Immuno Practice Questions w/Explanations Part 2

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Which one of the following molecules is important for the production of IgE antibodies? A. CD28 B. CD40 C. IFN-γ D. IL-2 E. TGF-β

B. CD40 Cytokines play essential roles in regulating the switch to particular heavy chain isotypes. IFN-γ is important in switching to the IgG isotype (specifically IgG3), whereas TGF-β is a stimulator of IgA production. The cytokine that promotes IgE production is IL-4, but this is not an answer choice. However, the process of isotype switching in general is known to depend on signaling through CD40L-CD40, and is also dependent on the activity of the enzyme activation-induced deaminase (AID). CD28 is a costimulatory molecule that is important for T cell activation and CD40L up-regulation. However, other costimulatory molecules are also present on T cells that can cause up-regulation of CD40L. IL-2 is a growth factor cytokine for T cells.

C. CD40L Because both a maternal uncle and an older brother, but not the patient's sister, are affected, the inheritance pattern is most likely X-linked recessive. The CD40L gene is located on the X-chromosome.

Which of the following antigenic structures might activate B cell antibody production without the aid of T cells? A. Lysozyme B. Benzene C. Glucose-6-phosphate D. ABO blood group antigen E. Rh factor antigen

D. ABO blood group antigen T cell-independent antigens consist of polysaccharides, glycolipids, and nucleic acids with multiple repeated epitopes, so that maximal cross-linking of the B cell receptor is induced, thus bypassing the need for T cell help. Of the answer choices, the best choice is the ABO blood group antigen, because of its polyvalent glycolipid structure. Lysozyme and the Rh factor are protein antigens. Benzene and glucose-6-phosphate are not polyvalent.

Injections of the mycobacterium Bacillus Calmette-Guérin (BCG) at the sites of tumor growth helps to activate which of the following effector immune cells? A. B cells B. Cytolytic T lymphocytes C. Natural killer cells D. Macrophages E. Neutrophils

D. Macrophages Mycobacterial bacillus Calmette-Guérin (BCG) injections have been used for nonspecific immune stimulation at the sites of tumors and work by inducing a delayed-type hypersensitivity (DTH) reaction. The effector cells of a DTH response are macrophages.

A 5-year-old boy has a history of recurrent pneumococcal pneumonia, Pneumocystis carinii pneumonia (PCP), and bacterial ear infections. His maternal uncle and an older brother experienced the same symptoms, but he has an older sister who is healthy. Laboratory studies indicate normal numbers of B cells and T cells, and the serum contains mostly IgM and very little IgG. Which of the following abnormalities would NOT be likely in this patient? A. The IgG antibodies that are present are of lower affinity for antigen than of those of a healthy individual. B. Lymph nodes are without well-developed follicles containing germinal centers. C. Macrophage killing of intracellular microbes is impaired. D. There is limited diversity in the repertoire of IgM antibodies produced. E. There is no evidence of somatic mutation of IgM variable regions.

D. There is limited diversity in the repertoire of IgM antibodies produced. This is a common presentation of hyper-IgM syndrome. Patients with this disease have B cells that are unable to undergo isotype switching, and therefore contain only IgM in the serum but very low levels of IgG, IgA, and IgE. Clinically, these patients are susceptible to bacterial infections and often present with a history of recurrent pneumonia, otitis media, and gastrointestinal infections. Mutations in genes coding for CD40L, CD40, and activation-induced deaminase (AID) have been identified in these patients. During an immune response, T cell interactions with B cells via CD40L-CD40, as well as active AID, are both essential for numerous processes, including isotype switching, somatic mutation, and germinal center formation. Thus, patients with hyper-IgM syndrome produce antibodies that typically have a lower affinity for antigen (due to the lack of somatic mutation) and do not develop large follicles containing a light zone and dark zone (germinal center) within lymph nodes. Mechanisms of generation of diversity of the Ig repertoire should not be impaired in this patient. Although somatic mutation of variable regions will be impaired, this will not be manifest in IgM antibodies. In addition, patients with either CD40L or CD40 mutations, but not AID mutations, will have an increased susceptibility to certain intracellular infections (such as Pneumocystic carinii pneumonia), because the microbicidal activity of macrophages is partially dependent on CD40-mediated signals.

All of the following molecules act as transcription factors in T cell activation signaling EXCEPT: A. NF-κB B. Jun C. Fos D. NFAT E. Ras

E. Ras All of these proteins are involved in the activation of T cells. However, Ras is not a transcription factor but a guanosine triphosphate (GTP)-binding protein present in the cytosol and in association with the plasma membrane. On exchange of guanosine diphosphate (GDP) for GTP, the Ras protein becomes functional and acts as an allosteric activator of MAP kinases, which leads the transcription of Fos.

Which of the following comparisons between TH1 and TH2 cells is true? A. TH1 cells produce interleukin (IL)-1 but not IL-2, and TH2 cells produce IL-2 but not IL-1. B. TH1 cells are class I major histocompatibility complex (MHC) restricted, and TH2 cells are class II MHC restricted. C. The chemokine receptors CXCR3 and CCR5 are more highly expressed on TH2 cells than on TH1 cells. D. TH2 cells are more likely to bind to E-selectin and P-selectin on endothelial cells than are TH1 cells. E. TH1 cells produce interferon (IFN)-γ but not IL-4, and TH2 cells produce IL-4 but not IFN-γ.

E. TH1 cells produce interferon (IFN)-γ but not IL-4, and TH2 cells produce IL-4 but not IFN-γ. The signature cytokines of TH1 and TH2 cells are interferon-γ and interleukin (IL)-4, respectively. IL-5 and IL-13 are also very specific for TH2 cells. IL-1 is not typically produced by helper T cells of either subset. IL-2 is produced by naive T cells and TH1 cells. Both TH1 and TH2 cells are CD4+ helper T cells, and therefore are both restricted to recognizing peptide antigens bound to class II MHC molecules. The trafficking patterns of TH1 and TH2 cells differ, and this is related to differences in the expression of adhesion molecules and chemokine receptors. TH1 cells express abundant functional ligands for E-selectin and P-selectin and the chemokine receptors CXCR3 and CCR5, which bind to various chemokines found at sites of active innate immune responses. TH2 cells bind poorly to endothelial selectins and express less CXCR3 and CCR5.

Antibody feedback is mediated by which of the following molecules? A. Ig FcγRIIB B. Ig Fcε C. Ig FcγRI D. CR1 E. IgM

A. Ig FcγRIIB Antibody feedback is the mechanism of regulation of humoral immune responses and is mediated by the Ig FcγRIIB receptor, which delivers inhibitory signals into the B cells on binding the Fc portion of IgG.

Which of the following molecules is NOT important in the interaction between a cytolytic T lymphocyte and a target cell? A. B7-1 B. ICAM-1 C. LFA-1 D. T cell receptor E. Class I MHC

A. B7-1 Although naive CD8+ T cells require second signals, such as B7 costimulation, in order to differentiate into effector cytolytic T lymphocyte (CTL), once differentiated, the CTL can kill a target cell that does not express costimulatory molecules. The CTL only requires one signal for killing of the target cell, which depends on the T cell receptor binding to a peptide-class I MHC complex on the surface of the target cell. Tight adhesion between the CTL and target cell is also required, and this is often mediated by T cell integrin LFA-1 binding to target cell ICAM-1.

Which one of the following signaling molecules, if mutated, would affect B cell maturation and function primarily without affecting T cell function? A. Btk B. Itk C. Tec D. PI-3 kinase E. Zap-70

A. Btk Btk is a Tec family protein tyrosine kinase that is particularly important in pre-B cell receptor complex signaling, and therefore in B cell maturation and activation. Mutations in Btk are responsible for X-linked agammaglobulinemia. Itk and Tec are other members of the Tec family that are important in T cells. PI-3 kinase is a phospholipid kinase involved in signaling in many cell types, including B and T cells, and Zap-70 is a protein tyrosine kinase particularly important in TCR signaling in T cells.

Which of the following descriptions about affinity maturation is correct? A. Depends on somatic mutation of V genes B. Depends on negative selection of B cells that can bind antigen in the germinal center C. Depends on antigen processing and presentation by dendritic cells within the germinal center D. Depends on the autoimmune regulator (AIRE) gene E. Depends on somatic recombination of Ig V genes

A. Depends on somatic mutation of V genes Somatic mutation of V genes is the basis for production of immunoglobulins with different affinities, which are then positively selected in the germinal center; B cells that cannot bind antigen with high affinity die through a default pathway of apoptosis. Antigen processing and presentation by dendritic cells are required to generate helper T cells outside the follicle, but not to activate B cells in the follicle. Autoimmune regulator (AIRE) is involved in thymic expression of tissue antigens but is not involved in affinity maturation. Somatic recombination of V genes is involved in producing functional Ig genes during B cell development, but it is not involved in germinal center reactions.

Activated macrophages perform all of the following functions EXCEPT: A. Inhibition of fibroblast proliferation and angiogenesis within damaged tissues B. Production of lysosomal enzymes and reactive oxygen species that kill phagocytosed microbes C. Presentation of antigen to helper T cells D. Secretion of inflammatory cytokines such as tumor necrosis factor and interleukin-1 E. Production of nitric oxide, which helps kill microorganisms

A. Inhibition of fibroblast proliferation and angiogenesis within damaged tissues Activated macrophages, through the secretion of growth factors, promote fibroblast proliferation and angiogenesis in an effort to repair damaged tissues.

A 56-year-old woman sees her primary care physician complaining of flank pain and hematuria and is found to have a hematocrit of 56%. She is subsequently diagnosed with advanced renal cell carcinoma. Part of the patient's management involves systemic cytokine therapy; however, the patient develops severe pulmonary edema as a result of the treatment. Which of the following cytokines was most likely used in this patient's therapy? A. Interleukin (IL)-2 B. IL-6 C. IL-12 D. GM-CSF (granulocyte-macrophage colony-stimulating factor) E. TNF (tumor necrosis factor)

A. Interleukin (IL)-2 The classic clinical findings of renal cell carcinoma include flank pain and hematuria. These patients commonly have elevated hematocrits secondary to the overproduction of erythropoietin, which increases red blood cell production in the bone marrow. Of the systemic cytokine therapies used in cancer therapy, only interleukin (IL)-2 and IL-6 have been used frequently for renal cancer. Whereas IL-6 has not demonstrated any clinical benefit in these patients, IL-2 has been effective in inducing measurable tumor regression responses in a small percentage of patients (<15%). IL-2 therapy is highly toxic and can induce fever, pulmonary edema, and vascular shock.

Which one of the following statements about humoral immune responses is true? A. Naive B cells are required for initiation of primary responses and memory B cells are required for initiation of secondary responses. B. Antibody responses to bacterial polysaccharide antigens require CD4+ helper T cells. C. Heavy chain isotype switching typically occurs in response to bacterial polysaccharide antigens. D. Affinity maturation does not require helper T cells. E. Antibody-secreting cells generated during a humoral immune response live for only a few hours.

A. Naive B cells are required for initiation of primary responses and memory B cells are required for initiation of secondary responses. Humoral responses require antigen-dependent activation of B cells through binding of the antigen to membrane Ig on naive B cells or on memory B cells, for primary or secondary responses, respectively. In most cases, nonprotein antigens do not stimulate isotype switching or affinity maturation because these changes require T cell help, and only protein antigens can stimulate T cells. For both nonprotein and protein antigens, antibody-secreting cells that are generated may live for months, often in the bone marrow.

Which of the following molecules is involved in the principal mechanism by which the immune system kills tumor cells? A. Perforin B. Complement C3 C. IgG D. TGF-β E. Interleukin-2

A. Perforin Cytolytic T lymphocyte (CTL) killing of tumor cells is the principal known mechanism for tumor immunity in vivo. This requires class I MHC expression by the tumor cells. In addition, natural killer cells (NK cells) can kill tumor cells that lack class I MHC. CTL and NK cells employ the same mechanism to kill tumor cells, which depends on perforin and granzyme B release from cytoplasmic granules. Although antibodies (e.g., IgG) and complement can kill tumor cells in vitro and tumor-specific antibodies can be detected in patients, it is not known if Ig or complement plays a significant role in tumor immunity in vivo. TGF-β (transforming growth factor-β) is an immunoregulatory cytokine produced by T cells and other cell types. TGF-β does not kill tumor cells. Interleukin-2 has been used in protocols to treat certain tumors, but its effect is indirect and it does not directly kill tumor cells.

Which one of the following accurately depicts the correct order of events in a TCR signal transduction pathway? A. TCR → Lck → Zap-70 → LAT → Grb-2 → SOS → Ras → Erk → Fos B. TCR → Lck → Zap-70 → LAT → SOS → Grb-2 → Ras → Erk → Fos C. TCR → Lck → ITK → LAT → Grb-2 → SOS → Ras → Erk → Fos D. TCR → Lck → Zap-70 → LAT → SOS → Grb-2 → Ras → Erk → Jun E. TCR → Lck → Zap-70 → LAT → PLCγ → DAG → calcium release

A. TCR → Lck → Zap-70 → LAT → Grb-2 → SOS → Ras → Erk → Fos Activated Zap-70 phosphorylates the transmembrane adapter protein LAT at tyrosine residues, which serve as docking sites for SH2 domains of other proteins. In one pathway, the SH2 domain of Grb-2 binds to phosphorylated LAT. Grb-2 is then able to recruit Sos to the membrane. Sos catalyzes GDP/GTP exchange on Ras, a G protein that is active when guanosine triphosphate (GTP) is bound and inactive when guanosine diphosphate (GDP) is bound. Active Ras functions as an allosteric activator of mitogen-activated protein kinases (MAPK), leading to downstream activation of Erk through phosphorylation. Activated Erk stimulates the transcription of Fos (through intermediate activation of a protein called Elk). In a second pathway, PLCγ binds directly to activated LAT and is then phosphorylated by Zap-70. Activated PLCγ leads to the cleavage of PIP2 to IP3 and DAG. Although DAG activates protein kinase C (PKC), it is IP3 that causes a release of calcium into the cytosol.

Most effective vaccines that are currently in widespread use are specific for pathogenic viruses, and the immunity induced by the vaccines is mediated largely by antibodies. Which of the following statements accurately describes the major mechanism by which these vaccine-dependent antibody responses function? A. The antibodies bind extracellular viral particles and prevent them from infecting cells. B. The antibodies bind to viral antigens on the surface of infected cells and promote phagocytosis of the cells. C. The antibodies bind to viral antigens on the surface of infected cells and promote complement-mediated lysis of the cells. D. The antibodies bind to extracellular viral particles and target Fc receptor-expressing cytolytic T lymphocytes to kill the viruses. E. The antibodies bind to viral envelope proteins and induce signals that inhibit viral replication.

A. The antibodies bind extracellular viral particles and prevent them from infecting cells. Antiviral vaccines work by generating long-lived antibody-producing cells and memory B cells that can secrete high affinity neutralizing antibodies, which prevent viral particles from entering host cells. The antibodies may prevent primary infection as well as prevent reinfection of cells after virions are released from an infected cell. Some vaccine-induced antiviral antibodies may opsonize viral particles and promote their phagocytosis. Antibody-dependent complement activation may also promote phagocytes or lysis of extracellular enveloped viruses. However, opsonization and lysis of virally infected host cells may not always be protective since these mechanisms could promote spread of viruses from cell to cell. Cytolytic T lymphocytes do not have Fc receptors, and they cannot directly kill virions but only kill host cells expressing viral proteins. Membrane proteins of enveloped virions are not linked to signal transduction pathways.

A 23-year-old man who was recently infected by the HIV virus volunteered for investigative studies of his immune response to the virus. Investigators identified cytolytic T lymphocytes (CTLs) in the patient's blood that recognized a particular peptide derived from a protein encoded by the HIV gag gene. Six months later, viral isolates from the patient showed point mutations in the gag gene sequence encoding that peptide. Which of the following statements about the HIV gag mutations is most likely to be correct? A. The patient's CTL response to the virus provided selective pressure for the emergence of virus carrying the mutation. B. The CTL that recognized the original gag-encoded peptide will still be able to recognize the mutated Gag peptide. C. The CTLs specific for the original Gag peptide were incapable of killing HIV-infected cells. D. The gag mutation will enhance the ability of natural killer cells to recognize and kill HIV infected cells. E. The gag mutations have more relevance to the viral evasion of the antibody response rather than the CTL response.

A. The patient's CTL response to the virus provided selective pressure for the emergence of virus carrying the mutation. Cytolytic T lymphocytes (CTLs) are highly specific for short peptide epitopes of viral proteins bound to self-MHC molecules. Random mutations in the viral genome that alter these peptide sequences will lead to escape from CTL detection. Therefore, CTLs do provide a selective pressure for such mutations. Given these selective pressures, it is most likely that the mutations that are found in the virus that has survived in the patient are no longer recognized by the CTL. Because only one or two amino acid residues of a viral peptide will contact a particular TCR, point mutations that ablate T cell recognition are likely to occur. The emergence of escape variants with mutated peptides implies that the CTLs that recognized the original peptide were capable of killing the infected cells, but mutations arose before all infected cells were killed. Natural killer cells recognize alterations in self class I MHC expression but do not recognize specific viral peptide sequences. Although antibodies may be produced specific for distinct epitopes of the same proteins that elicit CTL responses, the information given about changes in a T cell epitope implicate the relevance of the CTL response.

Damage to neurons in patients with multiple sclerosis (MS) may be caused by autoreactive T cells that recognize peptides derived from myelin proteins presented by self MHC molecules. These autoreactive T cells secrete interferon (IFN)-γ and promote inflammation, which damages the myelin sheath surrounding neurons. The exact immunodominant epitopes recognized by autoreactive T cells in MS patents have been identified. One potential method of therapy for patients with MS is to administer therapeutic peptides that differ from the immunodominant epitopes by one or two amino acids. Which one of the following statements best describes the basis for this therapeutic approach? A. The therapeutic peptides, called "altered peptide ligands," could inactivate T cells specific for myelin proteins, or drive them to differentiate into T cells that do not produce IFN-γ. B. The therapeutic peptides, called "altered peptide ligands," could interfere with processing of the natural myelin proteins by the patient's antigen-presenting cells. C. The therapeutic peptides could bind to the TCRs of myelin-specific T cells but not to the self MHC molecules, thereby blocking T cell activation. D. The therapeutic peptides could down-regulate MHC expression. E. The therapeutic peptides could replace the damaged myelin and restore neuronal function.

A. The therapeutic peptides, called "altered peptide ligands," could inactivate T cells specific for myelin proteins, or drive them to differentiate into T cells that do not produce IFN-γ. Altered peptide ligands are synthetic peptides in which the TCR contact residues have been changed, so that the peptide induces only partial responses by the responding T cell. These peptides still bind to the same MHC molecules as the original peptides, but they can cause T cell inactivation (anergy) or change in the cytokines the T cell produces. Altered peptide ligands do not interfere with processing of the natural proteins nor can they bind to TCRs without being presented by MHC molecules. There is no basis to say that peptides can down-regulate major MHC expression or replace damaged proteins in the myelin sheath.

A 7-month-old boy, the only child of second-degree cousins, saw a pediatrician for immunologic evaluation after developing Pneumocystis carinii pneumonia. Serum IgG, IgM, and IgA levels were normal. Blood cell count showed 10,600 leukocytes/mm3 and 80% lymphocytes; 90% of the lymphocytes were TCR αβ+ CD4+. In vitro lymphocyte-proliferative responses to PHA and anti-CD3 were absent, and the pattern of tyrosine-phosphorylated cytoplasmic proteins after anti-CD3 treatment of the T cells was distinctly abnormal. This boy most likely carries homozygous mutations in the gene encoding which one of the following proteins? A. Zap-70 B. RAG-1 C. CD3 D. Pre-Tα E. TCRα

A. Zap-70 The patient shows signaling defects in TCR-mediated T cell activation, as well as defects in CD8+ T cell maturation. Zap-70 is a tyrosine kinase required for TCR-mediated T cell activation. Mutations in Zap-70 result in impaired TCR signaling, with abnormal tyrosine phosphorylation of downstream signaling molecules, and also a defect in CD8+ T cell maturation. It is not known why CD8+ maturation is selectively impaired in Zap-70 deficiency. VDJ recombination, and therefore RAG-1 function, must still be intact because TCR-expressing CD4+ T cells do mature. CD3, pre-Tα, and TCRα are also required for maturation of CD4+ T cells, and therefore these molecules must all be expressed by this patient.

Which of the following mechanisms contributes to the change from B cell production of membrane Ig to secreted Ig? A. V(D)J recombinase-mediated deletion of the exon encoding the transmembrane domain B. Alternative processing of primary RNA transcripts to remove the transmembrane domain and include a secretory tail piece C. Increased vesicular exocytosis of intracellular stores of the secretory form of Ig D. Switch recombinase-mediated recombination of the heavy chain locus to juxtapose the V(D)J segment with the exon encoding a secretory tail piece E. Up-regulation of ectoenzymes that proteolytically cleave membrane Ig heavy chains just proximal to the membrane

B. Alternative processing of primary RNA transcripts to remove the transmembrane domain and include a secretory tail piece Primary transcripts of Ig genes include sequences encoding both transmembrane and secretory tail piece domains. Alternative splicing of these transcripts determines which form of Ig is ultimately made. V(D)J recombinases are not involved in modifications of Ig heavy chain expression, and switch recombinases are only involved in changes in DNA related to isotype switching. Membrane Ig is not cleaved to form secretory Ig.

Which of the following binds to and is readily phagocytosed by mononuclear phagocytes and neutrophils? A. Antigen-IgM complexes B. Bound complement protein C3b C. Free serum IgG D. IgE bound to a helminthic parasite E. Mannose-binding lectin (MBL)

B. Bound complement protein C3b Mononuclear phagocytes and neutrophils bind to complement protein C3b primarily through the CR1 receptor, which then stimulates phagocytosis of the complement-bound pathogen. Although phagocytes have Fc receptors of IgG isotypes, free IgG molecules without bound antigen do not bind tightly to these receptors to stimulate phagocytosis. There are no IgM Fc receptors and therefore antigen-IgM complexes are not phagocytosed readily, unless they have activated complement. Mannose-binding lectin (MBL) promotes complement activation on mannose-containing microbial surfaces and mannose can bind to phagocyte mannose receptors, but MBL alone does not bind to phagocyte receptors.

Patients with which of the following disorders would be LEAST likely to develop Epstein-Barr virus-associated Burkitt's lymphoma? A. AIDS B. Bruton's disease C. DiGeorge syndrome (congenital absence of the thymus) D. Malarial infection E. Immunosuppressive therapy for renal allograft

B. Bruton's disease Epstein-Barr virus (EBV) is a double-stranded DNA virus of the herpesvirus family that infects nasopharyngeal epithelial cells as well as B cells. The virus establishes a latent infection in these cells, and T cell-mediated immunity is required for control of EBV infections and, in particular, for killing of EBV-infected B cells. It has been demonstrated that loss of normal T cell function allows latently infected B cells to progress toward malignant transformation. Thus, patients with disorders that cause T cell immunodeficiencies (e.g., AIDS, DiGeorge syndrome, malarial infection, and transplantation patients taking immunosuppressive therapies) are at increased risk of developing Burkitt's lymphoma. Bruton's disease is an isolated B cell deficiency due to mutation of Btk, a tyrosine kinase required for the maturation of B cells in the bone marrow. Therefore, patients with Bruton's disease are not likely to develop B cell lymphomas.

B. CD40 If the patient's sister is also affected with hyper-IgM syndrome, then the inheritance pattern is autosomal recessive. Both the AID and CD40 genes are located on autosomal chromosomes, and mutations in both have been identified as causes of hyper-IgM syndrome. However, only a mutation in CD40 will result in reduced macrophage function and susceptibility to Pneumocystis carinii pneumonia, as is observed in this patient.

Which of the following statements about cell-mediated immunity (CMI) is NOT true? A. Deficiencies in CMI result in susceptibility to infections by viruses and intracellular bacteria. B. CMI can be adoptively transferred by injecting serum from one individual to another. C. Delayed-type hypersensitivity (DTH) is not a protective response against intracellular bacteria such as Mycobacterium tuberculosis. D. The principal form of CMI that protects against viral infections is mediated by CD8+ cytolytic T lymphocytes. E. Phagocytes are essential in the effector phase of CMI responses to bacteria such as Listeria monocytogenes.

B. CMI can be adoptively transferred by injecting serum from one individual to another. The original definition of cell-mediated immunity (CMI), which is still valid, is protection against infection that can be transferred by T cells but not by serum. Serum is a cell-free fraction of blood that includes antibodies, and therefore serum transfer can provide passive humoral immunity. CMI is required for protection against microbes that can reside within cells and therefore are inaccessible to antibodies. These organisms include microbes that are phagocytosed and viruses that replicate in the cytoplasm. Immunodeficiency states in which CMI is impaired (e.g., AIDS) result in infections by viruses and intracellular bacteria or fungi. Delayed-type hypersensitivity (DTH), like all hypersensitivity reactions, causes tissue damage and disease, but not protection. It is true that DTH reactions involve the same cells and molecules as does CMI.

All of the following are accurate statements about neonatal immunity EXCEPT: A. Transfer of maternal IgG across the placenta is mediated by an Fc receptor structurally similar to class I MHC. B. IgA is absorbed in the gut from breast milk and re-secreted by the infant into the bronchial mucosa. C. IgA secretion into breast milk involves transport through breast epithelial cells, and is dependent on the poly-Ig receptor. D. Transport of IgG across the neonatal intestinal epithelium is mediated by an Fc receptor structurally similar to class I MHC. E. Loss of maternal antibodies is partly responsible for increased frequency of infections in infants at about 6 months of age.

B. IgA is absorbed in the gut from breast milk and re-secreted by the infant into the bronchial mucosa. IgA is secreted into breast milk via poly-Ig receptor-mediated transcellular transport, but it is not reabsorbed in the infant's gut. Rather, IgA remains in the lumen of the alimentary canal as a defense against intestinal microbes. IgG from breast milk is reabsorbed into the circulation from the gut lumen by the class I MHC-like neonatal Fc receptor (FcRN). This same receptor also mediates transplacental transport of IgG. Passive immunity mediated by maternal antibodies wanes with time; at about 6 months, infants have a nadir of circulating antibodies because maternal antibodies are depleted and antibodies produced by the infant have not reached maximal levels. This nadir corresponds to a period of increased susceptibility to infections, which is even more exaggerated in children with immunodeficiency diseases.

Which of the following anatomic regions is normally protected from pathogens only by humoral immune responses and not by cell-mediated immune responses? A. Skin B. Intestinal lumen C. Intestinal epithelium D. Central nervous system E. Spleen

B. Intestinal lumen The lumen of mucosal lined tissues, such as the intestinal and bronchial lumen, are protected by IgA, which is actively secreted at these sites. T cells do not normally migrate into these lumen and are usually involved in immune responses to organisms that breach the surface linings of these structures. The epithelial linings of mucosal tissues and the skin do contain lymphocytes that protect against invading pathogens. Both antibodies and T cells are involved in responses to infections within most other tissues.

A 15-year-old girl is brought to a pediatric clinic with severe abdominal pain, nausea, and vomiting. She does not have a fever, peritoneal signs, or an elevated white blood cell count. The symptoms resolve in 48 hours. She has a history of multiple transient episodes of facial edema without pruritus. Laboratory examination is most likely to reveal which of the following abnormalities in this patient? A. C4 deficiency B. Reduced levels of C1 inhibitor (C1 INH) C. Absence of C3 D. Presence of C3 nephritic factor E. Deficiency of factor I

B. Reduced levels of C1 inhibitor (C1 INH) This patient's presentation and history are consistent with a diagnosis of hereditary angioneurotic edema, which is due to genetic or acquired deficiencies in C1 inhibitor (C1 INH). C1 INH normally blocks excessive C1 activation and proteolysis of C2 and C4. Reduced levels of C1 INH cause excessive proteolysis and reduced levels of C4 and C2, as well as generation of vasoactive peptides derived from C4 and C2. These peptides cause edema. Gastrointestinal symptoms are due to bowel wall edema. Laryngeal edema can be life threatening. C4 deficiency due to gene mutations, which constitutes the most common complement system deficiency, predisposes to systemic lupus erythematosus (SLE) or SLE-like illness. Deficiency of C3 is associated with severe, recurrent bacterial infections at an early age and immune complex glomerulonephritis. C3 nephritic factor is an autoantibody against the alternative pathway C3 convertase. Patients with this antibody present with an illness similar to C3 deficiency. Factor I deficiency is associated with a failure to regulate C3 convertase, so that C3 becomes depleted and patients suffer recurrent infections and glomerulonephritis.

Which one of the following statements about MHC-TCR interactions is NOT true? A. Antigen receptors on T cells bind to MHC molecules for only brief periods of time. B. The affinity of most TCRs for peptide-MHC complexes is similar to the affinity of antibodies for their antigens. C. Only 1% or less of the MHC molecules on any antigen-presenting cell (APC) display a peptide recognized by a particular T cell. D. T cells usually require multiple engagements with an APC before a threshold of activation is reached. E. A subthreshold number of MHC-TCR interactions can lead to T cell inactivation.

B. The affinity of most TCRs for peptide-MHC complexes is similar to the affinity of antibodies for their antigens. In general, the TCR binds to peptide-MHC complexes with lower affinity than antigen-antibody interactions. This relatively low-affinity interaction occurs briefly; thus, a T cell may need multiple engagements with the antigen-presenting cell (APC) before a threshold of activation occurs. If this threshold is not reached, the T cell may enter into an inactive state known as anergy. On any given APC, less than 1% of the MHC molecules display the same peptide.

The first experiments that demonstrated protective adaptive immune responses to tumors involved transplantation of chemical carcinogen-induced tumors between rodents. Which of the following facts was learned from these experiments? A. There are only a limited number of antigens that can evoke a protective anti-tumor response. B. Transplanted sarcomas can evoke protective cytolytic T lymphocyte responses. C. Carcinomas express tumor antigens that are recognized by T lymphocytes. D. Protective immune responses against tumors are largely mediated by antibodies. E. Spontaneously arising tumors are often eradicated by cytolytic T lymphocytes.

B. Transplanted sarcomas can evoke protective cytolytic T lymphocyte responses. The chemical carcinogen used in many of the rodent tumor immunology experiments was methylcholanthrene (MCA), which causes tumors derived from mesenchymal cells of the skin, called sarcomas. When transplanted into naive mice, these MCA-induced sarcomas would evoke protective immune responses. Adoptive transfer studies showed that cytolytic T lymphocytes, and not antibodies, were mediating the protective effect. Interestingly, the T cells specific for one MCA-induced sarcoma usually could not recognize another MCA-induced sarcoma, indicating that there are innumerable potential T cell antigens expressed by these tumors. Most of these antigens are now known to be different, randomly mutated cellular proteins, which are presented by the class I MHC pathway on the surface of the tumor cells. These chemical carcinogen-induced sarcoma studies do not provide any information about antigens on carcinomas, nor do they prove that there are protective immune responses to spontaneously arising tumors in people.

Which of the following mechanisms does NOT contribute to the generation of a cytolytic T lymphocyte (CTL) response to a viral infection? A. Dendritic cells phagocytose infected cells or viral particles and present them to naive CD8+ T cells via the class I MHC pathway. B. Dendritic cells are infected with the virus and present viral peptides to naive CD8+ T cells via the class I MHC pathway. C. CTLs are directly activated by CD40L expressed on activated helper T cells through CD40. D. Helper T cells secrete cytokines, such as interleukin-2, that promote the proliferation and differentiation of CD8+ T cells. E. Helper T cells activate infected antigen-presenting cells (APCs) via the CD40 ligand-CD40 pathway, and the activated APCs present viral peptides to naive CD8+ T cells via the class I MHC pathway.

C. CTLs are directly activated by CD40L expressed on activated helper T cells through CD40. T cells do not express CD40, and they do not respond directly to CD40 ligand. There is clear evidence that CD8+ cytolytic T lymphocyte (CTL) responses to viral infections require professional antigen-presenting cells (APCs) as well as CD4+ helper T cells. How this works is complicated; all viruses do not infect professional APCs, and helper T cells are class II MHC restricted whereas CD8+ CTL precursors are class I MHC restricted. Several mechanisms have been shown to contribute to naive CD8+ T cell activation in experimental systems. One mechanism is cross presentation of viral peptides by professional APCs that were not infected but acquired the viral antigens from other cells. Infected APCs may present viral peptides to CD4+ T cells, stimulating a helper T cell response, which then, via secreted cytokines, helps activate CD8+ T cells. Helper T cells may also enhance APC function of infected cells via CD40-CD40 ligand interactions.

The induction phase of a cell-mediated immune response includes which of the following events? A. CD4+ T cell secretion of interferon-γ leading to macrophage activation B. CD8+ T cell lysis of a virally infected cell C. Clonal expansion of CD8+ T cells within a lymph node D. Migration of CD4+ effector T cells from blood vessels into a tissue site of infection E. Migration of a naive CD4+ T cell from the thymic medulla into the circulation

C. Clonal expansion of CD8+ T cells within a lymph node The induction phase of cell-mediated immune responses occurs in lymphoid tissues and includes antigen presentation to naive T cells, leading to clonal expansion and differentiation of those T cells into effector cells. Migration into infection sites and interferon-γ secretion by CD4+ helper T cells, as well as target cell killing by CD8+CTL, are part of the effector phases of cell-mediated immune responses. Naive T cell migration out of the thymus is the last step in T cell maturation and occurs regardless of the presence of antigen.

A 17-year-old boy is taken to the emergency department because of severe abdominal and lumbar pain. Physical examination reveals splenomegaly, and laboratory studies reveal hemoglobinemia and thrombocytopenia. A urine sample is remarkable for gross hemoglobinuria. The patient reports a history of bloody urine on multiple occasions in the past. Flow cytometric analysis of the patient's red blood cells (RBC) will most likely indicate reduced or absent expression of which pair of molecules that is normally present on RBC membranes? A. Complement receptor 1 (CR1) and CR2 B. C1 inhibitor (C1 INH) and membrane cofactor protein (MCP, CD46) C. Decay accelerating factor (DAF, CD55) and CD59 D. C4 binding protein (C4bp) and factor H E. Complement receptor 3(CR3) and complement receptor 4(CR4)

C. Decay accelerating factor (DAF, CD55) and CD59 The patient's history is consistent with a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH; Marchiafava-Micheli syndrome), which is due to a genetic defect in the synthesis of glycosyl-phosphatidyl-inositol (GPI) anchors for membrane proteins. Two important regulatory proteins of the complement system, DAF (CD55) and CD59, are expressed as GPI-linked membrane proteins, and therefore their expression is reduced in PNH. DAF normally promotes dissociation of C3 convertase that spontaneously forms on blood cells at a low level. CD59 prevents assembly of poly-C9 and MAC-mediated lysis of blood cells. Without sufficient expression of CD55 and CD59, red blood cells and platelets are susceptible to complement-mediated membrane damage, causing thrombosis and hemolysis. CR1 and CR2 deficiencies have not been reported. C1 INH deficiency causes hereditary angioneurotic edema. C4bp and factor H are not membrane proteins, but rather are soluble plasma proteins that block classical and alternative C3 convertase formation, respectively. CR3 and CR4 are integrins that function as adhesion molecules on leukocytes as well as on complement receptors. Leukocyte adhesion deficiency I, caused by mutations in the gene encoding the CD18 β chain of these integrins, manifests as an immunodeficiency disease.

In 1890, Emil von Behring and Shibasaburo Kitasato demonstrated the efficacy of serum transfer at conferring infection resistance—a process now known as "passive immunity." The researchers isolated serum from animals that had recovered from infection with the diphtheria bacilli and subsequently injected the serum into other healthy animals. This procedure conferred specific resistance against the pathologic effects of diphtheria infection in the recipient animals. Which of the following immune phenomena were primarily responsible for these effects? A. Pathogen-specific B and T cells from the original infected animals triggered a robust immune response after re-exposure to diphtheria antigens in the recipient animal. B. Inflammatory cytokines in the transferred serum increased the strength and efficacy of innate immune system activity. C. Diphtheria-specific antibodies in the transferred serum neutralized bacillus toxins and promoted bacterial elimination by innate effector cells. D. Serum complement proteins in the transfer directly promoted bacterial cell lysis and phagocytosis. E. The recipient animal's immune response to the foreign serum further activated host immune system function, allowing greater response to the bacillus infection.

C. Diphtheria-specific antibodies in the transferred serum neutralized bacillus toxins and promoted bacterial elimination by innate effector cells. The serum from infected animals contains diphtheria-specific antibodies. Some of these antibodies can bind to and neutralize diphtheria toxin, reducing symptoms of infection, whereas others interact with the bacilli themselves, inducing bacterial death by phagocytosis and complement fixation. Antibodies have a half-life of several weeks in the circulation, and therefore promote short-term disease resistance and immunity. No B cell or T cell would have been transferred with the serum, which is a cell-free fraction of blood. It is unlikely that there are inflammatory cytokines in the serum donor, because it had already recovered from infection, and cytokines alone would not impart resistance to infection. Serum transfer should not provide any complement components not already present in the recipient. Although it is possible that the foreign serum elicited an immune response to allelic differences in the transferred serum proteins, this should not impart specific resistance to diphtheria.

All of the following are early T cell events that occur after antigen recognition by the TCR EXCEPT: A. Formation of the immunologic synapse B. Recruitment of signaling molecules, such as LAT, to glycolipid-enriched domains known as lipid rafts C. Enhanced adhesion between T cells and antigen-presenting cells (APCs) via T cell integrin LFA-1 and its ligand on the APC, ICAM-1, at the central zone of the immunologic synapse D. Clustering of the TCR and coreceptors leading to phosphorylation of ITAMs on CD3 by Lck E. Binding of CD28 with costimulators on APCs in the cSMAC, resulting in signal transduction activation

C. Enhanced adhesion between T cells and antigen-presenting cells (APCs) via T cell integrin LFA-1 and its ligand on the APC, ICAM-1, at the central zone of the immunologic synapse On binding of the TCR complex with MHC-associated peptides on an antigen-presenting cell (APC), several T cell surface proteins and intracellular signaling molecules are rapidly mobilized to the site of contact, known as the immunologic synapse. Molecules that are recruited to the central supramolecular activation cluster, or center of the synapse, include the TCR complex (TCR, CD3, and ζ chains), CD4 or CD8 coreceptors, and costimulatory molecules (CD28). The clustering of signaling molecules results in the phosphorylation of ITAMs on CD3 by CD4- or CD8-associated Lck. Integrins remain at the peripheral zone of the synapse and stabilize the binding of the T cell to the APC. LAT is a transmembrane adaptor molecule recruited to the synapse whose cytoplasmic tail forms part of a scaffold of signaling molecules.

Which one of the following statements about the molecules B7-1 and B7-2 is NOT true? A. B7-1 and B7-2 expression on antigen-presenting cells (APCs) is upregulated by the presence of "danger" signals, such as lipopolysaccharide, as well as cytokines, such as interferon (IFN)-γ. B. B7-1 and B7-2 are expressed at low levels on some resting APCs. C. Induction of B7-1 usually occurs before the induction of B7-2 in an immune response. D. B7-1 and B7-2 bind to CD28 on T cells and provide "second signals" for naive T cell activation. E. Activated helper T cells can induce expression of B7-1 and B7-2 on APCs via CD40L binding to CD40.

C. Induction of B7-1 usually occurs before the induction of B7-2 in an immune response. The temporal patterns of B7-1 and B7-2 expression differ. B7-2 is expressed constitutively at low levels and induced early after activation of antigen-presenting cells (APCs), whereas B7-1 is not expressed constitutively and is induced hours or days later. The expression of B7-1 and B7-2 on APCs is induced by "danger signals" of infection. These signals are mediated by binding of lipopolysaccharide (LPS), unmethylated CpG DNA, and other ligands of Toll-like receptors. Signals mediated through cytokines, such as interferon (IFN)-γ, as well as through CD40 ligand, can also up-regulate B7-1 and B7-2 expression on APCs. Both B7-1 and B7-2 bind to CD28 on naive T cells, thus providing the second signal needed for activation of T cells.

Which one of the following statements about T cells involved in an immune response is NOT true? A. Activated T cells receive survival signals from antigen during an infection. B. Activated T cells contribute to the activation of antigen-presenting cells via CD40 ligand. C. Memory T cells generated during a primary immune response express high levels of interleukin-2 receptors and actively proliferate long after the primary response is completed. D. The major effector function of helper T cells is to activate macrophages and other cells by releasing cytokines. E. When an infection is eliminated, activated T cells die by apoptosis.

C. Memory T cells generated during a primary immune response express high levels of interleukin-2 receptors and actively proliferate long after the primary response is completed. Memory T cells are not actively proliferating and do not express high levels of IL-2 receptors. Instead, these cells are functionally quiescent and are not performing effector functions after a primary immune response. Effector T cells continue to survive in the periphery via proliferative signals from MHC-antigen binding to the TCR. Effector helper T cells can then activate macrophages and other lymphocytes via release of cytokines such as IFN-γ, as well as through CD40 ligand on the cell surface. On elimination of the infection, the effector T cells die by apoptosis.

Which one of the following statements accurately describes antigen recognition events in a lymph node during a helper T cell-dependent antibody response to a protein antigen? A. Naive B cells and naive T cells simultaneously recognize the intact protein antigen. B. Naive B cells recognize intact proteins, generate peptide fragments of these proteins, and present them in complexes with major histocompatibility complex (MHC) molecules to naive helper T cells. C. Naive B cells recognize intact proteins, generate peptide fragments of these proteins, and present them in complexes with MHC molecules to differentiated helper T cells. D. Naive T cells recognize peptides bound to MHC molecules presented by dendritic cells, and naive B cells recognize the intact protein antigen bound to the surface of follicular dendritic cells. E. Differentiated helper T cells recognize peptides bound to MHC molecules on dendritic cells, and the T cells secrete cytokines that promote antibody production by any nearby B cells that have recognized different protein antigens.

C. Naive B cells recognize intact proteins, generate peptide fragments of these proteins, and present them in complexes with MHC molecules to differentiated helper T cells. T cells and B cells cannot recognize the same protein antigen molecule simultaneously because T cells only recognize peptide-MHC complexes. B cells bind intact proteins, internalize them via surface Ig, and then present peptide-MHC complexes to helper T cells, not to naive T cells. The helper T cells specific for the peptide-MHC complexes have been differentiated from naive T cells that recognized the same peptide-MHC complexes presented by dendritic cells. Follicular dendritic cells display intact protein antigens to previously activated (but not naive) B cells during the germinal center reaction. Collaboration of T cells and B cells requires direct contact of T cells and B cells specific for the same antigen, even though the antigen recognition events are not simultaneous, because the bidirectional activation requires membrane-bound molecules (i.e., CD40 ligand on the T cells and CD40 on the B cells).

An experiment is performed in which a point mutation is introduced randomly into the Zap-70 gene for a particular strain of mice. The mutant mice display a defect in T cell development. However, precursor T cells isolated from the thymus of these mice show normal expression levels of Zap-70 of the correct molecular weight. On further in vitro analysis, the mutant Zap-70 is found to bind to ITAM motifs in the cytoplasmic tail of the ζ chain, but only when the ζ chain is phosphorylated. No phosphorylated LAT is detected, however. Given these data, in which of the following protein domains is the mutation most likely to be present? A. Pleckstrin homology (PH) domain B. Proline-rich (PR) domain C. SH1 domain D. SH2 domain E. SH3 domain

C. SH1 domain In this experiment, the mutant Zap-70 can still bind to the phosphorylated ζ chains but cannot phosphorylate LAT. This suggests that the SH2 domains are normal but that the SH1 kinase domain has been mutated. Zap-70 does not contain a PH, PR, or SH3 domain. The PH domain allows proteins to localize to the membrane by binding to PIP3. PR domains mediate protein-protein interactions via binding to SH3 domains.

Which of the following statements about Ig Fc receptors is NOT true? A. Some Fc receptors or Fc receptor-associated signaling chains contain ITAMs in their cytoplasmic tails. B. Some Fc receptors are linked to signal transduction pathways that cause granule exocytosis. C. There are Fc receptors specific for all common Ig isotypes. D. Some Fc receptors with ITIMs in their cytoplasmic tails transduce inhibitory signals. E. Fc receptor signaling may enhance generation of reactive oxygen intermediates in phagocytes.

C. There are Fc receptors specific for all common Ig isotypes. There are no IgM-binding Fc receptors. Most Fc receptors transduce activating signals on binding Ig. The signals may be linked to many different functional responses. In phagocytes, these include generation of reactive oxygen intermediates that are toxic to ingested microbes. In mast cells, eosinophils, and natural killer cells, Fc receptor signaling stimulates granule exocytosis. Signaling depends on recruitment of molecules to ITAM motifs that are in the cytoplasmic tails of the Ig binding polypeptide, or non-Ig-binding signaling chains that are associated with the Fc receptor. The FcγRIIB receptor on B cells transduces inhibitory signals via a tyrosine phosphatase-binding ITIM domain in its cytoplasmic tail.

Which of the following statements about C3 is NOT correct? A. C3 contains an internal thioester bond that participates in covalent linkage to cell surfaces. B. C3 is the most abundant complement protein in the serum. C. A proteolytic fragment of C3 is part of both the C3 and C5 convertases. D. Activated C3 is a serine protease that cleaves C4. E. C3 in the plasma is spontaneously cleaved into C3b.

D. Activated C3 is a serine protease that cleaves C4. C3, the most abundant complement protein in plasma, is not a protease. The proteolytic fragment of C3, called C3b, is a component of both classical and alternative pathways C3 convertase, which are proteolytic enzymes. An internal thioester bond in C3 becomes metastable when C3 is proteolytically cleaved and contributes to covalent linkage of C3b to cell surfaces. Spontaneous cleavage of C3 in the plasma, called C3 tickover, generates C3b, which initiates the alternative pathway.

In patients with hyper IgM syndrome, there is a genetically based deficiency in expression of CD40 ligand. In addition to defects in antibody isotype switching, these patients have defects in T cell-mediated immune responses and become infected with intracellular parasites. Which one of the following normal functions of CD40 ligand is important in T cell-mediated immunity? A. CD40-dependent isotype switching is required to produce antibody isotypes that activate T cells. B. CD40 ligand is required for CTL killing of CD40-expressing infected cells. C. CD40 ligand is required for maturation of CD4+ T cells in the thymus. D. CD40 ligand on activated T cells binds to CD40 on antigen-presenting cells (APCs), and this enhances the expression of B7-1, B7-2, and cytokines by the APCs. E. CD40 ligand on T cells binds to B7-1 and B7-2 on APCs, and this enhances the function of the APCs.

D. CD40 ligand on activated T cells binds to CD40 on antigen-presenting cells (APCs), and this enhances the expression of B7-1, B7-2, and cytokines by the APCs. CD40 ligand, a membrane-bound protein in the tumor necrosis factor (TNF) family of proteins, is expressed after T cell activation. When it binds to its receptor CD40, a TNF-receptor family member expressed on macrophages, and other antigen-presenting cells, signals are transmitted that enhance costimulator and cytokine expression (as well as other functions of macrophages). This serves to amplify the T cell response and enhance the killing of microbes ingested by macrophages. Antibodies are not required to activate T cells. CD40 does not transduce pro-apoptotic signals. CD40 ligand is not involved in T cell maturation and does not bind to B7-1 or B7-2.

Class I MHC-restricted T cell responses to tumors can be demonstrated in patients with various types of tumors, yet most of these tumors do not express costimulatory molecules. Which mechanism most likely explains how naive CD8+ T cells specific for antigens expressed by these tumors are stimulated to differentiate into cytolytic T lymphocytes? A. Malignant transformation of CD8+ T cells B. Tumor secretion of T cell-activating cytokines C. Cross reaction of microbe-specific CD8+ T cells with tumor antigens D. Cross priming E. Antigenic modulation

D. Cross priming Tumor cells, or the protein antigens they produce, may be taken up by professional antigen-presenting cells (APCs), especially dendritic cells, and the antigens may then be delivered into the cytoplasm to gain access to the class I MHC pathway of antigen presentation. In this way, naive T cells specific for the tumor antigens can be activated by the APCs; i.e., through cross-presentation. Once differentiated into cytolytic T lymphocytes (CTLs), the T cells can then be activated by and kill the tumor cells, which present the same antigen, even in the absence of costimulation. There is no reason why malignant transformation of the T cells should occur. There is no evidence for cross reactivity between microbes and tumor antigens, nor of tumors secreting T cell-activating cytokines. Antigenic modulation is a mechanism by which tumors evade T cells, not activate them.

Differentiation of TH2 cells from naive precursor cells is dependent on which of the following? A. Toll-like receptor (TLR) ligands B. T-bet C. Interleukin-12 D. GATA-3 E. Interferon-α

D. GATA-3 GATA-3 is a transcription factor that is expressed during differentiation and is required for TH2 differentiation. T-bet is a protein that regulates genetic changes required for TH1 differentiation. In general, innate immune responses, many of which are stimulated microbial products binding Toll-like receptors (TLRs) on antigen-presenting cells (APCs), promote TH1 differentiation. In part, the positive influence of innate immune responses on TH1 differentiation is mediated by cytokines secreted by activated APCs, including interleukin-12 and type I interferons (IFN-α and IFN-β).

All of the following statements about immune responses to tumors are true EXCEPT: A. T cells specific for tumor antigens can be found in many human tumor patients. B. Antibodies specific for tumor antigens can be found in many human tumor patients. C. The presence of lymphocytic infiltrates in certain tumors is associated with a better prognosis than lymphocyte-poor tumors of the same histologic type. D. Immunodeficient individuals are more likely to develop the most common forms of cancer than are immunocompetent individuals. E. The host immune response is usually incapable of eradicating tumors once they are established.

D. Immunodeficient individuals are more likely to develop the most common forms of cancer than are immunocompetent individuals. The most common tumors are carcinomas, originating from epithelial cells of organs such as the lung, colon, breast, and prostate. These tumors do not occur more frequently in immunocompromised hosts than in the general population. The types of tumors that do occur more frequently in immunocompromised hosts, such as AIDS patients or allograft recipients receiving chronic immunosuppressive therapy, are those with a clear viral etiology. Examples include Epstein-Barr virus-associated lymphomas and human papillomavirus-associated cervical and skin carcinomas. It is true that T cells and antibodies specific for molecules expressed exclusively or abundantly on tumor cells can be found in tumor patients and that lymphocytic infiltrates are a histologic indication of better prognosis for a limited number of tumors. Nonetheless, the naturally occurring immune responses that occur against tumor antigens are usually not capable of eliminating tumors.

The initial cellular events that are induced by antigen-mediated cross-linking of the B cell receptor (BCR) complex include all of the following EXCEPT: A. Increased percentage of time spent in mitosis, resulting in rapid proliferation B. Increased expression of B7, resulting in enhanced APC function C. Increased expression of bcl-2, resulting in improved survival D. Increased expression of CCR7, promoting migration into lymph node follicles E. Increased expression of the interleukin-2 receptor, resulting in enhanced proliferation and response to T cell signals

D. Increased expression of CCR7, promoting migration into lymph node follicles In the initial events after antigen binding to the B cell receptor, B cells migrate out of, not into, the lymph node follicles and toward the T cell zones by increasing expression of CCR7, a chemokine receptor that responds to chemokines produced in the T cell zone. Helper T cells play an important role in the activation of B cells, inducing proliferation, isotype switching, and somatic mutation both by the release of cytokines as well as through direct interactions with the B cell via CD40L. T cell-mediated activation of B cells can only occur in the presence of protein antigens. Other early events that occur in B cell activation include increased proliferation and time spent in mitosis, increased expression of B7 to enhance the B cell's ability to activate T cells, increased expression of the anti-apoptotic protein bcl-2 to promote survival, and increased expression of cytokine receptors to enhance survival and proliferative signals coming from T cells.

An 8-month-old boy infant with a 3-month history of recurrent upper and lower respiratory tract infections is admitted to the hospital. The physicians consider the possibility of a hereditary immune disorder and run several tests, eventually determining that the patient has undetectable levels of serum IgA. The infant is treated with strong antibiotics and recovers. Which of the following is NOT a medical problem likely to occur in this patient as he gets older? A. Anaphylactic reactions to blood transfusions B. Chronic gastrointestinal infections C. Lactose and wheat gluten intolerance D. Inflammatory skin disease E. Recurrent nasal sinus congestion

D. Inflammatory skin disease Lack of IgA causes decreased immune function in the respiratory and gastrointestinal mucosa, resulting in increased risk of sinus, lower respiratory tract, and gastrointestinal tract infections. In addition, IgA binds to and prevents immune responses to food constituents such as lactose and wheat gluten. Finally, the complete lack of IgA in some of these patients means that IgA itself is immunogenic. Because antibodies that are capable of interacting with IgA-like molecules are often being produced by B1 B cells, it is not uncommon to see a hypersensitivity reaction, including anaphylaxis, if these patients receive a blood transfusion. Normally, IgA is not on the skin, and there is no connection between IgA deficiency and inflammatory skin diseases.

Which one of the following descriptions of cytokine interleukin-2 is NOT true? A. Expression of its gene requires multiple transcription factors, such as Fos, Jun, and NFAT. B. It acts as an autocrine growth factor for T cells. C. It binds to CD25 on the cell membrane of T cells. D. It is only involved in the proliferation of helper T cells and not CTLs. E. It promotes susceptibility of T cells to apoptosis.

D. It is only involved in the proliferation of helper T cells and not CTLs. IL-2 is involved in the proliferation of both CD4+ and CD8+ T cells. Activation of the naive T cell results in signals transduced via the TCR (signal 1) and CD28 (signal 2). This signaling results in the activation of transcription factors, such as Fos, Jun, and NFAT, which increase transcription of the IL-2 gene. IL-2 is then secreted and acts as both a paracrine and autocrine growth factor for T cells by binding to the IL-2 receptor (one component of which is CD25). In addition to its growth factor activity, IL-2 also "primes" T cells for apoptotic death, and this role for IL-2 is important in homeostasis of the immune system.

Which of the following is NOT a property of the classical pathway C3 convertase? A. Composed of proteolytic fragments of C4 and C2 B. Has protease activity specific for C3 to form C3b C. Inhibited by decay acceleration factor (DAF) D. Stabilized by C4 binding protein (C4bp) E. Same substrate specificity as the alternative pathway C3 convertase

D. Stabilized by C4 binding protein (C4bp) The classical pathway C3 convertase C4b2a cleaves C3 to generate C3b and C3a. The alternative pathway C3 convertase C3bBb has the same activity. C3 convertases are highly regulated, preventing complement activation on autologous cell surfaces. The classical pathway C3 convertase is not stabilized but is inhibited by C4bp, which competitively binds C4b, displacing C2 from the complex. C4bp also acts as a cofactor for the proteolytic cleavage of C4b by factor I. DAF and complement receptor 1 (CR1) and membrane cofactor proteins (MCP) also inhibit classical pathway C3 convertase formation. Similar mechanisms exist to block alternative pathway C3 convertase formation.

Which of the following statements about Ig isotype switching is NOT true? A. Interleukin-4 promotes switching to the IgE isotype by increasing germline transcription of the Cε exon. B. Isotype switching involves recombination of a V(D)J complex with downstream C region genes and the deletion of intervening DNA including other C region genes. C. Activation-induced deaminase (AID) is required for switch recombination. D. The enzymes that mediate isotype switching recognize conserved heptamer and nonamer DNA sequences adjacent to the constant region exons. E. The same recombined V(D)J gene complex is used to encode the antigen-binding region of the antibodies produced by a B cell before and after isotype switching.

D. The enzymes that mediate isotype switching recognize conserved heptamer and nonamer DNA sequences adjacent to the constant region exons. Heptamer and nonamer sequences are part of the recombination signal sequences recognized by V(D)J recombinases, and not by the enzymes that mediate switch recombination. I exons and S (switch) regions are the DNA "landmarks" just upstream of each constant region gene that dictates where switch recombination will occur. Switch recombination is incompletely understood, but requires AID as well as other enzymes that gain access to the S regions when germline transcription through the I, S, and C exons is induced by cytokines. The same V(D)J unit is used to encode the antigen-binding site after switch recombination, and this preserves antigen specificity of the antibodies produced while effector functions of the antibodies change.

All of the following protein-protein interactions are involved in activation of naive helper T cells by antigen-presenting cells (APCs) EXCEPT: A. Binding of peptide-MHC complexes on the APC to the TCR on the T cell B. Binding of CD4 on the T cell to nonpolymorphic regions of class II MHC molecules on the APC C. Binding of integrins on the T cell with adhesion ligands on the APC D. Binding of B7-2 on the APC with CD28 on the T cell E. Binding of CD40L on the T cell with CD40 on the APC

E. Binding of CD40L on the T cell with CD40 on the APC CD40L is not expressed on naive T cells and is only up-regulated subsequent to activation by an antigen-presenting cell (APC). In the naive helper T cell, the TCR binds to the MHC-peptide complex whereas the CD4 coreceptor engages a conserved region on the MHC II molecule. Integrins on the T cell interact with adhesion ligands on the APC. This region of binding between the T cell and the APC is known as the immunologic synapse and also includes costimulatory interactions, such as CD28 on the T cell binding to B7 on the APC.

Up to half of the IgG found in the serum of a normal individual is produced by which of the following cells? A. Naive B cells in lymph nodes B. Activated B cells in the spleen C. B cells in germinal centers of lymph nodes D. B lymphocytes in the gastrointestinal tract E. Long-lived plasma cells in the bone marrow

E. Long-lived plasma cells in the bone marrow During a humoral immune response, naive B cells differentiate into antibody-producing cells, and some of these migrate to the bone marrow, where they can reside and produce antibodies for years. Many of these cells are called plasma cells, based on their histologic appearance. Naive B cells do not secrete antibodies. Although activated B cells in spleen or lymph node germinal centers produce large amounts of antibody during an active humoral immune response, they do not account for most of the serum IgG normally. Intestinal B cells secrete large amount of IgA, which is transported into the lumen.

The B cell receptor (BCR) complex and the signaling cascades to which it is linked share many similarities with the T cell receptor (TCR) complex and its linked signaling cascades. Which of the following comparisons between BCR and TCR signaling is NOT true? A. There are ITAMs in the cytoplasmic tails of CD3 in the TCR complex and in the cytoplasmic tails of Igα and Igβ in the BCR complex. B. The cytoplasmic tails of membrane Ig and TCR αβ antigen receptors are very short and lack intrinsic signaling functionality. C. Early signaling events induced by antigen binding to both BCR and TCR involve both Src family and Zap-70 family protein tyrosine kinases. D. Phospholipase C-mediated generation of IP3 and DAG occurs downstream of both BCR and TCR signaling. E. CD4/CD8 coreceptors in T cells and the CR2 coreceptor in B cells both enhance responses to antigen by a PI3 kinase-dependent mechanism.

E. CD4/CD8 coreceptors in T cells and the CR2 coreceptor in B cells both enhance responses to antigen by a PI3 kinase-dependent mechanism. The CR2 coreceptor, in association with CD19 and CD81, activates PI3-kinase. CD4 and CD8 do not activate PI3-kinase but, rather, bring the Src family tyrosine kinase Lck into proximity of the TCR complex.

Which one of the following B cell responses is NOT stimulated by CD40 ligand? A. Association of TRAFs with the cytoplasmic tails of CD40 molecules B. Activation of NF-κB C. Enhanced expression of B7-1 and B7-2 D. Enhanced Ig isotype switch recombinase activity E. Enhanced production of membrane Ig

E. Enhanced production of membrane Ig CD40 ligand binding to B cell CD40 enhances production of secreted, not membrane, Ig. CD40 signaling involves recruitment of signaling intermediates, called tumor necrosis factor-receptor associated factors (TRAFs), to the cytoplasmic tails of CD40 and the downstream activation of NF-κB, as well as other transcription factors. The signaling cascades result in increased expression of various genes, including B7 costimulators, and increased Ig isotype switching, which is mediated by switch recombinases.

A 47-year-old woman had a mastectomy because she had breast carcinoma that was previously diagnosed by biopsy. Pathologic examination revealed that several axillary lymph nodes contained metastatic tumors. A test was performed on tumor cells extracted from the mastectomy specimen, which indicated that the tumor cells overexpressed a certain cellular proto-oncogene. On the basis of this test result, the patient was treated with an FDA-approved monoclonal antibody specific for the protein encoded by that gene. Which of the following was most likely the protein target of this antibody therapy? A. p53 B. H-Ras C. HPV E7 D. Rb E. Her2

E. Her2 Her2 is encoded by the Her-2/neu oncogene. It is a cell surface, transmembrane glycoprotein with intracellular tyrosine kinase activity. Presumably, HER-2/neu generates signals that regulate epithelial cell growth and differentiation. Twenty to 40 percent of breast cancers show amplification of the Her2/neu oncogene and overexpression of the product. A monoclonal antibody specific for the Her2 protein inhibits tumor growth and may have some clinical efficacy. H-Ras and HPV-E7 are oncogene products, but they are intracellular and inaccessible to monoclonal antibody treatment. p53 and Rb are intracellular tumor suppressor gene products, and there is no antibody-mediated therapy directed at these proteins.

Which of the following events does NOT occur within germinal centers? A. Somatic mutation of Ig V genes B. Generation of memory B cells C. B cell proliferation D. Affinity maturation E. Ig gene V(D)J recombination

E. Ig gene V(D)J recombination V(D)J recombination to form functional Ig genes occurs only in developing B cells, mostly in the bone marrow. Germinal centers are sites of differentiation of mature B cells, in response to T cell-dependent protein antigens. The germinal center "reaction" begins with helper T cell signals delivered to B cells via CD40 ligand and cytokines. This results in B cell movement back into the follicle and brisk B cell proliferation of one or a few clones of B cells specific for an inciting antigen. The proliferating B cells undergo somatic mutation of the variable genes, at which point mutations are introduced that may alter the affinity of the encoded antibodies for their antigens. Antigens are displayed in limited concentrations on the surfaces of follicular dendritic cells in the germinal center, and only B cells whose high-affinity Ig receptors can bind these antigens are selected to survive. Some of these cells become antibody-secreting cells, and others become memory B cells.

Which of the following is NOT a mechanism by which tumors evade immune responses? A. Decreased synthesis of TAP B. Increased expression of glycocalyx C. Lack of costimulatory molecule expression D. Increased expression of TGF-β E. Increased expression of Fas

E. Increased expression of Fas Many tumor cells will up-regulate expression of Fas-ligand, not Fas, to signal for apoptosis in Fas-expressing leukocytes recruited to the site of the tumor. Other mechanisms of tumor evasion include down-regulation of MHC I molecules as well as the components of the antigen-processing machinery needed for MHC I presentation, such as proteasome subunits and the TAP transporter. Some tumors can also down-regulate costimulatory molecules such as B7. Tumors can also up-regulate expression of immunosuppressive cytokines, such as TGF-β, as well as increase production of glycocalyx polysaccharides that hide or "mask" tumor surface antigens from the immune system.

Which one of the following statements about the molecule Lck is NOT true? A. It is a member of the Src family of kinases. B. It binds to the cytoplasmic tails of T cell coreceptors CD4 or CD8. C. It phosphorylates ITAM motifs on the CD3 complex. D. It phosphorylates tyrosine residues on Zap-70 and activates it. E. It phosphorylates PIP2 to PIP3 and leads to the activation of Itk.

E. It phosphorylates PIP2 to PIP3 and leads to the activation of Itk. PI-3 kinase is responsible for the phosphorylation of PIP2 to PIP3, leading to the activation of Itk in T cells and Btk in B cells.

Which one of the following cell types would be most potent at activating naive T cells? A. Kupffer cells B. B cells C. Follicular dendritic cells D. Neutrophils E. Langerhans cells

E. Langerhans cells Antigen-presenting cells (APCs) are responsible for presenting peptide-MHC complexes and costimulatory molecules to naive T cells; this leads to activation of the T cells. The most potent APCs are the dendritic cells, because they constitutively express high levels of costimulatory molecules. Langerhans cells are dendritic cells found in epidermis. Other APCs include macrophages and B cells. Kupffer cells are a type of macrophage found in the liver. Neither neutrophils nor follicular dendritic cells (FDCs) are involved in antigen presentation to T cells. FDCs are unrelated to dendritic cells and are found within the germinal centers of lymph nodes.

Treatment of antibodies with the enzyme papain under conditions of limited proteolysis results in hinge-region cleavage, yielding monovalent antigen-binding Fab fragments that lack a constant region. Which effector function of antibodies would Fab fragments be able to perform? A. Complement pathway activation B. Antibody-dependent cell-mediated cytotoxicity C. Opsonization D. Antigen cross-linking and precipitation E. Microbe neutralization

E. Microbe neutralization Fab fragments lack the Fc constant region and are therefore not recognized by immune effector cells or complement. In addition, they are monovalent and therefore are incapable of cross-linking antigen. However, Fab fragments are able to bind and neutralize toxins and inhibit the activity of pathogens by compromising the function of cell-surface proteins. These effects, called "neutralization" of pathogens, are the only mechanisms of antibody action that depend solely on antigen binding.

A 17-year-old girl from southern China has had a sore throat and fever for 1 week. On physical examination, generalized lymphadenopathy is noted. A rapid strep test for streptococcal infection is negative and a CBC shows 20% atypical lymphocytes. A Monospot test for the presence of heterophile antibodies is positive. This illness is associated with eventual development of which of the following malignancies? A. Kaposi's sarcoma B. Cervical carcinoma C. Follicular lymphoma D. Human T cell lymphoma E. Nasopharyngeal carcinoma

E. Nasopharyngeal carcinoma The clinical manifestations described are classic for infectious mononucleosis secondary to Epstein-Barr virus (EBV) infection. These include sore throat, fever, fatigue, and generalized lymphadenopathy. The differential diagnosis for sore throat includes streptococcal infection; however, the rapid strep test for streptococcal infection is negative in this patient. In addition, the peripheral blood smear of patients with mononucleosis often contains abundant numbers of large morphologically atypical lymphocytes. EBV infection is one of the etiologic factors associated with malignant tumors, including nasopharyngeal carcinoma in Chinese populations, Burkitt's lymphoma in equatorial African populations, and other B cell lymphomas in immunosuppressed populations.

Which pair of molecules is a component of cytolytic T lymphocyte (CTL) granules and is important in the mechanism of CTL killing of target cells? A. Perforin and Fas ligand B. P-selectin and tumor necrosis factor C. Major basic protein and granzyme B D. C9 and interferon-γ E. Perforin and granzyme B

E. Perforin and granzyme B Perforin and granzyme B are the cytolytic T lymphocyte (CTL) granule constituents of most importance in killing of target cells. CTL granules are emptied by exocytosis into the intercellular space between the CTL and target cell. Here perforin polymerizes to form pore-like structures that insert into the target cell plasma membrane and/or in the membranes of endocytic vesicles in the target cell. Granzyme B is a proteolytic enzyme that cleaves substrates in the cytoplasm of the target cell, leading to a cascade of enzyme activation that ends in apoptosis. Granzyme B enters the target cell either through perforin pores or by receptor-mediated endocytosis. FasL is expressed on the surface of the CTL, not in granules. FasL binding to Fas on target cells may induce apoptosis of the target cells by a caspase-dependent pathway, but this is a minor mechanism of CTL killing relative to perforin- and granzyme B-dependent mechanisms. P-selectin is an endothelial adhesion molecule stored in cytoplasmic granules, and MBP is a cationic protein found in eosinophil granules. Although perforin is homologous to the complement protein C9, C9 is not present in CTL granules. CTLs do produce interferon-γ, but they do not store this cytokine in granules.

Which one of the following statements about primary and secondary antibody responses is NOT true? A. Antibodies in primary responses generally have lower affinity for antigen than those produced in secondary responses. B. Secondary responses reach peak levels more quickly than primary responses. C. Primary responses require higher concentrations of antigen for initiation than secondary responses. D. Primary responses occur to all types of antigens, but secondary responses mostly occur only to protein antigens. E. Primary responses are characterized by IgG antibodies, whereas secondary responses are dominated by IgM antibodies.

E. Primary responses are characterized by IgG antibodies, whereas secondary responses are dominated by IgM antibodies. In a primary immune response, IgM antibodies are initially produced against antigens. IgG production requires T cell-dependent isotype switching and is seen predominantly in secondary responses. Primary antibody responses can be mounted to any type of antigen, but secondary responses usually require CD4+ T cell help, and therefore the antigen must be a protein. Primary responses do require higher concentrations of antigen for initiation. The affinity of membrane Ig for antigen is lower on naive B cells, which are responsible for primary responses, compared with memory B cells, which are responsible for secondary responses. Secondary responses develop more quickly and produce higher peak levels of antibody as compared with primary responses.

The mechanisms by which TH1 cells protect against microbes include all of the following EXCEPT: A. Secretion of interferon (IFN)-γ, which activates microbicidal functions of macrophages B. Expression of CD40 ligand, which binds to CD40 on macrophages and activates them C. Secretion of IFN-γ, which promotes B cell production of opsonizing antibodies D. Secretion of lymphotoxin and tumor necrosis factor, which enhance neutrophil killing of ingested microbes E. Release of granzyme B, which stimulates apoptosis of bacteria

E. Release of granzyme B, which stimulates apoptosis of bacteria Granzyme B, a product of CD8+ cytolytic T lymphocytes, promotes death of infected host cells, but not of extracellular microbes. The principal function of TH1 cells is to enhance phagocyte defense against intracellular infections. Interferon (IFN)-γ and CD40 ligand, produced by TH1 cells, enhance killing of microbes ingested by macrophages, in part by stimulating the production of inducible nitric oxide synthase and phagocyte oxidase. IFN-γ, produced by TH1 cells, is an isotype switch factor, promoting the production of IgG subtypes that bind to Fc receptors on phagocytes and fix complement. Therefore, these opsonizing IgG subtypes facilitate the phagocytosis of the microbes to which they bind. TH1 cells also secrete tumor necrosis factor and lymphotoxin, two cytokines that can activate neutrophil killing of internalized microbes.

Which of the following events initiates activation of the alternative complement pathway? A. C1q binding to a microbial surface B. Mannose-binding lectin (MBL) binding to a microbial surface C. Complement receptor 1 (CR1) binding of C3b D. Factor I cleavage of C3 E. Spontaneous cleavage of C3 to C3b

E. Spontaneous cleavage of C3 to C3b The alternative pathway is initiated when C3b, generated by spontaneous cleavage of C3 in the fluid phase, covalently binds to a cell surface. C1q is required for initiation of the classical pathway. It does not bind directly to cell surfaces but rather to the constant regions of two Ig molecules, which may be bound to cell surface antigens. Mannose-binding lectin (MBL) binds to mannose on microbial surfaces to initiate the lectin pathway. Factor D is a constitutively active serum protease that cleaves factor B after it binds C3b in the alternative pathway. Factor I is a protease that cleaves C3b and C4b and regulates both alternative and classical pathways. CR1 on phagocytes binds C3b-opsonized microbes.

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