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TABLE OF CONTENTS Preface Acknowledgments Author Biographies PART I: BASIC IMMUNOLOGY CHAPTER 1: PERSPECTIVE ON IMMUNITY AND IMMUNOLOGY A. WHAT IS IMMUNOLOGY? B. WHY HAVE AN IMMUNE SYSTEM AND WHAT DOES IT DO? C. TYPES OF IMMUNE RESPONSES: INNATE AND ADAPTIVE D. WHAT IS ¿INFECTION¿? E. PHASES OF HOST DEFENSE F. HOW ARE ADAPTIVE AND INNATE IMMUNITY RELATED? G. LEUKOCYTES: CELLULAR MEDIATORS OF IMMUNITY H. WHERE DO IMMUNE RESPONSES OCCUR? I. CLINICAL IMMUNOLOGY: WHEN THE IMMUNE SYSTEM DOES NOT WORK PROPERLY CHAPTER 2: INTRODUCTION TO THE IMMUNE RESPONSE A. GENERAL FEATURES OF INNATE IMMUNITY B. GENERAL FEATURES OF ADAPTIVE IMMUNITY I. SPECIFICITY II. IMMUNOLOGIC MEMORY III. DIVERSITY IV. TOLERANCE V. DIVISION OF LABOR C. ELEMENTS OF IMMUNITY COMMON TO THE INNATE AND ADAPTIVE RESPONSES I. INTRODUCING CYTOKINES II. INTRODUCING INTRACELLULAR SIGNALING D. ELEMENTS OF IMMUNITY EXCLUSIVE TO THE ADAPTIVE RESPONSE I. ANTIGENS VERSUS IMMUNOGENS II. INTRODUCING SPECIFIC ANTIGEN RECOGNITION: B CELLS III. INTRODUCING SPECIFIC ANTIGEN RECOGNITION: T CELLS AND THE MAJOR HISTOCOMPATIBILITY COMPLEX IV. INTRODUCING ANTIGEN PROCESSING V. INTRODUCING CORECEPTORS AND COSTIMULATORY MOLECULES VI. INTRODUCING B CELL EFFECTOR FUNCTIONS VII. INTRODUCING T CELL EFFECTOR FUNCTIONS VIII. INTRODUCING PRIMARY AND SECONDARY ADAPTIVE IMMUNE RESPONSES CHAPTER 3: CELLS AND TISSUES OF THE IMMUNE RESPONSE A. CELLS OF THE IMMUNE SYSTEM I. TYPES OF HEMATOPOIETIC CELLS II. CELLS OF THE MYELOID LINEAGE III. CELLS OF THE LYMPHOID LINEAGE IV. DENDRITIC CELLS V. HEMATOPOIESIS B. LYMPHOID TISSUES I. PRIMARY LYMPHOID TISSUES II. SECONDARY LYMPHOID TISSUES CHAPTER 4: INNATE IMMUNITY A. MECHANISMS OF INNATE IMMUNITY I. ANATOMIC AND PHYSIOLOGICAL BARRIERS TO INFECTION II. CELLULAR INTERNALIZATION MECHANISMS THAT FIGHT INFECTION III. INFLAMMATION AS A RESPONSE TO INFECTION OR INJURY B. PATTERN RECOGNITION IN INNATE IMMUNITY I. PATTERN RECOGNITION BY PRRs II. PATTERN RECOGNITION BY RECEPTORS OF NK, NKT, AND ?? T CELLS III. PATTERN RECOGNITION BY SOLUBLE MOLECULES CHAPTER 5: B CELL RECEPTOR STRUCTURE AND EFFECTOR FUNCTION A. THE STRUCTURE OF IMMUNOGLOBULINS I. GENERAL STRUCTURAL PROPERTIES OF IMMUNOGLOBULIN MOLECULES II. CHANGES TO Ig STRUCTURE ASSOCIATED WITH FUNCTION III. THE B CELL ANTIGEN RECEPTOR COMPLEX IV. Fc RECEPTORS B. EFFECTOR FUNCTIONS OF ANTIBODIES I. NEUTRALIZATION II. OPSONIZATION III. ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY IV. COMPLEMENT-MEDIATED CLEARANCE OF ANTIGEN C. IMMUNOGLOBULIN ISOTYPES IN BIOLOGICAL CONTEXT I. NATURAL DISTRIBUTION OF ANTIBODIES IN THE BODY II. MORE ABOUT IMMUNOGLOBULIN M III. MORE ABOUT IMMUNOGLOBULIN D IV. MORE ABOUT IMMUNOGLOBULIN G V. MORE ABOUT IMMUNOGLOBULIN A VI. MORE ABOUT IMMUNOGLOBULIN E CHAPTER 6: THE NATURE OF ANTIGEN¿ANTIBODY INTERACTION A. THE NATURE OF B CELL IMMUNOGENS I. WHAT MOLECULES CAN FUNCTION AS IMMUNOGENS? II. IMMUNOGENS IN THE HUMORAL RESPONSE III. PROPERTIES OF Td IMMUNOGENS B. B CELL¿T CELL COOPERATION IN THE HUMORAL IMMUNE RESPONSE I. THE DISCOVERY OF B¿T COOPERATION: RECONSTITUTION EXPERIMENTS II. THE MOLECULAR BASIS OF B¿T COOPERATION: THE HAPTEN¿CARRIER EXPERIMENTS III. HAPTEN¿CARRIER COMPLEXES IN VIVO IV. THE RATIONALE FOR LINKED RECOGNITION C. THE MECHANICS OF ANTIGEN¿ANTIBODY INTERACTION I. IDENTIFICATION OF B EPITOPE STRUCTURAL REQUIREMENTS II. WHERE ANTIBODY AND ANTIGEN INTERACT: THE COMPLEMENTARITY-DETERMINING REGIONS III. FORCES AT WORK IN SPECIFIC ANTIGEN¿ANTIBODY BINDING IV. AFFINITY AND AVIDITY OF ANTIBODY BINDING V. ANTIBODY CROSS-REACTIVITY CHAPTER 7: EXPLOITING ANTIGEN¿ANTIBODY INTERACTION A. SOURCES OF ANTIBODIES I. ANTISERA II. HYBRIDOMAS AND MONOCLONAL ANTIBODIES B. TECHNIQUES BASED ON IMMUNE COMPLEX FORMATION I. CROSS-LINKING AND THE FORMATION OF IMMUNE COMPLEXES II. TECHNIQUES BASED ON THE PRECIPITIN REACTION III. TECHNIQUES BASED ON AGGLUTINATION IV. TECHNIQUES BASED ON COMPLEMENT FIXATION C. ASSAYS BASED ON UNITARY ANTIGEN¿ANTIBODY PAIR FORMATION I. GENERAL CONCEPTS II. DETECTION OF ANTIGEN BY TAG ASSAYS III. ISOLATION AND CHARACTERIZATION OF ANTIGEN USING ANTIBODIES CHAPTER 8: THE IMMUNOGLOBULIN GENES A. CHROMOSOMAL ORGANIZATION OF Ig GENES I. Ig LOCI II. GENERAL STRUCTURE OF Ig LOCI III. FINE STRUCTURE OF LIGHT CHAIN GENES IV. FINE STRUCTURE OF HEAVY CHAIN GENES B. Ig GENE REARRANGEMENT I. THE ROLE OF V(D)J RECOMBINATION II. VDJ JOINING IN THE Igh LOCUS III. VJ JOINING IN THE Igl AND Igk LOCI IV. PRODUCTIVITY TESTING V. ALLELIC EXCLUSION VI. KAPPA/LAMBDA EXCLUSION VII. INTRODUCING KNOCKOUT MICE C. MOLECULAR MECHANISMS OF Ig GENE REARRANGEMENT I. HOW DO VDJ SEGMENTS JOIN IN THE RIGHT ORDER? THE RSS II. THE RECOMBINASE ENZYMES: RAG-1 AND RAG-2 III. SYNAPSIS, SIGNAL JOINTS, AND CODING JOINTS IV. MUTATIONS OF V(D)J RECOMBINATION D. ANTIBODY DIVERSITY GENERATED BY GENE REARRANGEMENT I. MULTIPLICITY OF GERM-LINE GENE SEGMENTS II. COMBINATORIAL DIVERSITY III. JUNCTIONAL DIVERSITY IV. HEAVY¿LIGHT Ig CHAIN PAIRING E. CONTROL SEQUENCES IN THE Ig LOCI I. ENHANCERS II. DNA BINDING MOTIFS AND NUCLEAR TRANSCRIPTION FACTORS CHAPTER 9: THE HUMORAL RESPONSE: B CELL DEVELOPMENT AND ACTIVATION A. THE MATURATION PHASE OF B CELL DEVELOPMENT I. PRO-B CELLS II. PRE-B CELLS B. THE DIFFERENTIATION PHASE OF B CELL DEVELOPMENT I. THE THREE-SIGNAL MODEL OF B CELL ACTIVATION II. CELLULAR INTERACTIONS DURING B CELL ACTIVATION III. PROLIFERATION AND SOMATIC HYPERMUTATION IV. AFFINITY MATURATION V. ISOTYPE SWITCHING: GENERATING FUNCTIONAL DIVERSITY VI. DIFFERENTIATION OF MEMORY B CELLS AND PLASMA CELLS CHAPTER 10: MHC: THE MAJOR HISTOCOMPATIBILITY COMPLEX A. HISTORICAL NOTES I. DISCOVERY OF THE MHC II. MHC INVOLVEMENT IN T CELL RECOGNITION III. ELUCIDATION OF THE ANTIGEN-PRESENTING FUNCTION OF THE MHC B. GENERAL ASPECTS OF THE MHC IN HUMANS AND MICE I. OVERVIEW OF THE MHC PROTEINS II. OVERVIEW OF THE MHC LOCI III. INTRODUCING MULTIPLICITY AND POLYMORPHISM IN THE MHC LOCI IV. INTRODUCING HAPLOTYPES C. MHC PROTEINS I. MHC CLASS I PROTEINS II. MHC CLASS II PROTEINS D. MHC GENES I. DETAILED ORGANIZATION OF THE H-2 COMPLEX II. DETAILED ORGANIZATION OF THE HLA COMPLEX E. EXPRESSION OF MHC MOLECULES I. THE SXY¿CIITA REGULATORY SYSTEM II. TNF- AND IFN?-INDUCED EXPRESSION OF MHC CLASS I III. EXPRESSION OF MHC CLASS Ib GENES IV. OTHER REGULATORY PATHWAYS GOVERNING MHC CLASS II GENE EXPRESSION F. PHYSIOLOGY OF THE MHC I. POLYMORPHISM AND THE BIOLOGICAL ROLE OF THE MHC II. ALLOREACTIVITY III. MHC AND IMMUNE RESPONSIVENESS IV. INTRODUCING MHC AND DISEASE PREDISPOSITION CHAPTER 11: ANTIGEN PROCESSING AND PRESENTATION A. EXOGENOUS OR ENDOCYTIC ANTIGEN PROCESSING PATHWAY I. HISTORICAL NOTES II. CELLS THAT CAN FUNCTION AS APCs III. MECHANISM OF ANTIGEN PROCESSING BY APCs IV. FACTORS AFFECTING ANTIGEN PROCESSING AND PRESENTATION BY APCs B. ENDOGENOUS OR CYTOSOLIC ANTIGEN PROCESSING PATHWAY I. HISTORICAL NOTES II. CELLS THAT CAN FUNCTION AS TARGET CELLS III. MECHANISM OF ANTIGEN PROCESSING BY TARGET C. OTHER PATHWAYS OF ANTIGEN PRESENTATION I. CROSS-PRESENTATION II. ANTIGEN PRESENTATION BY NON-CLASSICAL AND MHC-LIKE MOLECULES CHAPTER 12: THE T CELL RECEPTOR: STRUCTURE OF ITS PROTEINS AND GENES A. HISTORICAL NOTES I. INTRODUCTION II. DISCOVERY OF THE GENES AND PROTEINS OF THE TCR III. A SECOND T CELL RECEPTOR B. THE STRUCTURE OF T CELL RECEPTOR PROTEINS I. OVERVIEW C. GENOMIC ORGANIZATION OF THE TCR AND CD3 LOCI I. THE TCR? LOCUS II. THE TCR? LOCUS III. THE TCR? LOCUS IV. THE TCR? LOCUS V. THE CD3 GENES D. EXPRESSION OF TCR GENES I. MECHANISM OF V(D)J RECOMBINATION IN THE TCR LOCI II. TCR GENE TRANSCRIPTION AND PROTEIN ASSEMBLY E. DEVELOPMENTAL ASPECTS OF V(D)J RECOMBINATION IN THE TCR LOCI I. TCR? LOCUS REARRANGEMENT II. TCR? LOCUS REARRANGEMENT III. TCR? AND ? LOCUS REARRANGEMENT IV. TCR LOCUS KNOCKOUT MICE F. GENERATION OF DIVERSITY OF THE T CELL RECEPTOR REPERTOIRE I. MULTIPLICITY OF GERMLINE GENE SEGMENTS II. COMBINATORIAL DIVERSITY III. JUNCTIONAL DIVERSITY IV. CHAIN PAIRING G. REGULATION OF TCR GENE EXPRESSION H. STRUCTURE AND FUNCTION OF THE CD3 COMPLEX I. CD3 PROTEIN STRUCTURE II. FUNCTIONS OF THE CD3 COMPLEX III. CD3 KNOCKOUT MICE I. THE CD4 AND CD8 CORECEPTORS I. DISCOVERY OF CD4 AND CD8 II. WHAT IS A ¿CORECEPTOR¿? III. STRUCTURE OF CD4 IV. STRUCTURE OF CD8 V. FUNCTIONS OF CD4 AND CD8 J. PHYSICAL ASPECTS OF THE INTERACTION OF THE TCR WITH ANTIGEN I. STUDYING TCR¿PEPTIDE¿MHC INTERACTION II. BINDING AFFINITY OF TCR?? FOR ITS LIGAND III. X-RAY CRYSTAL STRUCTURE OF T CELL RECEPTORS CHAPTER 13: T CELL DEVELOPMENT A. T CELL DEVELOPMENT IN THE BONE MARROW B. T CELL DEVELOPMENT IN THE THYMUS I. OVERVIEW II. DN (TN) PHASE (TCR-CD4-CD8-) III. THE DP PHASE (CD4+CD8+) IV. THE SP PHASE: CD4/CD8 LINEAGE COMMITMENT C. MATURE SP THYMOCYTES IN THE PERIPHERY D. T CELL DEVELOPMENT IN AN EMBRYOLOGICAL CONTEXT CHAPTER 14: T CELL ACTIVATION A. BRINGING T CELLS AND APCs TOGETHER I. L-SELECTIN II. LFA-1 B. SIGNAL ONE: BINDING OF PEPTIDE¿MHC TO THE TCR I. MODELS OF TCR TRIGGERING II. FORMATION OF THE IMMUNOLOGICAL SYNAPSE (SMAC) III. TCR DOWNREGULATION IV. TCR SIGNAL TRANSDUCTION C. SIGNAL TWO: COSTIMULATION I. CD28-B7 II. ICOS-ICOSL III. PD1-PDL1/PDL2 IV. ???/B7-H3 V. THE TNF/TNFR-RELATED COSTIMULATORY MOLECULES VI. CD27/CD70 VII. OTHER MINOR COSTIMULATORY CONTACTS D. SIGNAL THREE: CYTOKINES I. THE IL-2/IL-2R SYSTEM II. CONTROL OF TRANSCRIPTION OF THE IL-2 GENE CHAPTER 15: T CELL DIFFERENTIATION AND EFFECTOR FUNCTION A. Th CELL DIFFERENTIATION AND EFFECTOR FUNCTION I. WHAT ARE ¿Th1 AND Th2 RESPONSES¿? II. PROCESS OF Th CELL DIFFERENTIATION III. ACTIVATION OF EFFECTOR Th1 AND Th2 CELLS IV. EFFECTOR FUNCTIONS OF Th CELLS B. Tc CELL DIFFERENTIATION AND CTL EFFECTOR FUNCTION I. GENERATION OF EFFECTOR CTLs II. MECHANISMS OF TARGET CELL DESTRUCTION BY CD8+ CTLs C. COMPARISON OF NAIVE AND EFFECTOR T CELLS I. TRAFFICKING AND ADHESION II. ACTIVATION III. FUNCTIONS AND PRODUCTS D. ELIMINATION OF EFFECTOR T CELLS I. ACTIVATION-INDUCED CELL DEATH (AICD) II. T CELL EXHAUSTION E. MEMORY T CELLS I. GENERATION OF MEMORY T CELLS II. MEMORY T CELL MARKERS III. MEMORY T CELL DISTRIBUTION IV. MEMORY T CELL ACTIVATION V. MEMORY T CELL DIFFERENTIATION AND EFFECTOR FUNCTION VI. MEMORY T CELL LIFE SPAN CHAPTER 16: IMMUNE TOLERANCE IN THE PERPHERY A. CONTEXT OF PERIPHERAL TOLERANCE I. HISTORICAL NOTES II. EVIDENCE FOR PERIPHERAL SELF-TOLERANCE MECHANISMS B. T CELL PERIPHERAL SELF-TOLERANCE I. THE IMPORTANCE OF DCs AND ¿DANGER SIGNALS¿ II. MECHANISMS OF PERIPHERAL T CELL SELF-TOLERANCE C. B CELL PERIPHERAL SELF-TOLERANCE I. DEMONSTRATION OF B CELL ANERGY II. MECHANISMS OF PERIPHERAL B CELL TOLERANCE D. REGULATORY T CELLS I. CD4+CD25+ Treg CELLS II. Th3 AND Tr1 CELLS III. CD8+ Ts CELLS IV. INFECTIOUS TOLERANCE AND LINKED SUPPRESSION E. EXPERIMENTAL TOLERANCE I. CHARACTERISTICS OF EXPERIMENTAL TOLERANCE II. CHARACTERISTICS OF TOLEROGENS III. DEGREE AND PERSISTENCE OF TOLERANCE IV. ¿SPLIT¿ TOLERANCE V. SPECIAL SITUATIONS CHAPTER 17: CYTOKINES AND CYTOKINE RECEPTORS A. OVERVIEW I. GENERAL PROPERTIES OF CYTOKINES B. FUNCTION, PRODUCTION, AND RECEPTORS OF CYTOKINES I. THE INTERFERONS II. THE INTERLEUKINS III. TNK AND RELATED MOLECULES IV. TRANSFORMING GROWTH FACTORS V. HEMOTOPOIETIC GROWTH FACTORS VI. CHEMOKINES AND THEIR RECEPTORS C. CYTOKINES AND THEIR RECEPTORS IN PHYSIOLOGICAL CONTEXT CHAPTER 18: BRIDGING INNATE AND ADAPTIVE IMMUNITY: NK, ?? T, AND NKT Cells A. NATURAL KILLER (NK) CELLS I. HISTORICAL NOTES II. WHAT AND WHERE ARE NATURAL KILLER CELLS? III. FUNCTIONS OF NK CELLS IV. ACTIVATORY AND INHIBITORY NK RECEPTORS V. NK CELL DEVELOPMENT, INHIBITORY RECEPTOR EXPRESSION, AND TOLERANCE B. ?? T CELLS I. WHAT ARE ?? T CELLS? II. ANTIGEN RECOGNITION III. ACTIVATION IV. EFFECTOR FUNCTIONS AND MEMORY V. DEVELOPMENT C. NKT CELLS I. WHAT ARE NKT CELLS? II. ANTIGEN RECOGNITION AND ACTIVATION III. EFFECTOR FUNCTIONS IV. DEVELOPMENT CHAPTER 19: COMPLEMENT A. HISTORICAL NOTES B. OVERVIEW OF THE COMPLEMENT SYSTEM I. SOURCES OF SOLUBLE COMPLEMENT COMPONENTS II. THREE PATHWAYS OF COMPLEMENT ACTIVATION III. AMPLIFICATION AND SENSITIVITY IV. CONTROL V. COMPLEMENT SYSTEM NOMENCLATURE C. THE CLASSICAL PATHWAY OF COMPLEMENT ACTIVATION I. C1 II. C4 III. C2 IV. C3 D. THE ALTERNATIVE PATHWAY OF COMPLEMENT ACTIVATION I. C3 AND FACTOR B II. FACTOR D AND THE ALTERNATIVE C3 CONVERTASE III. PROPERDIN AND THE ALTERNATIVE C5 CONVERTASE E. THE LECTIN PATHWAY OF COMPLEMENT ACTIVATION I. MBL II. CRP F. TERMINAL COMPONENTS OF THE COMPLEMENT CASCADE AND FORMATION OF THE MAC I. C5 II. C6 AND C7 III. C8 AND C9 IV. TARGETS OF THE MAC G. REGULATION OF THE COMPLEMENT SYSTEM I. REGULATION OF THE CLASSICAL PATHWAY II. REGULATION OF THE ALTERNATIVE PATHWAY III. REGULATION OF THE LECTIN PATHWAY IV. REGULATION OF TERMINAL COMPONENTS H. COMPLEMENT RECEPTORS AND THEIR BIOLOGICAL ROLES I. CR1 II. CR2 III. CR3 IV. CR4 V. C1q ¿RECEPTORS¿ VI. RECEPTORS FOR C3a, C4a, AND C5a I. COMPLEMENT DEFICIENCIES I. DEFICIENCY OF C1, C4, OR C2 II. DEFICIENCY OF C3 III. DEFICIENCY OF ALTERNATIVE PATHWAY COMPONENTS IV. DEFICIENCY OF LECTIN PATHWAY COMPONENTS V. DEFICIENCY OF TERMINAL COMPONENTS (C5¿C9) VI. DEFICIENCY OF REGULATORY PROTEINS VII. DEFICIENCY OF COMPLEMENT RECEPTORS J. NEW ROLES FOR COMPLEMENT? CHAPTER 20 A. MUCOSAL IMMUNITY I. GALT II. BALT/NALT III. IMMUNE RESPONSES IN THE MAJOR MALT IV. IMMUNE RESPONSES IN THE MINOR MALT B. CUTANEOUS IMMUNITY I. COMPONENTS OF SALT II. IMMUNE RESPONSES IN SALT CHAPTER 21: MUCOSAL AND CUTANEOUS IMMUNITY A. OVERVIEW I. REPRISE OF THE ANIMAL KINGDOM II. FORCES SHAPING THE EVOLUTION OF IMMUNE RECOGNITION B. ELEMENTS OF INNATE IMMUNITY I. ANATOMICAL AND PHYSIOLOGICAL BARRIERS II. INNATE IMMUNE RESPONSE CELLS AND THEIR RECOGNITION STRUCTURES III. CYTOKINES IV. PATHOGEN ELIMINATION C. ELEMENTS OF ADAPTIVE IMMUNITY I. LYMPHOID TISSUES II. BCR III. MHC IV. TCR PART II: CLINICAL IMMUNOLOGY CHAPTER 22: IMMUNITY TO PATHOGENS A. IMMUNITY TO EXTRACELLULAR BACTERIA I. WHAT ARE EXTRACELLULAR BACTERIA? II. EFFECTOR MECHANISMS III. EVASION STRATEGIES B. IMMUNITY TO INTRACELLULAR BACTERIA I. WHAT ARE INTRACELLULAR BACTERIA? II. EFFECTOR MECHANISMS III. EVASION STRATEGIES C. IMMUNITY TO VIRUSES I. WHAT ARE VIRUSES? II. EFFECTOR MECHANISMS III. EVASION STRATEGIES D. IMMUNITY TO PARASITES I. WHAT ARE PARASITES? II. EFFECTOR MECHANISMS III. EVASION STRATEGIES E. IMMUNITY TO FUNGI I. WHAT ARE FUNGI? II. EFFECTOR MECHANISMS III. EVASION STRATEGIES F. THE MYSTERIOUS PRIONS CHAPTER 23: VACCINES AND CLINICAL IMMUNIZATION A. VACCINATION: PUBLIC HEALTH SUCCESSES AND CHALLENGES B. HISTORICAL NOTES C. GENERAL PRINCIPLES OF VACCINE DESIGN I. BIOLOGICAL PURPOSE OF A VACCINE II. VACCINE EFFICACY AND SAFETY D. TYPES OF VACCINES I. LIVE, ATTENUATED VACCINES II. KILLED VACCINES III. TOXOIDS IV. SUBUNIT VACCINES V. PEPTIDE VACCINES VI. RECOMBINANT VECTOR DNA VACCINES VII. ¿NAKED DNA¿ VACCINES VIII. ANTI-IDIOTYPIC VACCINES E. FACTORS AFFECTING VACCINATION I. SCHEDULING OF VACCINE ADMINISTRATION AND BOOSTING II. ROUTES OF VACCINE ADMINISTRATION III. ADJUVANTS AND DELIVERY VEHICLES F. PROPHYLACTIC VACCINES I. ANTHRAX II. CHOLERA III. DIPHTHERIA, TETANUS, AND PERTUSSIS IV. HEMOPHILUS INFLUENZAE TYPE b V. HEPATITIS VI. HEPATITIS B VII. INFLUENZA VIRUS VIII. JAPANESE B ENCEPHALITIS IX. MEASLES, MUMPS, AND RUBELLA X. MENINGOCOCCUS XI. PLAGUE XII. POLIO XIII. RABIES XIV. STREPTOCOCCUS PNEUMONIAE XV. TUBERCULOSIS XVI. TYPHOID FEVER XVII. VARICELLA ZOSTER (CHICKEN POX) XVIII. VARIOLA XIX. YELLOW FEVER G. THE ¿DARK SIDE¿ OF VACCINES I. ADVERSE EFFECTS OF VACCINES II. FAILURE TO VACCINATE AND OPPOSITION TO VACCINATION H. PROPHYLACTIC VACCINES OF THE FUTURE I. PASSIVE IMMUNIZATION J. THERAPEUTIC VACCINES I. VACCINES TO COMBAT TUMORS II. VACCINES TO CURE CHRONIC VIRAL DISEASES III. VACCINES TO MITIGATE INDIRECT EFFECTS OF INFECTIOUS DISEASE IV. VACCINES TO MITIGATE AUTOIMMUNITY V. VACCINES TO MITIGATE ALLERGY VI. VACCINES TO SUPPRESS FERTILITY VII. VACCINES TO SUPPRESS ADDICTION CHAPTER 24: PRIMARY IMMUNODEFICIENCIES A. GENERAL CONCEPTS I. DIAGNOSIS OF PIs II. TREATMENT OF PIs III. FOCUS OF PI RESEARCH B. PRIMARY IMMUNODEFICIENCIES DUE TO DEFECTS IN ADAPTIVE IMMUNE RESPONSES I. COMBINED IMMUNODEFICIENCIES II. T CELL-SPECIFIC IMMUNODEFICIENCIES III. B CELL-SPECIFIC IMMUNODEFICIENCIES IV. ADAPTIVE IMMUNODEFICIENCIES DUE TO DEFECTS IN DNA REPAIR V. LYMPHOPROLIFERATIVE IMMUNODEFICIENCY SYNDROMES VI. OTHER ADAPTIVE IMMUNODEFICIENCIES C. PRIMARY IMMUNODEFICIENCIES DUE TO DEFECTS IN THE INNATE IMMUNE RESPONSE I. IMMUNODEFICIENCIES AFFECTING PHAGOCYTE RESPONSES II. COMPLEMENT DEFICIENCIES CHAPTER 25: HIV AND ACQUIRED IMMUNODEFICIENCY SYNDROME A. WHAT IS HIV? I. OVERVIEW OF THE HIV-1 LIFE CYCLE II. OVERVIEW OF HIV STRUCTURE B. STRUCTURE AND FUNCTION OF HIV PROTEINS I. VIRAL PROTEINS DERIVED FROM THE gag GENE II. VIRAL PROTEINS DERIVED FROM THE pol GENE III. VIRAL PROTEINS DERIVED FROM THE env Gene IV. REGULATORY PROTEINS V. ACCESSORY PROTEINS C. HIV INFECTION AND AIDS I. CLINICAL VIEW OF HIV INFECTION II. MOLECULAR EVENTS UNDERLYING HIV INFECTION D. THE IMMUNE RESPONSE DURING HIV INFECTION I. Th RESPONSES II. CTL RESPONSES III. ANTIBODY RESPONSES IV. CYTOKINES V. CEM-15 (APOBEC3G) VI. NK Cells VII. COMPLEMENT E. HOST FACTORS INFLUENCING THE COURSE OF HIV INFECTION I. RESISTANCE TO HIV INFECTION II. CLINICAL COURSE VARIABILITY F. EPIDEMIOLOGY AND SOCIOLOGY OF HIV INFECTION I. TRANSMISSION OF HIV II. EPIDEMIOLOGY III. SOCIETAL AND ECONOMIC IMPACT OF AIDS G. ANIMAL MODELS OF AIDS I. PRIMATE MODELS OF AIDS II. MOUSE MODELS OF AIDS H. HIV VACCINES I. BARRIERS TO HIV VACCINE DEVELOPMENT II. EXPERIMENTAL AIDS VACCINES IN ANIMALS III. EXPERIMENTAL AIDS VACCINES IN HUMANS IV. PASSIVE IMMUNIZATION I. TREATMENT OF HIV INFECTION WITH ANTI-RETROVIRAL DRUGS I. PROTEASE INHIBITORS II. NUCLEOSIDE RT INHIBITORS III. NON-NUCLEOSIDE RT INHIBITORS IV. FUSION INHIBITORS V. IMMUNE RESPONSES AND ANTI-RETROVIRAL THERAPY VI. OTHER DRUG THERAPY ISSUES CHAPTER 26: TUMOR IMMUNOLOGY A. TUMOR BIOLOGY I. WHAT IS A TUMOR AND WHAT IS A CANCER? II. CARCINOGENESIS III. TUMORIGENIC GENETIC ALTERATIONS IV. CARCINOGENS B. IMMUNE RESPONSES TO CANCER I. THE CONCEPT OF IMMUNOSURVEILLANCE II. TUMOR ANTIGENS III. IMMUNE RESPONSES TO TUMOR CELLS IV. HURDLES TO EFFECTIVE ANTI-TUMOR IMMUNITY C. CANCER THERAPY I. RADIATION THERAPY II. CHEMOTHERAPY III. TUMOR HYPOXIA IV. IMMUNOTHERAPY CHAPTER 27: TRANSPLANTATION A. THE MOLECULAR BASIS OF ALLORECOGNITION I. DIRECT ALLORECOGNITION II. INDIRECT ALLORECOGNITION B. MINOR HISTOCOMPATIBILITY ANTIGENS C. TYPES OF CLINICAL REJECTION AND THEIR MECHANISMS I. HYPERACUTE GRAFT REJECTION II. ACUTE GRAFT REJECTION III. CHRONIC GRAFT REJECTION IV. THE ROLE OF CYTOKINES AND CHEMOKINES IN GRAFT REJECTION V. A ROLE FOR TLRs IN GRAFT REJECTION? VI. GRAFT-VERSUS-HOST DISEASE (GvHD) IN SOLID ORGAN TRANSPLANTS D. HLA TYPING I. SEROLOGICAL TECHNIQUES II. TYPING BY CELLULAR RESPONSE: MLR III. TYPING AT THE DNA LEVEL E. IMMUNOSUPPRESSION I. AZATHIOPRINE II. CYCLOSPORINE A III. TACROLIMUS IV. MYCOPHENOLATE MOFETIL V. SIROLIMUS VI. MALONONITRILAMIDES (MNAs) VII. FTY720 VIII. FLUDARABINE IX. ANTI-LYMPHOCYTE ANTIBODIES X. CYTOKINES F. INDUCTION OF GRAFT TOLERANCE I. BONE MARROW MANIPULATION II. THYMIC MANIPULATION III. COSTIMULATORY BLOCKADE IV. REGULATORY T CELLS V. REGULATION BY NKT CELLS VI. TOLEROGENIC DCs VII. CAVEATS G. XENOTRANSPLANTATION I. CHOICE OF SPECIES FOR XENOTRANSPLANTATION II. XENOGRAFT REJECTION III. TRANSMISSION OF ZOONOTIC DISEASES IV. REGULATORY AND LEGAL OBSTACLES V. ETHICAL AND MORAL CONSIDERATIONS H. BLOOD TRANSFUSIONS I. ALLOREACTIVITY IN BLOOD TRANSFUSIONS II. ENSURING THE SAFETY OF THE BLOOD SUPPLY I. HEMATOPOIETIC CELL TRANSPLANTATION (HCT) I. GRAFT REJECTION IN HCT II. GRAFT-VERSUS-HOST DISEASE (GvHD) IN HCT III. GRAFT-VERSUS-LEUKEMIA (GvL) EFFECT IV. BENEFICIAL EFFECTS OF ALLOGENEIC NK CELLS V. INFECTION CONTROL J. GENE THERAPY IN TRANSPLANTATION CHAPTER 28: ALLERY AND HYPERSENSITIVITY A. TYPE I HYPERSENSITIVITY: IMMEDIATE OR IGE-MEDIATED I. WHAT IS TYPE I HS? II. MECHANISMS UNDERLYING TYPE I HS III. EXAMPLES OF TYPE I HS IV. ROLES OF Fc?R AND IGE IN TYPE I HS V. ALLERGEN BIOLOGY VI. DIAGNOSIS AND THERAPY OF TYPE I HS B. TYPE II HYPERSENSITIVITY: DIRECT AB-MEDIATED CYTOTOXICITY I. WHAT IS TYPE II HS? II. MECHANISMS UNDERLYING TYPE II HS III. EXAMPLES OF TYPE II HS: CYTOTOXICITY AGAINST MOBILE CELLS IV. EXAMPLES OF TYPE II HS: CYTOTOXICITY AGAINST FIXED TISSUES C. TYPE III HYPERSENSITIVITY: IMMUNE COMPLEX-MEDIATED INJURY I. WHAT IS TYPE III HS? II. MECHANISM UNDERLYING TYPE III HS III. EXAMPLES OF TYPE III HS D. TYPE IV HYPERSENSITIVITY: DELAYED-TYPE OR CELL-MEDIATED HYPERSENSITIVITY I. WHAT IS TYPE IV HS? II. CHRONIC DTH REACTIONS III. CONTACT HYPERSENSITIVITY (CHS) IV. HYPERSENSITIVITY PNEUMONITIS (HP) CHAPTER 29: AUTOIMMUNE DISEASE A. OVERVIEW I. HISTORICAL NOTES II. WHAT CHARACTERIZES AN AUTOIMMUNE DISEASE? III. OUR APPROACH TO DISCUSSING AUTOIMMUNITY B. EXAMPLES OF HUMAN AUTOIMMUNE DISEASES I. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) II. RHEUMATOID ARTHRITIS (RA) III. RHEUMATIC FEVER (RF) IV. TYPE 1 DIABETES MELLITUS (T1DM) V. MULTIPLE SCLEROSIS (MS) VI. ANKYLOSING SPONDYLITIS (AS) VII. SJÖGREN SYNDROME (SS) VIII. AUTOIMMUNE THYROIDITIS IX. AUTOIMMUNE THROMBOCYTOPENIC PURPURA X. SCLERODERMA (SD) XI. MYASTHENIA GRAVIS (MG) XII. KAWASAKI DISEASE (KD) XIII. POLYMYOSITIS (PM) XIV. GUILLAIN¿BARRÉ SYNDROME (GBS) XV. PSORIASIS (PS) XVI. ANTI-PHOSPHOLIPID SYNDROME (APS) XVII. INFLAMMATORY BOWEL DISEASE (IBD): CROHN¿S DISEASE (CD) AND ULCERATIVE COLITIS (UC) XVIII. PEMPHIGUS (PG) XIX. GOODPASTURE¿S SYNDROME (GS) XX. IMMUNODYSREGULATION, POLYENDOCRINOPATHY, ENTEROPATHY X-LINKED (IPEX) SYNDROME C. ANIMAL MODELS OF AUTOIMMUNE DISEASE I. NZB/W F1 MICE II. MRL/lpr AND gld MICE III. NOD MICE IV. Scurfy MICE V. THYMECTOMY OF NEONATAL MICE VI. IBD MODELS VII. EXPERIMENTAL AUTOIMMUNE ENCEPHALITIS (EAE) VIII. COLLAGEN-INDUCED ARTHRITIS (CIA) IX. EXPERIMENTAL AUTOIMMUNE MYASTHENIA GRAVIS (EAMG) X. EXPERIMENTAL AUTOIMMUNE THYROIDITIS (EAT) XI. EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU) XII. EXPERIMENTAL AUTOIMMUNE MYOCARDITIS (EAM) XIII. OTHER POTENTIAL AID MODELS D. DETERMINANTS OF AUTOIMMUNE DISEASE I. GENETIC PREDISPOSITION II. ENVIRONMENTAL TRIGGERS III. HORMONAL INFLUENCES IV. REGIONAL/ETHNIC DIFFERENCES E. MECHANISMS UNDERLYING AID I. PATHOGEN-RELATED MECHANISMS II. INHERENT DEFECTS IN IMMUNE SYSTEM CELLS III. ALTERATIONS TO CYTOKINE EXPRESSION IV. DEFECTS IN THE COMPLEMENT SYSTEM V. EPITOPE SPREADING F. THERAPY OF AID I. CONVENTIONAL TREATMENTS II. IMMUNOTHERAPEUTICS G. RELATIONSHIP BETWEEN AID AND CANCER CHAPTER 30: HEMATOPOIETIC CANCERS A. OVERVIEW OF HEMATOPOIETIC CANCER BIOLOGY I. WHAT ARE HEMATOPOIETIC CANCERS? II. HEMATOPOIETIC CANCER CARCINOGENESIS B. TERMS USED IN CLINICAL ASSESSMENT AND TREATMENT OF HC C. LEUKEMIAS I. ACUTE MYELOID LEUKEMIA (AML) II. CHRONIC MYELOGENOUS LEUKEMIA (CML) III. ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) IV. CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) V. OTHER LEUKEMIAS D. PLASMA CELL DYSCRASIAS I. MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS) II. WALDENSTRÖM¿S MACROGLOBULINEMIA (WM) III. MYELOMA E. LYMPHOMAS I. HODGKIN¿S LYMPHOMA (HL) II. NON-HODGKIN¿S LYMPHOMAS Appendix: CD Molecules Cumulative Glossary Index
Library of Congress Subject Headings for this publication:
Immunology.
Immunity.
Immune System.
Immunity.
Immune System Diseases.