Immunology: Cytokine Classification Quiz

Introduction to Sensations: Receptors and Signaling

• The presentation discusses sensations, receptors, and signaling pathways.
• It also details supporting literature, research, and specific questions for discussion.
• The content covers various aspects of the immune response to internal and external cues.

Supporting Literature

• Kuby Chapters (Chapter 3): This section refers to a textbook chapter.
• AP-1, NF-kB, NFAT Pathways: These pathways are essential signaling pathways in cells.
• Innate Lymphoid Cells: These cells play a crucial role in the innate immune system.
• CXC44 and HIV: This refers to a protein and a virus.
• HIV-membrane Fusion, CXCR4-HIV: These terms relate to how HIV enters cells.
• TCR/TLR: These are receptors involved in immune responses.
• Overview of TCR, TLR Minireview: A review on these T-cell receptors and Toll-like receptors.

Discussion Points

• Cytoplasmic Signaling Molecules: What are the cytoplasmic signaling molecules and their function?
• Principal Functions of TNF: What are the primary functions of Tumor Necrosis Factor (TNF)?
• Transcription Factors in T-cell Activation: What are the three primary transcription factors involved in antigen-dependent T-cell activation, and how do they work?

Session 2

• A quote by Anne Morrow Lindbergh emphasizes the importance of communication in her work.

Ligand-Receptor Interactions

• Non-covalency: Cell-to-cell communication in immunology relies on non-covalent receptor-ligand interactions.
• Affinity: The strength of individual noncovalent bonds tends to be weak.
• Avidity: Multiple bonds creating a strong cumulative interaction.
• Valency: Increasing the number of binding sites on receptors.

Univalent vs Bivalent Interactions

• Univalent interactions involve a single binding site.
• Bivalent interactions involve two or more binding sites, resulting in greater avidity.

Receptor Expression Changes

• Space: Receptor expression can dynamically change its structure in response to external stimuli.
• Time: Receptor expression can change over time during an infection process.

Receptor-Ligand Interactions

• Conformational Change: When a ligand binds to a receptor, it induces a conformational change.
• Dimerization/Clustering: Receptor binding often leads to dimerization or clustering.
• Membrane Location Changes: The receptor's location within the membrane can change.
• Covalent Modifications: Covalent modifications of the receptor can occur as a result of the ligand-receptor interaction.

Benefits of Receptor Multimerization

• Cell-cell Interactions: Cell-cell interactions often rely on long-duration contacts with high-affinity binding.
• Cytokine Signal Exchange: Extended contacts facilitate signal transduction, optimizing the exchange of cytokine signals.

Adaptive Immune Receptors

• Immunoglobulin (Ig) Domains: Immune receptors possess immunoglobulin domains.
• B-cell Receptor (BCR): The BCR binds foreign antigens. (Antibody).
• T-cell Receptor (TCR): The TCR recognizes foreign or self-peptides presented on MHC molecules.
• CD4/CD8 Co-receptors: These receptors help define T-cell subsets.

Co-receptors and Their Role

• Enhanced Interactions: Antigen-immune receptor interactions are enhanced via co-receptor binding.
• Separate Receptor Interactions: Co-receptors are separate receptor-ligand interactions.
• Insufficient Single Interaction: A single receptor-ligand interaction often isn't sufficient, emphasizing the need for co-receptors.

Immunoglobulin Structure

• Two Heavy Chains, Two Light Chains: Immunoglobulins are composed of two heavy chains and two light chains.
• Covalent Disulfide Bonds: These chains are held together by intra- and interchain disulfide bonds.
• Variable and Constant Regions: Heavy and light chains have variable regions and constant regions.

Antibody Structural Differences

• Five Major Isotypes: Secreted antibodies are categorized into five major isotypes (classes).
• Different Functions: Each isotype performs different functions within the immune response.
• Kappa and Lambda Light Chains: Common light chain types are kappa (κ) and lambda (λ).

Immunoglobulin (BCR) Details

• Antigen Binding Domains: Each antibody can bind two antigens.
• Hinge Region: The hinge region extends the "arms" of the antibody.
• Glycosylation: Glycosylation helps spread heavy-chain domains apart, playing a functional role.
• Hydrophobic Tail: Membrane-bound antibodies often have a hydrophobic tail.
• Alternative RNA Splicing: Secretion of antibodies is frequently processed via alternative RNA splicing.

T-cell Receptor (TCR) Details

• Immunoglobulin Domains: Similar to BCRs, TCRs possess immunoglobulin domains.
• Subunits alpha and beta: TCRs contain subunits alpha and beta.
• CDRs (Complementarity Determining Regions): Three CDRs in the variable regions enable peptide-specific binding.
• Transmembrane Regions: Constant regions contain transmembrane regions.
• Types: Common are alpha-beta (αβ) and gamma-delta (γδ), exhibiting diverse antigen-binding characteristics.

Signal Transduction Pathways (TCR and BCR)

• CD3 Complex and ITAMs: In T-cells, the CD3 complex is involved in signal transduction, relying on immunoreceptor tyrosine-based activation motifs (ITAMs).
• Iga/Igb and ITAMs: In B-cells, Iga/Igb proteins initiate signal transduction through ITAMs.

Innate Immune Receptors

• Pattern Recognition Receptors (PRRs): PAMPs (Pathogen-Associated Molecular Patterns) trigger PRRs, which broadly recognize many pathogens.
• Uniform Recognition of PAMPs: The same PRR can recognize large numbers of pathogens that share the same PAMPs.
• Equal Expression on Cells: PRRs are expressed equally across the same cell types, unlike unique receptors on adaptive immune cells.

Human PRRs (Toll-like, C-type lectin, RIG-I-like, NOD-like, AIM-like)

• Cellular Locations and Ligands: These receptors differ in their location within the cell and the types of ligands they recognize.
• Cellular Functions: These receptors perform various functions like producing antimicrobial compounds, cytokines, etc.

Cytokine Signaling Molecules

• Cytokine Signals: These signals are generated when ligands bind to their complementary cell-bound receptors.
• Generally High Affinity (Non-covalent): The binding is typically of high, non-covalent affinity.
• Cytokine-receptor Signal Outcomes: These interactions result in changes to the target cell's transcriptional program (e.g., metabolic or proliferative changes).

Cytokine Action Mechanisms

• Endocrine: Cytokines released into the bloodstream act on distant cells.
• Paracrine: Cytokines act on nearby cells.
• Autocrine: Cytokines act on the cell that produced them.

Cytokine Action Patterns

• Pleiotropic: A single cytokine can have multiple effects.
• Redundant: Multiple cytokines can produce similar effects.
• Synergistic: The combination of cytokines can produce a greater effect.
• Antagonistic: One cytokine can inhibit the effect of another.
• Cascading: One cytokine can induce the production of additional cytokines.

Practical Examples of Cytokine Action

• Immune Cell Activation, Proliferation and Differentiation: Activated T cells can stimulate the proliferation, differentiation, and activation of other immune cells in response to specific stimuli and signals.

The Six Cytokine Families (Interleukin, Interferon, Tumor Necrosis Factor, Interleukin-17, Chemokines)

• Representative Members: Specific cytokines provide examples of each type of cytokine family.
• Common Features: General features (e.g., functions or actions) of each cytokine family are listed.

IL-1 Family

• Inflammation: This family of cytokines promotes inflammation.
• Early Immune Response: Secreted early in immune responses, acted on by macrophages and dendritic cells.
• Actions: Acts on capillary permeability and pulls leukocytes to infected sites.
• Acute Phase Proteins: Systemic signalling promotes acute phase protein production.

Class 1 Cytokine Family

• Diverse Function: Class 1 cytokines are diverse in actions and targets.
• Single Protein Family: Structurally, class 1 cytokines are typically single proteins (but may have multiple subunits).
• Common Subunits: Multiple cytokine types can use common cytokine receptor subunits, leading to functional similarities.

Interferon (IFN) Family

• Antiviral Effects: Type I interferons have antiviral effects.
• Immunomodulation: Type II (IFN-γ) interferons are important modulators of adaptive immunity.
• Viral Replication Control: Type III interferons regulate genes controlling viral replication and host cell proliferation.

Tumor Necrosis Factor (TNF) Family

• Development and Homeostasis: TNF affects development, effector function, and homeostasis in skeletal, neuronal, and immune systems.
• Soluble / Membrane-Bound: TNF cytokines can be membrane-bound or soluble.

IL-17 Family

• Proinflammatory: IL-17 family cytokines are proinflammatory.
• Cellular Targets: Receptors are found on cells important for immune interactions (i.e., neutrophils).
• Homodimers: The family members tend to exist as homodimers.

Chemokines

• Leukocyte Migration: They are small proteins driving the migration of leukocytes.
• Disulfide Bonds: Conserved disulfide bonds dictate the structure of each type.

Chemokine Receptors

• G-protein-Coupled Receptors: These are transmembrane proteins coupled to G-proteins.
• Signal Transduction: Signal transduction follows binding to their G-proteins.
• Chemokine Recognition: One receptor can sometimes bind more than one chemokine. Conversely, more than one chemokine can sometimes bind the same receptor.

Cellular Signaling Summary

• Ligand-Receptor Binding: Cellular signals are frequently triggered by ligand binding to receptor proteins.
• Programmed Changes: Signaling mechanisms frequently induce changes (in the cell's metabolic or proliferative state).
• Ligand Expression: A cell's responsiveness to a signal can change through regulation of receptor expression for that ligand.

Multiple Signals and Cellular Response

• Transcription Program Changes: Cell signaling frequently results in changes to the cell's transcriptional program.
• Integration and Outcomes: Various signaling pathways, potentially involving multiple receptors, frequently work together (integrate) to produce overall outcomes within a recipient cell.

Summary of Immune Responses and Signaling

• The steps of immune cell involvement in antigen response.
• The critical role of immune cells in antigen presentation.

Test your knowledge on the classification and functions of various cytokines in the immune system. This quiz covers topics including Class 1 (hematopoietin) and Class 2 (interferon) cytokines, their functions, and key receptors. Challenge yourself with questions about IL-1, TNF-α, and more.