Cover -- Title page -- Copyright page -- Contents -- List of Contributors -- Volume 1 -- SECTION 1: History/Introduction -- Introduction -- CHAPTER 1: A Brief History of Clinical Organ Transplantation -- Introduction -- The concept of transplant surgery -- Transplant biology -- Early clinical implementation -- The modern era of immune management -- Ethical challenges -- Summary -- References -- SECTION 2: Transplantation Biology -- Immunology -- CHAPTER 2: An Overview of Physiologic Immunity -- Introduction -- Generalized protective barriers and defense factors -- Tissues and organs of the immune system -- Cells of the innate and adaptive immune system -- Innate immune cells -- Granulocytes -- Natural killer (NK) cells -- Mononuclear phagocytes -- Adaptive immune cells -- T-cell immunobiology -- CD8+ T cells -- CD4+ T cells -- Need for APC costimulation for T-cell activation -- The cytokine milieu and Th-cell polarization -- T-cell plasticity -- B-cell immunobiology -- B-cell activation -- The complement system -- Cytokines -- Structural features and categories (families) of cytokines -- The importance of cytokines -- Synergistic and antagonistic interactions -- Stimulatory and inhibitory properties of cytokines -- Redundancy and pleiotropy -- Immunological tolerance -- T-cell central tolerance -- T-cell peripheral tolerance -- B-cell central tolerance -- B-cell peripheral tolerance -- Immunological memory -- T-cell memory -- B-cell memory -- Summary -- Acknowledgments -- References -- CHAPTER 3: Transplant Antigens: A Brief History of HLA -- Introduction -- Early investigations -- HLA and disease -- HLA and transplantation -- HLA antibodies -- Summary -- References -- CHAPTER 4: Transplant Antigen Biology -- Introduction -- Genetics of the major histocompatibility complex (MHC) -- MHC class I -- MHC class II -- MHC class III.

Nature of HLA polymorphism -- Human diversity in HLA repertoire -- HLA nomenclature -- HLA epitopes and the structural basis of cross-reactivity -- Structure and function of HLA molecules -- HLA class I molecular structure -- HLA class II molecular structure -- Structural basis of peptide binding to HLA class I and class II molecules -- Antigen processing and presentation -- Differential expression of HLA class I and class II molecules -- HLA Class Ib molecules -- HLA-mediated signal transduction -- Killer cell immunoglobulin-like receptors (KIR) -- Non-HLA transplant antigens -- Anti-MICA antibodies -- Summary -- Acknowledgments -- References -- CHAPTER 5: Cellular Mechanisms of Adaptive Immunity -- Introduction -- T-cell recognition of alloantigens: Direct, semidirect, and indirect presentation -- Structural recognition of alloantigens by the TCR -- T-cell costimulation and differentiation -- Innate immune signals that influence T-cell responses -- Where are T cells primed after transplantation? -- Effector phase of the alloimmune response: T cells go to the graft -- Effector T cells: Th1, Th2, Th17, and cytotoxic T cells -- Therapeutic implications -- Summary -- Acknowledgments -- References -- CHAPTER 6: Humoral Mechanisms of Adaptive Immunity -- Introduction -- Antibodies -- Antigens -- Complement -- Complement regulation -- Cells -- Types of humoral rejection -- Hyperacute rejection -- Acute rejection -- Chronic rejection -- Accommodation and tolerance -- Summary -- References -- CHAPTER 7: Innate Immunity -- Introduction -- The innate immune system -- Dendritic cells -- Monocytes and macrophages -- Natural killer cells -- Innate sensors -- Complement -- Innate responses to transplants -- Ischemia reperfusion injury (IRI) -- Acute rejection -- Chronic rejection -- Graft acceptance or tolerance -- Summary -- Acknowledgments -- References.

CHAPTER 8: Mechanisms of Immune Regulation -- Introduction -- Cell death -- Central deletion of alloantigen reactive T cells -- Peripheral deletion of alloantigen reactive T cells-activation-induced cell death or immune exhaustion -- Deletion of alloantigen reactive B cells -- Anergy -- T-cell anergy -- B-cell anergy -- Immunoregulation -- Regulatory T cells -- Regulatory B cells -- Dendritic cells -- Myeloid-derived suppressor cells -- Regulatory macrophages -- Ignorance -- Summary -- Acknowledgments -- References -- CHAPTER 9: The Spectrum of Alloimmunity, Heterologous Immunity, and Relevant Autoimmunity -- Introduction -- The spectrum of alloreactivity -- Lymphocytes as effectors of alloimmunity following transplantation -- The T-cell repertoire and its recognition of pathogens and alloantigens -- Impact of T-cell precursor frequency on T-cell behavior -- The molecular basis of alloreactivity -- Heterologous immunity: Interactions of pathogen exposure and alloreactivity -- Evidence for alloreactivity among memory -- Heterologous immunity and the generation of alloreactive T-cell memory -- Existence of alloreactive memory as a result of TCR cross-reactivity -- Specific donor/recipient combination impacts degree of alloreactive T-cell memory -- Impact of bystander activation on allospecific immunity and graft rejection -- Aging and alloreactive immune competence -- Impact of pre-existing autoimmunity on alloreactivity -- Increased alloreactivity as a result of cross-reactive autoreactive T cells or autoantibody -- Therapeutic interventions targeting alloreactive and autoreactive T-cell memory -- Summary -- References -- CHAPTER 10: Fundamental Concepts Regarding Graft Injury and Regeneration: Tissue Injury, Tissue Quality, and Recipient Factors -- Introduction and definitions -- Population lessons-causes and consequences of delayed graft function.

AKI probably does not program late graft deterioration -- Role of the interaction of donor age with recipient age and the ECD paradox -- Biology of aging is not linear -- Experimental models -- Molecular changes associated with AKI in human kidney transplants -- Post-transplant biopsies -- Implantation biopsies -- Some key issues in AKI -- Does inflammation increase/extend injury? -- Does injury increase immunogenicity and either TCMR or ABMR? -- Aging and somatic cell senescence in relation to organ injury -- Is somatic cell senescence a factor in organ survival? -- Can the somatic cell senescence mechanisms be bypassed or treated by drugs? -- Clinical treatment of AKI -- Are the AKI biomarkers useful in the clinic? -- Therapeutics of AKI: Lessons from failure -- Management of high-risk early allograft dysfunction -- Summary -- References -- CHAPTER 11: Mechanisms of Allograft Tolerance -- Introduction -- Conceptual considerations -- Chimerism -- Depletion -- Costimulation blockade -- Regulation -- B cells -- Summary -- References -- CHAPTER 12: Xenoimmunity -- Introduction -- Rejection of porcine vascularized xenografts -- Hyperacute xenograft rejection -- Acute humoral xenograft rejection -- Role of innate immune cells -- Dysregulated coagulation -- Chronic xenograft rejection -- Rejection of porcine islet xenografts -- The instant blood-mediated inflammatory reaction -- Acute cellular rejection of pig islet xenografts -- The role of αGal in pig islet xenograft rejection -- Strategies to protect pig islet xenografts -- Rejection of other types of porcine xenograft -- Neuronal cell xenografts -- Corneal xenografts -- Reducing the immunosuppressive burden -- Induction of accommodation -- Induction of tolerance -- Graft-mediated (local) immunosuppression -- Limitations of the pig-to-NHP model -- Summary -- References -- Experimental Transplantation.

CHAPTER 13: In Vitro Models of Alloreactivity -- Introduction -- Stimulation of alloreactive T-cell proliferation -- Presentation of alloantigens to T cells -- Analysis of alloreactive precursor frequencies -- Naïve versus memory T-cell proliferation to alloantigens -- Skewed functional development of alloreactive T cells in vitro -- Summary -- References -- CHAPTER 14: Small Animal Models of Transplantation -- Introduction -- Evolution of solid organ transplant models in rodent models -- Availability of strains -- Models of alloimmune injury: acute injury -- Acute cellular rejection -- Acute antibody-mediated injuries -- BK polyomavirus nephropathy -- Models of alloimmune injury: "chronic" injury -- Kidney chronic injury -- Cardiac vasculopathy -- Vessel allografts-an alternative model for accelerated arteriosclerosis? -- Bronchiolitis obliterans syndrome and lung allografts -- The toxicity of immunosuppressive agents -- Small animal models of transplantation tolerance -- Limitations of small animal models in tolerance studies -- Transplant tolerance in small animals -- Peripheral transplantation tolerance -- Role of the graft microenvironment in tolerance -- Ischemia-reperfusion injury -- History of cold preservation -- Cold ischemic injury -- Pathophysiology of IRI -- The immune response of IRI -- Targeting IRI -- Tissue repair after renal IRI -- The limitations of existing animal models of IRI -- Xenotransplantation -- Choice of species -- Immunological barriers to transplantation -- Cell-mediated xenotransplant rejection -- Prospects for xenotransplantation -- Summary -- References -- CHAPTER 15: Large Animal Models of Transplantation -- Introduction -- Why use large animals? -- Common large animal models -- Canine models in transplantation -- Porcine models in transplantation -- Studies of organ allograft tolerance.

NHP models in transplantation.