondrial protein, Bcl-2

B. The phosphoinositide, PIP3 C. Increases in cytoplasmic Ca2+

. B-1 B cells are considered a component of the innate rather than the adaptive immune response. The antibodies produced by B-1 B cells generally recognize capsular polysaccharide antigens found on many bacteria and viruses. These antibodiesare considered part of the innate immune response because: A. They recognize pathogens rather than innocuous harmless antigens. B. They are produced prior to the exposure to the pathogen. C. They are specific for carbohydrate rather than protein antigens. D. They are secreted by B-1 B cells starting at 48 hour post-infection. E. They are not generated by the process of VD-J recombination of immunoglobulingenes.

B. They are produced prior to the exposure to the pathogen.

Experimental mouse models have been developed to study the mechanisms leading to the breakdown of self-tolerance and the onset of autoimmunity. One strategy is to express a foreign antigen, such as a viral protein, in a single defined cell type in a peripheral organ. For instance, the lymphocytic choriomeningitis virus (LCMV) glycoprotein has been expressed in β-islet cells of the pancreas by making a line of mice that is transgenic for a construct linking the LCMV-glycoprotein gene to the insulin promoter. In these transgenic mice, the LCMV protein is expressed only in pancreatic -islet cells. Thymocytes with T-cell receptors specific for a peptide of LCMV-glycoprotein bound to MHC class I develop normally in the thymus, and do not undergo negative selection. The fate of these T cells once they emigrate from the thymus would likely be: A. They would be activated in the periphery and attach and kill the pancreatic -isletcells. B. They would either be deleted in the periphery or would become unresponsive. C. They would induce an inflammatory response in the pancreas that would up-regulate co-stimulatory molecules on antigen-presenting cells. D. They would secrete cytokines that promote T cell proliferation. E. They would differentiate into virus-specific memory T cells that would protect mice upon infection with LCMV.

B. They would either be deleted in the periphery or would become unresponsive.

The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together: A. In all cells of the body to encode a V region sequence B. To generate maximum diversity in the CDR3 sequence of the V region C. By alternative RNA splicing to encode a V region sequence D. By a precise mechanism that never adds or loses nucleotides at the junction E. To generate a single exon encoding the entire immunoglobulin protein

B. To generate maximum diversity in the CDR3

While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because: A. B cells and T cells recognize the same form of antigen expressed by an infecting pathogen. B. Animals with B cells developed first, and later evolving species then developed T cells. C. B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens. D. Antibody and T-cell receptor gene segments are both flanked by similar recombination signal sequences. E. B cells and T cells both secrete their antigen receptor proteins after they are activated by antigen-binding

C. B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens.

While many cell types in the thymus are able to induce negative selection of developing self-reactive thymocytes, bone marrow-derived antigen-presenting cells, such as macrophages and dendritic cells, appear to be the most important for this process. One likely reason for the prominent role of bone marrow-derived antigen-presenting cells in inducing negative selection of developing thymocytesis: A. Bone marrow-derived antigen-presenting cells are the most abundant stromal cells in the thymus. B. Bone marrow-derived antigen-presenting cells are very good at inducing mature T cell activation .C. Bone marrow-derived antigen-presenting cells are highly phagocytic and have specialized mechanisms for presenting peptides on both MHC class I and class II. D. Bone marrow-derived antigen-presenting cells are concentrated in the thymic medulla where negative selection is most prominent

C. Bone marrow-derived antigen-presenting cells are highly phagocytic and have specialized mechanisms for presenting peptides on both MHC class I and class II.

'Checkpoint blockade' is a therapeutic strategy based on enhancing T cell responses by inhibiting the function of inhibitory receptors, such as CTLA-4, and PD-1. Patients being treated with these protein-based therapeutics would likely be suffering from: A. An autoimmune disease B. An immunodeficiency disease C. Cancer D. Inflammatory bowel disease E. A neurodegenerative disease

C. Cancer

Three major cell types, dendritic cells, macrophages, and B cells, present peptides bound to MHC class II molecules for recognition by CD4 T cells. In general, these peptides are derived from proteins or pathogens taken up by the cell by endocytosis, phagocytosis, or macropinocytosis. Based on these pathways of antigen uptake, some of the enzymes that degrade proteins to generate peptides for MHC class II presentation are: A. Ubiquitin ligases that tag proteins for degradation by the proteasome B. ATP transporter proteins that deliver endocytic proteins into the cytosol for degradation C. Cysteine proteases like cathepsins that function at acidic pH D. The lysosomal thiol reductase found in the endosomes E. The lysosome-associated membrane trafficking protein, LAMP-2

C. Cysteine proteases like cathepsins that function at acidic pH

The thymic cortex has a substantial population of macrophages in addition to the developing T cells (i.e., thymocytes). These macrophages are extremely useful in: A. Eliminating bacterial infections in the thymus B. Producing cytokines that promote T cell maturation C. Engulfing apoptotic thymocytes D. Maintaining the structural integrity of the thymic organ E. Inducing inflammatory signals to increase blood flow to the thymus

C. Engulfing apoptotic thymocytes

The B cell co-receptor, composed of CD19/CD21/CD81, is a receptor that binds to complement fragments such as C3dg. When an antigen bound by the BCR on a B cell has also been tagged with C3dg, the B cell co-receptor is stimulated togetherwith the BCR. Signaling through the co-receptor: A. Inhibits BCR signaling by leading to ITAM dephosphorylation B. Inhibits BCR signaling by leading to PIP3 dephosphorylation C. Enhances BCR signaling by recruiting and activating PI 3-kinase D. Enhances BCR signaling by bringing the Src-kinase together with Ig- and Ig-. E. Inhibits BCR signaling by sequestering the antigen away from the BCR.

C. Enhances BCR signaling by recruiting and activating PI 3-kinase

TCR and CD28 signaling together lead to maximal production of IL-2 by the activated T cell. Experiments investigating the mechanism underlying the CD28 co-stimulation-mediated increase in IL-2 production show that T cells stimulated through the TCR plus CD28 have increased levels of IL-2 mRNA compared to cells stimulated through the TCR alone. One important component contributing to increased IL-2 mRNA levels is: A. Increased protein synthesis due to increased production of ribosomes B. Increased glucose metabolism due to increased production of glycolytic enzymes C. Increased mRNA stability after transcription and splicing D. Enhanced mRNA transport from the nucleus to the cytoplasm E. Increased levels of splicing enzymes that increase IL-2 mRNA splicing efficiency

C. Increased mRNA stability after transcription and splicing

Small GTPases, such as Ras, Rho, and cdc42, are activated when they exchange their bound GDP for GTP. In the GTP-bound state, these proteins contribute to signaling by: A. Hydrolyzing the bound GTP back to GDP B. Interacting with GTPase-activating proteins (GAPs) C. Interacting with target proteins and altering their activity D. Diffusing from the membrane and entering the nucleus E. Inducing calcium release from the endoplasmic reticulum

C. Interacting with target proteins and altering their activity

The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to: A. Intracellular pathogens that can survive inside macrophage endocytic vesicles B. Intracellular pathogens that are able to evade antibody responses C. Intracellular pathogens that do not infect and replicate in dendritic cells D. Intracellular pathogens that can spread from cell to cell by inducing cell fusion E. Intracellular pathogens that infect and replicate in red blood cells

C. Intracellular pathogens that do not infect and replicate in dendritic cells

The integrin LFA-1 is constitutively expressed on the surface of restingT cells. Yet, integrin-dependent T cell adhesion to antigen-presenting cells increases substantially following TCR stimulation. This increased integrin-dependent adhesion is mediated in part by: A. Increased synthesis of the LFA-1 protein B. Increased transport of intracellular pools of LFA-1 to the cell surface C. LFA-1 conversion to a high affinity binding state D. Increased phosphorylation of the LFA-1 cytoplasmic tail E. Activation of cdc42 and WASp

C. LFA-1 conversion to a high affinity binding state

NKG2D is an activating receptor expressed on NK cells, : T cells, and some cytotoxic : T cells. When stressed or infected cells up-regulate receptors that bind to and activate NKG2D molecules, the stressed or infected cells will be killed. This pathway relies on the fact that stressed or infected cells up-regulate: A. All classical MHC class I molecules B. HLA-C molecules that bind KIRs C. MHC class Ib genes such as MICA, MICB, and RAET1 D. Qa-1 and HLA-E molecules that bind leader peptides of other HLA class I molecules E. HLA-G molecules just like those expressed on the fetal-derived cells in the placenta

C. MHC class Ib genes such as MICA, MICB, and RAET1

The virus shown in the diagram below is only able to infect and replicate in epithelial cells. In order for the cross-presenting dendritic cell to display viral peptides, rather than self peptides on its surface MHC class I proteins, which of the following procedures could be utilized, starting with the components shown in Figure Q6.8? A. Mix epithelial cells with heat-killed virus, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells. B. Mix epithelial cells with viral peptides, wait 24 hrs, wash away any viral peptides not bound to the epithelial cells, then add epithelial cells to dendritic cells. C. Mix epithelial cells with live virus particles, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells. D. Mix dendritic cells with viral nucleic acids and epithelial cells for 24 hrs. E. MIx epithelial cells will viral nucleic acids, wait 24 hrs, wash away any viral nucleic acid remaining outside the epithelial cells, then add epithelial cells to dendritic cells.

C. Mix epithelial cells with live virus particles, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells.

The extensive polymorphism of MHC genes in the population is thought to represent an evolutionary response to outflank the evasive strategies of pathogens. This polymorphism makes it difficult for pathogens to eliminate all potential MHC binding epitopes from their proteins. Based on this reasoning, it would seem advantageous for each individual to encode more than three different MHC class I and three different MHC class II genes per chromosome copy. If some individuals in the population had MHC loci that encoded 10 different MHC class I and 10 different MHC class II genes, the T cell repertoire in those individuals would likely be: A. Much more diverse than in the rest of the individuals of that population B. Much better at recognizing rare pathogens not encountered by most individuals in that population C. Much less diverse than the rest of the individuals in that population D. Much more alloreactive than the T cells found in the other individuals of that population E. Very reactive to bacterial and viral superantigens

C. Much less diverse than the rest of the individuals in that population

Proteins found in the circulation travel throughout the body, including the thymus. One example is serum albumin. Developing T cells with T-cell receptors specific for peptides of human serum albumin bound to MHC class II molecules would likely be: A. Positively selected and would mature into CD4 T cells B. Positively selected and would mature into CD8 T cells C. Negatively selected in the thymus and deleted from the mature repertoire D. Targeted for peripheral mechanisms of self-tolerance after emigrating from the thymus E. Excluded from the T cell zones of the spleen after emigrating from the thymus

C. Negatively selected in the thymus and deleted from the mature repertoire

T cells with defective TCR signaling are discovered, and found to havean inactivating mutation in a key TCR signaling protein. Using an antibody that recognizes the phosphorylated (activated) form of the Erk Map-kinase, stimulated T cellsare permeabilized, stained with this antibody, and analyzed on the flow cytometer. These data are shown in Figure Q7.21.Additional experiments examining Ca2+ influx into T cells following TCR stimulation showa normal response in the mutant T cells. One likely candidate gene that could be mutated in the defective cells is: A. PLC- B. ITK C. RasGRP D. Calcineurin E. WASp

C. RasGRP

A potential candidate molecule for the gene that is defective in Mutant-2 is: A. CD4 B. MHC class II C. Th-POK D. MHC class I E. Runx3

C. Th-POK

MHC polymorphism at individual MHC genes appears to have been strongly selected by evolutionary pressures. In other words, there appears to be selection for maintaining hundreds to thousands of different alleles of each MHC gene inthe population. This notion is based on the observation that nucleotide differences between alleles that lead to amino acid substitutions are more frequent than those that are silent substitutions (i.e., not changing the amino acid sequence of the protein). In addition, the positions within the MHC protein where most of the allelic sequence variation occurs are not randomly distributed, but are concentrated in certain regions of the MHC protein. This latter point indicates: A. That some nucleotide sequences within the MHC genes are hot-spots for mutation B. That MHC genes are more susceptible to point mutations than to larger nucleotide deletions C. That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity D. That MHC genes are more susceptible to all types of mutations than are other genes in the genome E. That MHC polymorphism has evolved to prevent pathogens that infect non-human primates from infecting humans

C. That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity

A key step in the development of B cells is the expression of the RAG-1 and RAG-2 recombinase proteins. The up-regulation of RAG-1 and RAG-2 in early pro-B cells is induced by: A. The cytokine IL-7, which is made by bone marrow stromal cells B. The chemokine CXCL12, which is made by bone marrow stromal cells C. The B cell-specific transcription factors E2A and EBF D. Signaling through the Igα subunit of the B-cell receptor complex E. Signaling through the FLT3 receptor tyrosine kinase binding to membrane-bound FLT3

C. The B cell-specific transcription factors E2A and EBF

A mutagenesis screen performed on mice identified a gene with an important function in B cells. Analysis of B cells from the spleens of these mutant mice showed the results shown in Figure Q5.23A. However, when the C coding sequences were determined, no mutations in these DNA sequences were found. To study this further, genetic crosses were set-up with another mouse strain carrying an allelic variant of the immunoglobulin heavy chain locus.Based on these data, the mutation in the original mutant mouse strain most likely inactivates: A. The gene for a transcription factor required for IgD gene transcription B. A regulatory region in the immunoglobulin heavy chain gene locus required for IgD gene transcription C. The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript D. The gene encoding the RAG-1 or RAG-2 recombinase E. The gene for a factor that is required for IgD surface expression

C. The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript

For immunoglobulin heavy and light chain genes, and for T-cell receptor chain genes, there are a large number of V gene segments, and relatively fewJ and/or D segments that rearrange to form the final coding sequence for each gene. The TCR locus is different in this regard, and this difference is thought to reflect the fact that nearly all : T-cell receptors recognize a peptide bound to an MHC molecule. This unique feature of the T-cell receptor locus is: A. The presence of only five different V gene segments B. The presence of two different C coding sequences C. The presence of over sixty different J gene segments D. The absence of D gene segments E. The large sequence distance separating the V gene segments from the Jgene segments

C. The presence of over sixty different J gene segments

The TCR and BCR are multi-subunit receptor complexes. Experimentsexamining the synthesis and transport of these receptors to the lymphocyte cell surface have shown that the signaling subunits of each receptor complex are required for transport of the ligand-binding receptor subunits to the cell surface. One possible reasonfor this stringent control on cell surface expression is: A. To ensure that very few complete TCRs or BCRs are expressed on the lymphocyte surface B. To ensure that each lymphocyte expresses only a single specificity of antigen receptor C. To prevent surface expression of receptors that will bind ligand but fail to induce signals D. To prevent lymphocytes from triggering antigen receptor signaling pathways from intracellular forms of the receptors E. To ensure that equimolar amounts of all antigen receptor signaling subunits are produced

C. To prevent surface expression of receptors that will bind ligand but fail to induce signals

True/False: Most eukaryotic genes are encoded in a set of exons that are brought together to form a contiguous protein coding sequence by the process of mRNA splicing.In contrast, immunoglobulin genes use somatic recombination of gene segments and notmRNA splicing to generate the final mRNA that is translated into protein.

False

In different mammalian species, the ratio of B cells expressing versus light chain-containing antibodies is about 65%:35%. In other species, such as mice, this ratio is vastly different, at 95%:5%. If a routine blood test performed on an individual revealed that their -expressing versus -expressing B cells were seen at a ratio of 95%:5%, this would likely indicate that the individual had: A. An increased number of functional V gene segments compared to the average human in the population B. A defect in allelic exclusion of antibody light chain genes C. A defect in isotypic exclusion of antibody light chains D. A lymphoproliferative disorder E. A genetic defect in one of their two light chain alleles

D. A lymphoproliferative disorder

IgM is the first antibody isotype secreted following activation of a naive B cell. IgM is found at high concentrations in the serum, and is found as a very high molecular weight complex. This high molecular weight complex is composed of: A. A single IgM monomer plus monomers of IgA and IgG B. A single IgM monomer bound to several non-immunoglobulin serum proteins C. A single IgM monomer bound to serum complement components D. A pentamer of IgM monomers E. Two dimers of IgM plus IgD forming a tetrameric complex

D. A pentamer of IgM monomers

Like the : T cells in other specific mucosal surfaces, the : T cells that reside in the epithelial surface of the skin: A. Are slow to respond to activation signals, requiring several days of priming and differentiation B. Are able to produce cytokines that simultaneously induce type I, type II, and type III immune responses C. Are primarily responsible for recruiting macrophages and dendritic cells to the tissue D. Are characterized by the homogeneous expression of a single specific V and Vin their T-cell receptors E. Are unlikely to play any role in immunity to infection, but are likely important for tissue repair

D. Are characterized by the homogeneous expression of a single specific V and Vin their T-cell receptors

Wiskott-Aldrich syndrome is an immunodeficiency disease due to mutations in the gene encoding WASp. Individuals with this disease make poor antibody responses to protein antigens, due to impaired T cell help for B cells. WASp-deficient T cells are likely impaired in providing adequate help to B cells due to: A. Defects in up-regulating expression of genes encoding cytokines required by B cells B. Defects in up-regulating metabolic pathways for T cell macromolecular synthesis C. Defects in up-regulating expression of genes needed for T cell survival D. Defects in cytoskeletal reorganization needed for directed T cell cytokine secretion E. Defects in up-regulating T cell integrin adhesion for stable interactions with B cells

D. Defects in cytoskeletal reorganization needed for directed T cell cytokine secretion

Scaffold proteins are often phosphorylated at multiple sites, allowing the recruitment of several different signaling proteins. In antigen receptor signaling pathways, this mechanism is used to bring enzymes in close proximity to their substrates. Termination of this signaling mechanism would be most efficiently accomplished by: A. Ubiquitination of the scaffold protein, leading to its degradation B. Binding of the enzyme to a GTPase activating protein (GAP) C. Depletion of the substrate due to enzyme catalysis D. Dephosphorylation of the scaffold by a phosphatase E. Ubiquitination of the enzyme by K63-linkage of polyubiquitin

D. Dephosphorylation of the scaffold by a phosphatase

A mutant B cell line is examined by confocal microscopy after incubation with a microbial pathogen recognized by the BCR on these B cells. The B cells have been stained with antibodies to visualize the localization of polymerized actin and microtubules. As a control, wild-type B cells are examined. The results are shown in Figure Q7.32, with the numbers indicating the proportion of cells examined that show each pattern of staining.To identify the specific signaling defect in these mutant B cells, a reasonable biochemical assay would be to: A. Determine if BCR stimulation of mutant B cells produces enhanced binding of theB cell to the microbe. B. Determine whether the mutant B cells have reduced levels of the enzyme Proteinkinase C- C. Determine whether the mutant B cells are overexpressing the enzyme Vav D. Determine whether BCR stimulation of mutant B cells promotes exchange of GDP for GTP on cdc42 E. Determine whether BCR stimulation of mutant B cells produces increased levels of DAG

D. Determine whether BCR stimulation of mutant B cells promotes exchange of GDP for GTP on cdc42

The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that: A. It involves DNA rearrangements at multiple gene segments in the MHC locus. B. It requires different enzymes than the RAG1/RAG2 recombinase required for antigen receptor rearrangements. C. It results in a diverse repertoire of clonally distributed receptors on dendritic cells,rather than on lymphocytes. D. It creates diversity between individuals in the population rather than within a single individual. E. It does not contribute to the transplant rejection responses that occur after organ transplantation between unrelated individuals.

D. It creates diversity between individuals in the population rather than within a single individual.

Humans with defective expression of the integrin LFA-1 have an immunodeficiency disease characterized by the failure of lymphocytes and granulocytes to migrate to tissues at sites of infection or inflammation. A similar immunodeficiency would be expected if individuals had mutations disrupting the gene for: A. CD3 B. The complement receptor, CD21 C. WASp D. Rap1 E. SLP-76

D. Rap1

Following TCR stimulation, the small GTPase Ras is activated. Ras activation is induced by the Ras GTP-exchange factor (GEF), RasGRP. Both Ras and RasGRP are constitutively expressed in resting T cells. The reason Ras activation is only induced following TCR stimulation is: A. RasGRP undergoes a Ca2+-dependent conformational change required for its activity. B. RasGRP requires tyrosine phosphorylation for its activity. C. RasGRP is ubiquitinated and degraded in the absence of TCR stimulation D. RasGRP recruitment to the plasma membrane requires TCR stimulation E. Ras is only recruited to the activated TCR following assembly of the LAT:Gads:SLP-76 complex.

D. RasGRP recruitment to the plasma membrane requires TCR stimulation

Antigen receptor signaling pathways are initiated by the action of a Src-family kinase. In T cells, the predominant Src-kinase is Lck. In resting T cells, Lck is maintained in an inactive state by allosteric interactions involving multiple domains of theenzyme. When T cells are treated with a small molecule inhibitor of the tyrosine kinase Csk, TCR signaling is initiated even in the absence of a ligand to stimulate the TCR. Thisoccurs because: A. Csk phosphorylates Lck in its kinase domain, leading to Lck activation. B. Csk phosphorylates ZAP-70, maintaining ZAP-70 in an auto-inhibited state. C. Csk phosphorylates the ITAM motifs in the TCR chain, leading to ZAP-70 recruitment. D. Csk phosphorylates and activates the membrane tyrosine phosphatase CD45. E. Csk phosphorylates the C-terminal negative regulatory tyrosine in Lck

E. Csk phosphorylates the C-terminal negative regulatory tyrosine in Lck

The experiment shown in Figure Q6.19 uses two strains of mice that differ in their MHC genes. Strain A is H-2a and Strain B is H-2b. Mice of each strain are infected with the virus LCMV, and T cells are isolated at day 8 post-infection. These T cells are mixed with target cells that express either H-2a or H-2b; in each case, the target cells are either uninfected or infected with LCMV. After a four-hour incubation of T cells with target cells, the percentage of target cells lysed by the T cells is shown in the graph. The explanation for the results of this experiment is: A. Mice of strain B do not make a T cell response to LCMV. B. Mice of strain A make a more robust T cell response to LCMV than mice of strainB. C. Target cells that express H-2b cannot be infected with LCMV. D. T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a. E. LCMV peptides do not bind to MHC class I molecules from H-2b mice.

D. T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a.

The final stages of T cell development occur in the thymic medulla, after the developing cells become CD4 or CD8 single-positive. One important change that occurs during this final maturation is: A. The down-regulation of the pre-T-cell receptor (pre-T) chain protein B. The up-regulation of genes encoding effector cytokines and cytolytic effector proteins C. The increased susceptibility to T-cell receptor-induced apoptosis D. The loss of susceptibility to T-cell receptor-induced apoptosis E. The up-regulation of signaling proteins required for T cell activation

D. The loss of susceptibility to T-cell receptor-induced apoptosis

Different individuals can have different numbers of functional V gene segments as well as different numbers of constant region genes. This type of genetic polymorphism between individuals indicates that: A. The antibody heavy and light chain loci undergo more frequent mutation than other genes in the genome. B. The recombination machinery is active in germ cells. C. Individuals only need or light chains, but not both. D. The precise number of antibody gene segments in an individual is not important. E. Antibody gene segments underwent more frequent duplication during evolution than other genes in the genome.4.

D. The precise number of antibody gene segments in an individual is not important.

. Virus infections induce production of interferons that act on infected cells to enhance their recognition by CD8 cytotoxic T cells. To counter these mechanisms, viruses often encode proteins that interfere with antigen processing and presentation. In an experiment, cells infected with Virus X are treated with interferon andcompared with uninfected cells treated with interferon. Proteasomes are isolated from the two cell populations and their enzymatic activities are compared. The data in Figure Q6.4 show the amino acid preferences for cleavage of peptides by the two samples of proteasomes. Based on these data, Virus X most likely encodes a protein that interferes with: A. The expression of MHC class I on the surface of the infected cell B. The rate at which peptides are produced from intact proteins in the infected cell C. The transport of peptides from the cytosol to the endoplasmic reticulum in the infected cell D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell E. The development of CD8 T cells in the thymus by inhibiting the thymoproteasome

D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell

Experiments performed with T-cell receptor transgenic mice identified the fate of developing thymocytes that failed positive selection. Based on these findings, examination of thymocytes in MHC class I-MHC class II-deficient mice (lacking all MHC class I and class II expression in the thymus) would show: A. A 100-fold decrease in total thymocytes numbers B. A block in T cell development at the CD4-CD8- double-negative stage C. Normal numbers and subsets of thymocytes and peripheral T cells D. Normal numbers of thymocytes, but no peripheral T cells E. A block in T cell development at the CD4+CD8+ double-positive stage

E. A block in T cell development at the CD4+CD8+ double-positive stage

Individuals that overexpress the cytokine BAFF show increased susceptibility to autoimmune diseases such as Sjögren's syndrome, a disease that targets the exocrine glands that produce saliva, tears, and other bodily secretions. If oneexamined the circulating antibodies in these patients, one would expect to find: A. Increased development of B cells in the bone marrow B. A failure of receptor editing of immunoglobulin light chain genes in the bone marrow C. An increased rate of immature B cell export from the bone marrow D. Reduced B-cell receptor signaling following strong cross-linking of the receptor E. An increased number of circulating mature autoreactive B cells

E. An increased number of circulating mature autoreactive B cells

A new strain of immunodeficient mice has been discovered, and found to have T cells that are unresponsive to TCR stimulation. The T cells from these mice have normal levels of the TCR complex on their surface, but when this TCR is stimulated, the cells fail to secrete IL-2. As a first step in determining the signaling defectresponsible for this immunodeficiency, the T cells are stimulated with a phorbol ester (PMA) and Ionomycin. It is found that this treatment elicits IL-2 production by the immunodeficient T cells. Based on this information, candidate genes that could be mutated in these T cells include all of the following EXCEPT: A. ZAP-70 B. PLC- C. SLP-76 D. ITK E. Calcineurin

E. Calcineurin

True/False: MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.

False

Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents: A. The accumulation of empty MHC molecules on the cell surface which would interfere with T cells recognizing pathogen-derived peptide:MHC complexes B. Pathogens from evading the immune response by inducing peptide release from cell surface MHC molecules C. MHC class I molecules from being internalized into endosomes and binding endosome-derived peptides D. HLA-DM from trafficking to the cell surface with MHC class II E. Inappropriate T cell recognition of healthy cells that are not infected, nor have ingested a pathogen

E. Inappropriate T cell recognition of healthy cells that are not infected, nor have ingested a pathogen

An important transcription factor activated by antigen receptor signaling in lymphocytes is an NFB heterodimer of the two subunits, p50 and p65Rel. Defects in the IB-kinase complex (NEMO) or mutations in IB that prevent its phosphorylation interfere with NFB activation and result in severe immunodeficiency diseases. This is due to the important function of: A. NEMO in targeting p50:p65Rel for ubiquitination and degradation B. NEMO in ubiquitinating IB causing its release from NFB C. IB in blocking the DNA binding activity of NFB D. IB as a chaperone to promote NFB nuclear localization E. NEMO in phosphorylating IB inducing its degradation, thereby releasing NFB

E. NEMO in phosphorylating IB inducing its degradation, thereby releasing NFB

During MHC class I synthesis and folding in the endoplasmic reticulum(ER), a process of peptide editing takes place as the newly synthesized MHC class I protein is held in a 'peptide receptive' state by binding to the calreticulin:ERp57:tapasin complex. Peptide editing ensures that the MHC class I molecules that reach the cell surface have stable, high affinity binding for their peptide cargo. Peptide editing is important to the immune response because it: A. Maintains high levels of surface MHC class I expression B. Ensures that MHC class I molecules are not degraded in the ER C. Retains the nascent MHC class I molecule in a peptide receptive state D. Allows surface MHC class I molecules to bind new peptides from the extracellular milieu E. Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface

E. Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface

The addition and subtraction of nucleotides at the junctions between V,D, and J gene segments creates antibody proteins with wide variations in the numbers ofamino acids in their CDR3 regions. This variability in CDR3 length is important as: A. Overall variability in CDR3 sequence is needed to create a sufficiently diverse antibody repertoire. B. The CDR3 region is more important in binding antigen than the CDR1 and CDR2regions are. C. Some light chains bind better to heavy chains with longer CDR3 region sequences. D. Longer CDR3 sequences generally create antibodies with higher affinity for the antigen. E. Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen

E. Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen

Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with VH CDR3 loops of >30 amino acids are readily detected in the repertoire. These antibody heavy chains with CDR3 lengths of >30 amino acids would likely be missing in individuals lacking: A. RAG-1 and RAG-2 B. DNA-dependent protein kinase (DNA-PK) C. The nuclease, Artemis D. The Ku70:Ku80 complex E. Terminal deoxy nucleotidyl transferase (TdT)

E. Terminal deoxy nucleotidyl transferase (TdT)

B cell development in the bone marrow is an inherently wasteful process. Nearly half of the pro-B cells produced will die without progressing on to the next stage of B cell development. This massive loss of pro-B cells is due to: A. The failure of many pro-B cells to up-regulate Pax5 and become committed to the B cell lineage. B. The inability of many pro-B cells to proceed with rearranging a VH to their rearranged DJH sequence. C. Large insertions of untemplated nucleotides into the rearranged gene by TdT. D. Detrimental DJH rearrangements on both alleles of the immunoglobulin heavy chain locus. E. The failure of the pro-B cell to make a complete immunoglobulin heavy chain protein

E. The failure of the pro-B cell to make a complete immunoglobulin heavy chain protein

True/False: Diacyl-glycerol (DAG) is one of the two products generated when PLC-cleaves the membrane phospholipid, PIP2. This small lipid mediator remains associated with the plasma membrane and functions to inhibit tyrosine phosphatases that remove activating phosphate groups from ZAP-70 and the Tec-family kinase, ITK

False

Genetically inherited immunodeficiency diseases can result from defects in nearly any component of the immune response. The most severe forms of immunodeficiency occur when T cells are absent or non-functional. An individual with normal B cells, but an absence of T cells might have a defect in :A. RAG-1 or RAG-2 recombinase proteins B. Terminal deoxynucleotidyl transferase (TdT) C. Hematopoietic stem cells D. Bone marrow stromal cells E. Thymic stromal cells

E. Thymic stromal cells

True/False: All of the modular protein domains used for signaling protein interactions bind to ligands that are transiently generated following receptor stimulation.

False

True/False: Alloreactivity refers to the ability of T cells to respond to allelic polymorphisms in MHC molecules when mixed with antigen-presenting cells from a genetically different individual. The T-cell receptors involved in alloreactive responses are recognizing amino acid sequences on foreign MHC molecules and do not interact at all with the peptides bound to these MHC molecules.

False

True/False: Following TCR or BCR signaling, the most important events downstream of the activation of ZAP-70 or SYK, respectively, are the activation of transcription factors leading to new gene expression.

False

BCR signaling on B cells is initiated by antigen binding, leading to mTOR activation. This occurs, for instance, when the antigen is a live microbe that bindsto the BCR on the B cells. Which one of the forms of antigen shown below the graph would correctly account for the data shown in Figure Q7.40.

The answer is A

True/False: B and T lymphocytes develop from multipotent hematopoietic stem cells in the bone marrow. This process entails a continuum of development in which cells show progressive loss of multipotent potential, eventually becoming committed to a single lineage.

True

True/False: The LAT:Gads:SLP-76 complex that assembles following TCR stimulation provides the scaffold for initiating multiple downstream signaling modules, leading to actin polymerization, integrin activation, and gene expression.

True

True/False: The MHC locus encodes a large number of genes spanning over four million bp of DNA. These include many genes involved in antigen processing and presentation, as well as receptors recognized by non-conventional T cells and natural killer (NK) cells. In addition, the MHC locus encodes genes with no function in immunity at all.

True

True/False: The genes encoding MHC proteins are closely linked with genes encoding proteins involved in antigen processing and presentation. This genetic linkage facilitates the coordinate regulation of these genes by interferons

True

True/False: When a B cell differentiates into a plasma cell, it goes from expressing membrane-bound IgM to making mostly the secreted form of IgM. A deletion of the first polyadenylation site in the μ heavy chain gene would prevent activated B cells from making the secreted form of IgM.

True