Deck 5: T Cell–Mediated Immunity

Question 1

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

A)Zap-70
B)RAG-1
C)CD3
D)Pre-Tα
E)TCRα

Answer 1

Zap-70

Question 2

All of the following protein-protein interactions are involved in activation of naive helper T cells by antigen-presenting cells (APCs) EXCEPT:

A)Binding of peptide-MHC complexes on the APC to the TCR on the T cell
B)Binding of CD4 on the T cell to nonpolymorphic regions of class II MHC molecules on the APC
C)Binding of integrins on the T cell with adhesion ligands on the APC
D)Binding of B7-2 on the APC with CD28 on the T cell
E)Binding of CD40L on the T cell with CD40 on the APC

Answer 2

Binding of CD40L on the T cell with CD40 on the APC

Question 3

Which one of the following statements about the molecules B7-1 and B7-2 is NOT true?

A)B7-1 and B7-2 expression on antigen-presenting cells (APCs) is upregulated by the presence of "danger" signals, such as lipopolysaccharide, as well as cytokines, such as interferon (IFN)-ƴ
B)B7-1 and B7-2 are expressed at low levels on some resting APCs.
C)Induction of B7-1 usually occurs before the induction of B7-2 in an immune response.
D)B7-1 and B7-2 bind to CD28 on T cells and provide "second signals" for naive T cell activation.
E)Activated helper T cells can induce expression of B7-1 and B7-2 on APCs via CD40L binding to CD40.

Answer 3

Induction of B7-1 usually occurs before the induction of B7-2 in an immune response.

Question 4

Which one of the following cell types would be most potent at activating naive T cells?

A)Kupffer cells
B)B cells
C)Follicular dendritic cells
D)Neutrophils
E)Langerhans cells

Question 5

In patients with hyper IgM syndrome, there is a genetically based deficiency in expression of CD40 ligand. In addition to defects in antibody isotype switching, these patients have defects in T cell-mediated immune responses and become infected with intracellular parasites. Which one of the following normal functions of CD40 ligand is important in T cell-mediated immunity?

A)CD40-dependent isotype switching is required to produce antibody isotypes that activate T cells.
B)CD40 ligand is required for CTL killing of CD40-expressing infected cells.
C)CD40 ligand is required for maturation of CD4⁺ T cells in the thymus.
D)CD40 ligand on activated T cells binds to CD40 on antigen-presenting cells (APCs), and this enhances the expression of B7-1, B7-2, and cytokines by the APCs.
E)CD40 ligand on T cells binds to B7-1 and B7-2 on APCs, and this enhances the function of the APCs.

Question 6

All of the following are early T cell events that occur after antigen recognition by the TCR EXCEPT:

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

Question 7

Which one of the following accurately depicts the correct order of events in a TCR signal transduction pathway?

A)TCR → Lck → Zap-70 → LAT → Grb-2 → SOS → Ras → Erk → Fos
B)TCR → Lck → Zap-70 → LAT → SOS → Grb-2 → Ras → Erk → Fos
C)TCR → Lck → ITK → LAT → Grb-2 → SOS → Ras → Erk → Fos
D)TCR → Lck → Zap-70 → LAT → SOS → Grb-2 → Ras → Erk → Jun
E)TCR → Lck → Zap-70 → LAT → PLCƴ → DAG → calcium release

Question 8

Which one of the following descriptions of cytokine interleukin-2 is NOT true?

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

Question 9

Which one of the following statements about T cells involved in an immune response is NOT true?

A)Activated T cells receive survival signals from antigen during an infection.
B)Activated T cells contribute to the activation of antigen-presenting cells via CD40 ligand.
C)Memory T cells generated during a primary immune response express high levels of interleukin-2 receptors and actively proliferate long after the primary response is completed.
D)The major effector function of helper T cells is to activate macrophages and other cells by releasing cytokines.
E)When an infection is eliminated, activated T cells die by apoptosis.

Question 10

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)-ƴ and promote inflammation, which damages the myelin sheath surrounding neurons. The exact immunodominant epitopes recognized by autoreactive T cells in MS patents have been identified. One potential method of therapy for patients with MS is to administer therapeutic peptides that differ from the immunodominant epitopes by one or two amino acids. Which one of the following statements best describes the basis for this therapeutic approach?

A)The therapeutic peptides, called "altered peptide ligands," could inactivate T cells specific for myelin proteins, or drive them to differentiate into T cells that do not produce IFN-ƴ
B)The therapeutic peptides, called "altered peptide ligands," could interfere with processing of the natural myelin proteins by the patient's antigen-presenting cells.
C)The therapeutic peptides could bind to the TCRs of myelin-specific T cells but not to the self MHC molecules, thereby blocking T cell activation.
D)The therapeutic peptides could down-regulate MHC expression.
E)The therapeutic peptides could replace the damaged myelin and restore neuronal function.

Question 11

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 chain, but only when the chain is phosphorylated. No phosphorylated LAT is detected, however. Given these data, in which of the following protein domains is the mutation most likely to be present?

A)Pleckstrin homology (PH) domain
B)Proline-rich (PR) domain
C)SH1 domain
D)SH2 domain
E)SH3 domain

Question 12

Which one of the following statements about the molecule Lck is NOT true?

A)It is a member of the Src family of kinases.
B)It binds to the cytoplasmic tails of T cell coreceptors CD4 or CD8.
C)It phosphorylates ITAM motifs on the CD3 complex.
D)It phosphorylates tyrosine residues on Zap-70 and activates it.
E)It phosphorylates PIP2 to PIP3 and leads to the activation of Itk.

Question 13

Which one of the following statements about MHC-TCR interactions is NOT true?

A)Antigen receptors on T cells bind to MHC molecules for only brief periods of time.
B)The affinity of most TCRs for peptide-MHC complexes is similar to the affinity of antibodies for their antigens.
C)Only 1% or less of the MHC molecules on any antigen-presenting cell (APC) display a peptide recognized by a particular T cell.
D)T cells usually require multiple engagements with an APC before a threshold of activation is reached.
E)A subthreshold number of MHC-TCR interactions can lead to T cell inactivation.

Question 14

All of the following molecules act as transcription factors in T cell activation signaling EXCEPT:

A)NF-ĸB
B)Jun
C)Fos
D)NFAT
E)Ras

Question 15

Which one of the following signaling molecules, if mutated, would affect B cell maturation and function primarily without affecting T cell function?

A)Btk
B)Itk
C)Tec
D)PI-3 kinase
E)Zap-70