Immunology / 3rd ed.

Table Of Contents:
Foreword xvii
Preface xix
PART I Introduction 1(84)

Overview of the Immune System 3(22)

Historical Perspective 3(3)

Discovery of Humoral and Cellular Immunity 5(1)

Early Theories of Immunity 6(1)

Components of Immunity 6(1)

Innate (Nonspecific) Immunity 6(6)

Anatomic Barriers 7(1)

Physiologic Barriers 8(1)

Endocytic and Phagocytic Barriers 9(1)

Barriers Created by the Inflammatory Response 10(2)

Acquired (Specific) Immunity 12(10)

Cells of the Immune System 12(1)

B Lymphocytes 12(1)

T Lymphocytes 12(1)

Antigen-Presenting Cells 13(1)

Functions of Humoral and Cell-Mediated Immune Responses 13(1)

Recognition of Antigen by B and T Lymphocytes 14(2)

Generation of Lymphocyte Specificity and Diversity 16(1)

Role of the Major Histocompatibility Complex 16(1)

Processing and Presentation of Antigens 17(1)

Clonal Selection of Lymphocytes 17(3)

Cellular Interactions Required for Generation of Immune Responses 20(1)

Activation and Proliferation of T Helper Cells 20(1)

Generation of the Humoral Response 21(1)

Generation of the Cell-Mediated Response 21(1)

Summary 22(1)

References 22(1)

Study Questions 23(2)

Experimental Systems 25(22)

Experimental Animal Models 25(4)

Inbred Strains 26(2)

Adoptive-Transfer Systems 28(1)

SCID Mice and SCID-Human Mice 28(1)

Cell-Culture Systems 29(3)

Primary Lymphoid Cell Cultures 29(1)

Cloned Lymphoid Cell Lines 29(2)

Hybrid Lymphoid Cell Lines 31(1)

Recombinant DNA Technology 32(5)

Restriction-Endonuclease Cleavage of DNA 32(1)

Cloning of DNA Sequences 32(1)

Cloning Vectors 32(1)

Cloning of cDNA and Genomic DNA 33(1)

Selection of DNA Clones 34(1)

Southern Blotting 35(1)

Northern Blotting 35(1)

Polymerase Chain Reaction 36(1)

Analysis of DNA Regulatory Sequences 37(2)

DNA Footprinting 38(1)

Gel-Shift Analysis 39(1)

CAT Assay 39(1)

Gene Transfer into Mammalian Cells 39(4)

Transfer of Cloned Genes into Cultured Cells 39(1)

Transfer of Cloned Genes into Mouse Embryos 40(1)

Transgenic Mice 40(1)

Gene-Targeted Knock-Out Mice 41(2)

Summary 43(1)

References 44(1)

Study Questions 44(3)

Cells and Organs of the Immune System 47(38)

Hematopoiesis 47(12)

Hematopoietic Growth Factors 49(2)

Regulation of Hematopoiesis 51(2)

Programmed Cell Death 53(1)

Regulatory Abnormalities and Leukemia 54(1)

Enrichment of Hematopoietic Stem Cells 55(2)

Clinical Uses of Pluripotent Stem Cells 57(1)

Transplantation of Bone Marrow 58(1)

Gene Therapy with Engineered Stem Cells 58(1)

Immune-System Cells 59(11)

Lymphoid Cells 59(2)

B Lymphocytes 61(1)

T Lymphocytes 62(1)

Null Cells 63(1)

Mononulear Cells 64(1)

Phagocytosis 65(1)

Antimicrobial and Cytotoxic Activities 65(1)

Antigen Processing and Presentation 66(1)

Secretion of Factors 67(1)

Granulocytic Cells 67(1)

Neutrophils 67(1)

Eosinophils 68(1)

Basophils 68(1)

Mast Cells 68(1)

Dendritic Cells 69(1)

Organs of the Immune System 70(10)

Primary Lymphoid Organs 71(1)

Thymus 71(2)

Bone Marrow 73(1)

Lymphatic System 74(1)

Secondary Lymphoid Organs 74(1)

Lymph Nodes 75(2)

Spleen 77(1)

Mucosal-Associated Lymphoid Tissue 78(1)

Cutaneous-Associated Lymphoid Tissue 78(2)

Summary 80(1)

References 81(1)

Study Questions 82(3)
PART II Generation of B-Cell and T-Cell Responses 85(226)

Antigens 87(20)

Immunogenicity Versus Antigenicity 87(1)

Factors That Influence Immunogenicity 88(4)

Contribution of the Immunogen to Immunogenicity 88(1)

Foreignness 88(1)

Molecular Size 88(1)

Chemical Composition and Heterogeneity 89(1)

Susceptibility to Antigen Processing and Presentation 90(1)

Contribution of the Biological System to Immunogenicity 90(1)

Genotype of the Recipient Animal 90(1)

Immunogen Dosage and Route of Administration 91(1)

Adjuvants 91(1)

Epitopes 92(8)

Properties of B-Cell Epitopes 92(6)

Properties of T-Cell Epitopes 98(2)

Haptens and the Study of Antigenicity 100(1)

Mitogens 101(3)

Summary 104(1)

References 105(1)

Study Questions 105(2)

Immunoglobulins: Structure and Function 107(36)

Basic Structure of Immunoglobulins 108(1)

Immunoglobulin Sequencing Studies 109(2)

Role of Multiple Myeloma 109(1)

Light-Chain Sequencing 110(1)

Heavy-Chain Sequencing 110(1)

Immunoglobulin Fine Structure 111(10)

Immunoglobulin Domains 111(2)

Variable-Region Domains 113(2)

CDRs and Antigen Binding 115(2)

Conformational Changes Induced By Antigen Binding 117(1)

Constant-Region Domains 118(1)

CH1 and CL Domains 118(1)

Hinge Region 119(1)

Other Constant-Region Domains 120(1)

B-Cell Receptor 121(1)

Antigenic Determinants on Immunoglobulins 122(1)

Isotypic Determinants 122(1)

Allotypic Determinants 122(1)

Idiotypic Determinants 123(1)

Immunoglobulin Classes 123(6)

Immunoglobulin G (IgG) 123(1)

Immunoglobulin M (IgM) 123(2)

Immunoglobulin A (IgA) 125(2)

Immunoglobulin E (IgE) 127(2)

Immunoglobulin D (IgD) 129(1)

The Immunoglobulin Superfamily 129(2)

Monoclonal Antibodies 131(8)

Formation and Selection of Hybrid Cells 132(1)

Production of Monoclonal Antibodies 132(1)

Clinical Uses for Monoclonal Antibodies 133(2)

Engineered Monoclonal Antibodies 135(1)

Chimeric and Hybrid Monoclonal Antibodies 136(2)

Monoclonal Antibodies Constructed From IG-Gene Libraries 138(1)

Catalytic Monoclonal Antibodies (Abzymes) 138(1)

Summary 139(1)

References 140(1)

Study Questions 140(3)

Antigen-Antibody Interactions 143(22)

Strength of Antigen-Antibody Interactions 144(3)

Antibody Affinity 144(2)

Antibody Avidity 146(1)

Cross-Reactivity 147(1)

Precipitation Reactions 148(6)

Precipitation Reactions in Fluids 148(2)

Precipitation Reactions in Gels 150(1)

Radial Immunodiffusion (Mancini Method) 150(1)

Double Immunodiffusion (Ouchterlony Method) 150(2)

Immunoelectrophoresis 152(2)

Agglutination Reactions 154(2)

Hemagglutination 154(1)

Bacterial Agglutination 155(1)

Passive Agglutination 155(1)

Agglutination Inhibition 155(1)

Radioimmunoassay 156(1)

Enzyme-Linked Immunosorbent Assay 156(2)

Indirect ELISA 157(1)

Sandwich ELISA 157(1)

Competitive ELISA 157(1)

Western Blotting 158(1)

Immunofluorescence 159(1)

Immunoelectron Microscopy 160(2)

Summary 162(1)

References 162(1)

Study Questions 162(3)

Organization and Expression of Immunoglobulin Genes 165(30)

Genetic Model Compatible with lg Structure 166(3)

Germ-Line and Somatic-Variation Models 166(1)

Dryer and Bennett Two-Gene Model 166(2)

Early Verification of the Dryer and Bennett Hypothesis 168(1)

Multigene Organization of lg Genes 169(2)

λ-Chain Multigene Family 169(1)

k-Chain Multigene Family 169(1)

Heavy-Chain Multigene Family 170(1)

Variable-Region Gene Rearrangements 171(7)

V-J Rearrangements in Light-Chain DNA 171(1)

V-D-J Rearrangements in Heavy-Chain DNA 171(1)

Mechanism of Variable-Region DNA Rearrangements 172(1)

Recombination Signal Sequences 172(1)

Enzymatic Joining of Gene Segments 173(2)

Experimental Identification of Rag-1 and Rag-2 Genes 175(1)

Deffects in Ig-Gene Rearrangement 176(1)

Productive and Nonproductive Rearrangements 176(1)

Allelic Exclusion 177(1)

Generation of Antibody Diversity 178(6)

Multiple Germ-Line V,D, and J Gene Segments 179(1)

Combinatorial V-J and V-D-J Joining 179(1)

Junctional Flexibility 180(1)

P-Nucleotide Addition 181(1)

N-Region Nucleotide Addition 181(1)

Somatic Hypermutation 182(2)

Association of Heavy and Light Chains 184(1)

Class Switching among Constant-REgion Genes 184(1)

Expression of lg Genes 184(5)

Differential RNA Processing of Heavy-Chain Primary Transcripts 184(1)

Expression of Membrane-Bound or Secreted Immunoglobulin 185(2)

Simultaneous Expression of IGM and IgD 187(1)

Synthesis, Assembly, and Secretion of Immunoglobulins 188(1)

Regulation of lg-Gene Transcription 189(1)

Effect of DNA Rearrangement on Transcription 190(1)

Inhibition of lg-Gene Expression in T Cells 190(1)

Summary 190(1)

References 191(1)

Study Questions 192(3)

B-Cell Maturation, Activation, And Differentiation 195(28)

B-Cell Maturation 196(4)

Bone Marrow Environment 197(1)

Ig-Gene Rearrangements 197(1)

Pre-B Cell Receptor 198(1)

Selection of Immature Self-Reactive B Cells 199(1)

Negative Selection 199(1)

Rescue By Editing of Light-Chain Genes 200(1)

B-Cell Activation and Proliferation 200(11)

Thymus-Dependent and Thymus-Independent Antigens 200(2)

Origin of Activating Signals 202(1)

Transduction of Activating Signals 203(2)

B-Cell Coreceptor Complex 205(1)

Role of TH Cells in Humoral Response 205(1)

Formation of T-B Conjugate 206(1)

Contact-Dependent Help Mediated by CD40/CD40L Interaction 207(1)

Progression Signals Induced by TH-Cell Cytokines 207(1)

Negative Selection of Mature, Self-Reactive B Cells 208(3)

In Vivo Sites for Induction of Humoral Response 211(2)

B-Cell Differentiation 213(5)

Affinity Maturation 213(1)

Role of Somatic Hypermutation 213(1)

Antigen Selection of High-Affinity Centrocytes 214(1)

Class Switching 215(1)

Generation of Plasma Cells and Memory B Cells 216(2)

Regulation of B-Cell Development 218(1)

Summary 219(1)

References 220(1)

Study Questions 221(2)

Major Histocompatibility Complex 223(26)

General Organization and Inheritance of the MHC 224(3)

Location and Function of MHC Regions 224(1)

MHC Haplotypes 225(1)

Congenic MHC Mouse Strains 226(1)

MHC Molecules and Genes 227(11)

Structure of Class I Molecules 228(1)

Structure of Class II Molecules 229(2)

Organization of Class I and II Genes 231(1)

Peptide Binding by MHC Molecules 231(2)

Class I MHC-Peptide Interaction 233(1)

Class II MHC-Peptide Interaction 234(1)

Polymorphism of Class I and II Molecules 235(1)

Class III Molecules 236(2)

Detailed Genomic Map of MHC Genes 238(2)

Map of Class I MHC 239(1)

Map of Class II MHC 239(1)

Map of Class III MHC 239(1)

Cellular Distribution of MHC Molecules 240(1)

Regulation of MHC Expression 241(1)

MHC and Immune Responsiveness 241(3)

Determinant-Selection Model 243(1)

Holes-in-the-Repertoire Model 244(1)

MHC and Susceptibility to Infectious Disease 244(1)

Summary 245(1)

References 246(1)

Study Questions 246(3)

Antigen Processing and Presentation 249(14)

Self-MHC Restriction of T Cells 250(1)

Role of Antigen-Presenting Cells 251(2)

Early Evidence for the Necessity of Antigen Processing 251(1)

Cells That Function in Antigen Presentation 252(1)

Evidence for Two Processing and Presentation Pathways 253(2)

Endogenous Antigens: The Cytosolic Pathway 255(3)

Peptide Generation by Cytosolic Proteasomes 255(1)

Peptide Transport from the Cytosol to the RER 256(1)

Assembly of Peptides with Class I MHC Molecules 257(1)

Overview of Class I Endogenous Pathway 257(1)

Exogenous Antigens: The Endocytic Pathway 258(1)

Peptide Generation in Endocytic Vesicles 258(1)

Transport of Class II MHC Molecules to Endocytic Vesicles 258(1)

Assembly of Peptides with Class II MHC Molecules 259(1)

Overview of Class II Exogenous Pathway 259(1)

Clinical Applications 259(1)

Summary 260(1)

References 260(1)

Study Questions 261(2)

T-Cell Receptor 263(22)

Early Studies of the T-Cell Receptor 264(1)

Self-MHC Restriction of the T-cell Receptor 264(1)

Isolation of T-Cell Receptors 264(1)

Structure of T-Cell Receptors 265(1)

Organization and Rearrangement of TCR Genes 266(7)

Identifying and Cloning the TCR Genes 266(1)

TCR Multigene Families 267(1)

Variable-Region Gene Rearrangements 268(1)

Mechanism of TCR DNA Rearrangements 269(1)

Allelic Exclusion of TCR Genes 270(1)

Structure of Rearranged TCR Genes 270(1)

Generation of TCR Diversity 271(2)

T-Cell Receptor Complex: TCR-CD3 273(1)

T-Cell Accessory Membrane Molecules 274(3)

CD4 and CD8 Coreceptors 275(1)

Other Accessory Membrane Molecules 276(1)

Ternary TCR-Peptide-MHC Complex 277(3)

Evidence That TCR Alone Recognizes Peptide-MHC Complex 277(1)

Interactions Involved in Forming Ternary Complex 278(1)

Affinity of TCR for Peptide-MHC Complexes 279(1)

Influence of Peptide on Topology of Ternary Complex 280(1)

Alloreactivity of T cells 280(1)

Summary 281(1)

References 282(1)

Study Questions 282(3)

T-Cell Maturation, Activation, and Differentiation 285(26)

T-Cell Maturation 285(10)

Pre-T Cell Receptor 286(1)

T-Cell Developmental Pathways 286(2)

Thymic Selection of the T-Cell Repertoire 288(1)

Positive Selection 289(1)

Negative Selection 289(1)

Experimental Evidence for Postive Selection 290(1)

Experimental Evidence for Negative Selection 291(1)

Unsolved Questions Regarding Thymic Selection 292(3)

TH-Cell Activation 295(9)

TCR-Coupled Signaling Pathways 297(2)

The Co-stimulatory Signal 299(1)

Altered Peptide Ligands as Antagonists or Partial Agonists 300(1)

Clonal Expansion Versus Clonal Anergy 300(1)

Superantigen-Induced T-Cell Activation 300(4)

T-Cell Differentiation 304(2)

Generation of Effector and memory Cells 304(1)

Co-stimulatory Differences among Antigen-Presenting Cells 305(1)

Peripheral γδT Cells 306(1)

Distribution of γδ T Cells 306(1)

Ligands Recognized by γδ T Cells 306(1)

Functions of γδ T Cells 306(1)

Summary 307(1)

References 308(1)

Study Questions 309(2)
PART III Immune Effector Mechanisms 311(130)

Cytokines 313(22)

Properties of Cytokines 313(8)

General Structure of Cytokines 316(1)

Function of Cytokines 316(5)

Cytokine Receptors 321(4)

General Structure of Cytokine Receptors 321(1)

Subfamilies of Class I Cytokine Receptors 321(2)

IL-2 Receptor 323(1)

Signal Transduction Mediated by Cytokine Receptors 324(1)

Cytokine Antagonists 325(1)

Cytokine Secretion by TH1 and TH2 Subsets 326(3)

Development of TH1 and TH2 Subsets 327(1)

Cytokine Cross-Regulation 327(1)

Role of TH1/TH2 Balance in Determining Disease Outcomes 327(2)

Cytokine-Related Diseases 329(2)

Bacterial Septic Shock 329(1)

Bacterial Toxic Shock and Similar Diseases 329(1)

Lymphoid and Myeloid Cancers 330(1)

Chagas' Disease 330(1)

Therapeutic Uses of Cytokines and Their Receptors 331(1)

Summary 332(1)

References 333(1)

Study Questions 333(2)

The Complement System 335(22)

The Complement Components 335(1)

Complement Activation 336(9)

Classical Pathway 336(3)

Alternative Pathway 339(3)

Terminal Sequence: Formation of Membrane-Attack Complex 342(3)

Regulation of the Complement System 345(4)

Biological Consequences of Complement Activation 349(4)

Cell Lysis 349(2)

Inflammatory Response 351(1)

Opsonization of Antigen 352(1)

Viral Neutralization 352(1)

Solubilization of Immune Complexes 353(1)

Complement Deficiencies 353(1)

Summary 354(1)

References 355(1)

Study Questions 355(2)

Leukocyte Migration and Inflammation 357(22)

Lymphocyte Recirculation 357(1)

Cell-Adhesion Molecules 358(1)

Selection Family 358(1)

Mucin-like Family 358(1)

Integrin Family 358(1)

Immunoglobulin Superfamily 359(1)

Neutrophil Extravasation 359(2)

Lymphocyte Extravasation 361(4)

High-Endothelial Venules (HEVs) 361(1)

Homing of Lymphocytes 361(1)

Naive Lymphocytes 362(1)

Effector and Memory Lymphocytes 363(1)

Adhesion-Molecule Interactions 364(1)

Mediators of Inflammation 365(4)

Chemokines 365(2)

Plasma Enzyme Mediators 367(1)

Kinin System 367(1)

Clotting System 367(1)

Fibrinolytic System 367(1)

Complement System 367(1)

Lipid Inflammatory Mediators 368(1)

Cytokine Inflammatory Mediators 368(1)

The Inflammatory Process 369(6)

Central Role of Neutrophils in Inflammation 369(1)

Acute Inflammatory Response 370(1)

Localized Reponse 370(1)

Systemic Acute-Phase Response 370(3)

Chronic Inflammatory Response 373(1)

Role of IFN-γ and TNF- α 373(2)

Chronic Inflammatory Diseases 375(1)

Anti-Inflammatory Agents 375(1)

Agents That Reduce Leukocyte Extravasation 375(1)

Corticosteroids 376(1)

Nonsteroidal Anti-Inflammatory Drugs 376(1)

Summary 376(1)

References 377(1)

Study Questions 378(1)

Cell-Mediated and Humoral Effector Responses 379(34)

Effector Responses in the Cell-Mediated Branch 380(17)

General Properties of Effector T Cells 380(1)

Activation Requirements 380(1)

Cell-Adhesion Molecules 380(1)

Effector Molecules 381(1)

Direct Cytotoxic Responses 381(1)

CTL-Mediated Cytotoxicity 381(6)

NK Cell-Mediated Cytotoxicity 387(3)

Antibody-Dependent Cell-Mediated Cytotoxicity 390(1)

Experimental Assessment of Cell-Mediated Cytotoxicity 391(2)

Delayed-Type Hypersensitivity 393(1)

Phases of the DTH Response 393(2)

Cytokines Involved in the DTH Reaction 395(1)

Proective Role of the DTH Response 395(1)

Detection of the DTH Reaction 396(1)

Pathologic DTH Responses 397(1)

Effector Responses in the Humoral Branch 397(5)

Primary and Secondary Responses 397(1)

Experimental Assessment of Humoral Immunity 398(1)

Hemolytic Plaque Assays 399(1)

Elispot Assay 399(1)

Humoral Response to Hapten-Carrier Conjugates 400(2)

Regulation of the Immune Effector Response 402(6)

Antigen-Mediated Regulation 403(1)

Antibody-Mediated Suppression 403(1)

Immune Complexes as Regulators 404(1)

Idiotype Regulation: The Network Theory 404(2)

Neuroendocrine Regulation (Neuroimmunomodulation) 406(2)

Summary 408(1)

References 409(1)

Study Questions 410(3)

Hypersensitive Reactions 413(28)

Gell and Coombs Classification 414(1)

IgE-Mediated (Type I) Hypersensitivity 415(15)

Components of Type I Reactions 415(1)

Allergens 415(1)

Reginic Antibody (IgE) 416(1)

Mast Cells and Basophils 417(1)

IgE-Binding Fc Receptors 417(1)

Mechanism of IgE-Mediated Degranulation 418(1)

Receptor Cross-Linkage 419(1)

Intracellular Events Leading to Mast Cell Degranulation 419(1)

Mediators of Type I Reactions 420(1)

Histamine 421(1)

Leukotrienes and Prostaglandins 422(1)

Cytokines 422(1)

Consequences of Type I Reactions 423(1)

Systemic Anaphylaxis 423(1)

Localized Anaphylaxis (Atopy) 424(2)

Late-Phase Reaction 426(1)

Regulation of the Type I Response 426(1)

Detection of Type I Hypersensitivity 427(1)

Therapy for Type I Hypersensitivities 428(2)

Antibody-Mediated Cytotoxic (Type II) Hypersensitivity 430(1)

Transfusion Reactions 430(2)

Hemolytic Disease of the Newborn 432(1)

Drug-Induced Hemolytic Anemia 433

Immune Complex-Mediated (Type III) Hypersensitivity 430(6)

Localized Type III Reactions 434(1)

Generalized Type III Reactions 434(2)

TDTH-Mediated (Type IV) Hypersensitivity 436(1)

Summary 437(1)

References 438(1)

Study Questions 438(3)
PART IV The Immune System in Health and Disease 441(156)

Vaccines 443(16)

Active and Passive Immunization 444(2)

Passive Immunization 444(1)

Active Immunization 445(1)

Designing Vaccines for Active Immunization 446(2)

Whole-Organism Vaccines 448(3)

Attenuated Viral or Bacterial Vaccines 448(2)

Inactivated Viral or Bacterial Vaccines 450(1)

Purified Macromolecules As Vaccines 450(1)

Polysaccharide Vaccines 450(1)

Toxoid Vaccines 451(1)

Recombinant Antigen Vaccines 451(1)

Recombinant Vector Vaccines 451(1)

DNA Vaccines 452(1)

Synthetic Peptide Vaccines 453(1)

Multivalent Subunit Vaccines 454(1)

Anti-Idiotype Vaccines 455(1)

Summary 456(1)

References 457(1)

Study Questions 457(2)

Immune Response to Infectious Diseases 459(26)

Viral Infections 460(7)

Viral Neutralization by Humoral Antibody 460(1)

Cell-Mediated Antiviral Mechanisms 460(1)

Viral Evasion of Host-Defense Mechanisms 461(1)

Influenza 462(1)

Properties of Influenza Virus 462(3)

Host Response to Influenza Infection 465(2)

Bacterial Infections 467(7)

Immune Response to Extracellular and Intracellular Bacteria 467(1)

Bacterial Evasion of Host-Defense Mechanisms 467(3)

Contribution of the Immune Response to Bacterial Pathogenesis 470(1)

Diptheria (Corynebacterium diphtheriae) 470(1)

Tuberculosis (Mycobacterium tuberculosis) 471(2)

Lyme Disease (Borrelia burgdorferi) 473(1)

Protozoan Diseases 474(4)

Malaria (Plasmodium Species) 474(1)

Plasmodium Life Cycle and Pathogenesis of Malaria 474(1)

Host Response to Plasmodium Infection 475(1)

Design of Malaria Vaccines 476(1)

African Sleeping Sickness (Trypanosoma Species) 476(2)

Diseases Caused by Parasitic Worms (Helminths) 478(2)

Summary 480(1)

Refernces 481(1)

Study Questions 482(3)

Autoimmunity 485(22)

Organ-Specific Autoimmune Diseases 485(4)

Diseases Mediated by Direct Cellular Damage 486(1)

Hashimoto's Thyroiditis 486(1)

Autoimmune Anemias 487(1)

Goodpasture's Syndrome 487(1)

Insulin-Dependent Diabetes Mellitus 487(1)

Diseases Mediated by Stimulating or Blocking Antibodies 488(1)

Graves' Disease 488(1)

Myasthenia Gravis 489(1)

Systemic Autoimmune Diseases 489(1)

Systemic Lupus Erythematosus 489(1)

Multiple Sclerosis 490(1)

Rheumatoid Arthritis 490(1)

Reheumatoid Arthritis 490(1)

Animal Models for Autommune Disease 490(2)

Spontaneous Autoimmunity in Animals 490(2)

Experimentally Induced Autoimmunity in Animals 492(1)

Evidence Implicating the CD4+ T Cell, MHC, and TCR in Autoimmunity 492(3)

Role of CD4+ T-Cells and TH1/TH2 Balance 492(1)

Association with the MHC 493(2)

Association with the T-Cell Receptor 495(1)

Proposed Mechanisms for Induction of Autommunity 495(5)

Release of Sequestered Antigens 495(1)

Molecular Mimicry 495(1)

Mimicry Between MBP and Viral Peptides 496(1)

Mimicry Involving Heat-Shock Proteins 497(2)

Inappropriate Expression of Class II MHC Molecules 499(1)

Polyclonal B-Cell Activation 500(1)

Treatment of Autoimmune Diseases 500(3)

Current Therapies 500(1)

Experimental Therapeutic Approaches 500(1)

T-Cell Vaccination 500(1)

Peptide Blockade of MHC Molecules 501(1)

Monoclonal-Antibody Treatment 501(1)

Tolerance Induction by Oral Antigens 502(1)

Summary 503(1)

References 503(1)

Study Questions 504(3)

Immunodeficiency Diseases 507(16)

Phagocytic Deficiencies 507(4)

Reduction in Neutrophil Count 508(1)

Defective Phagocytic Function 508(1)

Adherence Defects 508(2)

Chemotatic Defects 510(1)

Killing Defects 510(1)

Humoral Deficiencies 511(3)

X-Linked Agammaglobulinemia 511(1)

X-Linked Hyper-IgM Syndrome 512(1)

Common Variable Hypogammaglobulinemia 513(1)

Selective Immunoglobulin Deficiencies 514(1)

Cell-Mediated Deficiencies 514(2)

DiGeorge Syndrome (Congenital Thymic Aplasia) 515(1)

Nude Mice 515(1)

Combined Immunodeficiencies 516(3)

Reticular Dysgenesis 516(1)

Bara-Lymphocyte Syndrome 516(1)

Severe Combined Immunodeficiency Disease (SCID) 517(1)

ADA Deficiency and PNP-Deficiency (SCID) 518(1)

SCID Mice and Scid-Human Mice 518(1)

Wiskott-Aldrich Syndrome 519(1)

Complement Deficiencies 519(1)

Summary 519(1)

References 520(1)

Study Questions 520(3)

The Immune System in Aids 523(32)

Discovery of AIDs and Its Causative Agent 523(1)

Human Immunodeficiency Virus (HIV) 524(12)

Relation Between HIV and Other Retroviruses 524(2)

Structure of HIV 526(1)

HIV Infection of Target Cells 526(1)

Entry of Hiv into Cells 527(3)

Integration of Hiv into Host Genome 530(1)

Activation of Hiv Provirus 530(1)

Transmission of Hiv 530(1)

Hiv Genome 531(1)

Factors That Promote Activation of Hiv Provirus 531(2)

Expression of Hiv Proviral Dna 533(1)

Genetic Variation in HIV 533(1)

Role of Immune Response in Emergence of HIV Variants 534(1)

Variation in the Envelope Glycoproteins 534(2)

Diagnosis of HIV Infection and AIDS 536(2)

Serologic Profile of HIV Infection 536(1)

Screening Tests for HIV Infection 537(1)

Clinical Diagnosis of AIDS 537(1)

Destruction of CD4+ T Cells 538(5)

Depletion of HIV-Infected CD4+ T Cells 538(2)

Depletion of Uninfected CD4+ T Cells 540(1)

Destruction Mediated By Anti-GP120 Antibody 540(1)

GP120-Induced Disruption of T-Cell Activation 541(1)

GP120-Stimulated Syncytia Formation 542(1)

Interference with T-Cell Maturation by GP120 543(1)

Immunologic Abnormalities in AIDS 543(4)

Pathologic Changes in Lymph Nodes 543(1)

Reduced Antigen-Specific Responses by TH Cells 543(2)

Ineffective Antibody Response 545(1)

Cytokine Imbalance 545(1)

Decreased DTH Response 546(1)

Impaired CTL Activity 547(1)

Development of an AIDS Vaccine 547(5)

Obstacles to Development of an AIDS Vaccine 548(1)

Experimental AIDS Vaccines 549(1)

Inactivated Whole Viruses 549(1)

Cloned Envelope Clycoproteins 549(1)

Attenulated Viruses 550(1)

Recombinant Viruses Carrying HIV Genes 551(1)

Synthetic Crown-Sequence Peptides 551(1)

Summary 552(1)

References 552(1)

Study Questions 553(2)

Transplantation Immunology 555(18)

Immunologic Basis of Graft Rejection 556(4)

Specificity and Memory of the Rejection Response 556(1)

Role of Cell-Mediated Responses 556(1)

Transplantation Antigens 557(1)

Mechanisms Involved in Graft Rejection 558(1)

Sensitization Stage 559(1)

Effector Stage 560(1)

Clinical Manifestations of Graft Rejection 560(2)

Hyperacute Rejection 560(2)

Acute Rejection 562(1)

Chronic Rejection 562(1)

Tissue Typing 562(1)

General Immunosuppressive Therapy 563(2)

Mitotic Inhibitors 563(1)

Corticosteroids 564(1)

Cyclosporin, A, FK506, and Rapamycin 564(1)

Total Lymphoid Irradiation 564(1)

Specific Immunosuppressive Therapy 565(2)

Monoclonal Antibodies to T-Cell Components or Cytokines 565(1)

Agents That Block the Co-stimulatory Signal 566(1)

Donor-Cell Microchimerism 566(1)

Clinical Transplantation 567(3)

Bone Marrow Transplants 567(1)

Organ Transplants 567(1)

Xenotransplants 568(1)

Transplants to Immunologically Privileged Sites 569(1)

Summary 570(1)

References 570(1)

Study Questions 571(2)

Cancer and the Immune System 573(24)

Cancer: Origin and Terminology 573(1)

Maliganant Transformation of Cells 574(1)

Oncogenes and Cancer Induction 574(5)

Function of Oncogenes 576(1)

Induction of Cellular Proliferation 576(1)

Inhibition of Cellular Proliferation 576(1)

Regulation of Programmed Cell Death 577(1)

Conversion of Proto-Oncogenes to Oncogenes 577(1)

Induction of Cancer: A Multistep Process 578(1)

Tumors of the Immune System 579(1)

Tumor Antigens 580(6)

Tumor-Specific Antigens 580(1)

Chemically or Physically Induced Tumor Antigens 580(3)

Virally Induced Tumor Antigens 583(1)

Tumor-Associated Antigens 584(1)

Oncofetal Tumor Antigens 584(1)

Oncegene Proteins as Tumor Antigens 585(1)

TATAs on Human Melanomas 586(1)

Immune Response to Tumors 586(1)

Role of NK Cells and Macrophages 586(1)

Immune Surveillance Theory 586(1)

Tumor Evasion of the Immune System 587(1)

Immunologic Enhancement of Tumor Growth 587(1)

Modulation of Tumor Antigens 587(1)

Reduction in Class I MHC Molecules 587(1)

Lack of Co-stimulatory Signal 587(1)

Cancer Immunotherapy 588(6)

Manipulation of Co-stimulatory Signal 588(1)

Enhancement of APC Activity 589(1)

Cytokine Therapy 590(1)

Interferons 590(1)

Tumor Necrosis Factors 591(1)

In Vitro-Activated Lak And Til Cells 592(1)

Monoclonal Antibodies 592(2)

Tumor-Cell Vaccines 594(1)

Summary 594(1)

References 595(1)

Study Questions 595(2)
Glossary 597(14)
Answers to Study Questions 611(22)
Credits 633(8)
Index 641