Basic Immunology Functions And Disorders of the Immune System 4th Edition by Abul K. Abbas - Test Bank

Basic Immunology Functions And Disorders of the Immune System 4th Edition by Abul K. Abbas – Test Bank

 

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Abbas: Basic Immunology, 4^th Edition

 

Chapter 05: T Cell–Mediated Immunity

 

Test Bank

 

MULTIPLE CHOICE

 

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

 

ANS: E

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

 

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

 

ANS: B

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

 

3. Which one of the following cell types would be most potent at activating naive T cells?
4. Kupffer cells
5. B cells
6. Follicular dendritic cells
7. Neutrophils
8. Langerhans cells

 

ANS: E

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

 

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

 

ANS: D

IL-2 is involved in the proliferation of both CD4+ and CD8+ T cells. Activation of the naive T cell results in signals transduced via the TCR (signal 1) and CD28 (signal 2). This signaling results in the activation of transcription factors, such as Fos, Jun, and NFAT, which increase transcription of the IL-2 gene. IL-2 is then secreted and acts as both a paracrine and autocrine growth factor for T cells by binding to the IL-2 receptor (one component of which is CD25). In addition to its growth factor activity, IL-2 also “primes” T cells for apoptotic death, and this role for IL-2 is important in homeostasis of the immune system.

 

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

 

ANS: C

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

 

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

 

ANS: C

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

 

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

 

ANS: D

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

 

8. All of the following molecules act as transcription factors in T cell activation signaling EXCEPT:
9. NF-kB
10. Jun
11. Fos
12. NFAT
13. Ras

 

AND: E

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

 

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

 

ANS: E

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

 

10. A 7-month-old boy, the only child of second-degree cousins, saw a pediatrician for immunologic evaluation after developing Pneumocystis carinii pneumonia. Serum IgG, IgM, and IgA levels were normal. Blood cell count showed 10,600 leukocytes/mm3and 80% lymphocytes; 90% of the lymphocytes were TCR ab+ CD4+. In vitro lymphocyte-proliferative responses to PHA and anti-CD3 were absent, and the pattern of tyrosine-phosphorylated cytoplasmic proteins after anti-CD3 treatment of the T cells was distinctly abnormal. This boy most likely carries homozygous mutations in the gene encoding which one of the following proteins?
11. Zap-70
12. RAG-1
13. CD3
14. Pre-Ta
15. TCRa

 

ANS: A

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

 

11. Which one of the following signaling molecules, if mutated, would affect B cell maturation and function primarily without affecting T cell function?
12. Btk
13. Itk
14. Tec
15. PI-3 kinase
16. Zap-70

 

ANS: A

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

 

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

 

ANS: C

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

 

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

 

ANS: C

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

 

14. Which one of the following accurately depicts the correct order of events in a TCR signal transduction pathway?
15. TCR → Lck → Zap-70 → LAT → Grb-2 → SOS → Ras → Erk → Fos
16. TCR → Lck → Zap-70 → LAT → SOS → Grb-2 → Ras → Erk → Fos
17. TCR → Lck → ITK → LAT → Grb-2 → SOS → Ras → Erk → Fos
18. TCR → Lck → Zap-70 → LAT → SOS → Grb-2 → Ras → Erk → Jun
19. TCR → Lck → Zap-70 → LAT → PLCg → DAG → calcium release

 

ANS: A

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

 

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

 

ANS: A

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