Edition Abbas Test Bank

Cellular and Molecular Immunology 8th Edition Abbas Test Bank

Abbas: Cellular and Molecular Immunology, 8th Edition

Activation of T Lymphocytes Test Bank Multiple Choice

• All of the following protein-protein interactions are involved in activation of naive

helper T cells by antigen-presenting cells (APCs) EXCEPT binding of:

• Peptide-MHC complexes on the APC to the TCR on the T cell
• CD4 on the T cell to nonpolymorphic regions of class II MHC molecules on the

APC

• Integrins on the T cell with adhesion ligands on the APC
• B7-2 on the APC with CD28 on the T cell
• 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.

• Which one of the following statements about MHC-TCR interactions is NOT true?
• Antigen receptors on T cells bind to MHC molecules for only brief periods of

time.

• The affinity of most TCRs for peptide-MHC complexes is similar to the affinity

of antibodies for their antigens.

• Only 1% or less of the MHC molecules on any antigen-presenting cell (APC)

display a peptide recognized by a particular T cell.

• T cells usually require multiple engagements with an APC before a threshold of

activation is reached.

• 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.

Matching 1 / 4

Questions 3-10 For each of the descriptions in questions 3-10, choose the T cell signaling molecule that best matches it from the list below (A-O).

A. CD3

• Lck
• Zap-70

D. LAT

• Ras

F. PLC

G. PIP2

H. PIP3

I. IP3

J. DAG

• Calcineurin

L. NFAT

• Jun
• Fos

O. NF-B

• This molecule becomes an active transcription factor on dephosphorylation.

ANS: L. NFAT is a transcription factor required by T cells for the expression of interleukin (IL)-2, IL-4, tumor necrosis factor (TNF), and other cytokine genes. NFAT is present in an inactive, phospN hoUryR lSateI dNfG oTrmB.inC OthM e cytosol of resting T cells. On dephosphorylation by calcineurin, a nuclear localization sequence is uncovered that permits NFAT to translocate to the nucleus. Once in the nucleus, NFAT induces transcription of these genes.

• This protein is a well-characterized proto-oncogene product that on mutation to a

constitutively active form has been associated with multiple neoplasms.

ANS: E. Ras was one of the first proto-oncogenes characterized. Normal ras is involved in TCR signaling pathways. On mutation to a constitutively active state, ras promotes the survival and proliferation of malignant cells.

• Binding of this molecule to Jun is needed for transcriptional activation of the IL-2

gene.

ANS: N. Fos combines with phosphorylated Jun to form activation protein-1 (AP-1). AP-

• is the name for a family of DNA-binding factors composed of dimers of two different

proteins. Transcription of fos is enhanced by the Erk pathway, whereas phosphorylation of preexisting Jun is induced through the Vav/Rac pathway. AP-1 physically associates with other transcription factors in the nucleus, and together they activate transcription of cytokine genes essential for T cell activation.

• This is a transcription factor that exists in the phosphorylated form within the nucleus. 2 / 4

Test Bank 3

ANS: M. On phosphorylation, c-Jun translocates to the nucleus and binds to Fos to form AP-1.

• Immunosuppressive therapy with the drugs cyclosporine and FK506 inhibits T cell

activation by blocking the protein phosphatase activity of this molecule.

ANS: K. Calcineurin is responsible for the dephosphorylation of NFAT, which is an essential transcription factor for the activation of T and B cells. The immunosuppressive drugs cyclosporine and FK506 function by inhibiting calcineurin. These drugs are commonly used to prevent transplant rejection.

• This molecule binds to a receptor on the endoplasmic reticulum and stimulates release

of calcium into the cytosol.

ANS: I. IP3 is generated from the cleavage of PIP2 in the membrane to DAG and IP3 by the enzyme PLC, and it stimulates release of calcium into the cytosol.

• This molecule has the same downstream effect as addition of the drug phorbol

myristate acetate (PMA) to T cells.

ANS: J. Both DAG and pharmacologic agents such as phorbol myristate acetate (PMA) activate protein kinase C (PKC). PKC has many substrates and is a potent activator of many transcription factors in T cells.

• This molecule is a transcriNptUioRn SfaIctNorGiTnvBo.lvCedO

Min the expression of several T cell activation genes activated when its bound inhibitor is phosphorylated.

ANS: O. NF-B is present in the cytoplasm and is bound to an inhibitor called I-B. On stimulation with antigen, I-B becomes phosphorylated, dissociates from NF-B, and is degraded by the ubiquitin-proteosomal pathway. NF-B then translocates to the nucleus, where it participates in transcriptional activation of several genes. 3 / 4

Abbas: Cellular and Molecular Immunology, 8th Edition

Antibodies and Antigens Test Bank Matching

Questions 1-5 Match each of the descriptions in questions 1-5 with the correct lettered antibody isotype (A-E). (Answers may be used more than once.)

• IgA
• IgD
• IgE
• IgG
• IgM

• The secreted form of this isotype forms pentamers around a J chain

ANS: E. IgM is secreted as a J chain–linked pentamer.

• The most abundant Ig isotype in the blood

ANS: D. The blood IgG concentration is about 3.5 mg/mL and includes four subtypes (IgG1 to IgG4).

• The isotype only found in membrane-bound form on naive B cells

ANS: B. IgD is not secreted and is found only on the surface of naive B cells. Its function is not well understood.

• The isotype found predominantly in mucosal secretions

ANS: A. IgA accounts for almost two thirds of the 3 g of antibody produced each day by an adult, most of which is produced in the gastrointestinal mucosa.

• The isotype most closely associated with immediate hypersensitivity (allergic)

disease

ANS: C. Most IgE that is secreted is bound to mast cells, and it plays a role in the activation of mast cells during allergic reactions.

Questions 6-10

Match each description in questions 6-10 with the appropriate lettered term (A-I).

• Conformational determinant
• Linear determinant
• Neoantigenic determinant
• Hinge region
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