Immunology - Lecture 10

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Questions and Answers

What are ITAMs primarily responsible for in the TCR complex?

Transferring phosphate groups to lipids

Serving as docking sites for protein-tyrosine kinases (correct)

Inhibiting signal transduction pathways

Catalyzing the cleavage of PIP2

Which molecule is cleaved by PLC during T-cell activation?

ITAMs

PIP2 (correct)

IP3

DAG

What is the key role of kinases in the signaling events of T-cell activation?

They bind to lipid molecules.

They directly activate ITAMs.

They inhibit phosphorylation of protein receptors.

They catalyze the transfer of phosphate groups. (correct)

Which of the following is not produced as a result of PIP2 cleavage?

PLC Signup and view all the answers

What is the first step in the signaling events for T-cell activation?

Phosphorylation and activation of PLC Signup and view all the answers

What is the role of ligand-receptor binding in lymphocyte function?

It alters cell function by starting signal transduction. Signup and view all the answers

What are the components that control proliferation and differentiation of lymphocytes?

Co-stimulatory molecules, adhesion molecules, cytokines, and chemokines. Signup and view all the answers

Which statement is true regarding the receptors involved in T cell activation?

TCRs are specifically activated by their ligands through peptide + MHC. Signup and view all the answers

What is signal transduction?

The transformation of an external signal into a cellular response. Signup and view all the answers

Which of the following describes the general structure of membrane receptors?

They have extracellular, transmembrane, and cytoplasmic domains. Signup and view all the answers

What is the role of IP3 in T-cell activation?

It signals the opening of calcium stores. Signup and view all the answers

Which molecule serves as a secondary messenger that diffuses to activate various target proteins in T-cell activation?

Ca2+ Signup and view all the answers

What is the function of calcineurin in the T-cell signaling pathway?

It dephosphorylates NFAT. Signup and view all the answers

Which transcription factor is formed by the interaction of Fos and Jun during T-cell activation?

AP-1 Signup and view all the answers

What is the primary initiation signal involved in the T-cell activation pathways described?

Co-stimulatory signals Signup and view all the answers

What phosphorylates IκB to activate NF-κB during T-cell signaling?

Protein kinase C Signup and view all the answers

Which gene is one of the most important for T-cell activation?

IL-2 Signup and view all the answers

What is the function of DAG in the T-cell activation pathway?

To activate protein kinase C. Signup and view all the answers

What is the primary role of IL-2 in T cells?

T-cell activation and proliferation Signup and view all the answers

Which cell type is primarily responsible for secreting IL-4?

Dendritic cells Signup and view all the answers

Which of the following cytokines is involved in T-cell activation?

IL-2 Signup and view all the answers

What mechanism drives B-cell activation upon antigen binding?

Clustering of B cell receptors (BCR) complexes Signup and view all the answers

Which cells are primarily responsible for the secretion of TNF-alpha?

Macrophages Signup and view all the answers

Which family of kinases is involved in B-cell receptor signal transduction?

Src family kinases Signup and view all the answers

What is the function of IL-10 in the immune response?

Anti-inflammatory activity Signup and view all the answers

Which cytokine aids in the activation of Th1 helper T cells?

IL-12 Signup and view all the answers

What role does CR2 play in B-cell coreceptor binding?

It binds to iC3b and C3d on pathogen surfaces. Signup and view all the answers

Which transcription factors are induced by Syk kinase in B cells?

AP-1, NFAT, NF-kB Signup and view all the answers

What is the main function of CD81 in B-cell signaling?

Stabilizes the coreceptor complex. Signup and view all the answers

Why is a single Ig binding to an antigen insufficient for B-cell activation?

Additional signals are required for full activation. Signup and view all the answers

How are inhibitory receptors like PD-1 significant in immune response?

Down-regulate immune responses. Signup and view all the answers

What is the effect of activated T cells expressing CTLA4?

It serves as an internal check mechanism. Signup and view all the answers

What is the function of guanine-exchange factors (GEFs) in B cells?

Catalyze the exchange of guanine nucleotides. Signup and view all the answers

What is a similarity between B-cell activation and T-cell activation?

Both are dependent on the coreceptor complex. Signup and view all the answers

Study Notes

General Principles of Signal Transduction

Signal transduction is the process of converting a signal from one form to another.
A receptor is a molecule that receives a signal from its ligand.
An antigen is a ligand for BCR, a peptide + MHC complex is a ligand for TCR
All membrane receptors have extracellular domains that bind ligands, transmembrane domains that span the plasma membrane, and cytoplasmic domains that participate in signal transduction.

T-Cell Activation

T-cell activation requires a co-stimulatory interaction between the T cell and APC.
ITAMs are cytoplasmic amino acid sequences containing tyrosine that are targets of phosphorylation and subsequent activation of signaling events.
TCR complex activation leads to three signaling pathways:
The phosphorylation and activation of PLCγ.
Cleavage of PIP2 into IP3 and DAG
IP3 signals the opening of calcium stores
Ca2+ activates target proteins
Calcineurin dephosphorylates NFAT
NFAT activates genes involved in T-cell expansion and differentiation.
DAG activates protein kinase C
PKC activates the transcription factor NF-κB
DAG also associates with the small GTPase, RAS, which triggers the MAPK cascade
MAPK activates another transcription factor, Fos
Fos interacts with Jun to form the transcription factor AP-1; Jun is activated via the co-stimulatory signal provided by CD28.

IL-2 Promoter

Multiple signaling pathways converge on the IL-2 promoter.
IL-2 is critical for T-cell proliferation and differentiation of effector T cells.

B-Cell Activation

B-cell activation requires clustering of BCR complexes.
Syk is a key kinase in B cells that induces 3 signal transduction pathways: NFAT, NF-κB, and AP-1.

Inhibitory Receptors

Inhibitory receptors on lymphocytes downregulate immune responses by interfering with co-stimulatory signaling pathways.
Inhibitory receptors include PD-1 and BTLA.

Checkpoint Questions

The costimulatory interaction required between T cells and APCs is the interaction between CD28 (on T cells) and B7 (on APCs).
The importance of activating protein-tyrosine kinases at the initiation of the formation of an immunological synapse between T cells and APCs is to initiate the phosphorylation cascade that leads to the activation of the three major signaling pathways.
The three transcription factors activated during T-cell activation are NFAT, NF-κB, and AP-1.
Binding of a single cell-surface Ig to an antigen is not sufficient for B-cell activation. The antigen must promote clustering of BCR complexes on the B-cell surface.
B-cell activation through the BCR complex is similar to T-cell activation through the TCR complex in that both involve the activation of protein-tyrosine kinases, the phosphorylation of ITAMs, and the activation of downstream signaling pathways.
Transcriptional activation in B cells during their activation is similar to that within T cells in that both involve the activation of the transcription factors NFAT, NF-κB, and AP-1.

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Description

This quiz explores the general principles of signal transduction and the mechanics of T-cell activation. Understand the roles of receptors, ligands, and different signaling pathways involved in T-cell responses. Test your knowledge on key concepts and processes in immune signaling.