Immunology FIT Board Review: Abbas 7th Ed

C, pages 4-5 Immunity can be conferred on an individual by transferring serum or lymphocytes from a specifically immunized individual, a process known as adoptive transfer in experimental situations. The recipient of such a transfer becomes immune to the particular antigen without ever having been exposed to or having responded to that antigen. Therefore, this form of immunity is called passive immunity. Passive immunization is a useful method for conferring resistance rapidly, without having to wait for an active immune response to develop. Passive immunization against toxins by the administration of antibodies from immunized animals is a lifesaving treatment for potentially lethal infections, such as tetanus, and snake bites.

A 42 year-old male arrives to the emergency room of his local hospital after having received a deep laceration to his hand while working in his backyard. The physician on duty decides to administer tetanus immune globulin as part of treatment. This is an example of which type of immunity? A. Innate immunity B. Active immunity C. Passive immunity D. Cell-mediated immunity

B, page 90 "A healthy 70-kg adult human produces about 2 to 3 g of antibodies every day."

A healthy 70-kg adult produces what quantity of antibodies every day? A. 10-15 g B. 2-3 g C. 1-5 mg D. 6-7 g

A, page 2 Mechanisms for defending the host against microbes are present in some form in all multicellular organisms. These mechanisms constitute innate immunity. The more specialized defense mechanisms that constitute adaptive immunity are found in vertebrates only.

A vaccine has been developed for elm trees that prevents infection with the fungus that causes Dutch elm disease. The vaccine contains a non-pathogenic fungus of a different species. What is the likely mechanism of action for this vaccine? A. Enhancement of innate immune mechanisms. B. Induction of an anti-fungal antibody response. C. Induction of a memory T cell response. D. Passive transfer of immunity.

A, page 18 Macrophages can acquire distinct functional capabilities, depending on the types of activating stimuli. The clearest example of this is the response of macrophages to different cytokines made by subsets of T cells. Some of these cytokines activate macrophages to become efficient at killing microbes, called classical activation. Other cytokines activate macrophages to promote tissue remodeling and repair, called alternative activation.

Alternative activation of macrophages promotes what function(s)? A. Tissue modeling and repair. B. Efficient ingestion and killing of microbes. C. Killing cells infected with viruses or intracellular bacteria. D. Secretion of enzymes that are toxic to the cell walls of parasites.

B, page 86 "The Epstein-Barr virus contains a gene homologous to human IL-10, and viral IL-10 has the same activities as the natural cytokine... Acquisition of the IL-10 gene has given the virus the ability to inhibit host immunity..."

An analog of which of these cytokines is produced by EBV, giving it the ability to inhibit host immunity? A. IL-1 B. IL-10 C. IL-12 D. IL-15

D, page 44, legend to figure 3-3 Macrophages that have encountered microbes produce cytokines, such as TNF and IL-1. Selectins on the endothelium mediate weak tethering and rolling of leukocytes on the endothelium. Integrins mediate firm adhesion. Chemokines increase the affinity of neutrophil integrins and stimulate the migration of cells through the endothelium to sites of infection.

Blood neutrophils, monocytes, and activated T lymphocytes use essentially the same mechanisms to migrate to sites of infection. This may include: A. Macrophages that have encountered microbes producing cytokines, such as INF- gamma and IL-10. B. Integrins mediating weak tethering and rolling of leukocytes on the endothelium. C. Selectins on the endothelium mediating tight binding to leukocytes. D. Chemokines increasing the affinity of leukocyte adhesion and stimulate the migration of cells through the endothelium to sites of infection.

C, page 52 The mechanisms by which different B cell populations migrate to different tissues are, not surprisingly, similar to the mechanisms we described for tissue-specific migration of effector T cells and depend on expression of distinct combinations of adhesion molecules and chemokine receptors on each B cell subset. For example, bone marrow-homing IgG- secreting plasma cells express VLA-4 and CXCR4, which bind respectively to VCAM-1 and CXCL12 expressed on bone marrow sinusoidal endothelial cells.

Bone marrow-homing IgG-secreting plasma cells express VLA-4 and CXCR4 which bind to which molecules on bone marrow sinusoidal endothelial cells? A. ICAM-1 and CCL25 B. ICAM-1 and CCL17 C. VCAM-1 and CXCL12 D. VCAM-1 and CXCL13

C, page 51 Two subsets of memory T cells, namely, central memory and effector memory T cells, were initially identified on the basis of differences in CCR7 and L-selectin expression. Central memory T cells were defined as human CD45RO+ blood T cells that express high levels of CCR7 and L-selectin; effector memory T cells were defined as CD45RO+ blood T cells that express low levels of CCR7 and L-selectin but express other chemokine receptors that bind inflammatory chemokines. These phenotypes suggest that central memory T cells home to secondary lymphoid organs, whereas effector memory T cells home to peripheral tissues.

Central memory T cells, in contrast to effector memory T cells, home to secondary lymphoid organs by expressing which surface marker? A. CD45RA B. CD45RO C. L-selectin D. P-selectin

C, page 43 Chemokines are essential for the recruitment of circulating leukocytes from blood vessels into extravascular sites... Extravascular chemokines stimulate movement of leukocytes and their migration toward the chemical gradient of the secreted protein, a process called chemokinesis... Chemokines are involved in the development of lymphoid organs, and they regulate the traffic of lymphocytes and other leukocytes through peripheral lymphoid tissues.... Chemokines are required for the migration of dendritic cells from sites of infection into draining lymph nodes.

Chemokine functions are diverse and include which of the following? A. Chemokines are anti-angiogenic B. Chemokines direct cells of host defense away from sites of infection. C. Chemokines are involved in the development of lymphoid organs. D. Chemokine secretion can only be induced by TLR signaling.

A, pages 41-42 The receptors for chemokines belong to the seven-transmembrane, GTP-binding (G) protein-coupled receptor (GPCR) superfamily. These receptors initiate intracellular responses through associated trimeric G proteins... Chemokine receptors may be rapidly downregulated by exposure to the chemokine, and this is a likely mechanism for termination of responses... Chemokine receptors are expressed on all leukocytes, with the greatest number and diversity seen on T cells.

Chemokines involved in inflammatory reactions are produced by leukocytes in response to external stimuli. Chemokine receptors: A. Are G-protein coupled receptors. B. Are never located on leukocytes. C. Exhibit distinct (non-overlapping) specificity for chemokines within each family. D. Are difficult and slow to down-regulate.

A, page 42, Table 3-2

Chemokines involved in neutrophil migration include which of the following? A. CXCL1 to 3 and CXCL5 to 8. B. CXCL13 C. CXCL9 to 11 D. CCL 24 and 26

D, page 90, Table 5-1

Compared to antigen binding of the TCR and the MHC molecule, antigen binding by antibodies consist of a: A. Slow on-rate, slow off-rate B. Slow on-rate, fast off-rate C. Fast on-rate, fast off-rate D. Fast on-rate, variable off rate

A, page 66 "Dectin-1 (dendritic cell-associated C-type lectin 1) and dectin-2 are dendritic cell receptors."

Dectins are typically expressed on the surface of which type of cell? A. Dendritic cells B. Endothelial cells C. Lymphocytes D. Neutrophils

A, page 136 "NKT cells express markers that are characteristic of both natural killer (NK) cells and T lymphocytes... NKT cells recognize lipids and glycolipids displayed by the class I-like "non- classical" MHC molecule called CD1...."

Glycolipids are recognized as antigens by a special population of T cells known as: A. NK-T cells B. γδ T cells C. αβ T cells D. GLA T cells

D, page Gut-homing effector T cells express the α4β7 integrin, which binds to MadCAM-1 on gut endothelial cells, and CCR9, which binds to CCL25, a chemokine expressed in inflamed bowel.

Gut-homing effector T cells express an integrin that binds to MadCAM-1 and what receptor for CCL25? A. CCR4 B. CCR10 C. CCR7 D. CCR9

D, pages 93-4 "Most of the sequence differences and variability among different antibodies are confined to three short stretches in the V region of the heavy chain and to three stretches in the V region of the light chain. These diverse stretches are known as hypervariable segments...[T]he hypervariable regions are also called complementarity-determining regions (CDRs)."

How many CDRs are there on an antibody? A. 4 on each heavy chain, 2 on each light chain B. 2 on each heave chain, 4 on each light chain C. 2 on each heavy chain, 2 on each light chain D. 3 on each heavy chain, 3 on each light chain

C, page 86 "Recombinant IL-1RA has been developed as a drug that is effective in the treatment of systemic juvenile rheumatoid arthritis and familial fever syndromes in which IL-1 production is dysregulated." See also the package insert for current FDA-approved indications.

Human recombinant IL-1RA (anakinra) is available for treatment of which of the following conditions? A. Multiple sclerosis B. Cryoglobulinemia associated with HCV infection C. Rheumatoid arthritis D. Hairy cell leukemia

D, page 6 Immune responses are specific for distinct antigens and, in fact, for different portions of a single complex protein, polysaccharide, or other macromolecule (Fig. 1-4). The parts of such antigens that are specifically recognized by individual lymphocytes are called determinants or epitopes.

Immune responses are specific even for different portions of a complex antigen. The parts of such complex antigens specifically recognized by individual lymphocytes are called what? A. Induction points B. Adjuvants C. Expanders D. Epitopes

A, page 13 The response of B cells to protein antigens requires activating signals ("help") from CD4+ T cells (which is the historical reason for calling these T cells "helper" cells). B cells can respond to many non-protein antigens without the participation of other cells.

In order to respond to protein antigen, additional help from what cell type is required? A. CD4+ T cells B. CD8+ T cells C. NK cells D. NKT cells

A, page 74 "Because IgM natural antibodies are very efficient at binding C1q, the classical pathway also participates in innate immunity. In addition, other innate immune system soluble proteins called pentraxins can also bind C1q and initiate the classical pathway."

In which of the following circumstances is the classical complement pathway a part of the adaptive immune response? A. When C1q binds to IgG3 antibodies B. When C1q binds to IgM natural antibodies C. When C1q binds to PTX3 D. When C1q binds to serum amyloid protein

C, page 51 Skin-homing effector T cells express a carbohydrate ligand for E-selectin called CLA-1 (cutaneous lymphocyte antigen 1) and the CCR4 and CCR10 chemokine receptors, which bind CCL17 and CCL27, chemokines that are commonly expressed in inflamed skin.

Inflamed skin expresses CCL17 and CCL27. Skin-homing effector cells are attracted via expression of CCR4, CCR10 and what ligand for E-selectin? A. PSGL-1 B. PNAd C. CLA-1 D. LFA-1

A, page 105 "When B cells are activated by foreign antigens, they may undergo a process called isotype (or class) switching in which the type of CH region, and therefore the antibody isotype, produced by the B cell changes, but the V regions and the specificity do not..."

Isotype (class) switching involves what portion of the B cell antibody: A. CH B. CL C. VH D. VL

C, page 32 Naive T cells express a receptor called CCR7 that binds the chemokines CCL19 and CCL21 produced by stromal cells in the T cell zones of the lymph node. These chemokines attract naïve T cells to move from the blood, through the HEV's into the T cell zone. Dendritic cells that drain into the node through the lymphatics also express CCR7, and this is why they migrate from the subcapsular sinus to the same area of the node as do naïve T cells.... CCR7 knockout mice lack T cell zones.

Knockout mice lacking CCR7 show which of the following abnormality? A. Absent marginal zone B. Absent germinal centers C. Absent T cell zones D. Hypertrophy of the periarteriolar lymphoid sheath (PALS)

A, page 40 CD18 refers to the β2-integrin, which is a component of LFA-1 (CD11aCD18) and Mac-1 (CD11bCD18).

Leukocyte adhesion deficiency type 1 results is characterized by defective leukocyte adhesion and migration with recurrent bacterial and fungal infections. It is caused by mutations in CD18, resulting in dysfunction of which of these molecules? A. LFA-1 and Mac-1 B. LFA-1 and VLA-4 C. ICAM-1, ICAM-2 and ICAM-3 D. VCAM-1 and MadCAM-1

B, page 39 The ligands on leukocytes that bind to E-selectin and P-selectin on endothelial cells are complex sialylated carbohydrate groups related to the Lewis X or Lewis A family, present on various surface glycoproteins of granulocytes, monocytes, and some previously activated effector and memory T cells. The best defined of these is the tetrasaccharide sialyl Lewis X (sLeX). A leukocyte membrane glycoprotein called P- selectin glycoprotein ligand 1 (PSGL-1) is post-translationally modified to display the carbohydrate ligands for P-selectin. Several different molecules may display the carbohydrate ligands for E-selectin, including the glycoproteins PSGL-1 and E-selectin ligand 1 and some glycolipids.

Leukocyte adhesion deficiency type 2 leads to failure of leukocyte migration into tisses and recurrent bacterial and fungal infections. It results from a mutation in a GDP- fucose transporter that is required for the synthesis of the sialyl Lewis X components of ligands for which molecules? A. ICAM-1 B. E-selectin C. PSGL-1 D. PNAd

D, page 32 Naive B cells express a chemokine receptor, CXCR5, that recognizes a chemokine, CXCL13, produced only in follicles by FDCs. Thus, B cells are attracted into the follicles, which are the B cell zones of lymph nodes. Another cytokine (which is not a chemokine) called lymphotoxin plays a role in stimulating CXCL13 production, especially in the follicles. CXCR5 knockout mice lack B cell-containing follicles in lymph nodes and spleen.

Naïve B cells express CXCR5, which attracts them to what chemokine and cell type? A. CCL19 produced by stromal cells in the T cell zones of the lymph node. B. CXCL12 produced in the bone marrow. C. CXCL9 produced by endothelium at sites of chronic inflammation. D. CXCL13 produced by follicular dendritic cells.

A, page 55 "Most of the mechanisms of innate immune defense that we will discuss in this chapter appeared very early in evolution, after the development of complex multicultural organisms, about 750 million years ago. An adaptive immune system, in contrast, is clearly recognizable only in vertebrates about 500 million years ago."

Nearly all forms of life possess innate immune mechanisms. Which of the following creatures possesses adaptive immunity? A. Amphibia B. Arthropoda C. Angiospermata D. Amoebidae

A, page 34 The B cells in the marginal zone, known as marginal zone B cells, are functionally distinct from follicular B cells and have a limited repertoire of antigen specificities. Both marginal zone and follicular B cells express CD21 and differentiate into plasma cells. Neither are predominantly located in the periarteriolar lymphatic sheath.

One feature that distinguishes marginal zone B cells from follicular B cells is: A. They have a more limited repertoire of antigen specificities. B. They are predominantly located in the periarteriolar lymphatic sheath. C. They express CD21 on their surface. D. They do not differentiate into plasma cells.

C, page 9 Cytokines are not usually stored as preformed molecules, and their synthesis is initiated by new gene transcription as a result of cellular activation. Such transcriptional activation is transient, and the messenger RNAs encoding most cytokines are unstable and often rapidly degraded, so cytokine synthesis is also transient. Once synthesized, cytokines are rapidly secreted, resulting in a burst of release when needed... Cytokines share many other general properties. One cytokine can act on diverse cell types and have multiple biologic effects, a property that is referred to as pleiotropism... Most cytokines act close to where they are produced, either on the same cell that secretes the cytokine (autocrine action) or on a nearby cell (paracrine action). .. When produced in large amounts, cytokines may enter the circulation and act at a distance from the site of production (endocrine action). Tumor necrosis factor (TNF) is an example of a cytokine that has important local and distant (systemic) effects.

One general property of cytokines is: A. They are stored as preformed molecules primed for rapid release. B. They are constitutively transcribed and released. C. They can act on many different kinds of cells. D. They have strictly local (autocrine or paracrine) biologic effects.

B, page 12 One of the earliest responses of CD4+ helper T cells is secretion of the cytokine interleukin-2 (IL-2). IL-2 is a growth factor that acts on the antigen-activated lymphocytes and stimulates their proliferation (clonal expansion)... Other CD4+ effector T cells secrete cytokines that stimulate the production of a special class of antibody called immunoglobulin E (IgE) and activate leukocytes called eosinophils, which are able to kill parasites that may be too large to be phagocytosed.

One important effect of IL-2 is A. It serves as a growth factor for naïve lymphocytes. B. It drives clonal expansion. C. It stimulates production of IgE antibodies. D. It prevents complement activation on host cells.

B, page 78 "P-selectin expression is induced on venular endothelial cells at sites of infection and tissue injury, but in large part, this is due to the effects of histamine and thrombin.."

P-selectin expression is induced on venular endothelial cells by: A. TNF and IL-1 B. Histamine and thrombin C. ICAM-1 and VCAM-1 D. IL-6

A, page 93, Figure 5-3

Papain digestion of IgG produces: A. 2 Fab + 1 Fc B. 2 Fab + 2 Fc C. F(ab')2 + 1 Fc D. F(ab')2 + peptide fragments

B, page 13 Polysaccharides and lipids stimulate secretion mainly of the antibody class called IgM. Protein antigens induce the production of antibodies of functionally different classes (IgG, IgA, IgE).

Polysaccharides and lipids stimulate secretion mainly of which antibody class? A. IgA B. IgM C. IgG D. IgE

A, page 133 "HLA-DM acts as a peptide exchanger, facilitating the removal of CLIP and the addition of other peptides to class II MHC molecules." See also figures 6-17 and 6-19.

Removal of CLIP from the MHC-II molecules is carried out by: A. HLA-DM B. Cathepsin S C. HLA-DR D. CLIP lyase

B, page 60 "Single-stranded RNAs... are distinguished from cellular cytoplasmic single-stranded RNA transcripts by their location within endosomes and by their high guanosine and uridine content."

TLR7 and TLR8 recognize viral ssRNA. Which of these features distinguishes viral ssRNA from cellular ssRNA transcripts? A. Location in the extranuclear cytoplasm B. High guanidine content C. High adenosine content D. Low uridine content

A, page 34 and Figure 2-15 The architecture of the white pulp is analogous to the organization of lymph nodes, with segregated T cell and B cell zones. In the mouse spleen, the central arteries are surrounded by cuffs of lymphocytes, most of which are T cells. Because of their anatomic location, morphologists call these T cell zones periarteriolar lymphoid sheaths... The architecture of the white pulp is more complex in humans than mice, with both inner and outer marginal zones and a perifollicular zone.

The T cell zones of the mouse spleen are primarily located in: A. Periarterioloar lymphatic sheath B. Marginal zones C. Lymphoid follicles D. Red pulp

D, page 11: See legend to figure 1-6 The response contracts (declines) as antigen-stimulated lymphocytes die by apoptosis, restoring homeostasis, and the antigen-specific cells that survive are responsible for memory.

The main mechanism by which contraction of the immune response occurs is: A. Differentiation B. Clonal expansion C. Clonal selection D. Apoptosis

D, page 63 "All TLRs except TLR3 signal through MyD88 and are therefore capable of activating NF-κB and inducing an inflammatory response."

The major signal transduction pathway that Toll-like receptors engage to induce inflammatory responses is: A. T-bet B. RORγt C. NFAT D. NFκB

C, page 11 Because the number of naive lymphocytes specific for any antigen is very small (on the order of 1 in 105 or 106 lymphocytes) and the quantity of the available antigen may also be small, special mechanisms are needed to capture microbes, to concentrate their antigens in the correct location, and to deliver the antigens to specific lymphocytes.

The number of naïve lymphocytes specific for a given antigen is on the order of A. <100 B. 10^2-10^3 C. 10^5-10^6 D. 10^8-10^9

A, page 117 "Some specialized DCs have the ability to ingest virus-infected cells or cellular fragments and present antigens from these cells to CD8+ T lymphocytes. This process is called cross-presentation, or cross-priming"

The phenomenon of cross-presentation refers to: A. The ability of dendritic cells to present antigens from virus-infected cells to CD8+ T cells. B. The ability of CD8+ T cells to present antigens to other CD8+ T cells. C. The ability of CD8+ T cells to present antigens to CD4+ T cells. D. The ability of dendritic cells to cross-link with other APCs during antigen ingestion.

D, page 115 "The major function of plasmacytoid DCs is the secretion of large amounts of type I interferons in response to viral infections..." Answer a applies to follicular DCs (see page 20), and answer c applies to conventional DCs (page 113).

The primary function of plasmacytoid dendritic cells is: A. Capture of antigens complexed to antibody and display to follicular B cells. B. Antibody production C. Capture of extracellular antigen and initiation of a corresponding T cell response. D. Secretion of type I interfreons in response to viral infections.

C, page 151 The region of physical contact between the T cell and the APC forms a bull's-eye like structure that is called an immunologic synapse or a supramolecular activation cluster (SMAC).

The region of physical contact between the immune cell and the APC is referred to as which of the following? A. TCR complex B. MHC C. SMAC D. SAP

C, page 100 "The long half-life of IgG is attributed to its ability to bind to a specific Fc receptor called the neonatal Fc receptor (FcRn)...."

To what receptor does IgG bind to prolong its half-life? A. FcεRI B. CD28 C. Neonatal Fc receptor (FcRn) D. FcγRII

D, page 162 PLCγ2 becomes active when it binds to BLNK and is phosphorylated by Syk and Btk.

To which of the following molecules does PLCγ2 bind which causes it to become active? A. Lyn B. Btk C. DAG D. BLNK

B, page 45 There are at least two populations of monocytes in the blood, and in both humans and mice, the populations are defined, in part, by chemokine receptor expression. Inflammatory monocytes, which are the main type recruited to inflammatory sites, express CCR2 in both mice and humans. This receptor binds several chemokines, but the most important one for monocyte recruitment is CCL2 (MCP-1). Thus, monocyte recruitment occurs when resident tissue cells express CCL2 in response to infection. The other population of monocytes, sometimes called nonclassical, lacks CCR2 but expresses CX3CR1. The ligand for this receptor, CX3CL1, is expressed both in soluble form and as a membrane-bound molecule that can support adhesion of monocytes to endothelium.

Two populations of monocytes can be defined by chemokine receptor expression. Which chemokine receptor distinguishes inflammatory monocytes? A. CX3CR1 B. CCR2 C. CXCL8 D. CXCR1

A, page 39 The ligands on leukocytes that bind to E-selectin and P-selectin on endothelial cells are complex sialylated carbohydrate groups related to the Lewis X or Lewis A family, present on various surface glycoproteins of granulocytes, monocytes, and some previously activated effector and memory T cells. The best defined of these is the tetrasaccharide sialyl Lewis X (sLeX). A leukocyte membrane glycoprotein called P- selectin glycoprotein ligand 1 (PSGL-1) is post-translationally modified to display the carbohydrate ligands for P-selectin. Several different molecules may display the carbohydrate ligands for E-selectin, including the glycoproteins PSGL-1 and E-selectin ligand 1 and some glycolipids.

What are the ligands on leukocytes that bind to E-selectin (CD62E) and P-selectin (CD62P) on endothelial cells? A. Sialylated carbohydrate groups related to the Lewis X or Lewis A family. B. ICAM-1 (CD54), ICAM-2 and ICAM-3 C. IL-1 and TNF D. Inactivated complement factor C3b (iC3b) and L-selectin

C, page 161 B lymphocytes express a receptor for C3d that is called the type 2 complement receptor (CR2, or CD21).

What binds to the B cell complement receptor? A. C2a B. C3a C. C3d D. C3b

A, page 75 "The molecular ligands of the ficolins include N-acetylglucosamine and the lipoteichoic acid component of the cell walls of gram-positive bacteria."

What is a target of the fibrinogen-like globular heads on ficolin? A. N-acetylglycosamine B. Mannose C. IgM bound to microbial surface antigens D. IgG1 antibodies bound to surface antigens

B, pages 47-49 The PNAd carbohydrate groups that bind L-selectin may be attached to different sialomucins on the HEV in different tissues. For example, on lymph node HEVs, the PNAd is displayed by two sialomucins, called GlyCAM-1 (glycan-bearing cell adhesion molecule 1) and CD34. In Peyer's patches in the intestinal wall, the L-selectin ligand is a molecule called MadCAM-1 (mucosal addressin cell adhesion molecule 1).

What is the L-selectin ligand in Peyer's patches? A. GlyCAM-1 B. MadCAM-1 C. ICAM-1 D. CD34

B, page 149 The CD4 and CD8 coreceptors greatly facility the activation process by bringing Lck (which is loosely associated with the tail of the coreceptor proteins) close to the CD3 and ζ ITAMs.

What is the Src family tyrosine kinase that mediates signal transduction events after T-cell recognition of peptide-MHC complexes on antigen presenting cells? A. AID B. Lck C. BTK D. RAG

D, page 100 "IgE has a very short half life of about 2 days in the circulation (although cell-bound IgE associated with the high-affinity IgE receptor on mast cells has a very long half-life)."

What is the half-life of IgE in circulation? A. 7 days B. 30 days C. 1 day D. 2 days

A, page 161 Phosphorylation of the tail of CD19 results in the efficient recruitment of Lyn, a Src family kinase that can amplify BCR signaling by greatly enhancing the phosphorylation of ITAM tyrosines in Igα and Igβ.

What is the name of the kinase that is associated with the B cell coreceptors? A. Lyn B. Lck C. Fyn D. Blk

C, page 104, legend to Figure 5-14 "Large complexes are formed at concentrations of multivalent antigens and antibodies that are termed the zone of equivalence..."

What is the name of the range of relative concentrations at which antibodies and antigens form a cross-linked network of attached molecules? A. Valency of interaction B. Linear determinant C. Zone of equivalence D. Affinity maturation

B, page 158 The CD28 molecule on T cells is the principal costimulatory receptor for delivery of second signals for T cell activation.

What is the principal co-stimulatory receptor on T cells for delivering second signals for T cell activation? A. CD2 B. CD28 C. LFA-1 D. ICAM-1

C, page 163 The prototypical inhibitory receptor of the CD28 family, CTLA-4 (also called CD152), has the ability to inhibit T cell responses induced on activated T cells and has a higher affinity than CD28 for B7 proteins.

What is the prototypical inhibitory receptor of the CD28 family? A. PD-1 B. Ubiquitin C. CTLA-4 D. ZAP-70

B, page 49 The exit of naive T cells from lymph nodes is dependent on a lipid chemoattractant called sphingosine 1-phosphate (S1P), which binds to a signaling receptor on T cells called sphingosine 1-phosphate receptor 1 (S1PR1) (Fig. 3-7). S1P is present at relatively high concentrations in the blood and lymph compared with tissues... Signals generated by S1P binding to S1PR1 stimulate directed movement of the naive T cells along the S1P concentration gradient out of the lymph node parenchyma. Circulating naive T cells have very little surface S1PR1 because the high blood concentration of S1P causes internalization of the receptor. Once a naive T cell enters a lymph node, where S1P concentrations are low, it may take several hours for the surface S1P1R to be re- expressed. This allows time for a naive T cell to interact with antigen-presenting cells before it is directed down the S1P concentration gradient into the efferent lymphatic. S1P and the S1PR1 are also required for mature naive T cell egress from the thymus, migration of activated T cells out of lymph nodes, and migration of antibody-secreting B cells from secondary lymphoid organs.

What is the role of sphingosine 1-phosphate (S1P) in T cell trafficking and homing? A. S1P is present in higher concentrations in tissues and lower concentrations in blood and lymph. B. Naive T cells move along a S1P concentration gradient and move into peripheral tissues after S1P binds to the S1PR1 receptor on T cells. C. Circulating naive T cells express high levels of S1PR1. D. S1PR1 expression is not required for cells to be able to leave the lymph node.

C, page 116, legend to Figure 6-5 "Immature dendritic cells in the skin (Langerhans cells) capture antigens that enter through the epidermis and transport the antigens to regional lymph nodes. During this migration the dendritic cells mature and become efficient APCs..."

Where does maturation of Langerhans cells occur? A. In the bone marrow B. In the follicles of the draining lymph nodes C. During migration from the skin to the regional lymph nodes D. In the thymus

C, page 63 "TLR3 signals through TRIF and therefore activates IRF3 and induces expression of type I interferons. TLR4 signals through both MyD88 and TRIF and is able to induce both types of responses."

Which TLR does not engage this pathway? A. TLR 1 B. TLR 2 C. TLR 3 D. TLR 4

A, page 71 "During an infection, the adaptive immune system produces antibodies that bind to infecting microbes and their antigens on infected cells, and CD16 on NK cells can bind to the Fc parts of these antibodies. As a result, CD16 generates activating signals... and the NK cells may kill the infected cells... This process is called antibody-dependent cell- mediated cytotoxicity"

Which activating receptor on NK cells is responsible for antibody-dependent cell- mediated cytotoxicity? A. CD16 B. CD94 C. KIRs D. NKG2D E. ILT-2

D, page 45 Both monocytes and neutrophils express L-selectin and P- and E-selectin ligands and use all three selectins to mediate initial rolling interactions with cytokine-activated endothelial cells. Neutrophils express the integrins LFA-1 and Mac-1, which, on activation, bind to endothelial ICAM-1 and mediate stable arrest of the cells on the vessel wall. Monocytes express the integrins LFA-1 and VLA-4, which bind to endothelial ICAM-1 and VCAM-1, causing stable arrest of these leukocytes.

Which adhesion molecules are expressed on monocytes? A. ICAM-1 and VCAM-1 B. LFA-1 and Mac-1 C. P-selectin, E-selectin and Mac-1 D. LFA-1, VLA-4 and L-selectin

D, page 68 "Dendritic cells express more different types of TLRs and cytoplasmic pattern recognition receptors than any other cell type, making them the most versatile sensors of PAMPs and DAMPs among all cell types in the body."

Which cell type expresses the most pattern recognition receptors? A. Epithelial cells B. Neutrophils C. Red blood cells D. Dendritic cells

A, page 111, Figure 6-2 "Dendritic cells are the most effective APCs for activating naïve T cells and therefore for initiating T cell responses. Macrophages and B lymphocytes also function as APCs, but mostly for previously activated CD4+ T helper T cells rather than for naïve T cells..."

Which cell type is the most effective for activating naïve T cells? A. Dendritic cells B. Macrophages C. B lymphocytes D. NK cells

B, page 146 The β chain V domain contains a fourth hypervariable region that does not appear to participate in antigen recognition but is the binding site for microbial products called superantigens.

Which chain contains a fourth CDR region? A. α B. β C. CD3 D. ζ

A, page 52 Once naive B cells enter the stroma of secondary lymphoid organs, they migrate into follicles, the site where they may encounter antigen and become activated. This migration of naive B cells into follicles is mediated by CXCL13, which is produced in follicles and binds to the CXCR5 receptor on naive B cells.

Which chemokine mediates the migration of naive B cells into follicles? A. CXCL13 B. CXCR5 C. E-selectin D. CCL25

D, page 17, legend to figure 2-2 Both dendritic cells and monocytes arise from a common precursor cell of the myeloid lineage in the bone marrow, and differentiation into monocytes or dendritic cells is driven by the cytokines monocyte colony-stimulating factor and Flt3 ligand, respectively.

Which cytokine promotes differentiation of the monocyte/dendritic cell precursor into the common dendritic cell precursor? A. G-CSF B. GM-CSF C. C-kit ligand D. Flt3 ligand

D, page 166 All type II cytokine receptors, like the type I receptors, engage JAK-STAT signaling pathways.

Which cytokine receptor family uses the JAK-STAT pathways? A. IL-1 receptor family B. G-protein C. TNF receptor family D. Type II cytokine receptor family

B, page 43 There are 10 distinct receptors for CC chemokines (called CCR1 through CCR10), six for CXC chemokines (called CXCR1 through CXCR6), and one for CX3CL1 (called CX3CR1).

Which family of chemokines has the largest number of receptors? A. CXC (α chemokines) B. CC chemokines (β chemokines) C. CX3C chemokines D. C chemokines

A, page 158 Another inhibitory phophatase that does not act on phosphoproteins but rather is specific for an inositol phospholipid is called SHIP (SH2 domain-containing inositol phosphatase).

Which inhibitory phosphatase is specific for an inositol phospholipid? A. SHIP B. DAG C. ERK D. JNK

B, page 90 "Almost two-thirds of [daily antibody production] is...IgA, which is produced by activated B cells and plasma cells in the walls of the GI and respiratory tracts...."

Which of the following antibodies is produced in the largest quantity daily? A. IgG B. IgA C. IgM D. IgD

D, page 66 "The HIV-1 gp120 envelope glycoprotein binds to DC-SIGN on dendritic cells in mucosal tissues."

Which of the following carbohydrate receptors on dendritic cells binds to HIV-1 gp120? A. CXCR4 B. Dectin-2 C. CD4 D. DC-SIGN

D, page 21, Table 2-2. Other phenotype markers: Helper T lymphocytes: CD3+/CD4+/CD8-; cytotoxic T lymphocytes: CD3+/CD4-/CD8+; B lymphocytes: CD19/CD21/Class II MHC.

Which of the following cells expresses CD16 on its surface? A. T helper lymphocytes B. Cytotoxic T lymphoctyes C. B lymphocytes D. Natural killer cells

D, pages 48-49, legend to figure 3-6 Naive T lymphocytes home to lymph nodes as a result of L-selectin binding to its ligand on high endothelial venules, which are present only in lymph nodes, and as a result of binding chemokines (CCL19 and CCL21) displayed on the surface of the high endothelial venule... Recall that both these chemokines bind to the chemokine receptor called CCR7, which is highly expressed on naive lymphocytes. This interaction of the chemokines with CCR7 ensures that naive T cells increase integrin avidity and are able to adhere firmly to HEVs.

Which of the following changes in surface molecule expression on T cells is necessary for naive T cell homing into lymph nodes? A. Increased L-selectin and decreased CCR7 B. Decreased L-selectin and increased CCR7. C. Decreased L-selectin and decreased CCR7. D. Increased L-selectin and increased CCR7.

D, page 43 Certain chemokine receptors, notably CCR5 and CXCR4, act as co-receptors for the human immunodeficiency virus (HIV) (see Chapter 20). Some activated T lymphocytes secrete chemokines that bind to CCR5 and block infection with HIV by competing with the virus.

Which of the following chemokine receptors act as co-receptors for the human immunodeficiency virus? A. CCR7 and CXCR5 B. CCL19 and CCL21 C. CXCL9 and CXCL10 D. CCR5 and CXCR4

C, page 24 Cytokines are essential for the survival of naïve lymphocytes. The most important of these cytokines are IL-7, which promotes survival and perhaps low-level cycling of naïve T cells, and BAFF which is required for naïve B cell survival.

Which of the following cytokines is essential for survival and proliferation of naïve T cells? A. IL-3 B. IL-5 C. IL-7 D. IL-13

C, page 168 There are five NF-κB proteins. The domain that is common to all NF-κB proteins is a DNA-binding domain called a Rel homology domain.

Which of the following domains is common to all NF-κB proteins? A. SH2 B. IKK C. Rel D. TLR

D, page 82 "TNF inhibits myocardial contractility and vascular smooth muscle tone, resulting in a marked fall in blood pressure, or shock... TNF stimulates endothelial cell expression of tissue factor, a potent activator of coagulation, and inhibits expression of thrombomodulin, an inhibitor of coagulation."

Which of the following effects are mediated by TNF? A. Decreased production of endothelial tissue factor B. Increased production of endothelial thrombomodulin C. Appetite stimulation D. Inhibition of myocardial contractility

C, page 104 "...Another Fc-dependent effector mechanism of humoral immunity is activation of the classical pathway of the complement system. The system generates inflammatory mediators and promotes microbial phagocytosis and lysis. It is initiated by the binding of a complement protein called C1q to the Fc portions of antigen-complexed IgG or IgM."

Which of the following generates inflammation and promotes microbial phagocytosis and lysis by binding to Fc portion of the antigen-complexed IgG or IgM: A. IgE B. IgG C. C1q D. C3a

C, page 3, Table 1-2, Diversity in innate immunity is limited and is germline encoded. Somatic recombination increases the diversity of adaptive immunity. Both the innate and adaptive immune system have mechanisms to avoid self-reactivity.

Which of the following is a distinguishing characteristic of the innate, as opposed to the adaptive, immune system? A. More diverse. B. Non-reactive to self. C. Germline-encoded. D. Diversity produced by somatic recombination

B, page 62 "TLR3 uses the adaptor protein TRIF and activates the IRF3 and IRF7 transcription factors." IRFs and AP-1 are transcription factors, TIR is a homology domain shared by TLRs, receptors for IL-1 and IL-18, and the adaptor proteins MyD88 and TRIF. For a definition of adaptor proteins, see page 143.

Which of the following is an adaptor protein? A. IRF7 B. TRIF C. AP-1 D. TIR

B, page 146 The alpha chain is part of the TCR. The remainder of the chains makes up the CD3 complex.

Which of the following is not a component of the CD3 receptor? A. γ B. α C. ε D. δ

D, page 168 Upstream signaling leads to the activation of a unique type of ubiquitin E3 ligase that can add a lysine-63 type of ubiquitin chain to a protein called NEMO or IKKγ that is a noncatalytic subunit of a trimeric enzyme complex called the IκB kinase (IKK) complex. This complex contains two other subunits called IKKα and IKKβ.

Which of the following is not included in the IκB kinase (IKK) complex? A. NEMO B. IKKα C. IKKβ D. IκBα

D, page 161 The CR2-CD19-CD81 complex is often called the B cell coreceptor complex because CR2 binds to antigens through attached C3d at the same time that membrane Ig binds directly to the antigen.

Which of the following is not part of the B cell coreceptor complex? A. CR2 B. CD19 C. CD81 D. CD5

D, page 146 The antigen receptor of ... T cells is a heterodimer consisting of two transmembrane polypeptide chains, designated TCR α and β, covalently linked to each other by a disulfide bridge between extracellular cysteine residues...the CD3 and ζ proteins are noncovalently associated with the TCR αβ heterodimer.

Which of the following is not part of the TCR complex? A. TCR B. ζ-chain C. CD3 D. CD4

D, page 83 "The receptor for type I interferons is expressed on all nucleated cells [and] signals to activate STAT1, STAT2, and IRF9 transcription factors, which induce expression of several different genes [for] antiviral defense."

Which of the following is true of type I interferons? A. Promote differentiation of naive T cells to the Th2 phenotype. B. Accelerate lymphocyte trafficking through lymph node by increasing their surface expression of S1PR1. C. Down-regulate expression of class I MHC molecules on virally infected cells. D. Lead to activation of STAT1, STAT2 and IRF9 transcription factors

C, page 110 A single T cell can recognize a specific peptide displayed by only one of the large number of different MHC molecules that exist. This phenomenon is called MHC restriction..."

Which of the following is true regarding T cells? A. They only recognize proteins bound to chemical haptens. B. They only recognize conformational determinants of antigens. C. They only recognize specific antigens presented by specific MHC molecules. D. They can function as antigen presenting cells.

D, page 129 "...proteins are targeted for proteasomal degradation by covalent linkage of several copies of a small polypeptide called ubiquitin."

Which of the following is true regarding the proteasome? A. It is a multiprotein enzyme found within the lysosomes of most cells B. Treating cells with IFN-gamma will result in degradation of the 1500-kD proteasomes C. The proteasome performs housekeeping functions through amino acid degradation D. Proteins targeted for degradation by linkage of ubiquitin

D, table 4-3, page 59 TLR3 and TLR9 and endosomal (see figure 4-2, page 51) and RIG-1 is in the cytoplasm (table 4-3).

Which of the following pattern recognition molecules are found on macrophage cell surfaces? A. TLR3 B. TLR9 C. RIG-1 D. CD36

B, page 166 Another subgroup of [type I cytokine] receptors uses the gp130 signaling component, and this includes the receptors for IL-6, IL-11, and IL-27.

Which of the following receptors does not use the gp130 signaling component? A. IL-6 receptor B. IL-10 receptor C. IL-11 receptor D. IL-27 receptor

C, page 65 "A type of inflammasome that uses a protein called AIM2 (absent in melanoma-2) rather than an NLRP-family protein, recognizes cytosolic dsDNA." TLR3 and TLR9 are endosomal and recognize dsRNA and CpG methylated DNA respectively (figure 4-2); RIG-I recognizes viral RNA (table 4-3).

Which of the following recognizes dsDNA in the cytoplasm? A. TLR3 B. TLR9 C. AIM2 (absent in melanoma-2) D. RIG-I (retinoic acid-inducible gene-I)

D, page 63 "When oligomers of NODs recognize their peptide ligands, a conformational change allows the CARD effector domains to recruit the kinase RIP2, forming a signaling complex that has been called the NOD signalosome...;" "...NOD2 is particularly highly expressed in intestinal Paneth cells...mutations of NOD2 that cause increased NOD signaling lead to a systemic inflammatory disease called Blau's syndrome."

Which of the following statements about NOD2 is true? A. Highly expressed in Peyer's patches. B. Mutations that decrease NOD2 signaling lead to Blau syndrome C. Their effector domain puts them in the Pyrin subfamily of NLRs. D. RIP2 kinases form the NOD signalosome and activate NFκB

B, page 19 Basophils are derived from bone marrow progenitors (a lineage different from that of mast cells), mature in the bone marrow, and circulate in the blood. Although they are normally not present in tissues, basophils may be recruited to some inflammatory sites. Basophils contain granules that bind basic dyes. Like mast cells, basophils express IgG and IgE receptors.

Which of the following statements about basophils is true? A. They are not normally found in the circulation but are constitutively present in healthy tissues. B. They are derived from a bone marrow lineage different from that of mast cells. C. Mature basophils express IgM and IgD receptors. D. Their granules contain basic proteins that bind acidic dyes.

C, pages 132-3 "The MIIC has a characteristic multilamellar appearance by electron microscopy... molecules involved in antigen presentation, such as DM, stay in the vesicles and are not expressed in the plasma membrane."

Which of the following statements about the MIIC is true? A. They are present in all nucleated cells. B. They contain all of the components required for peptide-class II association, including proteolytic enzymes, HLA-DM and TAP. C. They have a characteristic multilamellar appearance on electron microscopy. D. They eventually deliver bound class II molecules and HLA-DM to the cell surface.

B, page 156 Cyclosporine binds to a cytosolic protein called cyclophilin, and FK506-binding binds to a protein called FK506-binding protein (FKBP). Cyclosporine-cyclophilin complexes and FK506-FKBP complexes bind to and inhibit calcineurin and thereby block translocation of NFAT into the nucleus.

Which of the following transcription factors does cyclosporine block? A. AP-1 B. NFAT C. c-Jun D. NF-κB

A, page 26 The distinguishing features of naive, effector, and memory lymphocytes reflect different programs of gene expression that are regulated by transcription factors and by stable epigenetic changes. For example, a transcription factor called Kruppel-like factor 2 (KLF-2) is required for maintenance of the naive T cell phenotype. The phenotypes of functionally different types of CD4+ effector T cells, called TH1, TH2, and TH17 cells, depend on transcription factors T-bet, GATA-3, and RORγT, respectively, as well as epigenetic changes in cytokine gene loci.

Which of the following transcription factors is required for maintenance of the naïve T cell phenotype? A. Kruppel-like factor 2 (KLF-2) B. T-bet C. GATA3 D. RORγT

B, page 166 A distinct subgroup of type I receptors includes receptors that share a common β chain (CD131) subunit. This subgroup includes the receptors for IL-3, IL-5, and GM-CSF.

Which of the following type I cytokine receptors does not share a common β chain with the others? A. IL-3 receptor B. IL-4 receptor C. IL-5 receptor D. GM-CSF receptor

D, page 130 "On the luminal side of the ER membrane, the TAP protein associates with a protein called tapasin, which also has an affinity for newly synthesized empty class I MHC molecules. Tapasin thus brings the TAP transporter into a complex with the class I MHC molecules that are awaiting the arrival of peptides..."

Which of these mechanisms promotes antigen presentation by class I MHC molecules? A. TAP optimally transports peptides into the E.R. that are 16 to 30 amino acids long. B. Under the influence of interferon-gamma, the proteasomal caps preferentially recognize peptides with hydrophobic carboxy termini. C. The peptide-binding cleft of the class I MHC is occupied and stabilized by the class I- associated peptide (CLIP) until it is replaced by antigenic peptide. D. Tapasin protein physically links that TAP transporter to newly synthesized class I molecules.

D, page 66 "N-Formyl met-leu-phe receptors expressed by neutrophils and macrophages recognize bacterial peptides containing N-formylmethionyl residues and stimulate directed movement of the cells... All bacterial proteins and few mammalian proteins (only those synthesized within mitochondria) are initiated by N-formylmethionine..."

Which of these statements is true about N-formylmethionine? A. Initiates all mammalian proteins. B. Binds to TNF-family receptors. C. Is absent from human mitochondrial proteins. D. Can trigger chemotaxis of neutrophils.

C, page 153 The Ras pathway is activated in T cells after TCR ligation, leading to the activation of the extracellular receptor-activated kinase (ERK), a prominent member of the MAP kinase family, and eventually to the activation of downstream transcription factors.

Which pathway results in ERK activation? A. c-Jun B. Rac C. Ras D. PLCγ1

D, pages 153-154 The Rac-GTP...initiates a parallel MAP kinase cascade, resulting in the activation of a distinct MAP kinase called c-Jun N-terminal kinase (JNK).

Which pathway results in c-Jun activation? A. PLCγ1 B. ERK C. Ras D. Rac

B, page 39 P-selectin (CD62P), so-called because it was first found in platelets, is stored in cytoplasmic granules of endothelial cells and is rapidly redistributed to the surface in response to microbial products, cytokines, histamine from mast ce;;s and thrombin generated during blood coagulation. These granules are called Weibel-Palade bodies (page 32, updated 6th edition of Abbas). E-selectin is synthesized and expressed on the endothelial cell surface within 1 to 2 hours in response to the cytokines IL-1 and TNF and microbial products such as LPS.

Which selectin can be found in secretory granules of endothelial cells? A. E-Selectin B. P-Selectin C. L-Selectin D. N-Selectin