I&B Exam 1 Book Self-Assessment Questions

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

Answer: A (Activated macrophages, through the secretion of growth factors, promote fibroblast proliferation and angiogenesis which help repair damaged tissues.)

A vaccine administered in the autumn of one year may protect against the prevalent strain of influenza virus that originated in Hong Kong that same year, but it will not protect against another strain of influenza virus that originated in Russia. This phenomenon illustrates which property of the adaptive immune system? A. specificity B. loss of memory C. specialization D. cultural diversity E. self-tolerance

Answer: A (Adaptive immune responses are highly specific for distinct molecular structures, which may be present in a vaccine and be produced by one strain of virus but not by a closely related strain. The efficacy of the vaccine against the Hong Kong strain implies it has induced memory and this has not been lost. The same effector mechanisms would be required to combat different strains of influenza, and therefore failure of a vaccine to protect against two different strains of virus is not related to specialization of effector functions)

Which of the following properties of antibodies is not related to isotype? A. Antigen specificity B. Ability to act as an opsonin for phagocytosis of antigens C. Ability to activate complement D. Ability to be transported into the lumen of the gut E. Ability to activate mast cells

Answer: A (Antigen specificity is determined by the variable regions of the heavy and light chains, and not the isotype, which is defined by the structure of the constant region of the heavy chain. The other properties listed are all related to one or another istoype, whose Fc regions (part of the heavy chain constant region) interact with different kinds of Fc receptors on cells or with complement proteins.)

A drug that blocks the function of the chemokine receptor CCR7 would result in which of the following abnormalities? A. reduced number of T cells in lymph nodes B. absense of B cell follicles in the spleen C. reduced blood neutrophil count D. absence of follicular dendritic cells in lymph node follicles E. thin thymic cortex

Answer: A (CCR7 is a chemokine receptor expressed on naive T cells as well as mature dendritic cells. This receptor binds chemokines produced in the parafollicular zones of lymph nodes. T cell migration into lymph nodes is dependent on CCR7, and therefore a deficiency in CCR7 expression would result in reduced numbers of these cells in lymph nodes. B cell migration into the follicles in the spleen is not dependent on CCR7 expression. CCR7 is not involved in migration of neutrophils into or out of the blood, of follicular dendritic cells into lymphoid follicles, or of T cell precursors into the thymic cortex.)

Which of the following is the nonpolymorphic molecule that is structurally homologous to the class I MHC α chain, associates with β2-microglobulin, and displays lipid antigens for recognition by NKT cells? A. CD1 B. CD2 C. CD3 D. CD4 E. CD8

Answer: A (CD1 is encoded outside the MHC, but is structurally homologous to class I MHC molecules. Some subsets of T cells, all with relatively invariant T cell receptors, recognize lipid or glycolipid antigens bound to CD1 on antigen-presenting cells. CD2, CD3, CD4, and CD8 are all present on T cells. Although they are members of the Ig superfamily, like class I MHC, they are not otherwise homologous to class I MHC and do not bind and display antigens for T cell recognition.)

Which of the following statements about microbial antigen presentation is correct? A. Class I MHC molecules display peptides derived mainly from cytosolic microbial proteins for recognition by CD8+ T cells B. Class I MHC molecules display peptides derived mainly from cytosolic microbial proteins for recognition by CD4+ T cells C. Class II MHC molecules display peptides derived mainly from cytosolic microbial proteins for recognition by CD4+ T cells D. Class II MHC molecules display peptides derived mainly from extracellular microbial proteins for recognition by CD8+ T cells E. Class II MHC molecules display peptides derived mainly from extracellular microbial proteins for recognition by B cells

Answer: A (CD8+ T cells are class I MHC restricted, and most peptides that are displayed by class I MHC are derived from proteasomal processing of cytosolic proteins.)

CD4+ helper T cells are required for effective CD8+ T cell responses to some viral infections. Which of the following is a mechanism by which the CD4+ T cells promote CD8+ T cell response? A. The CD4+ T cells are activated by viral peptides bound to class II MHC on dendritic cells, and secrete cytokines that promote growth and differentiation of CD8+ T cells that are activated by viral peptides bound to class I MHC on dendritic cells. B. The CD4+ T cells express costimulatory molecules that that promote growth and differentiation of CD8+ T cells that are activated by viral peptides bound to class I MHC on dendritic cells. C. CD4+ T cells are activated by viral peptides bound to class II MHC can differentiate into CD8+ CTLs D. The CD4+ T cells express abundant type I interferons, which upregulate class I MHC expression on the virally infected cells.

Answer: A (Cytokines expressed by activated CD4+ helper T cells, such as IL-2, will enhance clonal expansion of antigen-activated CD8+ T cells. CD4+ T cells do not express abundant costimulatory molecules, do not re-differentiate into CD8+ T cells, nor do they express abundant type I interferons.)

Which of the following accurately describe the function of the selectin family of adhesion molecules? A. selectins support low affinity rolling of leukocytes on endothelial cells B. endothelial selectine increase their affinity for binding to leukocytes in response to chemokines C. selectins guide migration of leukocytes through interendothelial junctions D. selectins are expressed only on naive T cells E. selectins play a direct role in clonal selection

Answer: A (E-selectin and P-selectin expressed on cytokine-activated endothelial cells bind weakly to carbohydrate ligands expressed on various leukocytes including lymphocytes, monocytes, and granulocytes. The fluid shear force caused by the flow of blood causes the selectin-selectin ligand bonds to break and then reform as the cells are pushed along; the net result is rolling of the leukocytes along the endothelial surface. Rolling interactions are also mediated by L-selectin on some leukocytes binding to their carbohydrate ligand on the endothelium.)

Toll like receptors (TLRs) located in endosomal membranes of cells recognize which of the following? A. Nucleic acids B. Bacterial cell wall lipotechoic acid C. Bacterial cell wall lipopolysaccharide D. Uric acid crystals E. Peptides containing N-formylmethionyl residues

Answer: A (Endosomal TLR-3,-7, and -9, recognize dsRNA, ssRNA, and CpG dinucleotides which are components of ingested viruses (dsRNA, ssRNA) and other microbes (unmethylated CpG-rich oligonucleotides). Bacterial cell wall lipotechoic acid and lipopolysaccharide are recognized by plasma membrane TLRs. Uric acid crystals are recognized by cytosolic NLR proteins in inflammasomes, and bacterially derived peptides containing N-formylmethionyl residues are recognized by the plasma membrane fmet-leu-phe receptor)

The combination of TCR and costimulatory signals induces naïve T cells to express IL-2 and high affinity IL-2 receptors. This results in which of the following functional responses by the T cell? A. Clonal expansion B. Interferon γ expression C. CD40 ligand expression D. Granule exocytosis E. Migration out of a lymph node

Answer: A (IL-2 is the major autocrine growth factor for T cells. Naïve T cells express two chains of the IL-2 receptor which bind IL-2 with low affinity. Antigen and costimulatory signals induce IL-2 production and expression of a third chain (CD25) of the receptor, which increases the affinity for IL-2. The T cell thus enters the cell cycle in response to IL-2 signals, and undergoes several rounds of proliferation, thereby expanding the clone of T cells specific for the inciting antigen.)

The cytoplasmic tails of the signaling polypeptides found in lymphocyte antigen receptor complexes (BCR and TCR) contain regions that become phosphorylated upon antigen recognition and then bind ZAP family kinases. These regions are called: A. Immunoreceptor tyrosine-based activating motifs (ITAMs) B. Fc regions C. Toll-like IL-1R (TIR) domains D. Complementarity determining regions E. Nod like receptor (NLR) domains

Answer: A (ITAMs are found in the cytoplasmic tails of CD3 and ζ proteins of the TCR complex and Igα and Iβ proteins of the BCR complex. ITAMs contain pairs of tyrosine residues that become phosphorylated by Src family kinases after antigen recognition, and then serve as docking sites for ZAP70 in T cells or Syk in B cells. ZAP70 and Syk are tyrosine kinases that become active after binding to ITAMs and then phosphorylate adaptor proteins and other kinases.)

A standard treatment of animal bite victims, when there is a possibility that the animal was infected with the rabies virus, is administration of human immunoglobulin preparations containing anti-rabies virus antibodies. Which type of immunity would be established by this treatment? A. active humoral immunity B. passive humoral immunity C. active cell-mediated immunity D. passive cell-mediated immunity E. innate immunity

Answer: B ( Humoral immunity is mediated by antibodies. The transfer of protective antibodies made by one or more individuals into another individual is a form of passive humoral immunity. Active immunity to an infection develops when an individual's own immune system responds to the microbe. Cell-mediated immunity is mediated by T lymphocytes, not antibodies, and innate immunity is not mediated by either antibodies or T lymphocytes)

Which of the following statements correctly describes the migratory behavior of naïve T lymphocytes? A. They recirculate from blood into lymph nodes via high endothelial venules, and back into blood via lymphatics B. They recirculate from blood into inflamed tissues via activated post capillary venules, and back into blood via lymphatics C. They migrate into the thymus via high endothelial venules, where they mature into effector T cells, which then enter the blood via lymphatics D. They are stationary within lymph nodes and do not migrate E. After maturation in the thymus, they migrate into the blood via draining lymphatics and enter the spleen via high endothelial venules

Answer: A (Naïve T cells enter lymph nodes via high endothelial venules, a process dependent on the chemokine receptor CCR7 and L-selectin on the naïve T cells. If after several hours the naive T cell is not activated by antigen, it will exit the lymph node via efferent lymphatics, and flow via lymph channels back into the blood. Naïve T cells do not migrate into peripheral sites of inflammation, and although they are formed in the thymus, they do not exit via lymphatics but rather via blood vessels. Migration of naïve T cells into spleen is not via high endothelial venules (which are not present in the spleen).)

Receptor editing is a mechanism to achieve self tolerance if a self reactive lymphocyte develops. How, where, and when does self editing work? A. High avidity self antigen recognition by an immature B cell in the bone marrow leads to reactivation of RAG genes, production of a new Ig light chain, and a change in the B cell specificity. B. High avidity self antigen recognition by an immature T cell in the thymus leads to production of a new TCR and a change in the T cell specificity. C. High avidity self antigen recognition by an immature B cell in the bone marrow leads to enzymatic alteration of Ig light chain proteins, and a change in the B cell specificity. D. High avidity self antigen recognition by an immature T cell in the thymus leads to enzymatic alteration of the TCR α chain, and a change in the T cell specificity. E. High avidity self antigen recognition by an immature B cell in the bone marrow leads to reactivation of RAG genes, additional heavy chain V-D-J recombination events, production of a new Ig heavy chain, and a change in the B cell specificity.

Answer: A (Receptor editing occurs only in immature B cells in the marrow after high avidity recognition of self antigens, is due to re-expression of the RAG-1 and -2 genes and rearrangement of a previously rearranged Ig light chain gene locus.)

In both B and T cell development, there is stage when a pre-antigen receptor (pre B cell receptor or pre T cell receptor) is expressed. Which of the following accurately describes an important function of these pre-antigen receptors? A. Positively select for lymphocytes that have successfully undergone a first round of V-D-J recombination required to express functional antigen receptors B. Negatively select for self-reactive lymphocytes C. Instruct the differentiation of the lymphocytes into different subsets of effector cells D. Positively select lymphocytes that recognize microbial antigens E. Bind to chemokines that keep the lymphocytes from migrating out of the generative lymphoid organs

Answer: A (Signals generated by the pre-antigen receptors are required for survival of developing lymphocytes. Since the pre B cell receptor contains an Ig μ heavy chain, and the pre T cell receptor contains a TCR β chain, only developing lymphocytes that have successfully rearranged Ig μ or TCR β genes will survive, and have a chance of rearranging and expressing Ig light chain or TCR α chain genes. Therefore, the pre-antigen receptors provide a checkpoint mechanism by which useless cells that will never be able to express an antigen receptor are purged. The pre-antigen receptors do not stimulate lymphocyte differentiation into effector cells, but they do stimulate proliferation and further molecular events in development of mature naïve lymphocytes. Since pre-antigen receptors are not fully formed antigen receptors, they cannot mediate selection for or against self or foreign antigens, and they have no chemokine binding capacity.)

The differentiation of each major CD4+ T cell subset is controlled by a subset defining transcription factor. Which of the following correctly pairs each subset with its transcription factor? A. Th1:T-bet; Th2:GATA3; Th17:RORγT B. Th1:GATA3; Th2:T-bet; Th17:RORγT C. Th1:T-bet; Th2: RORγT; Th17: GATA3 D. Th1: RORγT; Th2:GATA3; Th17: T-bet E. Th1: GATA3; Th2:RORγT; Th17: T-bet

Answer: A (T-bet, GATA3, and RORγT are sometimes called "master regulators", and they are required for differentiation and function of the differentiated T cells. In each case the transcription of the subset defining cytokine genes is regulated by the subset defining transcription factors. Other transcription factors are also required for the differentiation of each subset.)

Which of the following is a proinflammatory cytokine of major importance in innate immunity that has been successfully targeted by drugs to treat rheumatoid arthritis (RA)? A. Tumor necrosis factor (TNF) B. Transforming growth factor-β (TGF-β) C. Interleukin 10 D. Interleukin 2 E. Interferon γ

Answer: A (TNF is secreted by macrophages in response to PAMPs and DAMPs and mediates acute inflammatory responses by activating endothelial cells and leukocytes. Anti-TNF antibodies and recombinant soluble TNF receptor-IgG fusion proteins have been highly successful in treating RA.)

Which enzyme contributes to antigen receptor junctional diversity by adding random nucleotides at the junctions between V, D, and J segments and is also useful as a marker of neoplasia of pro-B and pro-T cells? A. Terminal deoxyribonucleotidyl transferase (TdT) B. Activation-induced deaminase (AID) C. Recombinase activating gene-1 (RAG-1) D. DNA-dependent protein kinase E. DNA polymerase

Answer: A (Terminal deoxyribonucleotidyl transferase (TdT) is the enzyme that adds random nontemplate nucleotides (called N nucleotides) at the junctions between V, D and J segments, mainly in the recombined Ig heavy chain and TCRβ chain genes. The enzyme is expressed mainly during the time in B cell and T cell development when the IgH and TCR β chain genes are undergoing recombination. Activation-induced deaminase is an enzyme involved in somatic mutation and isotype switching of Ig genes. Recombinase activating gene-1 (RAG-1) is a component of the V(D)J recombinase that mediates the joining of the discrete gene segments, and DNA-dependent protein kinase participates in the recombination and joining process, but these enzymes do not contribute on their own to junctional diversity.)

In the class I MHC pathway of antigen presentation, peptides generated in the cytosol are translocated into the endoplasmic reticulum in which of the following ways? A. By ATP-dependent transport via TAP B. By passive diffusion C. By receptor-mediated endocytosis D. Through membrane pores E. Via the proteasome

Answer: A (The TAP1/TAP2 heterodimer is an ATP-dependent pump that delivers peptides generated by the proteasome into the endoplasmic reticulum. The proteasome is a proteolytic organelle in the cytosol that generates the MHC-bind peptides from proteins, prior to TAP transport of the peptides into the endoplasmic reticulum.)

Which of the following is one way a cytokine made by Th2 cells contributes to atopic disease (allergy)? A. IL-17 stimulates TNF production by macrophages B. IL-5 activates eosinophils C. IL-13 activates macrophages to produce nitric oxide D. IL-4 induces B cell class switching to IgA E. IL-22 causes mast cell degranulation

Answer: B (Atopic diseases often involve eosinophil activation and the release of pro-inflammatory and tissue damaging granule contents, such as major basic protein. Th2 cells underlie these events because they produce IL-5, which activates eosinophils. IL-17 and IL-22 are not made by Th2 cells. IL-13 does not activate macrophages to produce nitric oxide. IL-4 does induces B cell class switching to IgE not IgA)

The most important costimulators for naïve T cell activation are which of the following? A. ICOS Ligand B. B7-1 and B7-2 C. PD-L1 and PD-L2 D. OX40 -Ligand E. FAS Ligand

Answer: B (B7-1 (CD80) and B7-2 (CD86) are the major costimulators required for naïve T cell activation. They are expressed on mature myeloid DCs, and bind to CD28 on the T cells. ICOS-Ligand and OX40 ligand are costimulators for previously activated T cells; their receptors are not expressed on naïve T cells. PD-L1 and PD-L2 bind to PD-1 on T cells, which inhibits T cell activation. FAS Ligand binds to FAS on T cells, and induces apoptotic cell death.)

All of the following molecules are opsonins that facilitate efficient phagocytosis of microbes by neutrophils and macrophages EXCEPT: A. C3b B. C5a C. C-reactive protein D. IgG E. Mannose-binding lectin

Answer: B (C5a is a peptide released after cleavage of C5 protein upon activation of the complement cascade. It stimulates the influx of neutrophils to the site of infection, thus acting as a chemoattractant, not as an opsonin. C3b (covalently bound to microbes on which complement activation has taken place) and IgG bound to antigen, are potent opsonins, because phagocytes have receptors for both C3b and the Fc region of IgG. C-reactive protein and mannose-binding lectin also can coat microbes and be recognized by phagocyte receptors; thus they serve as opsonins.)

Detection of antibodies specific for a particular microbe is commonly used as evidence of prior infection by that microbe. To obtain these antibodies, blood is collected into tubes and allowed to clot. Antibodies are found in the fraction of the blood that remains fluid after clotting. What is this fluid fraction called? A. Plasma B. Serum C. Lymph D. Water E. Urine

Answer: B (Clots form from the cellular elements of blood, including platelets, and a meshwork of cross-linked coagulation proteins. The acellular fluid phase that is left after clotting is called serum, which contains most of the soluble protein elements of whole blood, except clotting factors. Plasma is the acellular fluid fraction of unclotted blood, and apart from coagulation proteins that form the clot, it contains all of the soluble protein components of whole blood, including antibodies. Lymph is extracellular fluid derived from blood; it may contain antibodies. Urine is the fluid filtrate of blood exclusively produced and excreted by the kidneys. It normally does not contain antibodies.)

Which of the following proteins involved in attenuation of immune signaling become associated with immunoreceptor tyrosine inhibitory motifs (ITIMs)? A. E3 ubiquitin ligases B. SH2 domain-containing tytrosine phosphatases (SHP-1, SHP-2) C. Suppressors of cytokine signaling (SOCS) D. CTLA-4 E. PD-1

Answer: B (ITIMs are found in the cytoplasmic tails of inhibitory receptors on NK cells, T cells, and B cells. ITIMs bind SHP-1, SHP-2, and SH2 domain-containing inositol phosphatase (SHIP). SHP-1, SHP-2 remove phosphates from tyrosines in signaling intermediates downstream of activating receptors. SHIP removes phosphates from phospholipid signaling intermediates also downstream of activating receptors. The other choices are not associated with ITIMs. E3 ubiquitin ligases are intracellular enzymes that tag proteins for lysosomal and proteosomal degradation, and some E3 ubiquitin ligases, such as Cbl-b, are involved in endocytosis and degradation of the TCR. Suppressors of cytokine signaling (SOCS) inhibit JAK-STAT and TLR signaling. CTLA-4 and PD-1 are membrane proteins that inhibit T cell activation when they bind ligands on other cells.)

Which of the following mechanisms contributes most to both Ig and TCR diversity? A. Multiple possible combinations of the different V, D, and J segments B. Changes in the nucleotide sequences at the junctions between recombined V, D, and J segments C. Somatic mutation of variable genes D. Isotype switching E. Polymorphism

Answer: B (Junctional diversity is caused by deletions and additions of base pairs between V, D, and J segments during somatic recombination, resulting in new junctional sequences not present in in inherited (germline) DNA. This accounts for the majority of Ig and TCR diversity. Combinatorial diversity is the second major mechanism for diversity, based on the large number of different V, D, and J segments inserted in the germline that can be used during somatic recombination, but it contributes much less to diversity than does junctional variability. Somatic mutation of variable genes occurs during the germinal center reaction in B cells only, and its impact on diversity is far less than the mechanism of junctional diversity. Isotype switching (of Ig molecules only) changes the non-antigen-binding region and does not contribute to diversity of antigen receptor specificity. Polymorphism refers to the presence of different alleles of a gene in the population, not in an individual, and is not a mechanism of diversity of the antigen receptor repertoires.)

Why do Ig and TCR genes only undergo rearrangements in B and T cells and not other cell types? A. The hepatmer/nonamer recombination signal sequences (RSSs) adjacent to V, D, and J gene segment are present only in B and T cells B. The Ig and TCR α genes are deleted in other cell types C. Recombinase activating genes (RAG-1 and RAG 2) are expressed only in developing lymphocytes D. Activation induced deaminase (AID) is expressed only in developing lymphocytes E. DNA-dependent protein kinase is only expressed in developing lymphocytes

Answer: C (A complex of RAG-1 and RAG-2 is the V-(D)-J recombinase that recognizes RSSs adjacent to V, D, and J gene segment, and cuts the DNA at these locations. This is an essential step for V-(D)-J rearrangements. The RAG proteins are only expressed in developing B and T cells, and only at certain times during development. The actual inherited Ig and TCR gene sequences in developing lymphocytes before recombination occurs, including coding gene segments and RSSs, are identical to the sequences in all other cells. AID is required for Ig gene switch recombination and somatic mutation of Ig V genes, but does not play a role in antigen receptor V-(D)-J rearrangements. DNA-dependent protein kinase is a DNA repair enzyme necessary but not sufficient for the antigen receptor rearrangements, and it is not unique to B and T cells.)

A child with a mutation in the gene encoding one of the polypeptide chains of the integrin LFA-1 (CD11aCD18) suffers from recurrent serious bacterial and fungal infections, and the sites of infection contain few inflammatory leukocytes. Which of the following accurately describes a required function of the LFA-1 integrin that is missing in this child? A. LFA-1 on endothelial cells binds to carbohydrate ligands on neutrophils and monocytes, causing these leukocytes to stably arrest on the endothelial surface. B. LFA-1 on neutrophils and monocytes binds to ICAM-1 on endothelial cells causing the leukocytes to stably arrest on the endothelial surface. C. LFA-1 on leukocytes binds to chemokines in tissues, which direct leukocytes to migrate into sites of infection D. LFA-1 on endothelial cells binds to VCAM-1 on T cells, which supports migration of activated T cells into tissues E. LFA-1 on neutrophils binds to ICAM-1 on bacterial cell walls, which supports phagocytosis of the bacteria.

Answer: B (LFA-1 is a leukocyte integrin that binds to the Ig superfamily adhesion molecule ICAM-1 on endothelial cells. LFA-1:ICAM-1 interactions allow rolling leukocytes to come to a full stop and stably adhere to the endothelium, a necessary step before the leukocytes can migrate between endothelial cells and out into tissue sites of infection. Genetic deficiencies in LFA-1 (called leukocyte adhesion deficiency-1) result in a failure of neutrophils and leukocytes to migrate to sites of bacterial and fungal infections, as well as defects in migration and activation of lymphocytes. Although chemokine binding to chemokine receptors on leukocytes can upregulate the affinity of the leukocyte's integrins for their ligands, chemokines do not bind directly to integrin. The integrin that binds to VCAM-1 is VLA-4.)

MHC genes are the most polymorphic of any in the human genome. Which of the following statements about MHC polymorphism is true? A. HLA-A, HLA-B, and HLA-C represent three different alleles of the same gene. B. Most of the polymorphic residues in any MHC protein are located in the peptide binding groove. C. Only class I MHC genes are polymorphic; class II MHC genes are not. D. Many unrelated people have identical MHC alleles E. MHC polymorphism is a result of somatic recombination of inherited nonpolymorphic MHC gene segments.

Answer: B (MHC polymorphism are concentrated in the peptide binding groove, resulting in differences in the range of peptides that can bind to each allelic form on each type of class I or class II MHC molecules. HLA-A,-B, and -C are different types of class I MHC molecules, encoded by three different genes, each one of which has many different alleles in the population. It is very rare for two individuals to have identical sets of HLA alleles, unless they are siblings. Both class I and class II MHC genes are polymorphic, although class I MHC genes are more polymorphic. MHC genes are not somatically rearranged, but rather the allelic variations are encoded in the germline and are inherited.)

Monoclonal antibodies used as drugs or diagnostic reagents are characterized by all of the following EXCEPT: A. Single antigen specificity B. Monovalent, with one antigen-binding site C. Single isotype D. Production by a B cell hybridoma E. Known antigen specificity

Answer: B (Monoclonal antibodies are, by definition, identical antibodies of a single isotype and antigen specificity, produced by a single clone of cells. They are usually produced in vitro by clonal B cell hybridomas and are structurally normal, with at least two antigen-binding sites and a known specificity. Tumors of B lymphocytes (e.g., myelomas) may produce monoclonal antibodies, usually of unknown specificity, or often single chains of antibody molecules.)

Which of the following cell types is a phagocyte? A. plasma cell B. neutrophil C. mast cell D. natural killer cell E. T lymphocyte

Answer: B (Neutrophils (and macrophages) are the major phagocytes in the immune system, and function to internalize and kill microbes. Phagocytes also internalize and break down dead cells and nonmicrobial foreign materials. The other cell types listed have minimal phagocytic capabilities)

According to the clonal selection hypothesis, which of the following is correct? A. lymphocyte specificity is determined by exposure to an antigen B. clones of lymphocytes specific for antigens develop prior to exposure to the antigens C. antigen binding to a lymphocyte receptor selects that lymphocyte to die D. antigen binding to secreted antibody stimulates proliferation of the B cell that secreted the antibody E. each clone of lymphocytes express receptors for many different antigens

Answer: B (The clonal selection hypothesis correctly predicted that lymphocyte antigen specificities are determined by molecular events prior to any exposure to antigen, and then, in response to exposure to a particular antigen, the clone that recognizes it will be selected to become activated, increase in size, and differentiate into effector cells.)

A 5-year-old boy with recurrent infections is discovered to have a genetic defect that impairs B cell maturation. Which of the following abnormalities is most likely to be found in this patient? A. small thymus B. absence of follicles in lymph nodes and spleen C. enlarged tonsils D. diminished parafollicular zones in lymph nodes E. hypocellular bone marrow

Answer: B (The follicles of the spleen and lymph nodes are largely made up of mature B lymphocytes. Thus, if this patient lacks mature B cells, he will lack follicles. The thymus is the site of T cell maturation, which should not be affected by a defect in B cell maturation. Tonsils, which normally contain many B cells, should be small, not enlarged, in this patient. The parafollicular zones of lymph nodes are sites where T cells are abundant and should be of normal size in this patient. Most bone marrow is composed of nonlymphoid hematopoietic elements, so a defect in B cell maturation should not influence the cellularity. Furthermore, with multiple infections, the patient may have increased production of neutrophils, resulting in hypercellular marrow.)

A previously healthy 8-year-old boy is infected with an upper respiratory tract virus for the first time. During the first few hours of infection, which one of the following events occurs? A. the adaptive immune system responds rapidly to the virus and keeps the viral infection under control B. the innate immune system responds rapidly to the viral infection and keeps the viral infection under control C. passive immunity mediated by maternal antibodies limits the spread of infection D. B and T lymphocytes recognize the virus and stimulate the innate immune response E. the virus causes malignant transformation of respiratory mucosal epithelial cells, and the malignant cells are recognized by the adaptive immune system

Answer: B (The innate immune response to microbes develops within hours of infection, well before the adaptive immune response. B and T lymphocytes are components of the adaptive immune response, and they would not be able to respond to a newly encountered virus before the innate immune response. An 8-year-old boy would no longer have maternal antibodies from transplacental passive transfer and is unlikely to be breast-feeding, which is another potential source of maternal antibodies. Malignant transformation takes months or years to develop.)

Which of the following can be accurately called a cytokine? A. a cell surface antigen receptor on lymphocyte B. an antibody secreted by a B cell C. a protein secreted by a T lymphocyte that activates a macrophage D. a lipid secreted by a Natural Killer cell that activates a B cell E. a nuclear protein that regulates lymphocyte gene expression

Answer: C (All cytokines are proteins. There are many cytokines produced by many cell types, which bind to receptors on the same or other cells, and induce various functional responses. Cytokines mediate much of the intercellular communication that is required for effective immune responses.)

The required number of complexes of a microbial peptide and a particular class II MHC allele on the surface of an antigen-presenting cell to initiate a T cell response specific for the viral peptide is: A. One B. All the MHC molecules on the cell must be complexed with the peptide C. About 0.1% of the total number of class II MHC molecules on the cell surface D. Greater than 106 E. Zero

Answer: C (As few as 100 complexes of a particular peptide and a particular class II MHC molecule are needed to activate naive T cells specific for that complex and thereby initiate a detectable T cell response. This represents less than 0.1% of the total class II MHC molecules on a typical antigen-presenting cell surface.)

Macrophages that accumulate in infected tissues are derived from which type of circulating blood cell? A. polymorphonuclear leukocyte B. small lymphocyte C. monocyte D. basophil E. lymphoblast

Answer: C (Blood monocytes migrate into tissues and become macrophages. Note that here are tissue resident macrophages present from birth in all tissues that are derived from fetal hematopoietic cells.)

Naïve viral-antigen specific CD8+ T cells require activation by viral-peptide bound to MHC molecules presented by dendritic cells, but dendritic cells may not be infected by many types of viruses. Which of the following mechanisms accounts for CD8+ T cell protection against viruses that do not infect dendritic cells? A. Cross presentation of viral peptides on class II MHC molecules B. Ingestion of viral mRNA by dendritic cells, and synthesis of the viral antigens in the dendritic cell endosomes. C. Ingestion of viral proteins into dendritic cell endosomes, and transport of the proteins into the cytosol where they are processed by proteasomes in to peptides that are pimped into the ER, where they bind to newly formed class I MHC molecules. D. CD8+ T cell responses to antigens made by viruses that infect dendritic cells will cross-react with antigens of viruses that do no infect dendritic cells. E. Natural killer cells will recognize viral peptides bound to class II MHC molecules on dendritic cells.

Answer: C (CD8+ T cells are restricted to recognizing class I MHC-peptide complexes. Cross presentation is a mechanism by which dendritic cells can take in proteins made by other cells, then delver them into the cytosol to enter the class I processing and presenting pathway. Cross presentation does not involve class II MHC. RNA taken up into endosomes will be destroyed, and not delivered to the cytosol. Natural killer cells do not recognize peptide-class II MHC antigens.)

CTLA-4-Ig is a soluble recombinant protein containing the ligand binding portion of CTLA-4 fused to the Fc portion of IgG. It is an approved drug used to treat autoimmune diseases. How does it work? A. Binds to CTLA-4 on T cells and induces inhibitory signals B. Binds to CTLA-4 and blocks its ability to bind to B7-1 and B7-2 C. Binds to B7-1 and B7-2 on antigen presenting cells, and blocks their ability to bind to CD28 on T cells D. Binds to inhibitory Fc receptors on B cells and inhibits the production of autoantibodies E. Binds to cytotoxic T lymphocytes and blocks their ability to kill other cells

Answer: C (CTLA-4-Ig is a costimulatory blocker. It has high affinity for B7-1 and B7-2, and therefore blocks costimulation by these molecules, which is required for naïve T cell activation. CTLA-4-Ig is not anti-CTLA-4 and does not bind to CTLA-4. The Ig Fc portion of the drug prolongs half-life, but is not involved in the immune inhibitory function of the drug.)

Which of the following is a property of exhausted CD8+ T cells? A. Low expression of CTLA-4 B. High expressing of IL-4 C. High expression of PD-1 D. Low expression of class I MHC E. High expression of interferon-γ

Answer: C (Exhausted CD8+ CTL arise when there is persistent exposure to antigen, such as in the setting of chronic infections or cancers. Exhausted CTLs have high expression of the inhibitory receptor PD-1 and other inhibitory molecules such as CTLA-4. Exhausted T cells produce less interferon-γ than normal CTL. CTL do not express IL-4, and class I MHC expression is not typically altered.)

Which type of T cell is most likely to promote acute neutrophillic inflammatory responses that defend against extracellular bacteria and fungi? A. Th1 B. Th2 C. Th17 D. CTL E. T follicular helper

Answer: C (IL-17 produced by Th17 cells induces many cell types to make chemokines such as IL-8, and cytokines such as IL-1 and TNF, all of which enhance neutrophil recruitment into tissues. Th1 cells and CTLs, which secrete IFN γ, are more typically associated with chronic inflammatory infiltrates rich in activated macrophages, and Th2 cells are associated with eosinophil-rich inflammation. T follicular helper cells do not promote inflammatory responses, but rather help B cells in germinal center reactions.)

Which of the following statements about the recognition receptors of the innate immune system, such as Toll like receptors (TLRs), is correct? A. They are encoded by genes produced by somatic recombination of gene segments that are separated in inherited germline DNA B. Each clone of macrophages express a unique set of these receptors that differs in specificity from those receptors on all other clones of macrophages C. They recognize pathogen associated molecular patterns, such as viral nucleic acids, bacterial cell wall constituents, and terminal mannose residues. D. They function to neutralize microbes, but do not initiate signal transduction pathways that activate cells. E. They undergo somatic mutation and affinity maturation in response to microbial antigens.

Answer: C (Innate immune receptors, called pattern recognition receptors, recognize pathogen associated molecular patterns (PAMPs), which are structures common to many microbial species and not made by mammalian cells, and are essential for microbial viability or infectivity. Pattern recognition receptors are encoded by nonclonally distributed, germline encoded genes, and engage cell activating signal transduction pathways.)

In the cannonical NF-κB signaling pathway downstream of the TNF receptor, TLRs, and antigen receptors, what role does IκB kinase (IKK) complex play? A. IKK enters the nucleus and phosphorylates NF-κB that has bound to the promoters of proinflammatory genes B. IKK binds to NF-κB, preventing it from entering the nucleus C. Activated IKK phosphorylates IκBα, which leads to IκBα degradation, allowing NF-κB to enter the nucleus D. IKK enters the nucleus and binds to the promoters of pro inflammatory genes E. IKK phosphorylates NF-κB, allowing NF-κB to enter the nucleus

Answer: C (NF-κB is kept in the cytoplasm by bound IκBα. The function of the IKK complex is to remove IκBα, allowing NF-κB to enter the nucleus and promote the transcription of proinflammatory genes. IKK must be activated by TRAF signals generated originating from cell surface receptors. This leads to activation of the IKKβ subunit of IKK which phosphoryaltes IκBα. Phosphorylated IκBα is then ubiquitinated and degraded by the proteasome.)

Which of the following is a human class I MHC molecule? A. HLA-DR B. HLA-DP C. HLA-B D. I-A E. CD8

Answer: C (The human class I MHC molecules are HLA-A, HLA-B, and HLA-C. The human class II MHC molecules are HLA-DP, HLA-DQ, and HLA-DR. I-A is a mouse class II MHC molecule. CD8 is not an MHC molecule, but it binds to class I MHC molecules.)

In DiGeorge syndrome, the thymus fails to develop. Which of the following characterizes the immunodeficiency state in this syndrome? A. deficiency in monocytes and tissue macrophages B. defect in naive B cell activation and antibody production in response to bacterial polysaccharides C. deficiency in T lymphocytes and associated defects in cell-mediated immunity D. normal numbers of naive T cells that cannot be activated by antigen E. deficiency in B cell maturation

Answer: C (The thymus is the principal site for production of mature T lymphocytes. Therefore, lack of a thymus results in a global defect in T cell-mediated immunity. There would not be a specific defect in naive T cell activation, but rather a lack of naive T cells. Monocytes and macrophages are produced independently of the thymus or mature T cells. B cell maturation is not dependent on T cells. Although B cell responses to protein antigens depend on helper T cells, B cells specific for polysaccharides can be activated and produce antibodies independently of T cells.)

Which of the following is a feature of Natural Killer (NK) cells? A. They express clonally distributed antigen receptors that directly bind antigens on the surface of microbes B. They are activated by recognizing microbial peptides bound to host class I MHC molecules C. They kill virally infected cells by a perforin/granzyme dependent mechanism D. Upon activation, they secrete abundant interleukin-4 E. They secrete natural IgM antibodies

Answer: C (Upon activation, NK cells release perforin and granzymes from cytoplasmic granules, and these proteins work together to induce apoptosis of the target cell. NK cells are activated by binding various ligands expressed on infected or stressed target cells. NK cells are inhibited by binding self class I MHC, a feature of healthy cells, but often not of virally infected or otherwise unhealthy cells. NK cells secrete several cytokines, including IFN-γ, but they do not secrete IL-4.)

Migration of leukocytes out of the blood into tissues mainly occurs in which type of vessel? A. arteries B. arterioles C. capillaries D. venules E. veins

Answer: D (All leukocytes mainly migrate into tissues through the walls of post capillary venules, because the flow characteristics in venules favor leukocyte endothelial interactions, and the endothelial cells lining post capillary venules are specialized to express adhesion molecules required for leukocyte interactions with endothelial cells, and to produce and display chemokines that promote binding to endothelium and migration of the leukocytes.)

Alternative macrophage activation is characterized by which one of the following? A. Reactive oxygen species (ROS) generation B. IL-1 production C. Microbial killing D. IL-10 and TGFβ secretion E. IL-4 and IL-13 secretion

Answer: D (Alternatively activated macrophages secrete the anti-inflammatory cytokines IL-10 and TGFβ. They also enhance angiogenesis and fibrosis. ROS generation, IL-1, and microbial killing are characteristic of classically activated macrophages. IL-4 and IL-13 are cytokines made by Th2 cells, which induce alternative macrophage activation.)

An antigen-binding site of an IgG antibody molecule is composed of which of the following? A. Twelve hypervariable loops, three each on two heavy chains and two light chains B. Three hypervariable loops on a light chain C. Three hypervariable loops on a heavy chain D. Six hypervariable loops, three each on one heavy chain and one light chain E. Six hypervariable loops, three each on two heavy chains

Answer: D (An IgG molecule has two antigen binding sites. Each one is composed of six hypervariable loops, three that extend from the variable domains of a heavy chain and three that extend from the variable domains of the covalently linked light chain.)

At the peak of a CD8+ T cell response to a new microbe, what is the fold increase in the number of microbe-specific T cells in an individual compared to the number of naïve CD8+ T cells specific for the microbe before infection? A. ~100 B. ~1000 C. ~10000 D. ~100,000

Answer: D (CD8+ T cells undergo tremendous clonal expansion in response to antigen stimulation. CD4+ clonal expansion is less, on the order of 1000 to 10,000 fold.)

How does the complement system enhance B lymphocyte activation? A. Generation of the membrane attack complex on B cell membrane allows calcium ions (Ca++) to enter the B cell and stimulate calcium-dependent enzymes B. Opsonization of protein antigens with C3b promotes B cell phagocytosis of protein antigens, enhancing B cell-T cell collaboration C. C1q binding to membrane IgM will activate BCR signaling D. C3d bound to a microbial surface will bind to complement receptor 2 (CR2) on B cells, generating kinase activity by the CR2-CD19-CD81 complex E. C5a binding to its receptor on B cells stimulates Ig heavy chain gene expression

Answer: D (CR2 is expressed on B cell membranes in a complex with CD19 and CD81. CR2 binds to C3d, a proteolytic product of C3b that remains covalently bound to microbial surfaces after complement activation. If CR2 binds C3d on a microbe at the same time that microbial surface antigens bind to membrane Ig, signaling through the CR2-CD19-CD81 complex enhances BCR signaling resulting in enhanced B cell activation.)

CTLs are the major defense against which of the following class of organisms? A. Extracellular bacteria B. Fungi C. Protozoans D. Viruses E. Helminths

Answer: D (CTLs kill host cells with intracellular infections. All viruses must reproduce within host cells, and are eradicated by CTL killing of the cells they infect. CTLs have limited capacity to kill extracellular microbes since they are activated by microbial-peptide self-class I MHC complexes. Many protozoans, fungi, and helminths are also extracellular.)

Which of the following is one of the major functions of chemokines in the immune system? A. Increase affinity of leukocyte selectins for their ligands on endothelial cells. B. Stimulate proliferation of B cells in response to antigen C. Increase vascular permeability during the innate immune response to microbes D. Maintain the spatial separation of B and T lymphocytes within lymphoid tissues E. Form pores in bacterial membranes

Answer: D (Chemokines have three major functions in the immune system. 1. Chemokines activate leukocytes to increase integrin affinity, which is needed for stable arrest of leukocytes on endothelial cells before they can migrate into tissues 2. Chemokines promote movement of leukocytes towards the source of the chemokines such as an infected phagocyte. 3. Distinct chemokines that are continually produced in follicles or interfollicular regions of lymphoid tissues maintain the location of B cells in the follicles and T cells outside the follicles.)

Which of the following accurately describes HLA gene expression by a single dendritic cell in an individual. A. Only class II HLA genes B. Only class I MHC genes C. Only one of the two inherited HLA alleles for each Class I and class II HLA gene D. All inherited class I and class II HLA alleles E. No HLA genes

Answer: D (HLA (MHC) genes are codominantly expressed, meaning both maternal and paternal inherited alleles of each HLA gene are expressed simultaneously in cells that can express HLA genes. Dendritic cells express both class I and class II HLA, and therefore they simultaneously express both inherited alleles of the class I genes ( HLA-A, -B, and -C) and both inherited alleles of the class II genes ( HAL-DP, -DQ, and- DR).)

In the class I MHC pathway of antigen presentation, cytoplasmic proteins are tagged for proteolytic processing by covalent linkage with which of the following molecules? A. Calreticulin B. Nuclear factor (NF)-κB C. Tapasin D. Ubiquitin E. Calnexin

Answer: D (In the class I pathway, proteins are tagged for proteasomal processing by covalent addition of several copies of the polypeptide ubiquitin. Ubiquitin-dependent proteasomal proteolysis is also important in many other cellular processes besides antigen presentation. For example, NF-κB is a transcription factor whose activation is dependent on ubiquitination and proteasomal degradation of an inhibitor (called IκB). Calreticulin, tapasin, and calnexin regulate the assembly of class I MHC proteins within the endoplasmic reticulum.)

What role does CD4 and CD8 on T cells play in the early signaling events during T cell activation? A. Like CD3 and ζ proteins, CD4 and CD8 contain ITAMs in their cytoplasmic tails that serve as docking sites for protein tyrosine kinases (PTKs) B. CD4 and CD8 have intrinsic phosphatase activity in their cytoplasmic tails that remove phosphates from ITAMs on CD3 and ζ proteins C. When CD4 and CD8 bind to MHC molecules on antigen presenting cells, the MHC molecules become active kinases that activate the APCs D. CD4 and CD8 have Src family PTKs associated with their cytoplasm tails, which are brought into proximity of and phosphorylate the CD3 and ζ ITAMs upon antigen recognition. E. Upon antigen recognition, the cytoplasmic tails of CD4 and CD8 became phosphorylated and bind JAK family kinases, which then phosphorylate STAT family proteins.

Answer: D (Lck, a Src family PTK, is noncovalently associated with the cytoplasmic tails of both CD4 and CD8, and Lck phosphorylates CD3 and ζ chain ITAMs when CD4 and CD8 bind to MHC molecules during antigen recognition. CD4 and CD8 do not have ITAMs, intrinsic kinases, phosphatases or JAK kinase binding sites in their cytoplasmic tails. MHC molecules also do not have intrinsic kinase activities.)

Microbial DNA stimulates innate immune responses through which of the following pathways? A. Plasma membrane TLR9 leading to activation of NF-κB B. Cytosolic RIG-like receptors leading to activation of interferon regulatory factors (IRFs) C. Blood C-reactive protein (CRP) leading to complement activation D. Cytosolic cyclic dinucleotides and endospermic STING leading to activation of interferon regulatory factors (IRFs) E. Plasma membrane mannose-binding lectin (MB) leading to complement activation

Answer: D (Microbial ds DNA in the cytosol induces synthesis of cyclic dinucleotides, which bind to endoplasmic STING, leading to signaling events that activate IRFs, which induce type I interferon production. TLR9 does respond to DNA in endosomes, not the cytosol. Neither CRP or MBL recognize or respond to DNA.)

At 15 months of age, a child received a measles-mumps-rubella vaccine (MMR). At age 22, she is living with a family in Mexico that has not been vaccinated and she is exposed to measles. Despite the exposure, she does not become infected. Which of the following properties of the adaptive immune system is best illustrated by this scenario? A. specificity B. diversity C. specialization D. memory E. self-tolerance

Answer: D (Protection against infections after vaccination is due to immunologic memory of the adaptive immune system. Memory is manifested as a more rapidly developing and vigorous response on repeat exposure to an antigen compared with the first exposure. Specificity and diversity are properties related to the range of antigenic structures recognized by the immune system, and specialization is the ability of the adaptive immune system to use distinct effector mechanisms for distinct infections. Self tolerance is the induced state of unresponsiveness to self-antigens)

A major function of Th1 cells is to activate macrophages. Which molecules expressed by Th1 cells are essential for this function? A. IL-1 and TNF B. CD8 and Fas ligand C. IL-17 and IL-22 D. Interferon γ and CD40 ligand E. IL-4 and ICOS

Answer: D (Th1 cells activate macrophages via secreted interferon γ and membrane CD40 ligand, which bind respectively to interferon γ receptors and CD40 on the macrophages. Th1 cells express CD4 and not CD8. Although Th1 cells express Fas ligand, this molecule does not activate macrophages, but rather binds to Fas on various cell types and induces apoptotic cell death. IL-17 and IL-22 are not made by Th17 cells but not Th1 cells. IL-4 is not made by Th1 cells, and ICOS does not activate macrophages.)

Th2 cells are defined in part by production of which of the following cytokines? A. TNF B. -1 C. IL-2 D. IL-4 E. IFNγ

Answer: D (Th1 cells are defined by production of IFNγ. Thh2 cells are defined by production of IL-4, IL-5, and IL-13. Thh17 cells are defined by production of IL-17A, IL-17F, and IL-22. Many T cells produce combinations of various cytokines, and polarized cells expressing restricted cytokine profiles tend to develop upon chronic or repeated stimulation.)

A 52-year-old man who receives radiation therapy and cytotoxic drugs for treatment of cancer sustains significant damage to his bone marrow. Which of the following changes will most likely occur? A. decreased production of monocytes but not B lymphocytes B. decreased production of B lymphocytes but not T lymphocytes C. decreased production of neutrophils and monocytes but not B lymphocytes D. decreased production of B and T lymphocytes, monocytes, neutrophils and red blood cells E. normal production of all blood cells due to compensatory extramedullary hematopoiesis

Answer: D (The bone marrow contains the hematopoietic precursor cells that give rise to all circulating leukocytes, including both B and T lymphocyte lymphocytes, neutrophils, monocytes and red blood cells, and all would be reduced if the marrow is damaged by irradiation. Although blood cell production (hematopoiesis) may occur in non-bone marrow (extramedullary) sites, such as liver, when bone marrow is damaged, full compensation for bone marrow loss is not usually achieved, and even extramedullary hematopoiesis is impaired by irradiation and cytotoxic drugs.)

Which one of the following statements about peptide binding to MHC molecules is true? A. MHC molecules preferentially bind peptides derived from foreign (e.g., microbial) proteins and not peptides derived from self proteins. B. Each type of MHC molecule and each allelic variant of each type have a narrow specificity for a single peptide with a particular amino acid sequence. C. The affinity of peptide binding to MHC molecules is higher, on average, after chemokine stimulation of a cell. D. An MHC molecule has only one peptide-binding site, which accommodates only a single peptide at a time. E. Peptide binding to class I MHC molecules involves noncovalent interactions, whereas peptide binding to class II MHC molecules is covalent.

Answer: D (There is only one peptide-binding site in both class I and class II MHC molecules that can fit only a single peptide at one time. MHC molecules do not distinguish foreign from self proteins; self-nonself discrimination is achieved by T cells. Each MHC molecule has a broad specificity for large numbers of peptides with varying sequences, although there are some structural constraints that result in each type of MHC molecule binding a different subset of peptides. The affinity of peptide-MHC interactions is not altered by chemokines. Peptide binding to both class I and class II MHC molecules involves only noncovalent interactions.)

Which one of the following is a correct description of the basic symmetric core structure of an IgG antibody? A. One heavy chain and two light chains B. One constant domain and one variable domain. C. Two heavy chains and one light chain D. Two heavy chains and two light chains E. One heavy chain and one light chain

Answer: D (Two γ heavy chains are covalently linked to each other, and each heavy chain is covalently linked to one light chain (κ or λ). IgM molecules contain 5 covalently linked copies of the basic IgM core structure, and IgA contain two copies. Each IgG heavy chain has one variable domain and three constant domains, and each light chain has one variable domain and one constant domain.)

A one year old boy with a history of severe infections is found to have very few circulating mature T cells or NK cells, but normal numbers of B cells. Genetic studies reveal he has X-linked severe combined immunodeficiency syndrome. Defective signaling by the receptor for which cytokine is the underlying cause of this disease? A. IL-1 B. IL-2 C. IL-4 D. IL-7 E. GM-CSF

Answer: D (X-linked severe combined immunodeficiency syndrome (X-linked SCID) caused by mutations in the common γ chain which is a signaling polypeptide in the multimeric cytokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Although signaling from all of these receptors would be defective in X-linked SCID, only IL-7 is required for early development of T cells and NK cells in the thymus of humans.)

Which of the following is an example of G protein-coupled receptor (GPCR)? A. T cell antigen receptor (TCR) B. The B cell antigen receptor (BCR) C. CD4 D. Interlukin-2 (IL-2) receptor E. Chemokine receptor CCR7

Answer: E (All chemokine receptors, including CCR7, are GPCRs. The lymphocyte antigen receptors (TCR, BCR), CD4, and IL-2 receptor signal via associated proteins or non-receptor tyrosine kinases.)

Which of the following is the most important antigen presenting cell for activation of naive CD4+ T cells in lymph nodes? A. B cells B. Macrophages C. Mast cells D. Neutrophils E. Dendritic cells

Answer: E (Dendritic cells take up protein in tissues, carry them through the lymph into lymph nodes, and present peptides derived from the proteins to naïve T cells that recirculate through the nodes. Dendritic cells express costimulatory molecules and class II MHC molecules. These properties make dendritic cells the only cell type that can efficiently present and activate naive CD4+ T cells. B cells and macrophages can present antigen to CD4+ T cells, but they mainly activate helper T cells, not naïve T cells. Mast cells and neutrophils have little or no antigen presenting capabilities.)

IgG has a longer half life in the blood than most other plasma proteins. This property is important for maintaining protection against pathogens, and has lead to the design of drugs with long half lives because they contain the part of IgG responsible for the long half life. Which of the following is the basis for prolonged IgG half life? A. Binding of C1q to the IgG Fc region B. Binding of the IgG Fc region the poly Ig receptor on gut epithelial cells C. Binding of the IgG variable regions to ubiquitous blood antigens D. Binding of the J chain to the IgG joining region E. Binding of the IgG Fc region to the neonatal Fc receptor (FcRn)

Answer: E (IgG molecules are internalized by endothelial cells and macrophages, and bind the FcRn in the membrane of endosomes. FcRn sequesters the IgG molecules, shunting them away from lysosomal degradation, and releases them back into the circulation.)

Which of the following mechanisms accounts for the fact that all of the TCRs produced by a single T cell have identical β chains? A. X inactivation B. Light chain isotype exclusion C. Antigen receptor gene homozygosity D. Linkage disequilibrium E. Allelic exclusion

Answer: E (In TCR allelic exclusion, expression of the β chain gene encoded by a successfully recombined gene on one chromosome inhibits recombination of the β chain gene on the other chromosome. The inhibitory signals are generated by the pre-TCR. This ensures that the T cell will not produce receptors with two different β chains. However, allelic exclusion does not occur for TCR α chain genes, and many T cells may express TCRs with two different α chains. Heavy chain allelic exclusion occurs by a similar mechanism in B cell development.)

In the T cell calcium signaling pathway induced by antigen recognition, which enzyme and transcription factor are activated? A. IκB kinase, NFκB B. Jun kiniase (JNK), AP-1 C. Erk kinase, Fos D. JAK3, STAT4 E. Calcineurin, NFAT

Answer: E (In the calcium pathway, TCR signaling leads to an increase in cytosolic calcium ion (Ca++) concentration, which activates the phosphatase calcineurin, leading to dephosphorylation of the transcription factor NFAT. Dephosphorylated NFAT enters the nucleus and stimulates transcription of various genes that promote T cell proliferation and differentiation. Calcineurin inhibitors, such as cyclosporin and tacrolimus, are widely used as immunosuppressant drugs for transplant recipients)

Which of the following is not a function of the innate immune system? A. Rapidly respond to microbial infections by promoting acute inflammation B. Respond to viral infections by inducing the expression of type I interferons C. Respond to microbial infections by inducing expression of T cell costimulators on antigen presenting cells D. Respond to damaged and dying host cells by inducing acute inflammation E. Respond to fungal infections by inducing antibodies that bind and kill the fungi

Answer: E (Innate immune responses do not induce antibody responses, which are part of the adaptive immune response.)

Most naïve T cell activation occurs where and in response to what? A. In the skin in response to cytokines B. In the infected tissues in response to antigen presentation by macrophages C. In the blood in response to antigen presentation by monocytes D. In the thymus in response to antigen presentation by thymic medullary epithelial cells E. In secondary lymphoid organs in response to antigen presentation by dendritic cells

Answer: E (Naive T cells home to lymph nodes, and dendritic cells (DCs) carrying antigens from sites of infection drain into lymph nodes. The chemokine CCR7 directs the co-localization of both cell types. Other types of antigen presenting cell do not activate naive T cells efficiently because they do not migrate to where naïve T cells are, and/or they do not express the costimulatory molecules required for naïve T cell activation.)

Which pair of molecules are found in cytotoxic T lymphocyte (CTL) granules and are important for 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

Answer: E (Perforin and granzyme B are the cytotoxic 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 and 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 via a perforin dependent mechanism. 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.)

Fingolimod is a drug used to treat autoimmune disease, which blocks the function of sphingosine-1 phosphate (S1P) by binding to its receptor S1PR1. Patients treated with fingolimod become lymphopenic, i.e. they have low numbers of lymphocytes in the blood. Why? A. S1P binding to S1PR1 is required for T cell maturation in the thymus B. S1P binding to S1PR1 stimulates ly mphocyte clonal expansion C. S1P binding to S1PR1 blocks lymphocyte migration out of the blood into lymph nodes D. S1P binding to S1PR1 inhibits lymphocyte apoptosis E. S1P binding to S1PR1 on lymphocytes is required for exit of lymphocytes from lymphoid tissues

Answer: E (The exit of naive T cells from lymph nodes and thymus requires the lipid chemoattractant S1P, which binds to S1PR1 on T cells. S1P is present at high concentrations in the blood and lymph compared with lymphoid tissues. Naive T cells in the blood have little surface S1PR1 because the high blood concentration of S1P causes receptor down regulation. When a naive T cell enters a lymph node, it takes several hours for the surface S1P1R to be re-expressed. This allows time for a naive T cell to interact with antigen-presenting cells and be activated. Activated T cells also transiently express the protein CD69, which binds to and down regulates S1PR1, thus enabling the T cell to remain in the lymph node long enough to complete the initial activation program. Following activation, the T cell loses CD69 and, since it is not exposed to S1P, it re-expresses S1PR1 and is thus directed down the S1P concentration gradient out of the lymph node and into the efferent lymphatics. Fingolimod interferes with this process, so that T cells remain trapped within lymph node and thymus)