Antigen Presentation and T cell interaction lecture

Introduction to Antigen Processing and T-Cell Responses

  • Welcome to the session on antigen processing and T-cell responses.

  • Focus of today: adaptive immune response, specifically T-cells, antigen presentation, and processing pathways.

Context Setting

  • Building on previous innate immunity sessions.

  • This is the first adaptive immune response lecture of the fourth week.

  • Focus will be on how antigens are processed and presented to T cells.

Learning Objectives

  • Understand the significance of MHC (Major Histocompatibility Complex) in antigen presentation.

  • Differentiate between MHC class I and MHC class II.

  • Explain the molecular interactions between T cells and presented peptide antigens.

  • Identify features of antigen processing pathways (MHC class I & II).

  • Appreciate the role of dendritic cells in immune response initiation.

Antigen Presentation

Why is Antigen Presentation Necessary?

  • Essential for T-cell activation; this classification can help distinguish between self and non-self antigens.

  • Ensures that T-cells are primed to respond appropriately to infections and other signals.

Key Functions of T-Cell Responses

  1. Defense Against Pathogens: Including bacteria, viruses, fungi, and parasites.

  2. Immune Surveillance: Monitoring for cancerous or infected cells by T-cells.

  3. Self-Recognition: Educating T-cells to distinguish self from non-self, critical for preventing autoimmune disorders.

T-Cell Types

  • CD4 T-Cells (Helper T-Cells): Orchestrate immune responses and help activate CD8 T-cells and B-cells.

  • CD8 T-Cells (Cytotoxic T-Cells): Kill infected or cancerous cells directly.

Overview of the Immune System

  • Comprises cells, proteins, organs, and signaling molecules that work harmoniously to combat diverse pathogens.

  • Key elements include chemokines, cytokines, and several immune cell types.

Lymphocyte Development and Activation

Lymphocyte Origin and Migration

  • Lymphocytes arise from bone marrow stem cells and migrate to the thymus.

  • Positive Selection in the Thymus: Ensures T cells can recognize peptide-MHC complexes.

  • Negative Selection: Eliminates T cells reactive to self-peptides, cultivating self-tolerance.

Role of Naive T-Cells

  • After development, mature but naive T-cells circulate until they encounter antigens, at which point they become primed and activated.

Antigen Processing Pathways

Classification

  1. MHC Class I Pathway: Processes endogenous (intracellular) antigens.

  2. MHC Class II Pathway: Processes exogenous (extracellular) antigens.

MHC Class I Pathway

  • Presents peptides generated from proteins within the cell.

  • Peptides must be between 8-11 amino acids for effective binding to MHC class I molecules.

  • Uses proteasomes and TAP (Transporter associated with Antigen Processing) for peptide loading.

Function of Proteasomes

  • Degrade misfolded or excess proteins via ubiquitin tagging.

  • Active during the immune response, influenced by interferon-gamma to preferentially generate suitable peptide sequences.

MHC Class II Pathway

  • Antigens are internalized, processed in endosomal compartments, and then presented on MHC class II.

  • Invariant chains prevent premature peptide binding in the endoplasmic reticulum and guide MHC class II to endosomal compartments.

HLA-DM's Role

  • Assists in loading high-affinity peptides onto MHC class II.

  • Regulates peptide exchange to optimize antigen presentation.

Differences in Antigen Presentation

  • MHC Class I: Typically presents shorter peptides from endogenous sources.

  • MHC Class II: Presents longer peptides from exogenous sources due to an open-ended peptide-binding groove for accommodating a broader range of peptide lengths.

Cross-Presentation Mechanism

  • Exogenous antigens can sometimes lead to MHC class I presentation, allowing CD8+ T-cells to recognize extracellular pathogens.

The Role of Dendritic Cells

Characteristics of Dendritic Cells

  • Serve as professional antigen-presenting cells (APCs) involved in bridging innate and adaptive immunity.

  • Highly effective at capturing, processing, and presenting antigens to T-cells in lymph nodes.

Dendritic Cell Maturation Process

  • Upon antigen uptake, maturation occurs, leading dendritic cells to migrate to lymphoid tissues and express co-stimulatory signals essential for T cell activation.

T Cell Activation Process

  • TCR (T-Cell Receptor) interaction with peptide-MHC complex is the first signal.

  • Co-stimulatory signals and cytokine signaling complete the activation process, ensuring T cells react appropriately.

Homing of Activated T-Cells

  • Following activation, T-cells express specific homing receptors, allowing them to migrate back to sites of inflammation or infection.

Conclusion

  • Understanding the mechanisms of antigen processing and presentation is vital for developing effective immunotherapies and vaccines.

  • Both MHC class I and II pathways play integral roles in T-cell activation, mediating the immune response to infections and cancers.