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Antigen Processing & Presentation
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MHC antigens codominate
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Mixed Lymphocyte Reaction
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Self MHC Restriction of T Cells
CD4+ & CD8+ cells Antigen must be in cleft of MHC MHC polymorphism ~500 antigens/cleft Self MHC Restriction of T Cells
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Haplotype Restricted Cytotoxicity
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“Antigen Pulse” “Antigen pulsed” macrophages
T helper (CD4+) cells can only be stimulated by macrophages with the same MHC Class II Cytotoxic (CD8+) T cells can only be stimulated by macrophages with the same MHC Class I “Antigen Pulse”
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T Cell Activation
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MHC I: Biological function
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MHC II: Biological function
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MHCII: Biologogical function (2)
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MHCII: Function 50
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Role of Antigen Presenting Cells
Immunize with native protein Boost with native protein B cell & T cell response Boost with denatured antigen T cell response only 2 different mechanisms APC for cell mediated & humoral Role of Antigen Presenting Cells
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Antigen Presenting Cells
Professional APC Dendritic cells Macrophages B Cells Non Professional APC Fibroblasts Glial cells Thymic epithelial cells Vascular endothelial cells
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Lot MHC-II co-stimulate activate T helpers Dendritic cells
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Macrophages Engulf microbe first co express with B7 membrane protein
digest antigen bind to MHC-II co express with B7 membrane protein Macrophages
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Constitutively express MHC-II
activated then express B7 B Cells
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Two Presentation Pathways
Cytosolic- MHC-I endogenous antigens Endocytic - MHC-II exogenous antigens Two Presentation Pathways
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Cytosolic Pathway: Endogenous Antigens
Ubiquitin & ATP Bind to peptide proteasomes Bind ubiquitin peptide transport Assembly of peptides in MHC-I Rough Endoplasmic reticulum Export to membrane Cytosolic Pathway: Endogenous Antigens
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TAP proteins Transports associated with Antigen Processing
TAP-1 TAP-2 Transfer Peptides from proteosome to RER TAP proteins
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TAP-1 TAP-2
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Calnexin & MHC-1
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Assembly in RER TAP-1 TAP-2 transport into ER Bind to Calnexin MHC-I
Add peptide to MHC-I Release calnexin Transport to Gogli Assembly in RER
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Endogenous Pathway MHC-i
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Endocytic Pathway: Exogenous Antigens
endocytic vesicles peptide transport Assembly of peptides in MHC-II Endocytic Pathway: Exogenous Antigens
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Endocytic Route From Outside- phagocytosis From Inside Fuse
Make MHC-II Bind Invariant chain CLIP- digests invariant chain Fuse MHC-II & clipped I & peptide peptide displaces clipped I chain Endocytic Route
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Invariant chain & MHC-II
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Exogenous Pathway MHC-II
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THANKS
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