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Lecture Outline:
Lecture Outline:
Lecture Outline:
Lecture Outline:
Lecture Outline:
Lecture Outline:
Lecture Outline:
Lecture Outline:
Lecture Outline:
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  • 1. February 27, 2009: Penny Morel (4-0343, morel@pitt.edu) T CELL DEVELOPMENT 1) The stages of T lymphocyte development 2) Generation of a functional T cell receptor 3) Intra-thymic positive selection 4) Intra-thymic negative selection. 5) Development of regulatory T cells in the thymus Reading: Immunobiology Textbook: Sections 7-7 – 7-22. Central tolerance: Learning self-control in the thymus. Hogquist et al. Nature Rev. Immunol. 5:772, 2005
  • 2. March 20, 2009: Penny Morel (4-0343, morel@pitt.edu) INITIATION OF THE IMMUNE RESPONSE 1) Organization of the immune system at rest - the role of chemokines and chemokine receptors 2) The role of antigen in determining the immune response 3) Structure and physiology of the responding lymph node. How does antigen get to the lymph node 4) Development of the specific T cell response – the role of dendritic cells. Dendritic cell subsets and maturation status 5) Consequences of activation – IL-2 production and T cell expansion Reading: Immunobiology textbook: Sections A1-A4, 7-23 – 7-25; 7-29; 8:1-8:15 Antigen presentation to naive CD4 T cells in the lymph node Itano AA and Jenkins MK. Nature immunol. 4:733, 2003 Visualizing the first 50hr of a primary immune responses to a soluble antigen Catron et at. Immunity 21:341, 2004
  • 3. March 23, 2009 Penny Morel (4-0343, morel@pitt.edu) T helper cell subsets 1) Role of DCs in determining Th ccll effector function in the periphery 2) Th cell subsets: Th1, Th2, Th3, Th17 and Tr1 cells 3) Cytokines that drive Th1 differentiation a) IL-12 b) IFN-γ 4) Cytokines that drive Th17 differentiation a) TGF-β + IL-6 a) IL-23 5) Cytokines that drive Th2 differentiation IL-4 6) Other factors that influence Th subset differentiation antigen dose and costimulatory molecules 7) Th3 cells and regulatory T cells a) role of cytokines, IL-10 and TGF-β b) role of local factors c) Functions of regulatory T cells Reading : Immunobiology textbook: Sections 8-11-8-20, 10-1 – 10-7, 14-1 – 14-7 Th17: An effector CD4 T cell lineage with regulatory T cell ties. Weaver CT et al. Immunity 24:677, 2006 Development in Motion: Helper T cells at work. Reiner SL. Cell 129:23, 2007
  • 4. March 27, 2009 Penny Morel (4-0343, morel@pitt.edu) T CELL-B CELL INTERACTION and GERMINAL CENTERS 1) B cells capture antigen and present it to T cells Where does it take place? 2) B cell activation requires T cell help 3) T cell cytokines influence Ig class switching 4) Germinal center reaction 5) Activated B cells undergo somatic hypermutation role of follicular dendritic cells Reading: Immunobiology textbook Section 9-1 – 9-13 Germinal center organization and cellular dynamics Allen CD et al Immunity 27:190, 2007
  • 5. March 30, 2009 Penny Morel (4-0343, morel@pitt.edu) T CELL-MACROPHAGE INTERACTIONS 1) What are macrophages good for? intracellular organisms 2) Th1 cells activate macrophages role of interferon-gamma and TNF-α 3) What do activated macrophages do? – importance of IFN-γ 4) Alternative activation of macrophages by Th2 cells – IL-10, IL-13 Reading : Immunobiology Textbook Sections 8-31 – 8-33; 13-19 Alternative activation of macrophages. Gordon S. Nature Rev. Immunol. 3:23, 2003
  • 6. April 3, 2009 Penny Morel (4-0343, morel@pitt.edu) Ig Isotypes and Fc Receptors 1) Distribution and function of immunoglobulin isotypes 2) What is an Fc receptor and where is it expressed? 3) FcR are multimolecular complexes 4) Functions of the FcεRI in mast cells and eosinophils 5) Cell activation via FcγR - the power of the ITAM 6) Inhibition of cell activation via FcγR - but the ITIM is king! 7) FcRn and IgG transport Reading: Immunobiology textbook: Sections 9-14 to 9-25 Fcγ Receptors: Old Friends and New Family Members Nimmerjahn F and JV Ravetch. Immunity 24:19, 2006
  • 7. January 21, 2009 Penny Morel (4-0343, morel@pitt.edu) NK Cells 1. Introduction 2. NK cell specificity 3. Function of NK cell receptors 4. NK cell function in immunity to viruses and tumors 5. Regulatory role of NK cells Paper to be discussed: Dendritic Cells Prime Natural Killer Cells by trans-Presenting Interleukin 15 Mathias Lucas, William Schachterle, Karin Oberle, Peter Aichele, Andreas Diefenbach Immunity 26: 503 – 517, 2007 Reading: Immunobiology: 2-30 – 2-33 MHC class I molecules and kirs in human history, health and survival Peter Parham Nature Reviews Immunology 5:201-214, 2005
  • 8. March 4, 2009 Penny Morel (4-0343, morel@pitt.edu) T cell repertoire selection 1) T cell positive selection: role of peptide, cell surface molecules and signaling complexes 2) Negative selection of self reactive T cells: role of peptide and mechanisms 3) Generation of regulatory T cells in the thymus Paper to be discussed: Regulation of CD8+ T Cell Development by Thymus-Specific Proteasomes. Murata S. et al. Science 316:1349, 2007 Reading: Positive and negative selection of T cells. Starr TK et al, Annu. Rev Immunol. 21:139, 2003 A central role for central tolerance. Kyewski B et al. Annu Rev Immunol. 24:571, 2006
  • 9. April 22, 2009 Penny Morel (4-0343, morel@pitt.edu) REGULATION OF THE IMMUNE RESPONSE 1) Levels of immune regulation: Homeostatic control initiation of immune response peripheral tolerance to self antigens termination of immune responses 2) Peripheral tolerance to self antigens: Anergy induction immune deviation regulatory/suppressor T cells 3) Termination of immune response: role of CTLA-4 AICD Antigen removal Paper to be discussed: FOXP3 Controls Regulatory T Cell Function through Cooperation with NFAT. Wu et al Cell 126:375-387, 2006 Reading: Immunobiology Textbook: Sections: 7-25 – 7-29; 8-20; 10-1 – 10-12; 14-1 - 14-7; Regulatory T cells and infection: a dangerous necessity, Belkaid Y, Nature Rev. Immunol. 7:875, 2007

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