41181 (Lecture 7) Antigen Processing Presentation Audio V1

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  • IMUNOLOGY 41181

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  • Antigen Processing and Presentation

    • (a) Antigen with APC fixation

    • (b) Antigen Fixation with T Helper (TH) cell

    • (c) Antigen peptides with TH cell

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  • Antigen Processing

    • Definition: The method of preparing antigen material for presentation to T cells.

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  • Experimental Evidence 1 (a)

    • T-Cell Activation

    • Key Findings:

      • Efficacy of chemical fixation, utilizing Paraformaldehyde and Glutaraldehyde for APC fixation.

      • Fixation limits phagocytosis ability in APC.

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  • Experimental Evidence 2 (b)

    • T-Cell Activation

    • Key Findings:

      • Phagocytosis can occur before fixation, enabling antigen interaction.

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  • Experimental Evidence 3 (c)

    • T-Cell Activation

    • Focus on Post-Fixation

      • Confirmation of APC interaction but no phagocytosis post-fixation.

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  • Experimental Evidence 4

    1. APC fixed with glutaraldehyde.

    2. Fixed APC incubated with various forms of ovalbumin.

    3. No TH activation with whole ovalbumin; TH activation observed with processed ovalbumin peptides.

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  • Experimental Evidence 5

    1. Target cells incubated with virus-derived peptides.

    2. Virus-specific T cell activation occurs when target cells are exposed to virus peptides.

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  • Antigen Processing and Presentation

    • Classification of MHC complexes:

      • Peptide-class I MHC Complex

      • Peptide-class II MHC Complex

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  • Antigen Presenting Cells (APCs)

    • Express MHC I or both MHC I and II.

    • Role of Target Cells: MHC I + peptide presented to CD8+ TC cells.

    • Role of APCs: MHC II + peptide presented to CD4+ TH cells.

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  • Professional APCs

    1. Dendritic cells: Most effective, express MHC II constitutively.

    2. Macrophages: Activated via phagocytosis to express MHC II.

    3. B cells: Constitutive expression of MHC II.

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  • Types of APCs

    • Professional APCs: Dendritic cells, Macrophages, B cells.

    • Nonprofessional APCs: Fibroblasts, Thymic epithelial cells, Glial cells, etc.

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  • MHC Restriction (Limitation)

    • Importance of MHC compatibility in CTL targeting.

    • H-2 compatibility levels among target cells.

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  • MHC Restriction Class Specificity

    • Specificity of TCR in recognizing MHC class I and II during antigen interaction.

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  • Experimental Evidence

    • Observations of antigen strain responses and lymph node cell interactions.

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  • MHC II Compatibility

    • Activation based on the presence of histocompatible macrophages and T cells.

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  • Peritoneal Exudate Cells

    • Composition and role in response: Macrophages and T cells; adherence interactions.

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  • Results from MHC Compatibility Studies

    • Observations on activation of T cells with respective macrophage strains.

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  • MHC II Restriction Results

    • Recognition of MHC II by CD4+ TH cells in APC interactions.

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  • MHC Restriction MHC I Specificity

    • TC cell activation through interaction with MHC I producing target cells.

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  • H-2K MHC Histocompatibility

    • The role of H-2K during immune responses and target cell interactions.

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  • MHC Compatibility Results

    • Effectiveness of activated TC cells in lysing LCM-infected target cells based on MHC compatibility.

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  • MHC I Restriction Results

    • Overview of CD8+ TC cell specificity towards MHC I expressing target cells.

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  • T Cell Immune Response Overview

    • Understanding antigen specificity through TCR interactions.

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  • MHC Histocompatibility

    • Comparison between self and non-self MHC responses.

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  • T Cell MHC Specificity

    • TH/CD4 specific for MHC II; TC/CD8 specific for MHC I.

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  • Antigen Processing/Presentation Pathways Overview

    • Endogenous Pathway (MHC I) vs Exogenous Pathway (MHC II)

    • Key differences in processing endogenous vs exogenous antigens.

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  • Endogenous Pathway

    • Detailed steps of peptide processing in MHC I pathway in target cells.

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  • Endogenous Pathway

    • Continuous focus on the importance of peptide class I MHC complex presentation.

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  • Endogenous Pathway

    • Role of the proteasome in protein degradation and peptide generation.

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  • Endogenous Pathway

    • Description of proteasomal activity in antigen presentation.

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  • HLA Haplotype

    • Overview of Human HLA complexes critical for immune response.

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  • Endogenous Pathway

    • Focus on generation of MHC I-specific peptides through proteolysis.

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  • TAP Functionality

    • Importance of TAP in transporting peptides into the ER for MHC I binding.

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  • TAP Proteins

    • Overview of the characteristics of TAP proteins related to antigen processing.

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  • HLA Haplotype Loci

    • Structural dynamics of Human HLA complex loci.

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  • MHC I Complex Assembly in ER

    • Detailed outline of MHC I complex formation in the ER.

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  • Peptide-MHC I Complex Assembly in ER

    • Chaperone assistance in polypeptide folding and proper structure.

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  • MHC I-Peptide Complex Assembly Process

    • Overview of the process leading to the expression of the MHC I-peptide complex on the cell surface.

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  • Endogenous Pathway Process

    • Importance of peptide degradation by exopeptidases in amino acid recycling.

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  • Cytoplasmic Peptide Processing

    • Interaction of cytosolic proteins and MHC complex setup.

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  • Exogenous Pathway Overview

    • Processing of endocytosed antigens for presentation by MHC II.

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  • Exogenous Pathway

    • Emphasis on the processing mechanisms of exogenous antigens in APCs.

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  • Exogenous Pathway Mechanism

    • Role of specific receptors in antigen endocytosis.

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  • Ig Activity

    • Overview of immunoglobulin activity in opsonization and phagocytosis.

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  • Exogenous Pathway Vesicle Dynamics

    • pH changes in compartments during antigen processing.

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  • Exogenous Pathway Steps

    • Critical sequence of events from early endosome through lysosome leading to peptide binding.

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  • MHC II-Peptide Complex

    • Dynamics of invariant chain interactions and peptide loading mechanisms.

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  • MHC II Formation Process

    • Outline of how MHC II peptide complexes prevent non-specific binding.

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  • HLA Haplotype Loci

    • Recapping human HLA complex organization.

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  • Exogenous Pathway Overview

    • The role of invariant chain and HLA-DM in MHC II peptide complex formation.

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  • Exogenous Pathway

    • Overview of complex rerouting after endocytosis of antigen.

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  • Processing Presentation Pathways Summary

    • A brief comparison of both endogenous and exogenous antigen processing pathways.

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  • Antigen Processing Overview

    • Final outline of antigen processing by APCs.