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Lecture 3: Antigen Recognition by T lymphocytes Questions to Consider How do B cells and T cells see antigen? How does a T cells distinguish between whether a foreign antigen is being presented to recruit help or because the cell is infected? Why do some T cells kill and others provide help? Phagocytosis by Macrophages Antigen Presenting Cells Activation of Macrophages Permits Elimination of Mycobacterium Infection Changes Exhibited by an Activated Macrophage Development of a Secondary Amplified Response T-cell Activation of Macrophages Transfer of Which Cells Will Protect This Mouse From TB? Activated monocytes T cells B cells T-cell Activation of Macrophages Permits Killing of Phagocytosed Pathogens How does the T cell know that the macrophage is infected with TB? B Cells and T Cells Use Different Antigen-specific Receptors T Cell Receptor Gene Genetic Rearrangement Generates T Cell Receptor Diversity Development of a Secondary Amplified Response T Cells and B Cells Recognize Antigen Differently Secondary Immune Response Primary Immunization Secondary Ag Challenge Native Protein Native Protein + + Denatured Protein Native Protein - + Denatured Protein Denatured Protein - + + + Native Protein Denatured Protein B Cell Response T Cell Response The T Cell Receptor Only Recognizes Antigen in the Presence of Antigen Presenting Cells Abbas- Cellular and Molecular Immunology Antigen Must Be Processed to Peptides to be Recognized by the T Cell Receptor Abbas- Cellular and Molecular Immunology Antibody and T Cell Receptors Recognize Different Antigenic Contexts B Cells use the Immunoglobulin Molecule to recognize 3D structures of the native molecules. T Cells use the T cell receptor to recognize primary structures. While the Majority of MHC-expressed Peptides are Self Self-reactive T Cells Are Not Present in the Periphery Abbas- Cellular and Molecular Immunology Two Different Types of MHC Molecules Are Capable of Presenting Peptides to T Cells Divergent Cellular Expression of Class I and Class II MHC Molecules Peripheral T Cells Express Either CD4 or CD8 Molecules TCR Interaction With APCs Is Limited by CD4 or CD8 to Either MHC Class I or II, Respectively Functional Implication of CD4 or CD8 Restricted Recognition of Class I or Class II MHC Molecules Abbas- Cellular and Molecular Immunology MHC Class I Molecules Only Present Peptides Derived From Endogenous Proteins Cells Expressing Foreign Peptides Recognized by Cytotoxic CD8+ T Cells Are Killed Antigen Presenting Cells B Cells Monocytes MHC Class II Molecules Present Only Peptides Derived From Exogenous Proteins CD4+ T Cells Stimulate Cells Expressing Foreign Peptides That They Recognize B Cells Present Peptides Derived From Proteins Recognized by Surface Antibody Correlation of Pathogen Location, MHC Presentation and T Cell Effector Function NATURE |VOL 391 | 22 JANUARY 1998 Natural Killer (NK) Cells Prevent Evasion of CTL Immunity by Downregulation of MHC Class I MHC Molecules Killer inhibitory receptors- KIR interact with MHC and prevent the NK cells from killing target cells HIV Can Evade This Immune Response Too Questions to Consider How do B cells and T cells see antigen? How does a T cells distinguish between whether a foreign antigen is being presented to recruit help or because the cell is infected? Why do some T cells kill and others provide help?