Basic Immunology of the Mouse (and Human) Nicholas P. Restifo, MD October 19, 2015.
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Transcript of Basic Immunology of the Mouse (and Human) Nicholas P. Restifo, MD October 19, 2015.
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Basic Immunology of the Mouse (and Human)
Nicholas P. Restifo, MD
October 19, 2015
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Life started on earth about 3.5 billion years ago:mammals are a ‘recent’ development
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Meet your great, great~50M-grandfather
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Figure 8-1
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Schematic Diagram Of The CD8 and CD4 Coreceptors
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How T cell receptors, peptides and MHC molecules fit together
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Schematic map of the human and mouse MHC superloci
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Nomenclature of major histocompatibility complex (MHC)
Mouse
Human
Kb
Location (locus)
Strain designation
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Naming MHC molecules is easy
All MHC molecules in this C57BL/6 mouse are called b
All MHC molecules in this BALB/c mouse are called d
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CD8+ T cell
CD4+ T cell
Tumor cell
AntigenPresenting
Cell
TumorAntigen
What do T cells “see?”
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T-cell recognition of antigens is MHC restricted
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Figure 3-22
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Pathways of antigen processing and presentation
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TCR-peptide-MHC Crystal Structure
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Figure 4-11The germline organization of the human
T-cell receptor and β loci
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The numbers of human T-cell receptor gene segments and the sources of T-cell receptor diversity compared with those of immunoglobulins
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Adoptive cell transfer (ACT) in mouse and man
Tumor isestablished
time
Ablate host immune system
Adoptively transfer T cells
Add vaccine and cytokine support
Tumor regression?
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‘TIL’-based adoptive immunotherapy
t
t
T
Infusion of tumour-specific T cells into
patient
T Fragmentation of
tumour mass
t
Activation and selection of T cells
T cell growth factors (such as IL-2)T cell growth factors
(such as IL-2)
Add T cell growth factors (such as IL-2)
tChemotherapy+/- irradiation
Restifo, NP, et al,Nat Rev Immunol,
April, 2012
Expansion of tumour-specific T cell populations
T
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Survival of patients with metastatic melanoma treated with adoptive cell transfer therapy and IL-2
93 patients treated with adoptive transfer of TIL: 9/13/2000-8/30/2009Dudley, J Clin Oncol, 2008; Rosenberg, Clin Cancer Res, 2011.
Median follow-up time 79 months (n=93)
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