MSMS Microbiology Exam 1 Practice Questions
The person in the above question is experiencing a primary infection with the virus. B cells activated in a primary infection secrete which class of antibody first? (A) IgA (B) IgD (C) IgE (D) IgG (E) IgM
28 The answer is E: IgM. The first antibody isotype pro- duced by B cells is IgM, that is, it is the first type of B cell antigen receptor. IgA (choice A) is the isotype of antibody synthesized and secreted primarily in the mucosa. IgD (choice B) is an isotype of antibody found in the blood in low levels and its exact function is unknown. IgE (choice C) is an isotype produced to mediate antibody-dependent cell cytotoxicity of parasites. It binds to Fc receptors on eosinophils, basophils, and mast cells and upon antigen binding results in granule release. IgG (choice D) is the high- est concentration of antibody in the serum, mediates complement activation, opsonization, and can cross the placenta to protect fetus.
Which of the following cytokines supports proliferation and differentiation of developing lymphocytes in the primary lymphoid tissue?(A) Interleukin-1 (B) Interleukin-4 ( C) Interleukin-7 (D) Interleukin-12 (E) Interleukin-18
C- IL-1α and β (choice A) are inflammatory cytokines produced by phagocytes (and others) to promote inflammation. IL-4 (choice B) supports differentiation of Th2-type CD4+ T cells, while IL-12 and IL-18 (choices D and E) operate to differentiate Th1-type CD4+ T cells.
Which cells utilize reactive oxygen and nitrogen spe- cies and lysosomal enzymes to kill pathogens? (A) Cytotoxic T cells (B) Natural killer T (NKT) cells (C) Macrophages (D) Natural killer (NK) cells (E) Th1cells
The answer is C: Macrophages. All of the cells listed have the capacity to kill target cells. Cytotoxic T cells (choice A) or activated CD8+ T cells kill primarily through Fas-FasL interactions or production of granzyme/per- forin. Eosinophils, basophils, mast cells, macrophages, and neutrophils kill targets by secreting reactive oxygen species and enzymes. NK (choice D) and NKT (choice B) cells use killer activating receptor (recognize MHC class I-negative cells) signaling and produce granzyme/ perforin. Th1 (choice E) cells can produce TNF-α and IFN-γ which has been shown to cause cell death.
Which cells are the source of interleukin-4, −5, −10, and −13? (A) Bcells (B) Macrophages (C) Mast cells (D) Th1 cells (E) Th2cells
The answer is E: Th2 cells. B cells (choice A) can pro- duce IL-4, IL-5, and IL-10. Macrophages (choice B) can produce IL-4 and IL-10. Mast cells (choice C) can produce IL-4. Th1 (choice D) cells do not produce any of these cytokines as these factors tend to sup- press Th1 activation and differentiation. Interestingly, natural killer T cells can produce these cytokines as well upon initial activation in the presence of IL-4 production by macrophages, B cells, or mast cells.
The viral infection in the above question began in the respiratory tract. Which antibody class would best pro- tect respiratory epithelial cells from viral infection? (A) IgA (B) IgD (C) IgE (D) IgG (E) IgM
29 The answer is A: IgA. The antibody secreted in mucosal tissues is IgA, all other antibody isotypes, IgD (choice B), IgE (choice C), IgG (choice D), and IgM (choice E) are found predominantly in other fluids.
The intracellular signal initiated by antigen binding to the T-cell receptor is generated by which set of molecules expressed on the T cell membrane? (A) CD3 (B) CD4 (C) CD28 (D) CD45 (E) CD152
The answer is A: CD3. CD4 (choice B) functions to stabilize interactions of TCR and MHC during T-cell activation. CD28 (choice C) is the costimulatory receptor for B7 molecules which promotes activation of T-cell responses. CD45 (choice D) is a cell surface marker of activation status but does not function in TCR signaling. CD152 or CTLA-4 (choice E) is a cos- timulatory receptor for B7 molecules which promotes suppression of T-cell responses.
Which one of the following cells is the major source of tumor necrosis factor alpha (TNF-α), interleukin-1, and interleukin-12? (A) Bcells (B) Macrophages (C) Mast cells (D) Th1 cells (E) Th2cells
The answer is B: Macrophages. TNF-α, IL-1, and IL-12 are produced by activated macrophages to promote Th1 differentiation and inflammation. B cells (choice A) do not produce TNF-α or IL-12 but can produce IL-1. Mast cells (choice C) can pro- duce only TNF-α and IL-1. Th1 (choice D) cells can produce TNF-α and IL-1 but not IL-12. However, activated CD8+ T cells (Tc1) can produce IL-12. Th2 (choice E) cells can only produce IL-1 of these three cytokines.
The interaction of which molecule on the membrane of cells with its ligand signals apoptosis?(A) B7 (CD80/86) (B) CD40 (C) CTLA-4 (CD152) (D) Fas (CD95) (E) Fc receptor (CD16)
The answer is D: Fas (CD95). B7 (choice A), expressed on antigen presenting cells, provides costimulatory signals for T-cell activation/suppression depend- ing upon the interacting receptor. CD40 (choice B) is the receptor for CD40L. Signals generated by CD40L-CD40 interactions result in activation as in the case for B cells or maturation when occurring in dendritic cells. CTLA-4 (choice C) signaling medi- ated by binding with B7 from antigen presenting cells, suppresses T cell activation. FcR (choice E) are sur- face receptors that bind to Fc regions of antibodies and result in antibody-dependent cell cytotoxicity (ADCC) or opsonization. Only Fas-FasL interactions result in apoptosis caspase activation.
The virus in the above question spreads from the respiratory tract and causes viremia. Which antibody class would be most important in fighting the virus as it spreads through the body? (A) IgA (B) IgD (C) IgE (D) IgG (E) IgM
30 The answer is D: IgG. The predominant antibody isotype within the blood (site of viremia) is IgG. It functions to activate complement cascade, antibody- dependent cell cytotoxicity and opsonization. IgM (choice E) is also of high levels within the blood but not as significant as IgG. IgA (choice A) is found pre- dominantly in the mucosal compartments. IgD (choice B) is found in low levels in the blood and its function is unknown. IgE (choice C) does not contribute to viral infection control. 31 The answer is B: CD40 ligand and interferon-g. Interferon-γ promotes isotype switching from IgM to IgG, IL-4 (IL-13) induces switching to IgE; IL-2 and IL-7 do not influence isotype switching (choices A, C, D, and E). T helper cells and B cells interact through CD40 ligand-CD40 interactions whereas CTLA-4 and B7 are costimulatory signals, inhibitory and stimula- tory, respectively. CD20 and antigen are not T helper cell-derived factors and cannot promote isotype switching. 32 The answer is E: Secretory piece. IgA is a structural dimer and is held together by the J chain (choice D). IgM can form pentamers also held together by the J chain. B cells produce IgA and the secretory piece permits translocation across mucosal epithelia, subse- quent secretion and protection from proteolysis. The hinge region (choice C) is the flexible portion connect- ing the Fab (choice A) and Fc regions of an antibody. Fc receptors (FcR) (choice B) are receptors on cells which bind Fc regions of antibodies. These interac-
In order for class switching from IgM to IgG to occur, B cells must receive two signals, one generated follow- ing binding to T helper cells and the other secreted by helper T cells. What are these two T helper cell- derived molecules? (A) Antigen and IL-2 (B) CD40 ligand and interferon-γ (C) CTLA-4 and IL-4 (D) B7 and IL-7 (E) CD20 and IL-13
31 The answer is B: CD40 ligand and interferon-g. Interferon-γ promotes isotype switching from IgM to IgG, IL-4 (IL-13) induces switching to IgE; IL-2 and IL-7 do not influence isotype switching (choices A, C, D, and E). T helper cells and B cells interact through CD40 ligand-CD40 interactions whereas CTLA-4 and B7 are costimulatory signals, inhibitory and stimula- tory, respectively. CD20 and antigen are not T helper cell-derived factors and cannot promote isotype switching.
What structural feature is uniquely found on IgA in breast milk and not found on serum IgM? (A) Fab (B) FcR (C) Hinge region (D) J chain (E) Secretory piece
32 The answer is E: Secretory piece. IgA is a structural dimer and is held together by the J chain (choice D). IgM can form pentamers also held together by the J chain. B cells produce IgA and the secretory piece permits translocation across mucosal epithelia, subsequent secretion and protection from proteolysis. The hinge region (choice C) is the flexible portion connecting the Fab (choice A) and Fc regions of an antibody. Fc receptors (FcR) (choice B) are receptors on cells which bind Fc regions of antibodies. These interactions result in cell signaling, activation, opsonization, and/or cytokine production.
Dendritic cells, macrophages, and what other cell types are considered "professional antigen present- ing cells," capable of antigen presentation to T helper cells? (A) Bcells (B) Basophils (C) Eosinophils (D) Mast cells (E) Neutrophils
The answer is A: B cells. Professional antigen pre- senting cells are those that express both MHC class I and II molecules. Basophils (choice B), eosinophils (choice C), mast cells (choice D), and neutrophils (choice D) all do not express MHC class II and thus cannot present antigens to CD4+ T cells. In addition, these cell types do not express the machinery for processing of exogenous antigens.
If a person had a genetic defect affecting perforin pro- duction, which cells and immune function would be affected? (A) Cytotoxic T cells and natural killer cells/cell killing (B) Dendritic cells/antigen presentation (C) Eosinophils and basophils/granule production (D) Macrophages and neutrophils/phagocytosis (E) Mast cells/fusion of granules to cell membrane
The answer is A: Cytotoxic T cells and natural killer cells/ cell killing. Perforin forms pores in the target cells and allows the passage of granzymes into the cyto- plasm of the cells. Granzyme then initiates the process of apoptosis. Only cytotoxic T cells and NK cells pro- duce perforin/granzyme while dendritic cells (choice B), eosinophils/basophils (choice C), macrophages/ neutrophils (choice D), and mast cells (choice E) do not produce these molecules.
Which one of the following represents the major role of negative selection in the thymus? (A) Elimination of self-reactive T cells (B) Expansion of nonself-reactive T cells (C) Maturation of professional antigen presenting cells such as dendritic cells (D) Expression of T-cell receptors on mature T cells (E) Differentiation of Th1 and Th2 CD4+ T cells
The answer is A: Elimination of self-reactive T cells. In fact, about 90% of all T cells that are produced are eliminated (apoptosis) during negative selection. Thymic medullary epithelial cells express the Aire gene (autoimmune regulator gene) and synthesize all self-antigens for presentation on MHC molecules to maturing thymocytes. Mature dendritic cells (DCs) also participate in the presentation of self-antigens to developing single positive T cells. Those T cells that respond too strongly or weakly undergo apop- tosis (undetermined signals) while those responding intermediately are provided survival factors and com- plete maturation, and they migrate out of the thymus to seed the lymphoid organs in the body. While there may be some expansion of nonself-reactive T cells (choice B) due to provided survival/growth factors, this is not the major role of negative selection. DCs do mature but only serve to present self-antigens (choice C). TCR expression is completed following positive selection (choice D). Differentiation of CD4+ T cells (choice E) occurs after antigen exposure in the periphery (tissue, spleen, or lymph node).
Activation of the complement system, directly results in which one of the following outcomes? (A) Enhancedphagocytosis (B) Expression of Toll-like receptors on phagocyte cell surface (C) Enhancement of immune-mediated neutralization (D) Proliferation of T cells (E) Interaction of Fc receptors with antibodies bound to antigens on the pathogen cell surface
The answer is A: Enhanced phagocytosis. Activation of complement has three outcomes: pro- motion of inflammation through recruitment of phagocytes (C3a, C5a), opsonization to enhance phagocytosis by complement receptor-expressing phagocytes (C3b, C4b), and target cell killing (C5b- C9). Expression of Toll-like receptors is constitutive on phagocytes although this expression can be increased (choice B). Neutralization (choice C) is the process of blocking pathogen binding to host receptors (usually accomplished by antibodies), and is not a function of complement activation. Complement activation does not directly result in T-cell proliferation (choice D). Complement activation does not directly promote antibody binding to Fc receptors (choice E).
Which cytokine is essential for T-cell proliferation and is also necessary for the production of CD25-positive regulatory T cells?(A) IL-2 (B) IL-3 (C) IL-4 (D) IL-5 (E) IL-6
The answer is A: IL-2. IL-3 (choice B) is a differentia- tion factor for plasmacytoid dendritic cells. IL-4 and IL-5 (choices C and D) are factors involved in the dif- ferentiation and growth, respectively, of Th2 CD4+ T cells. IL-6 (choice E) is a proinflammatory cytokine that has been reported to suppress regulatory T cell activities and in conjunction with TGF-β can differ- entiate Th17 CD4+ T cells.
Activation of macrophages is best achieved by which cytokine? (A) Interferon gamma (IFN-γ) (B) Granulocyte monocyte colony-stimulating factor (GM-CSF) (C) Interleukin-1 (D) Macrophage chemotactic protein (MCP) (E) Transforming growth factor beta (TGF-β)
The answer is A: Interferon gamma (IFN-g). Upon anti- gen uptake, macrophages through toll-like receptor signaling, produce interleukin-12 which in turn promotes the differentiation of Th1 cells from naïve CD4+ T cell pools. These Th1 cells can then produce IFN-γ which is bound by macrophage IFN-γ recep- tors signaling to promote macrophage phagocytosis. GM-CSF (choice B) serves to differentiate granulo- cytes from stem cells. IL-1 (choice C) is produced by macrophages upon activation and stimulates inflammation. MCP (choice D) is a chemotaxis fac- tor for both macrophages and T cells and at least at this point does not play a role in macrophage activa- tion. TGF-β (choice E) is produced by many cells and serves to stimulate embryogenesis but functions to suppress activities of T cells.
21 Which one of the following cytokines plays the most important role in protection against intracellular growth (reactivation) of Mycobacterium tuberculosis? (A) Interferon-γ (B) Interleukin-2 (C) Interleukin-5 (D) Interleukin-10 (E) Tumor necrosis factor
The answer is A: Interferon-g. In the formation of granulomas, two cell types predominate, Th1 cells and macrophages. Activated macrophages produce IL-12 which promotes Th1 differentiation. In turn, Th1 cells produce IFN-γ to further activate macrophages. IL-2 (choice B) is important in promoting early proliferation of Th1 cells but chronic infection (granuloma) with Mycobacterium would result in activation-induced cell cytotoxicity (AICC) driven by IL-2. IL-5 (choice C) and IL-10 (choice D) is produced by Th2 cells which do not play a role in Mycobacterium immunity. TNF-α (choice E) is produced by Th1 cells but in vivo studies suggests it only synergizes with IFN-γ in the contain- ment of the bacterium.
T cells stimulated by peptide-MHC complexes, dis- played on antigen presenting cells, in the absence of costimulation undergo which one of the following processes? (A) Activation (B) Anergy (C) Apoptosis (D) Differentiation (E) Proliferation
The answer is B: Anergy. Activation (choice A), dif- ferentiation (choice D), and proliferation (choice E) are T-cell outcomes following TCR interaction with peptide-MHC complexes in the presence of cos- timulatory signals (CD28-CD80/86 interactions). Apoptosis (choice C) is a signal generated in T cells through Fas-FasL (CD95-CD95L) and TNF-TNFR (tumor necrosis factor-TNF receptor) interactions. Anergy is a state of unresponsiveness, that is, upon re- exposure to the same antigen, even in the presence of appropriate costimulation, the T cells remain unable to proliferate although they do seem to be able to pro- duce cytokines.
Neutrophils are attracted to the sites of extracellular bacterial infections by which two important chemo- tactic substances? (A) Bacterial mannose and lipopolysaccharide (B) Complement C5a and interleukin-8 (CXCL-8) (C) Histamine and complement C3b (D) Interleukin-7 and interleukin-16 (E) Leukotriene B4 and granulocyte colony- stimulating factor (G-CSF)
The answer is B: Complement C5a and interleukin-8 (CXCL-8). Bacterial mannose and lipopolysaccharide (LPS) (choice A) serve as ligands for pattern recog- nition receptors found on phagocytes. Histamine is a vasoactive amine released upon degranulation of mast cells, while C3b is an opsonin (choice C). IL-7 and IL-16 function in cell activation and survival but do not operate in chemotaxis (choice D). While leuko- triene B4 is a pro-inflammatory product of mast cell activation, G-CSF is a growth stimulating factor for cells (choice E). Only the cleavage product C5a and IL-8 are both recruiting factors for neutrophils.
A person developed an extracellular bacterial infec- tion, and IgM was made in response. What is the most important protective function of IgM in this infection? (A) Antibody-dependent cell cytotoxicity (B) Complementactivation (C) Direct lysis of bacterial cells (D) Neutralization of bacterial toxins (E) Opsonization
The answer is B: Complement activation. The most important defense against extracellular bacteria are opsonins and neutrophils. Complement activation generates the opsonin C3b and attracts neutrophils to the area via the action of C5a. IgM is the most efficient class of antibody at activating complement. IgM can function in neutralization of toxins; however, that is not the most effective protective function (choice D). IgM is not itself an opsonin (choice E), in contrast to IgG. No antibody class can induce bacterial cell lysis directly (i.e., without the assistance of complement) (choice C). IgM does not participate in antibody- dependent cell cytotoxicity (choice A), a function which is carried out against viral-infected cells, but not against extracellular bacteria. Lastly, natural killer cells are not important in defense against extracellular bacteria.
Persons with helminth infections mount immunologic responses that involve IgE and eosinophils. Which two cytokines are most important for these responses to occur? (A) IL-1 and tumor necrosis factor (TNF) (B) IL-4 and IL-5 (C) IL-10 and transforming growth factor beta (TGF-β) (D) IL-12 and interferon gamma (IFN-γ) (E) IFN-α and IFN-β
The answer is B: IL-4 and IL-5. IL-1 and TNF (choice A) are cytokines produced by activated phagocytes and T cells promoting inflammation. IL-10 and TGF-β (choice C) are cytokines produced by Th2, macrophages, and regulatory T cells to suppress the immune response as a mechanism of regulating immunity. In addition, IL-10 can promote Th2 differ- entiation. TGF-β (combined with IL-6) can promote differentiation of Th17 cells involved in autoimmune diseases. TGF-β alone can promote differentiation of Th0 into regulatory T cells. IL-12 and IFN-γ (choice D) are cytokines which promote Th1 differentiation and activation of macrophages (enhance phagocyto- sis). Interferon alpha and beta (choice E) are cytokines induced by viral infections which result in establish- ment of the antiviral state. Since IgE bound to Fc receptor is critical for antibody-dependent cell cyto- toxicity of helminths, the cytokines of importance are those which promote isotype switching from IgM to IgE, and production and chemotaxis of eosinophils that is, IL-4 and IL-5 respectively.
Which one of the following leukocytes is considered a "granulocyte"? (A) Macrophage (B) Neutrophil (C) Dendritic cell (D) Natural killer cell (E) Natural killer T cell
The answer is B: Neutrophil. Granulocytes are immune cells that contain granules in their cytoplasms. These granules are filled with enzymes and other inflam- matory mediators which are released upon activa- tion of the granulocytes. Neutrophils, easinophils and basophils are considered granulocytes. Although both NK cells and NKT cells have granules, they are referred to as large, granular lymphocytes, not granu- locytes. Monocytic cells such as dendritic cells and macrophages (choices A and C) lack distinct cytoplas- mic granules.
A 1-year-old female presented with symptoms of systemic autoimmunity (lupus, diabetes, and arthritis), and upon genetic analysis it was found that the patient had a mutation in the Foxp3 gene locus. Which one of the following is an explanation for the clinical symptoms observed? (A) Patient cannot produce antigen presenting cells (B) Patient cannot generate regulatory CD4+CD25+ T cells (C) Patient is unable to produce antibodies (D) Patient cannot produce anti-inflammatory cytokines (E) Patient NK cells have no inhibitory signal
The answer is B: Patient cannot generate regulatory CD4+CD25+ T cells. CD4+CD25+ T regulatory (Treg) cells or natural Treg cells function in peripheral toler- ance to prevent self-antigen-specific T-cell activation. This is accomplished by still undefined cell-contact inhibitory mechanisms. What has been determined is that those inhibitory mechanisms are a product of the Foxp3 gene; thus, cells with active gene expression of Foxp3 (as determined by quantitative PCR) are regula- tory T cells. Foxp3 is a unique gene to Treg cells and not expressed in other cell types.
Thymocytes interacting with self-peptides undergo negative selection. The self-peptides in this reaction act as: (A) Allergens (B) Tolerogens (C) Haptens (D) Immunogens (E) Antigens
The answer is B: Tolerogens. Positive and negative selection processes make up the event termed central tolerance whose goal is to remove self-antigen-specific T cells. Allergens (choice A) are environmental anti- gens which are recognized by IgE molecules bound to Fc receptors on mast cells. Haptens (choice C) are chemicals which bind to carrier proteins and can then be immunogenic. Immunogens (choice D) are those antigens which promote immunity. The term antigens (choice E) refers to all chemical structures which can elicit immune responses, whether self- or foreign- derived in nature. Only tolerogens refers to self-anti- gens which are presented by thymic antigen presenting cells in order to facilitate negative selection.
The difference between tolerance and immunity depends upon the maturation status of the antigen-presenting dendritic cells. What is the T-cell outcome of an antigen presentation event by a mature dendritic cell? (A) Anergy (B) Apoptosis (C) Activation (D) Ignorance (E) Suppression
The answer is C: Activation. Maturation indicates that the dendritic cell (DC) has been stimulated by Toll-like receptor binding to pathogen components. This in turn upregulates expression of B7 (costimu- latory molecules) on the surface of the DC. Together with the MHC-peptide complex, the DC can now provide sufficient signaling to promote T-cell activa- tion. Such interactions deficient in B7 result in anergy (choice A). Apoptosis (choice B) signals are the result of ligand-receptor interactions involving Fas-Fas lig- and or TNF-related interactions. Ignorance (choice D) is the result of antigens being sequestered from access to T cells; thus, the T cells remain ignorant of the anti- gen presence (immune-privileged sites such as the sex organs utilize this mechanism). Suppression (choice E) is an active process mediated by cytokines or regu- latory cells such as regulatory T cells.
A 36-year-old woman with severe allergy to yellow jackets was stung multiple times at a soccer game. Within minutes she developed respiratory distress and became unconscious. Which mediator is prima- rily responsible for this reaction? (A) Complement (B) IgG (C) Histamine (D) TNF (E) Norepinephrin
The answer is C: Histamine. This is an allergic response to the yellow jacket venom involving mast cell degranulation. As a consequence of degranulation, histamine is released. Complement proteins (choice A) are a set of serum proteins which bind to micro- bial surfaces in order to promote opsonization and cell killing through formation of the membrane attack complex. IgG is an antibody isotype which can initiate complement activation and serve to promote opsoni- zation of pathogens. TNF or tumor necrosis factor is a proinflammatory cytokine released by phagocytes and activated T cells, which elicits inflammatory activity. Norepinephrin is a hormone growth factor that plays a role during stress responses but is not responsible for allergic reaction.
Plasma cells secreting IgA are especially abundant in which body site? (A) Bonemarrow (B) Germinal centers of cervical lymph nodes (C) Lamina propria of mucosa (D) Thoracic duct (E) White pulp of the spleen
The answer is C: Lamina propria of mucosa. IgA is the isotype associated with mucosal immunity. While it can be produced in other anatomical regions, it is abundant in the mucosa. The bone marrow (choice A) contains long-lived plasma cells producing anti- bodies. Germinal centers (choice B) within the cervi- cal nodes could also produce IgA, but B cells in the lamina propria produce significantly more IgA. The thoracic duct (choice D) is the lymph vessel responsi- ble for returning cells and fluid from the lymph back into circulation. The white pulp of the spleen (choice E) contains areas of B cell differentiation into plasma cells and can produce IgA, but as IgA is an impor- tant neutralizing agent in the mucosa, it is localized in high levels within the mucosa.
Following an initial expansion of B cells in response to microbial peptides, a memory pool of B cells is generated and maintained in the individual in many cases throughout life. Recently, it was discovered that two memory cell types were generated in response to microbial challenge. Upon rechallenge with the microbe, the patient is protected from infection. Which one of the following explanations accounts for this observation? (A) CirculatingmemoryBcellsareactively producing antibodies in the absence of antigen (B) Circulating memory B cells will produce antibodies, however, only upon encounter with the microbial antigen (C) Long-lived plasma cells are actively producing antibodies in the absence of antigen (D) Long-lived plasma cells will produce antibodies, however, only upon encounter with the microbial antigen (E) TLR signaling to the circulating memory B cells will induce rapid production of antibodies in response to antigen encounter
The answer is C: Long-lived plasma cells are actively producing antibodies in the absence of antigen. Following an initial B-cell proliferative event, cells termed plasmablasts differentiate into long-lived plasma cells which traffic to the bone marrow and reside there, actively producing antibodies to the specific antigen against which they were originally expanded (choice D). Circulatory memory B cells (choice A) also exist but do not actively secrete anti- body and appear to serve as replacements for the long-lived plasma cells in the bone marrow over time (choice B). TLR signaling in memory B cells has not been described to impact antibody produc- tion as these circulating cells appear not to synthe- size the antibodies (choice E).
Antigen presenting cells (APCs) are required for T-cell recognition of specific antigen and activation. APCs accomplish this task by presenting antigen in the con- text of which of the following molecules? (A) T-cell receptor (TCR) (B) Toll-like receptor (TLR) (C) Major histocompatibility complex (MHC) (D) Killer inhibitory receptor (KIR) (E) Fc receptor (FcR)
The answer is C: Major histocompatibility complex (MHC). APCs express TLR, FcR, and MHC. TLR (choice B) are innate pattern recognition receptors (PRR) which detect microbial antigens and initiate proinflammatory cytokine production by phagocytes (APCs as well). FcR (choice E) are important in the process of opsoni- zation (FcR binding to antibody bound to the antigen on the pathogen surface and subsequent phagocytosis via this interaction). All nucleated somatic cells express MHC class I while only the professional APCs (B cells, macrophages, and dendritic cells) also express MHC class II. MHC displays antigens for recognition by T cell receptors (TCRs) (choice A).
A 4-year-old child has atopic dermatitis due to severe allergies to dust, animal dander, and many kinds of pollens. Mediators released from which cell type are responsible for the clinical manifestations immedi- ately following exposure to these substances? (A) Bcells (B) Macrophages (C) Mast cells (D) Th1 cells (E) Th2cells
The answer is C: Mast cells. Allergens such as dust, animal dander, and pollen bind to IgE expressed on the surface of mast cells. Such IgE is produced dur- ing the first exposure to the allergen and this IgE binds to high affinity Fc receptors on mast cells. This is known as sensitization. Secondary encounter with the allergen results in binding of the antigen to the IgE and activation of the mast cells (degranula- tion). Macrophages (choice B) play a role in type IV delayed-type hypersensitivity. B cells (choice A) pro- duce the initial antibodies (IgE) to the allergen but do not release vasoactive amines as does mast cells. Th1 cells (choice D) are the mediators of type IV hyper- sensitivity and Th2 cells (choice E) do promote the IgE production but again are not responsible for the mediators.
Vaccination operates to generate a humoral immune response to the immunogen(s). Which one of the fol- lowing represents the critical function of the resultant humoral response in protecting vaccinated patients from future infections by targeted pathogenic agents? (A) Opsonization (B) Extravasation (C) Neutralization (D) Complement activation (E) Antibody-dependent cell cytoxicity (ADCC)
The answer is C: Neuralization. Antibodies generated by the vaccination are produced by antigen-specific memory B cells which reside in the bone marrow. These antibodies (most likely IgG) can promote opsonization (choice A), Fc receptor-mediated phago- cytosis, and complement activation (choice D) as well as ADCC (choice E). However, the infectious agent in most cases will have colonized tissues by the time these mechanisms act to limit growth. The most criti- cal function of a vaccine-mediated humoral response is to generate antibodies which block attachment of infectious agents to host cell surfaces or neutraliza- tion. This blockade completely inhibits microbial col- onization and ensures protection from the pathogen. Extravasation (choice B) refers to the process whereby immune cells can leave the circulation and enter tis- sues generally to migrate into areas of inflammation in order to destroy pathogens invading host tissues.
A person develops a viral infection and both T and B cells become activated to fight the infection. In which way is antigen recognition by B cells different from antigen recognition by T cells? (A) B cells home to the paracortex of lymph nodes where they recognize the antigens trapped by helper T cells (B) B cells recognize the antigens that have been processed and presented by follicular dendritic cells (C) B cells undergo receptor editing to change receptors that fail to bind to an antigen (D) B cells utilize membrane immunoglobulin molecules to bind to antigen in its natural state (E) The antigen receptors on a single B cell have a broad specificity, and are able to recognize several chemically unrelated antigens
The answer is D: B cells utilize membrane immu- noglobulin molecules to bind to antigen in its natural state. CD4+ and CD8+ T cells can only respond to antigens once they have been processed and loaded onto major histocompatibility complexes (MHC) and displayed by antigen presenting cells. B cells rec- ognize antigens directly. Upon initial B-cell encoun- ter with antigen, B cells traffick to the paracortex of the lymph nodes to interact with helper T cells. This interaction involves CD40 ligand-CD40 which promote B-cell expansion as plasma cells (choice A). Once receiving the CD40 signal, the B cells traffick back into the lymphoid follicle and form a germinal center. Antigen is presented to the developing B cells by follicular dendritic cells, FDC (choice B). Only B cells expressing the highest affinity immunoglobulin receptors will remain bound to the FDC. All other B cells will undergo apoptosis. Helper T cells then pro- duce the appropriate cytokines for isotype switching and cell survival signals are provided through CD40 ligand-CD40 interactions. Some of the B cells differ- entiate into antibody-producing plasma cells while others become memory B cells which leave the lymph node and traffick to the bone marrow where they remain as long-lived plasma cells. Receptor editing occurs in the bone marrow when B cells are undergo- ing central tolerance and involves rearrangement of Ig genes (choice C). Like all adaptive receptors each one is specific for only one antigen unlike innate receptors which recognize conserved sequences on pathogens (choice E).
T helper cells interacting with antigen-presenting cells require signals generated by the molecular interactions of the T-cell receptor with the MHC-peptide complex. Additionally, costimulationn is required to amplify the initial TCR signals provided through the T cell CD28 molecule interaction with which one of the following dendritic cells? (A) CD4(B) CD8(C) CD45 (D) CD80/86 (E) CD152
The answer is D: CD80/86. CD4 (choice A) and CD8 (choice B) are molecules that interact with antigen-presenting cell MHC molecules to stabilize the MHC-peptide-TCR interaction. CD45 (choice C) is a cell surface protein found on hematopoietic cells. CD152 (choice E) or CTLA-4, cytotoxic T lymphocyte antigen-4, is expressed on activated T cells (CD4 and CD8) and interacts with B7 (CD80/86) molecules to suppress further T-cell activities (a form of peripheral regulation). Only B7, expressed by antigen-presenting cells, is used to engage CD28 to promote T-cell activation. CTLA-4 has a higher affinity for B7 than does CD28, thus providing a means of regulating T-cell activation status.
What response of T cells plays a role in the patho- genesis of shock following the binding of TSST-1 and similar molecules? (A) Anergy (B) Apoptosis (C) Cell cytotoxicity (D) Cytokine secretion (E) Memory cell differentiation
The answer is D: Cytokine secretion. Superantigen binding to T cells leads either to cell activation or anergy. With regard to the pathogenesis of septic shock, TSST-1 acts as a polyclonal activator, stimulating a number of different T cells in a non-specific fashion and resulting in cytokine secretion. The hyper- secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha can lead to septic shock as occurred in this patient. Anergic cells would not participate in the pathogenesis of this condition. The other choices are not typical responses of T cells to superantigen stimulation and would also not play a role in the pathogenesis of septic shock induced by TSST-1.
A 45-year-old female presents with anorexia and some abdominal pain. Fecal smears reveal the presence of Taenia eggs, products of a parasitic tapeworm infection. Which one of the following cells would be most effective in defense against this parasite? (A) Platelets (B) Erythrocytes (C) Neutrophils (D) Eosinophils (E) Monocytes
The answer is D: Eosinophils. Platelets and erythro- cytes serve as blood components and do not generate immune responses against parasites (choices A and B). Neutrophils (choice C) are surveillance cells which may engage the parasite but the most effective response is generated by eosinophils which express Fc epsilon receptors. These receptors allow the eosinophils to bind to IgE directed against parasitic microbes. Such binding will result in antibody-dependent cell cytox- icity or ADCC. Monocytes (choice E) are bone mar- row and circulating blood cells which can differentiate into macrophages and dendritic cells. However, these cells would not be as effective as the eosinophils in killing the parasite.
A 14-year-old girl presented with an itchy, erythematous rash following exposure to poison ivy. Which term describes the role of poison ivy oils in this response? (A) Allergen (B) Carrier (C) Cytokine (D) Hapten (E) Immunogen
The answer is D: Hapten. Allergens (choice A) are agents which stimulate an IgE response and subse- quent re-exposure activates mast cells to degranulate. The allergens bind to IgE molecules captured by mast cell Fc receptors and these IgE-Fc receptor complexes are long-lived providing an opportunity to become re-exposed to the antigen. Cytokine (choice C) pro- duction is a result of hapten and allergen binding but does not define the role of urushiol (poison ivy oil). Immunogens (choice E) are chemicals which elicit an immune response. This response is correct but is a broad answer to the question posed. Carriers (choice B) are usually protein in nature and associate with haptens. These carriers do not necessarily induce an immune response. Haptens are small molecules which do induce an immune response only in the presence of a carrier.
Antigens from which one of the following microbes would be presented on MHC class I molecules by macrophages? (A) Ascaris lumbricoides (B) Candida albicans (C) Haemophilus influenzae (D) Influenza virus (E) Streptococcus pneumoniae
The answer is D: Influenza virus. MHC class I mol- ecules express endogenous antigens, that is, antigens that were derived from the presenting cell interior. A. lumbricoides (choice A), a parasitic worm, C. albi- cans (choice B), a fungus, H. influenzae (choice C), and S. pneumoniae (choice E), extracellular bacte- ria, will generally only produce exogenous antigens due to their inability to invade cells. However, exog- enous peptides from each of these pathogens can be presented on MHC class I molecules only by den- dritic cells through a process termed crosspresenta- tion. Macrophages do not have this capacity and thus could only present exogenous antigens on MHC class II molecules. Influenza virus by nature is an intracel- lular parasite and thus endogenous antigens would be loaded onto MHC class I and presented to T cells.
Which immune system cells recognize body cells with reduced expression of MHC class I molecules? (A) Cytotoxic T cells (B) Dendritic cells (C) Macrophages (D) Natural killer cells (E) Neutrophils
The answer is D: Natural killer cells. Cytotoxic T cells (choice A) are CD8+ T cells which recognize anti- gens presented on MHC class I molecules, and act to kill targets expressing those antigens. Dendritic cells (choice B) are specialized antigen presenting cells.Macrophages (choice C) and neutrophils (choice E) are phagocytes. Only natural killer cells recognize MHC class I expression on the surface of cells and kill those cells that have lost expression.
A blood sample from an individual with systemic lupus erythematosus was studied in a research project map- ping T-cell receptor specificities. Many T cells were discovered to express receptors specific for autolo- gous antigens. Failure of which process in the thymus leads to the large number of autoreactive T cells in the patient's blood? (A) Affinitymaturation (B) Antigenprocessing (C) Hematopoiesis (D) Negative selection ( E) Receptorediting
The answer is D: Negative selection. Affinity matura- tion (choice A) refers to the process whereby immune receptors for specific antigen during a response are mutated to generate higher affinity, thereby allow- ing formation of memory B and T cells with the most reactive receptors to sense antigens upon re-encoun- ter. Antigen processing (choice B) is the process of breaking down and loading antigen onto MHC mol- ecules for surface recognition by responding T cells. Hematopoiesis (choice C) is the production of blood cellular components such as the many types of immune cells, and occurs in the bone marrow. Receptor editing (choice E) is a B cell process occurring in the bone marrow during development, and serves as a mode to reconfigure B-cell receptors that recognize self- antigen to identify foreign-antigens, otherwise, the self-reactive B cell will undergo apoptosis.
Which type of hypersensitivity is associated with reac- tions to poison ivy oil? (A) TypeI (B) TypeII (C) Type III (D) Type IV
The answer is D: Type IV. Type I (immediate hypersen- sitivity) (choice A) is an immune response mediated by IgE triggering of mast cell and basophil degranulation. Type II (choice B) are antibody-mediated responses in which antibodies against cellular or extracellular matrix antigens may deposit in any tissue express- ing the target antigen. Thus, the disease is normally tissue-specific. An example of type II hypersensitiv- ity is Goodpasture syndrome and myasthenia gravis. Type III (choice C) are immune-complex mediated events where antibodies to soluble antigens bind and form complexes which deposit in areas of high pres- sure such as blood vessel branches and the kidney glomeruli. An example of type III hypersensitivity is systemic lupus erythematosus. Poison ivy induces a delayed-type hypersensitivity in which CD4+ T cells are activated and an inflammatory response develops.
Which one of the following represents the mecha- nism by which immune complexes (ICs) are normally cleared from the circulation? (A) ICs are solubilized by C3a (B) ICs are solubilized by C5a (C) Factor I releases complement-bound ICs to bind with complement receptors found on splenic/ hepatic neutrophils (D) Red blood cells capture ICs from blood via Fc receptors (E) C3b solubilizes ICs and attaches to red blood cells via complement receptors
The answer is E: C3b solubilizes IC and attaches to red blood cells via complement receptors. Defects in the complement pathway are associated with IC diseases due to the fact that complement is important for the removal of ICs that occur during normal B-cell immune responses to pathogens. ICs are created by soluble (or cell surface) antigen interaction with secreted antibodies. This normally results in opsoniza- tion and phagocytosis; however, another mechanism of clearance is mediated in the spleen and liver by macrophages. C3 cleavage product, C3b, binds to the ICs and is attached to complement receptors on red blood cells. These cells then pass through the spleen and liver, and a tissue factor removes the ICs from the red blood cells and resident macrophages take up the ICs for degradation (choices A-D).
Downregulation of T-cell activation is achieved by the binding of which molecule on the T cell with CD80/86 on the dendritic cell? (A) CD4 (B) CD8 (C) CD45 (D) CD28 (E) CD152
The answer is E: CD152. CD4 (choice A) and CD8 (choice B) are involved in MHC-TCR interactions. CD45 (choice C) is a cell surface marker for hemat- opoietic cells. CD28 (choice D) indeed binds to CD80/86 but the signal conveyed is stimulatory rather than inhibitory as for CD152 or CTLA-4.
Which of the following is the site at which lymphocytes can leave the blood and gain entry into the lymph nodes and what lymphocyte cell surface protein mediates such access? (A) Lymphoid follicle: CD4 (B) Germinal center: CD62L (L-selectin) (C) Lymphoid follicle: CD62L (L-selectin) (D) Periarterial lymphatic sheath (PALS): CCR7 (E) High endothelial venules (HEV): CD62L (L-selectin)
The answer is E: High endothelial venules (HEV): CD62L (L-selectin). Lymphocytes traffic between the blood and lymph circulation in order to maintain surveillance of the body for foreign invaders. Lymphoid and germi- nal center follicles (choices A-C) are areas in the lymph node where B cells and plasma cells, respectively, are found in high concentration. Periarterial lymphatic sheath (choice D) is the site in the spleen white pulp where T cells are heavily concentrated. In order for T cells to gain access to the lymph nodes from the circu- lation, specialized zones called high endothelial venules provide connections from the blood to the lymph node. The cells must arrest at the HEV via integrin binding, through CD62L found on naïve T cells, and then those arrested cells follow a chemokine (chemotactic) gradi- ent extravasating through the endothelial cells of the HEV into the cortex of the lymph node.
Macrophages recognize microorganisms through the interaction of microbial substances with what type of receptors on macrophages? (A) Antigen receptors (B) Complement receptors (C) Fc receptors (D) Membrane immunoglobulin (E) Pattern recognition receptors
The answer is E: Pattern recognition receptors. Microbes express conserved amino acid and carbo- hydrate sequences on their cell (or viral capsid) sur- faces called pathogen associated molecular patterns (PAMPs). These sequences are recognized by pat- tern recognition receptors (PRRs) on the surface of phagocytes. Antigen receptors (choice A) are adaptive immune response receptors structured to recognize specific antigens unique to pathogens. Complement receptors (choice B) are expressed on phagocytes and function to enhance phagocytosis of complement- coated (C3b, C4b) pathogens. Fc receptors (choice C) are expressed on numerous cell types and func- tion to bind to immunoglobulin for opsonization and antibody-dependent cell cytotoxicity (NK cells and granulocytes such as mast cells). Membrane immu- noglobulin (choice D) is expressed only on B cells and serves as the B cell antigen receptor.
A workup on an ill child revealed low levels of com- plement C3 in her blood. Which one of the following presentations did this child most likely manifest? (A) Chroniceczema (B) Immune hemolytic anemia (C) Incomplete recovery from viral infections (D) Poor response to vaccination (E) Recurrent infections with extracellular bacteria
The answer is E: Recurrent infections with extracellular bacteria. Complement proteins function in innate immunity through enzymatic cleavage of C3 to lib- erate C3b which directly binds to pathogen surfaces. Following C3b insertion, enzyme cascade events result in lysis of the target cell by the membrane attack complex (complement protein scaffold C5-C9) and recruitment of phagocytes by C3a and C5a cleavage products. Chronic eczema (choice A), immune hemo- lytic anemia (choice B), incomplete recovery from viral infections (choice C), and poor response to vaccination (choice D) would not involve complement pathways and thus would be unaffected by a C3 deficiency.
Positive selection in the thymus occurs when thymocytes express functional versions of which critical molecule? (A) CD28 (B) Fc receptor (C) MHC class I (D) MHC class II (E) T-cell receptor (TCR)
The answer is E: T-cell receptor (TCR). Immature T cells (double-positive or CD4+CD8+) interact with MHC class I and II-positive thymic epithelial cells and fol- lowing this interaction, the T cells assume single posi- tive status (either CD4 or CD8 expression) and express a functional TCR. CD28 (choice A) is a T-cell surface molecule involved in costimulation signals; however, it is not relevant for positive selection. While Fc recep- tors (choice B) and MHC class I (choice C) molecules are expressed by T cells, Fc receptors serve as a means to interact with antibodies and MHC to present anti- gens to T cells. There is, at present, some evidence that T cells can present antigens, albeit inefficiently, to other T cells, this interaction is included in the T-T interac- tions that have been described. T cells do not express MHC class II (choice D) molecules.
Which cell type is primarily responsible for the inflam- mation seen in poison ivy rash? (A) Bcells (B) Cytotoxic T cells (C) Eosinophils (D) Natural killer cells (E) Th1cells
The answer is E: Th1 cells. B cells (choice A) are asso- ciated with responses of type I, II, and III hypersensi- tivity. Cytotoxic T cells (choice B) can produce a type IV hypersensitive (cell-mediated) response by killing target cells expressing the antigen such as in rheuma- toid arthritis. Eosinophils (choice C) can participate in type I as they express Fc receptors for IgE. Natural killer cells (choice D) are recruited participants in inflammatory responses but are not primarily respon- sible for hypersensitivity reactions. Delayed-type hypersensitivity reactions are primarily driven by Th1 cells producing IFN-γ.
Which immune system cell is primarily responsible for the formation of granuloma in the lungs of tuberculosis patients? (A) Cytotoxic T cells (B) Dendritic cells (C) Eosinophils (D) Natural killer cells (E) Th1cells
The answer is E: Th1 cells. Granulomas are the product of the immune system effort to control Mycobacterium replication. The two cells responsible for formation of the granuloma are macrophages and Th1 cells. There are relatively few cytotoxic T cells (choice A), den- dritic cells (choice B), and natural killer cells (choice D) present in or near the granuloma. Eosinophils (choice C) do not appear to participate in the immune response against Mycobacterium.
A 47-year-old woman developed toxic shock follow- ing an infection with a strain of Staphylococcus aureus that produced toxic shock syndrome toxin (TSST)-1. This toxin binds directly to MHC Class II molecules on macrophages and which molecule on T cells? (A) CD3 (B) CD40ligand (C) Fas ligand (D) The gamma chain of the IL-2 receptor (E) The variable beta portion of the T-cell receptor
The answer is E: The variable beta portion of the T cell receptor. Superantigens are molecules of microbial origin which can non-specifically activate T cells. Superantigens bind to certain domains on MHC Class II molecules and to certain domains on the variable region of the beta chain on the T cell receptor, forming a bridge between the two cells. A superantigen can bind to T-cell receptors (TCRs) from a number of different T cells, as long as the TCRs share similar amino acid sequences in a key region of the variable portion of the beta chain. None of the other molecules, although expressed on T cells, binds directly with superantigens.
Antigen receptors on T and B cells share which similar feature? (A) Affinity maturation occurs following antigen recognition for both receptor types (B) Interaction with MHC molecules is required for antigen recognition by both receptor types (C) The constant regions of both receptor types are identical (D) The specificity of both receptor types is determined following exposure of mature cells to antigen (E) The variable portions of both receptor types are generated by random recombination of genes
The answer is E: The variable portions of both recep- tor types are generated by random recombination of genes. Innate receptors or pattern recognition receptors (PRRs) recognize conserved amino acid and carbohydrate sequences on the surface of pathogens.This detection allows a rapid response in the form of phagocytosis and cytokine production to lead to adap- tive immune activation. Antigen receptors on B and T cells are the product of gene segment rearrangement in order to devise receptors which can recognize vari- ous antigens from differing pathogens. Affinity mat- uration (choice A) is the process whereby activated B cells compete for binding with follicular dendritic cells in the germinal centers in order to generate the B cells synthesizing the highest affinity antibodies. T cells require interaction with MHC-peptide com- plexes in order to undergo activation, whereas B cells can recognize antigens in their natural state (choice B). The constant regions are not identical in nature, especially since soluble T-cell receptors do not bind to Fc receptors while B-cell receptors if solubilized will interact with Fc receptors (choice C). Specificity of both B- and T-cell antigen receptors is determined during development within the bone marrow and thy- mus, respectively, with those cells recognizing self- antigens undergoing apoptosis (choice D).
