Kuby Chapter 3: Sensations and Signaling

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Questions and Answers

What is the role of chemokine signaling in the immune system?

Enhancing apoptosis in all cells

Inducing B-cell differentiation exclusively

Directing leukocyte migration (correct)

Inhibiting leukocyte migration

What structure do chemokine receptors belong to?

Monomeric proteins

Dimeric receptors

Single-pass transmembrane proteins

G-protein-coupled receptors (correct)

What is a characteristic feature of chemokines?

They are always produced by lymphoid cells

They generally exist as heterodimers

They have highly conserved disulfide bonds (correct)

They possess variable cysteine residues

Which statement is true regarding the interaction of chemokines and their receptors?

Several chemokines can bind to multiple receptors Signup and view all the answers

What determines a cell's susceptibility to a ligand in a signaling pathway?

The expression level of receptors for that ligand Signup and view all the answers

What type of bonds are important for the structural integrity of chemokines?

Disulfide bonds Signup and view all the answers

What role do tyrosine phosphorylation and ITAMs play in T and B cells?

They transmit differentiation signals Signup and view all the answers

What is the primary role of chemokines in the immune response?

Attracting immune cells to sites of infection Signup and view all the answers

Which of the following co-receptors is essential for T-cell activation?

CD28 Signup and view all the answers

Which of the following statements about IL-17 family cytokines is correct?

They exist as homodimers Signup and view all the answers

Which receptor is primarily associated with B-cells?

B-cell receptor Signup and view all the answers

What types of antigens do B-cell receptors typically bind to?

Antigens and sometimes complement components Signup and view all the answers

Which transcription factors are involved in T-cell activation?

NF-κB and NF-AT Signup and view all the answers

Which of the following statements about dendritic cells is true?

They enhance antigen presentation and activate T-cells. Signup and view all the answers

What does the immuno-receptor tyrosine activation motif (ITAM) do?

Facilitates signal transduction in immune cells Signup and view all the answers

Which MHC class interacts with CD4 co-receptors?

MHC class II Signup and view all the answers

What role do adaptor proteins play in signaling pathways?

They help to gather members of signaling pathways. Signup and view all the answers

What happens to NFAT after it is activated by Calmodulin?

It migrates to the nucleus to activate immune-specific genes. Signup and view all the answers

Which factor is necessary for the activation of Ras?

Guanine-nucleotide Exchange Factors (GEFs) Signup and view all the answers

What is the function of GTPase activating proteins (GAPs) in relation to Ras?

They inhibit Ras by stimulating the breakdown of GTP. Signup and view all the answers

How does the Ras/MAP kinase cascade affect transcription?

By activating transcription through Elk-1. Signup and view all the answers

What initiates the activation of NF-κB in the cytoplasm?

Phosphorylation by PKC Signup and view all the answers

What is the outcome of phospholipase C gamma (PLCγ) activity on calcium ions?

It encourages calcium ions to bind to calmodulin. Signup and view all the answers

Which cells are involved in enhancing phagolysosome activity during immune responses?

Macrophages and neutrophils Signup and view all the answers

Study Notes

Sensations: Receptors and Signaling

The presentation is about sensations, receptors, and signaling.
Key concepts include receptor-ligand interactions, cytoplasmic signaling molecules, TNF functions, and transcription factors in T-cell activation.

Supporting Literature

Kuby Chapters (Chapter 3) are referenced.
Research on AP-1, NF-κB, NFAT pathways in innate lymphoid cells is discussed.
CXC44 and HIV interaction is explored.
Overview of TCR and TLR minireview is covered.

Discussion Questions

Question 1: What are the cytoplasmic signaling molecules, and what do they do?
Question 2: What are the principal functions of TNF?
Question 3: What are the three main transcription factors participating in antigen-dependent T-cell activation, and how do they work?

Session 2

"Good communication is as stimulating as black coffee, and just as hard to sleep after." – Anne Morrow Lindbergh (quote)

Let's Bond...

Receptor-ligand interactions involve non-covalent bonds.
- Non-covalency: In immunology, cell-to-cell communication occurs via receptor-ligand interactions (non-covalent)
- Affinity: Normally, the strength of the individual bonds is generally weak.
- Avidity: Multiple bonds resulting in a high cumulative bind strength.
- Valency: Increasing the valency of receptors increases avidity.

Immunoglobulin (BCR)

Antibodies extend from the hinge region.
Glycosylation helps spread heavy-chain domains apart, playing a functional role.
Antibodies have an antigen-binding domain, binding two antigen molecules.
Contains proline (flexible) and cysteine (heavy-chain dimer formation).
Membrane-bound antibodies have extracellular, hydrophobic transmembrane, and cytoplasmic tails.
Alternative splicing mechanisms produce secreted antibodies by removing/replacing these regions.

T-cell Receptor (TCR)

Similar to BCR, contains immunoglobulin domains.
TCR has α and β subunits, with constant and variable regions.
Variable regions possess three CDRs forming peptide-specific binding sites.
Constant regions contain transmembrane regions.
Two types (αβ and γδ) with diverse antigen-binding characteristics.

Co-receptors

Co-receptor binding enhances antigen-immune system receptor interactions.
Interactions occur near the original receptor-ligand interaction.
A single interaction may be insufficient for activation.
Co-receptors can provide a second signaling interaction for complete cell activation.

Immunoglobulin 2-D and Space-Fill Models

Two heavy chains (variable and constant regions) and two light chains held together by disulfide bonds.
Models show variable and constant regions, hinge regions, antigen binding sites, and effector function sites.

Structural Differences

Secreted antibodies are grouped into five major classes (IgA, IgD, IgE, IgG, IgM).
- Each class differs in their heavy chain types (α, δ, ε, γ, μ).
- Light chains are Kappa (κ) or Lambda (λ).
- Different classes have different functions in immune responses.

Innate Immune Receptors

Recognize PAMPs (Pathogen-Associated Molecular Patterns).
Receptors for PAMPs, like Toll-like receptors (TLRs), are uniformly distributed on cell types.
Receptors can be integral membrane proteins or intracellular proteins, recognizing recurring patterns on bacteria, yeast, and parasites.

Human PRRs

TLR, CLR, RLR, NLR, and ALR are examples of human pattern recognition receptors (PRRs).
Each PRR has a different cell location and recognizes different PAMPs.
PRRs play essential roles in immune responses.

Signaling Molecules

Cytokine signals are generated by ligand binding to cell receptors.
Cytokine-receptor binding is noncovalent (typically high affinity).
Cytokine-signaling results in changes in the target cell's transcriptional program, inducing metabolic or proliferative changes.

How Cytokines Work

Cytokines are proteins that mediate immune responses.
They act through three different mechanisms (endocrine, paracrine, and autocrine).

Cytokine Action

Cytokine action can be pleiotropic (different biological effects), redundant (similar effects), synergistic (combined effects greater than additive), antagonistic (opposite effects), and cascade effect. (multiple downstream cytokines).

Practical Examples

Presentation of many practical examples of cytokine actions on various immune cells.

The Six Cytokine Families

Summarization of six major cytokine families (IL-1, Class 1/2, TNF, IL-17, Interferons, etc.).
Each family has representative members with diverse functions and roles in immune responses.

Receptor Meets Ligand

Ligand binding to a receptor causes conformational changes, dimerization/clustering, membrane location changes, and covalent modifications.

Adaptive Immune Receptors

Summary of adaptive immune receptors (immunoglobulins – BCR, and TCR).
Important receptors are highlighted (immunoglobulin domains, variable and constant regions, etc.).
Additional related components like co-receptors (CD4, CD8), and tyrosine kinases with their specific roles are noted.

Putting It All Together

Summary of the overall process and key features of immune responses and cell signaling. Summarizes the process.

NFAT and NFκB Detail

Diagram illustrates the intricate interplay of NFAT and NFκB in response to antigen stimulation.

AP-1 Detail

Diagram showing AP-1 activation pathway induced by extracellular stimuli leading to changes in gene transcription.

Comparison of B and T Cells

Compares and contrasts B-cell and T-cell receptors, accessory proteins, ligands, co-receptors, tyrosine kinases, adaptor proteins, and effector molecules involved in their signaling pathways.

Lift Off...

Summary of immune cell functions in response to infection: leukocytes, macrophages, neutrophils, dendritic cells, B cells, and T cells.

Session 3 Prepare

Important questions regarding the innate immune system (innate components, role of phagocytes, and properties of neutrophils and macrophages).

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Description

Explore the intricate world of sensations, receptors, and cellular signaling as detailed in Kuby Chapter 3. Delve into receptor-ligand interactions, the roles of cellular signaling molecules, and critical transcription factors involved in T-cell activation. This quiz also addresses interesting questions related to TNF functions and immune cell pathways.