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