The immune response: basic and clinical principles ; [CD-ROM included]
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| Main Authors: | , |
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| Format: | Book |
| Language: | English |
| Published: |
Amsterdam [u.a.]
Elsevier Acad. Press
2006
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| Subjects: | |
| Online Access: | Table of contents only Publisher description Inhaltsverzeichnis |
| Physical Description: | XX, 1216 S. Ill., graph. Darst. 1 CD-ROM (12 cm) |
| ISBN: | 0120884518 9780120884513 |
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| 245 | 1 | 0 | |a The immune response |b basic and clinical principles ; [CD-ROM included] |c Tak W. Mak and Mary E. Saunders |
| 264 | 1 | |a Amsterdam [u.a.] |b Elsevier Acad. Press |c 2006 | |
| 300 | |a XX, 1216 S. |b Ill., graph. Darst. |e 1 CD-ROM (12 cm) | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Immunity | |
| 650 | 4 | |a Immune System | |
| 650 | 4 | |a Immune System Diseases | |
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| 700 | 1 | |a Saunders, Mary E. |e Verfasser |4 aut | |
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| _version_ | 1804135614501617664 |
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| adam_text | Contents
Preface VIII
Biographies IX
Acknowledgments XI
PARTI: BASIC IMMUNOLOGY 1
Chapter 1: Perspective on Immunity
and Immunology 3
A. WHAT IS IMMUNOLOGY? 4
B. WHY HAVE AN IMMUNE SYSTEM AND WHAT DOES IT DO? 7
C. TYPES OF IMMUNE RESPONSES: INNATE AND ADAPTIVE 7
D. WHAT IS INFECTION ? 10
E. PHASES OF HOST DEFENSE 11
F. HOW ARE ADAPTIVE AND INNATE IMMUNITY RELATED? 12
G. LEUKOCYTES: CELLULAR MEDIATORS OF IMMUNITY 13
H. WHERE DO IMMUNE RESPONSES OCCUR? 14
I. CLINICAL IMMUNOLOGY: WHEN THE IMMUNE SYSTEM
DOES NOT WORK PROPERLY 15
Chapter 2: Introduction to the Immune Response 17
A. GENERAL FEATURES OF INNATE IMMUNITY 18
B. GENERAL FEATURES OF ADAPTIVE IMMUNITY 19
I. SPECIFICITY 19
II. IMMUNOLOGIC MEMORY 19
III. DIVERSITY 20
IV. TOLERANCE 21
V. DIVISION OF LABOR 21
C. ELEMENTS OF IMMUNITY COMMON TO THE INNATE
AND ADAPTIVE RESPONSES 22
I. INTRODUCING CYTOKINES 22
II. INTRODUCING INTRACELLULAR SIGNALING 23
D. ELEMENTS OF IMMUNITY EXCLUSIVE TO THE
ADAPTIVE RESPONSE 24
I. ANTIGENS VERSUS IMMUNOGENS 24
II. INTRODUCING SPECIFIC ANTIGEN RECOGNITION: B CELLS 26
III. INTRODUCING SPECIFIC ANTIGEN RECOGNITION: T CELLS
AND THE MAJOR HISTOCOMPATIBILITY COMPLEX 26
IV. INTRODUCING ANTIGEN PROCESSING 27
V. INTRODUCING CORECEPTORS AND COSTIMULATORY MOLECULES 29
VI. INTRODUCING B CELL EFFECTOR FUNCTIONS 29
VII. INTRODUCING T CELL EFFECTOR FUNCTIONS 30
VIII. INTRODUCING PRIMARY AND SECONDARY ADAPTIVE
IMMUNE RESPONSES 31
Chapter 3: Cells and Tissues of the Immune Response 35
A. CELLS OF THE IMMUNE SYSTEM 36
I. TYPES OF HEMATOPOIETIC CELLS 36
II. CELLS OF THE MYELOID LINEAGE 36
III. CELLS OF THE LYMPHOID LINEAGE 41
IV. DENDRITIC CELLS 46
V. HEMATOPOIESIS 47
B. LYMPHOID TISSUES 51
I. PRIMARY LYMPHOID TISSUES 53
II. SECONDARY LYMPHOID TISSUES 56
Chapter 4: Innate Immunity 69
A. MECHANISMS OF INNATE IMMUNITY 70
I. ANATOMICAL AND PHYSIOLOGICAL BARRIERS TO INFECTION 70
II. CELLULAR INTERNALIZATION MECHANISMS THAT
FIGHT INFECTION 73
III. INFLAMMATION AS A RESPONSE TO INFECTION OR INJURY 78
B. PATTERN RECOGNITION IN INNATE IMMUNITY 84
I. PATTERN RECOGNITION BY PRRs 85
II. PATTERN RECOGNITION BY RECEPTORS OF NK, NKT,
AND yhJ CELLS 88
III. PATTERN RECOGNITION BY SOLUBLE MOLECULES 89
Chapter 5: B Cell Receptor Structure
and Effector Function 93
A. HISTORICAL NOTES 94
B. THE STRUCTURE OF IMMUNOGLOBUUNS 97
I. GENERAL STRUCTURAL PROPERTIES OF IMMUNOGLOBULIN
MOLECULES 97
II. CHANGES TO Ig STRUCTURE ASSOCIATED WITH FUNCTION 103
III. THE B CELL ANTIGEN RECEPTOR COMPLEX 108
IV. Fc RECEPTORS 108
C. EFFECTOR FUNCTIONS OF ANTIBODIES 113
I. NEUTRALIZATION 113
II. OPSONIZATION 113
III. ANTIBODY DEPENDENT CELL MEDIATED CYTOTOXICITY 114
IV. COMPLEMENT MEDIATED CLEARANCE OF ANTIGEN 115
D. IMMUNOGLOBULIN ISOTYPES IN BIOLOGICAL CONTEXT 116
I. NATURAL DISTRIBUTION OF ANTIBODIES IN THE BODY 116
II. MORE ABOUT IgM 116
III. MORE ABOUT IgD 118
IV. MORE ABOUT IgG 118
V. MORE ABOUT IgA 118
VI. MORE ABOUT IgE 119
Chapter 6: The Nature of Antigen Antibody
Interaction 121
A. THE NATURE OF B CELL IMMUNOGENS 122
I. WHAT MOLECULES CAN FUNCTION AS IMMUNOGENS? 122
II. IMMUNOGENS IN THE HUMORAL RESPONSE 122
III. PROPERTIES OF Td IMMUNOGENS 125
B. B CELL T CELL COOPERATION IN THE HUMORAL
IMMUNE RESPONSE 130
I. THE DISCOVERY OF B T COOPERATION: RECONSTITUTE
EXPERIMENTS 130
II. THE MOLECULAR BASIS OF B T COOPERATION: THE
HAPTEN CARRIER EXPERIMENTS 131
III. HAPTEN CARRIER COMPLEXES in vivo 134
IV. THE RATIONALE FOR LINKED RECOGNITION 136
C. THE MECHANICS OF ANTIGEN ANTIBODY INTERACTION 137
I. IDENTIFICATION OF B EPITOPE STRUCTURAL REQUIREMENTS 137
II. WHERE ANTIBODY AND ANTIGEN INTERACT: THE
COMPLEMENTARITY DETERMINING REGIONS 137
III. FORCES AT WORK IN SPECIFIC ANTIGEN ANTIBODY BINDING 139
IV. AFFINITY AND AVIDITY OF ANTIBODY BINDING 140
V. ANTIBODY CROSS REACTIVITY 143
Chapter 7: Exploiting Antigen Antibody
Interaction 147
A. SOURCES OF ANTIBODIES 149
I. ANTISERA 149
II. HYBRIDOMAS AND MONOCLONAL ANTIBODIES 150
B. TECHNIQUES BASED ON IMMUNE COMPLEX FORMATION 155
I. CROSS LINKING AND THE FORMATION OF
IMMUNE COMPLEXES 155
II. TECHNIQUES BASED ON THE PRECIPITIN REACTION 156
III. TECHNIQUES BASED ON AGGLUTINATION 159
IV. TECHNIQUES BASED ON COMPLEMENT FIXATION 159
C. ASSAYS BASED ON UNITARY ANTIGEN ANTIBODY
PAIR FORMATION 162
I. GENERAL CONCEPTS 162
II. DETECTION OF ANTIGEN BY TAG ASSAYS 167
III. ISOLATION AND CHARACTERIZATION OF ANTIGEN USING
ANTIBODIES 172
Chapter 8: The Immunoglobulin Genes 179
A. HISTORICAL NOTES 180
B. CHROMOSOMAL ORGANIZATION OF Ig GENES 183
I. THE Ig LOCI 183
II. GENERAL STRUCTURE OF Ig LOCI 184
III. FINE STRUCTURE OF LIGHT CHAIN GENES 185
IV. FINE STRUCTURE OF HEAVY CHAIN GENES 186
C. Ig GENE REARRANGEMENT 188
I. THE ROLE OF V(D)J RECOMBINATION 188
II. VDJ JOINING IN THE Igh LOCUS 188
III. VJ JOINING IN THE Igl AND Igk LOCI 190
IV. PRODUCTIVITY TESTING 191
V. ALLELIC EXCLUSION 192
VI. KAPPA/LAMBDA EXCLUSION 193
VII. INTRODUCING KNOCKOUT MICE 194
D. MOLECULAR MECHANISMS OF Ig GENE REARRANGEMENT 196
I. HOW DO VDJ SEGMENTS JOIN IN THE RIGHT ORDER? THE RSS 196
II. THE RECOMBINASE ENZYMES: RAG 1 AND RAG 2 197
III. SYNAPSIS, SIGNAL JOINTS, AND CODING JOINTS 198
IV. MUTATIONS OF V(D)J RECOMBINATION 200
E. ANTIBODY DIVERSITY GENERATED BY GENE
REARRANGEMENT 201
I. MULTIPLICITY OF GERM LINE GENE SEGMENTS 201
II. COMBINATORIAL DIVERSITY 201
III. JUNCTIONAL DIVERSITY 202
IV. HEAVY LIGHT Ig CHAIN PAIRING 204
F. CONTROL SEQUENCES IN THE Ig LOCI 204
I. ENHANCERS 204
II. DNA BINDING MOTIFS AND NUCLEAR TRANSCRIPTION
FACTORS 206
Chapter 9: The Humoral Response: B Cell
Development and Activation 209
A. THE MATURATION PHASE OF B CELL DEVELOPMENT 211
I. PRO B CELLS 211
II. PRE B CELLS 213
B. THE DIFFERENTIATION PHASE OF B CELL DEVELOPMENT 217
I. THE THREE SIGNAL MODEL OF B CELL ACTIVATION 218
II. CELLULAR INTERACTIONS DURING B CELL ACTIVATION 229
III. PROLIFERATION AND SOMATIC HYPERMUTATION 231
IV. AFFINITY MATURATION 234
V. ISOTYPE SWITCHING: GENERATING FUNCTIONAL DIVERSITY 235
VI. DIFFERENTIATION OF MEMORY B CELLS AND PLASMA CELLS 239
Chapter 10: MHC: The Major
Histocompatibility Complex 247
A. HISTORICAL NOTES 248
I. DISCOVERY OF THE MHC 248
II. MHC INVOLVEMENT INT CELL RECOGNITION 249
III. ELUCIDATION OF THE ANTIGEN PRESENTING FUNCTION
OF THE MHC 249
B. GENERAL ASPECTS OF THE MHC IN HUMANS AND MICE 254
I. OVERVIEW OF THE MHC PROTEINS 254
II. OVERVIEW OF THE MHC LOCI 255
III. INTRODUCING MULTIPLICITY AND POLYMORPHISM IN
THE MHC LOCI 255
IV. INTRODUCING HAPLOTYPES 259
C. MHC PROTEINS 260
I. MHC CLASS I PROTEINS 260
II. MHC CLASS II PROTEINS 262
D. MHC GENES 264
I. DETAILED ORGANIZATION OF THE H 2 COMPLEX 264
II. DETAILED ORGANIZATION OF THE HLA COMPLEX 267
E. EXPRESSION OF MHC MOLECULES 269
I. THE SXY CIITA REGULATORY SYSTEM 270
II. TNF AND IFN7 INDUCED EXPRESSION OF MHC CLASS I 271
III. EXPRESSION OF MHC CLASS Ib GENES 272
IV. OTHER REGULATORY PATHWAYS GOVERNING MHC
CLASS II GENE EXPRESSION 272
F. PHYSIOLOGY OF THE MHC 272
I. POLYMORPHISM AND THE BIOLOGICAL ROLE OF THE MHC 272
II. ALLOREACTIVITY 273
III. MHC AND IMMUNE RESPONSIVENESS 273
IV. INTRODUCING MHC AND DISEASE PREDISPOSITION 274
Chapter 11: Antigen Processing
and Presentation 279
A. THE EXOGENOUS OR ENDOCYTIC ANTIGEN PROCESSING
PATHWAY 281
I. HISTORICAL NOTES 281
II. CELLS THAT CAN FUNCTION AS APCs 282
III. MECHANISM OF ANTIGEN PROCESSING BY APCs 289
IV. FACTORS AFFECTING ANTIGEN PROCESSING AND
PRESENTATION BY APCs 294
B. THE ENDOGENOUS OR CYTOSOUC ANTIGEN
PROCESSING PATHWAY 295
I. HISTORICAL NOTES 295
II. CELLS THAT CAN FUNCTION AS TARGET CELLS 295
III. MECHANISM OF ANTIGEN PROCESSING BY TARGET CELLS 296
C. OTHER PATHWAYS OF ANTIGEN PRESENTATION 302
I. CROSS PRESENTATION 302
II. ANTIGEN PRESENTATION BY NON CLASSICAL AND
MHC LIKE MOLECULES 305
Chapter 12: The T Cell Receptor:
Structure of Its Proteins and Genes 311
A. HISTORICAL NOTES 312
I. INTRODUCTION 312
II. DISCOVERY OF THE GENES AND PROTEINS OF THE TCR 313
III. A SECOND T CELL RECEPTOR 315
B. THE STRUCTURE OFT CELL RECEPTOR PROTEINS 317
I. OVERVIEW 317
C. GENOMIC ORGANIZATION OF THE TCR AND CD3 LOCI 319
I. THE TCRa LOCUS 319
II. THE TCRp LOCUS 320
III. THE TCR /LOCUS 321
IV. THE TCR8 LOCUS 321
V. THE CD3 GENES 322
D. EXPRESSION OF TCR GENES 322
I. MECHANISM OF V(D)J RECOMBINATION IN THE TCR LOCI 322
II. TCR GENE TRANSCRIPTION AND PROTEIN ASSEMBLY 324
E. DEVELOPMENTAL ASPECTS OF V(D)J RECOMBINATION
IN THE TCR LOCI 325
I. TCRp LOCUS REARRANGEMENT 325
II. TCRa LOCUS REARRANGEMENT 326
III. TCR y AND 5 LOCUS REARRANGEMENT 327
IV. TCR LOCUS KNOCKOUT MICE 327
F. GENERATION OF DIVERSITY OF THE T CELL
RECEPTOR REPERTOIRE 327
I. MULTIPLICITY OF GERMLINE GENE SEGMENTS 327
II. COMBINATORIAL DIVERSITY 328
Contents
III. JUNCTIONAL DIVERSITY 328
IV. CHAIN PAIRING 329
G. REGULATION OF TCR GENE EXPRESSION 329
H. STRUCTURE AND FUNCTION OF THE CD3 COMPLEX 330
I. CD3 PROTEIN STRUCTURE 330
II. FUNCTIONS OF THE CD3 COMPLEX 331
III. CD3 KNOCKOUT MICE 331
I. THE CD4 AND CD8 CORECEPTORS 332
I. DISCOVERY OF CD4 AND CD8 332
II. WHATISA CORECEPTOR ? 332
III. STRUCTURE OF CD4 334
IV. STRUCTURE OF CD8 334
V. FUNCTIONS OF CD4 AND CD8 334
J. PHYSICAL ASPECTS OF THE INTERACTION OF THE
TCR WITH ANTIGEN 336
I. STUDYING TCR PEPTIDE MHC INTERACTION 336
II. BINDING AFFINITY OF TCRap FOR ITS LIGAND 336
III. X RAY CRYSTAL STRUCTURE OFT CELL RECEPTORS 337
Chapter 13: T Cell Development 341
A. HISTORICAL NOTES 342
B. CONTEXT AND OVERVIEW 344
I. COMPARISON OF B AND T CELL ONTOGENY 344
II. OVERVIEW OFT CELL DEVELOPMENT 346
C. T CELL DEVELOPMENT IN THE BONE MARROW 347
D. T CELL DEVELOPMENT IN THE THYMUS 347
I. OVERVIEW 347
II. DN (TN) PHASE (TCR~CD4 CD8 ) 351
III. THE DP PHASE (CD4+CD8+) 356
IV. THE SP PHASE: CD4/CD8 LINEAGE COMMITMENT 364
E. MATURE SPTHYMOCYTES IN THE PERIPHERY 368
F. T CELL DEVELOPMENT IN AN EMBRYOLOGICAL CONTEXT 368
Chapter 14: T Cell Activation 373
A. BRINGING T CELLS AND APCs TOGETHER 375
I. L SELECTIN 376
II. LFA l 376
B. SIGNAL ONE: BINDING OF PEPTIDE MHC TO THE TCR 378
I. MODELS OF TCR TRIGGERING 378
II. FORMATION OF THE IMMUNOLOGICAL SYNAPSE (SMAC) 380
III. TCR DOWNREGULATION 382
IV. TCR SIGNAL TRANSDUaiON 383
C. SIGNAL TWO: COSTIMULATION 392
I. CD28 B7 393
II. ICOS ICOSL 396
III. PD 1 PDL1/PDL2 397
IV. 7?? B7 H3 397
V. THE TNF/TNFR RELATED COSTIMULATORY MOLECULES 397
VI. CD27/CD70 398
VII. OTHER MINOR COSTIMULATORY CONTACTS 398
D. SIGNAL THREE: CYTOKINES 398
I. THE IL 2/IL 2R SYSTEM 399
II. CONTROL OF TRANSCRIPTION OF THE IL 2 GENE 399
Chapter 15: T Cell Differentiation
and Effector Function 403
A. HISTORICAL NOTES 404
B. Th CELL DIFFERENTIATION AND EFFECTOR FUNCTION 405
I. WHAT ARE Thl AND Th2 RESPONSES ? 405
II. PROCESS OF Th CELL DIFFERENTIATION 406
III. ACTIVATION OF EFFECTOR Thl AND Th2 CELLS 413
IV. EFFECTOR FUNCTIONS OF Th CELLS 415
C. Tc CELL DIFFERENTIATION AND CTL EFFECTOR FUNCTION 417
I. GENERATION OF EFFECTOR CTLs 418
II. MECHANISMS OF TARGET CELL DESTRUCTION BY CD8+ CTLs 419
D. COMPARISON OF NAIVE AND EFFECTOR T CELLS 422
I. TRAFFICKING AND ADHESION 422
II. ACTIVATION 423
III. FUNCTIONS AND PRODUCTS 424
E. ELIMINATION OF EFFECTOR T CELLS 424
I. ACTIVATION INDUCED CELL DEATH (AICD) 424
II. T CELL EXHAUSTION 427
F. MEMORY T CELLS 427
I. GENERATION OF MEMORY T CELLS 428
II. MEMORY T CELL MARKERS 428
III. MEMORY T CELL DISTRIBUTION 429
IV. MEMORY T CELL ACTIVATION 429
V. MEMORY T CELL DIFFERENTIATION AND EFFECTOR
FUNCTION 430
VI. MEMORY T CELL LIFE SPAN 430
Chapter 16: Immune Tolerance in the
Periphery 433
A. CONTEXT OF PERIPHERAL TOLERANCE 434
I. HISTORICAL NOTES 434
II. EVIDENCE FOR PERIPHERAL SELF TOLERANCE MECHANISMS 436
B. T CELL PERIPHERAL SELF TOLERANCE 437
I. THE IMPORTANCE OF DCs AND DANGER SIGNALS 437
II. MECHANISMS OF PERIPHERAL T CELL SELF TOLERANCE 439
C. B CELL PERIPHERAL SELF TOLERANCE 447
I. DEMONSTRATION OF B CELL ANERGY 447
II. MECHANISMS OF PERIPHERAL B CELL TOLERANCE 448
D. REGULATORY T CELLS 450
I. CD4+CD25+Treg CELLS 450
II. Th3 AND Trl CELLS 452
III. CD8+TS CELLS 452
IV. INFECTIOUS TOLERANCE AND LINKED SUPPRESSION 453
E. EXPERIMENTAL TOLERANCE 454
I. CHARACTERISTICS OF EXPERIMENTAL TOLERANCE 454
II. CHARACTERISTICS OF TOLEROGENS 454
III. DEGREE AND PERSISTENCE OF TOLERANCE 457
III. C2 559
IV. C3 559
D. THE ALTERNATIVE PATHWAY OF COMPLEMENT
ACTIVATION 561
I. C3 AND FACTOR B 562
II. FACTOR D AND THE ALTERNATIVE C3
CONVERTASE 562
III. PROPERDIN AND THE ALTERNATIVE C5
CONVERTASE 562
E. THE LECTIN PATHWAY OF COMPLEMENT
ACTIVATION 562
I. MBL 562
II. CRP 563
F. TERMINAL COMPONENTS OF THE COMPLEMENT
CASCADE AND FORMATION OF THE MAC 564
I. C5 564
II. C6ANDC7 564
III. C8ANDC9 565
IV. TARGETS OF THE MAC 566
G. REGULATION OF THE COMPLEMENT SYSTEM 566
I. REGULATION OF THE CLASSICAL PATHWAY 567
II. REGULATION OF THE ALTERNATIVE PATHWAY 570
III. REGULATION OF THE LECTIN PATHWAY 571
IV. REGULATION OF TERMINAL COMPONENTS 571
H. COMPLEMENT RECEPTORS AND THEIR
BIOLOGICAL ROLES 572
I. CRl 573
II. CR2 574
III. CR3 574
IV. CR4 575
V. Ciq RECEPTORS 575
VI. RECEPTORS FOR C3a, C4a, AND C5a 575
I. COMPLEMENT DEFICIENCIES 575
I. DEFICIENCY OF C1,C4, OR C2 576
II. DEFICIENCY OF O 577
III. DEFICIENCY OF ALTERNATIVE PATHWAY
COMPONENTS 578
IV. DEFICIENCY OF LECTIN PATHWAY COMPONENTS 578
V. DEFICIENCY OF TERMINAL COMPONENTS (C5 C9) 578
VI. DEFICIENCY OF REGULATORY PROTEINS 578
VII. DEFICIENCY OF COMPLEMENT RECEPTORS 579
J. NEW ROLES FOR COMPLEMENT? 579
Chapter 20: Mucosal and Cutaneous Immunity 583
A. MUCOSAL IMMUNITY 584
I. GALT 586
II. BALT/NALT 591
III. IMMUNE RESPONSES IN THE MAJOR MALT 593
IV. IMMUNE RESPONSES IN THE MINOR MALT 599
B. CUTANEOUS IMMUNITY 600
I. COMPONENTS OF SALT 600
II. IMMUNE RESPONSES IN SALT 605
Chapter 21: Comparative Immunology 611
A. OVERVIEW 612
I. REPRISE OF THE ANIMAL KINGDOM 612
II. FORCES SHAPING THE EVOLUTION OF IMMUNE
RECOGNITION 614
B. ELEMENTS OF INNATE IMMUNITY 618
I. ANATOMICAL AND PHYSIOLOGICAL BARRIERS 618
II. INNATE IMMUNE RESPONSE CELLS AND THEIR
RECOGNITION STRUCTURES 618
III. CYTOKINES 620
IV. PATHOGEN ELIMINATION 621
C. ELEMENTS OF ADAPTIVE IMMUNITY 626
I. LYMPHOID TISSUES 626
II. BCR 628
III. MHC 632
IV. TCR 634
PART II: CLINICAL IMMUNOLOGY 629
Chapter 22: Immunity to Pathogens 641
A. OVERVIEW 642
I. WHAT IS A PATHOGEN 642
II. WHAT IS DISEASE 644
III. INNATE DEFENSE AGAINST PATHOGENS 645
B. IMMUNITY TO EXTRACELLULAR BACTERIA 647
I. WHAT ARE EXTRACELLULAR BACTERIA? 647
II. EFFECTOR MECHANISMS 652
III. EVASION STRATEGIES 654
C. IMMUNITY TO INTRACELLULAR BACTERIA 656
I. WHAT ARE INTRACELLULAR BACTERIA? 656
II. EFFECTOR MECHANISMS 658
III. EVASION STRATEGIES 662
D. IMMUNITY TO VIRUSES 664
I. WHAT ARE VIRUSES? 664
II. EFFECTOR MECHANISMS 669
III. EVASION STRATEGIES 672
E. IMMUNITY TO PARASITES 680
I. WHAT ARE PARASITES? 680
II. EFFECTOR MECHANISMS 683
III. EVASION STRATEGIES 686
F. IMMUNITY TO FUNGI 688
I. WHAT ARE FUNGI? 688
II. EFFECTOR MECHANISMS 689
III. EVASION STRATEGIES 690
C. THE MYSTERIOUS PRIONS 691
Chapter 23: Vaccines and Clinical Immunization 695
A. VACCINATION: PUBLIC HEALTH SUCCESSES
AND CHALLENGES 696
B. HISTORICAL NOTES 698
C. GENERAL PRINCIPLES OF VACCINE DESIGN 703
I. BIOLOGICAL PURPOSE OF A VACCINE 703
II. VACCINE EFFICACY AND SAFETY 704
D. TYPES OF VACCINES 705
I. LIVE, ATTENUATED VACCINES 705
II. KILLED VACCINES 708
III. TOXOIDS 709
IV. SUBUNIT VACCINES 709
V. PEPTIDE VACCINES 710
VI. RECOMBINANT VECTOR DNA VACCINES 711
VII. NAKED DNA VACCINES 713
VIII. ANTI IDIOTYPIC VACCINES 716
E. FACTORS AFFECTING VACCINATION 718
I. SCHEDULING OF VACCINE ADMINISTRATION AND BOOSTING 718
II. ROUTES OF VACCINE ADMINISTRATION 722
III. ADJUVANTS AND DELIVERY VEHICLES 722
F. PROPHYLACTIC VACCINES 727
I. ANTHRAX 727
II. CHOLERA 729
III. DIPHTHERIA, TETANUS, AND PERTUSSIS 729
IV. HAEMOPHILUSINFLUENZAETYPEb 730
V. HEPATITIS A 731
VI. HEPATITIS B 731
VII. INFLUENZA VIRUS 731
VIII. JAPANESE B ENCEPHALITIS 732
IX. MEASLES, MUMPS, AND RUBELLA 732
X. MENINGOCOCCUS 734
XL PLAGUE 734
XII. POLIO 734
XIII. RABIES 735
XIV. STREPTOCOCCUS PNEUMONIAE 735
XV. TUBERCULOSIS 735
XVI. TYPHOID FEVER 736
XVII. VARICELLA ZOSTER (CHICKEN POX) 738
XVIII. VARIOLA (SMALLPOX) 738
XIX. YELLOW FEVER 739
G. THE DARK SIDE OF VACCINES 739
I. ADVERSE EFFECTS OF VACCINES 739
II. FAILURE TO VACCINATE AND OPPOSITION TO
VACCINATION 740
H. PROPHYLACTIC VACCINES OF THE FUTURE 740
I. PASSIVE IMMUNIZATION 741
J. THERAPEUTIC VACCINES 744
I. VACCINES TO COMBAT TUMORS 744
II. VACCINES TO CURE CHRONIC VIRAL
DISEASES 745
III. VACCINES TO MITIGATE INDIRECT EFFECTS OF
INFECTIOUS DISEASE 745
IV. VACCINES TO MITIGATE AUTOIMMUNITY 745
V. VACCINES TO MITIGATE ALLERGY 746
VI. VACCINES TO SUPPRESS FERTILITY 746
VII. VACCINES TO SUPPRESS ADDICTION 747
Chapter 24: Primary Immunodeficiencies 751
A. GENERAL CONCEPTS 752
I. DIAGNOSIS OF Pis 752
II. TREATMENT OF Pis 753
III. FOCUS OF PI RESEARCH 754
B. PRIMARY IMMUNODEFICIENCIES DUE TO DEFECTS
IN ADAPTIVE IMMUNE RESPONSES 754
I. COMBINED IMMUNODEFICIENCIES 754
II. T CELL SPECIFIC IMMUNODEFICIENCIES 763
III. B CELL SPECIFIC IMMUNODEFICIENCIES 765
IV. ADAPTIVE IMMUNODEFICIENCIES DUE TO DEFECTS IN
DNA REPAIR 768
V. LYMPHOPROLIFERAT1VE IMMUNODEFICIENCY SYNDROMES 773
VI. OTHER ADAPTIVE IMMUNODEFICIENCIES 774
C. PRIMARY IMMUNODEFICIENCIES DUE TO DEFECTS
IN THE INNATE IMMUNE RESPONSE 776
I. IMMUNODEFICIENCIES AFFECTING PHAGOCYTE
RESPONSES 776
II. COMPLEMENT DEFICIENCIES 780
Chapter 25: HIV and Acquired
Immunodeficiency Syndrome 785
A. HISTORICAL NOTES 786
B. WHAT IS HIV? 788
I. OVERVIEW OF THE HIV 1 LIFE CYCLE 788
II. OVERVIEW OF HIV STRUCTURE 789
C. STRUCTURE AND FUNCTION OF HIV PROTEINS 791
I. VIRAL PROTEINS DERIVED FROM THE gag GENE 792
II. VIRAL PROTEINS DERIVED FROM THE pol GENE 792
III. VIRAL PROTEINS DERIVED FROM THE em GENE 793
IV. REGULATORY PROTEINS 794
V. ACCESSORY PROTEINS 795
D. HIV INFECTION AND AIDS 796
I. CLINICAL VIEW OF HIV INFECTION 796
II. MOLECULAR EVENTS UNDERLYING HIV INFECTION 798
E. THE IMMUNE RESPONSE DURING HIV INFECTION 802
I. Th RESPONSES 802
II. CTL RESPONSES 803
III. ANTIBODY RESPONSES 803
IV. CYTOKINES 804
V. CEM 15 (APOBEC3G) 805
VI. NK CELLS 805
VII. COMPLEMENT 805
F. HOST FACTORS INFLUENCING THE COURSE OF HIV
INFECTION 805
I. RESISTANCE TO HIV INFECTION 806
II. CLINICAL COURSE VARIABILITY 806
G. EPIDEMIOLOGY AND SOCIOLOGY OF HIV INFECTION 808
I. TRANSMISSION OF HIV 808
II. EPIDEMIOLOGY 808
III. SOCIETAL AND ECONOMIC IMPACT OF AIDS 812
H. ANIMAL MODELS OF AIDS 813
I. PRIMATE MODELS OF AIDS 813
II. MOUSE MODELS OF AIDS 814
I. HIV VACCINES 815
I. BARRIERS TO HIV VACCINE DEVELOPMENT 815
II. EXPERIMENTAL AIDS VACCINES IN ANIMALS 816
III. EXPERIMENTAL AIDS VACCINES IN HUMANS 818
IV. PASSIVE IMMUNIZATION 819
J. TREATMENT OF HIV INFECTION WITH
ANTI RETROVIRAL DRUGS 819
I. PROTEASE INHIBITORS 820
II. NUCLEOSIDE RT INHIBITORS 820
III. NON NUCLEOSIDE RT INHIBITORS 820
IV. FUSION INHIBITORS 820
V. IMMUNE RESPONSES AND ANTI RETROVIRAL THERAPY 821
VI. OTHER DRUG THERAPY ISSUES 821
Chapter 26: Tumor Immunology 825
A. HISTORICAL NOTES 826
B. TUMOR BIOLOGY 829
I. WHAT IS A TUMOR AND WHAT IS A CANCER? 829
II. CARCINOGENESIS 832
III. TUMORIGENIC GENETIC ALTERATIONS 834
IV. CARCINOGENS 839
C. IMMUNE RESPONSES TO CANCER 842
I. THE CONCEPT OF IMMUNOSURVE1LLANCE 842
II. TUMOR ANTIGENS 842
III. IMMUNE RESPONSES TO TUMOR CELLS 845
IV. HURDLES TO EFFECTIVE ANTI TUMOR IMMUNITY 849
D. CANCER THERAPY 851
I. RADIATION THERAPY 851
II. CHEMOTHERAPY 852
III. TUMOR HYPOXIA 853
IV. IMMUNOTHERAPY 856
Chapter 27: Transplantation 873
A. HISTORICAL NOTES 874
B. THE MOLECULAR BASIS OF
ALLORECOGNITION 880
I. DIRECT ALLORECOGNITION 881
II. INDIRECT ALLORECOGNITION 881
C. MINOR HISTOCOMPATIBILITY ANTIGENS 881
D. TYPES OF CLINICAL REJECTION AND THEIR MECHANISMS 885
I. HYPERACUTE GRAFT REJECTION 885
II. ACUTE GRAFT REJECTION 886
III. CHRONIC GRAFT REJECTION 888
IV. THEROLEOFCYTOKINESANDCHEMOKINESIN
GRAFT REJECTION 888
V A ROLE FOR TLRs IN GRAFT REJECTION? 888
VI. GRAFT VERSUS HOST DISEASE (GvHD) IN SOLID
ORGAN TRANSPLANTS 890
E. HLA TYPING 890
I. SEROLOGICAL TECHNIQUES 891
II. TYPING BY CELLULAR RESPONSE: MLR 892
III. TYPING AT THE DNA LEVEL 893
F. IMMUNOSUPPRESSION 896
I. AZATHIOPRINE 896
II. CYCLOSPORINE A 896
III. TACROLIMUS 897
IV. MYCOPHENOLATE MOFETIL 897
V. SIROLIMUS 897
VI. MALONONITRILAMIDES (MNAs) 898
VII. FTY720 898
VIII. FLUDARABINE 898
IX. ANTI LYMPHOCYTE ANTIBODIES 898
X. CYTOKINES 899
C. INDUCTION OF GRAFT TOLERANCE 899
I. BONE MARROW MANIPULATION 900
II. THYMIC MANIPULATION 901
III. COSTIMULATORY BLOCKADE 901
IV. REGULATORY T CELLS 903
V. REGULATION BY NKT CELLS 904
VI. TOLEROGENIC DCs 905
VII. CAVEATS 905
H. XENOTRANSPLANTATION 906
I. CHOICE OF SPECIES FOR XENOTRANSPLANTATION 907
II. XENOGRAFT REJECTION 907
III. TRANSMISSION OF ZOONOTIC DISEASES 909
IV. REGULATORY AND LEGAL OBSTACLES 910
V. ETHICAL AND MORAL CONSIDERATIONS 910
I. BLOOD TRANSFUSIONS 910
I. ALLOREACTIVITY IN BLOOD TRANSFUSIONS 910
II. ENSURING THE SAFETY OF THE BLOOD SUPPLY 913
J. HEMATOPOIETIC CELL TRANSPLANTATION (HCT) 913
I. GRAFT REJECTION IN HQ 914
II. GRAFT VERSUS HOST DISEASE (GvHD) IN Ha 915
III. GRAFT VERSUS LEUKEMIA (GvL) EFFEa 916
IV. BENEFICIAL EFFEaS OF ALLOGENEICNK CELLS 916
V. INFECTION CONTROL 917
K. GENE THERAPY IN TRANSPLANTATION 917
Chapter 28: Allergy and Hypersensitivity 923
A. HISTORICAL NOTES 924
B. TYPE I HYPERSENSITIVITY: IMMEDIATE OR
IgE MEDIATED 925
I. WHAT IS TYPE I HS? 925
II. MECHANISMS UNDERLYING TYPE I HS 927
III. EXAMPLES OF TYPE I HS 930
IV. ROLESOFFceRANDIgEINTYPEIHS 934
V. ALLERGEN BIOLOGY 937
VI. DIAGNOSIS AND THERAPY OF TYPE I HS 940
Contents
C. TYPE II HYPERSENSITIVITY: DIRECT ANTIBODY MEDIATED
CYTOTOXICITY 949
I. WHAT IS TYPE II HS? 949
II. MECHANISMS UNDERLYING TYPE II HS 949
III. EXAMPLES OF TYPE II HS: CYTOTOXICITY AGAINST
MOBILE CELLS 949
IV. EXAMPLES OF TYPE II HS: CYTOTOXICITY AGAINST
FIXED TISSUES 953
D. TYPE III HYPERSENSITIVITY: IMMUNE
COMPLEX MEDIATED INJURY 954
I. WHAT IS TYPE III HS? 954
II. MECHANISM UNDERLYING TYPE III HS 954
III. EXAMPLES OF TYPE III HS 956
E. TYPE IV HYPERSENSITIVITY: DELAYED TYPE OR
CELL MEDIATED HYPERSENSITIVITY 957
I. WHAT IS TYPE IV HS? 957
II. CHRONIC DTH REACTIONS 957
III. CONTACT HYPERSENSITIVITY (CHS) 958
IV. HYPERSENSITIVITY PNEUMONITIS (HP) 960
Chapter 29: Autoimmune Disease 963
A. OVERVIEW 964
I. HISTORICAL NOTES 964
II. WHAT CHARACTERIZES AN AUTOIMMUNE DISEASE? 965
III. OUR APPROACH TO DISCUSSING AUTOIMMUNITY 969
B. EXAMPLES OF HUMAN AUTOIMMUNE DISEASES 969
I. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) 970
II. RHEUMATOID ARTHRITIS (RA) 971
III. RHEUMATIC FEVER (RF) 972
IV. TYPE 1 DIABETES MELLITUS (T1 DM) 973
V. MULTIPLE SCLEROSIS (MS) 974
VI. ANKYLOSING SPONDYLITIS (AS) 977
VII. SJOGREN SYNDROME (SS) 977
VIII. AUTOIMMUNE THYROIDITIS 978
IX. AUTOIMMUNE THROMBOCYTOPENIC PURPURA 980
X. SCLERODERMA (SD) 981
XI. MYASTHENIA GRAVIS (MG) 982
XII. KAWASAKI DISEASE (KD) 982
XIII. POLYMYOSITIS (PM) 983
XIV. GUILLAIN BARRE SYNDROME (GBS) 984
XV. PSORIASIS (PS) 984
XVI. ANT1 PHOSPHOLIPID SYNDROME (APS) 985
XVII. INFLAMMATORY BOWEL DISEASE (IBD): CROHN S
DISEASE (CD) AND ULCERATIVE COLITIS (UC) 985
XVIII. PEMPHIGUS (PG) 986
XIX. GOODPASTURE S SYNDROME (GS) 986
XX. IMMUNODYSREGULATION, POLYENDOCRINOPATHY,
ENTEROPATHY X LINKED (IPEX) SYNDROME 986
C. ANIMAL MODELS OF AUTOIMMUNE DISEASE 986
I. NZB/W Fl MICE 988
II. MRL/lpr AND gld MICE 988
III. NOD MICE 989
IV. Scurfy M Ct. 990
V. THYMECTOMY OF NEONATAL MICE 991
VI. IBD MODELS 991
VII. EXPERIMENTAL AUTOIMMUNE ENCEPHALITIS (EAE) 991
VIII. COLLAGEN INDUCED ARTHRITIS (CIA) 992
IX. EXPERIMENTAL AUTOIMMUNE MYASTHENIA CRAVIS (EAMG) 992
X. EXPERIMENTAL AUTOIMMUNE THYROIDITIS (EAT) 993
XI. EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU) 993
XII. EXPERIMENTAL AUTOIMMUNE MYOCARDITIS (EAM) 994
XIII. OTHER POTENTIAL AID MODELS 994
D. DETERMINANTS OF AUTOIMMUNE DISEASE 995
I. GENETIC PREDISPOSITION 995
II. ENVIRONMENTAL TRIGGERS 998
III. HORMONAL INFLUENCES 1000
IV. REGIONAL/ETHNIC DIFFERENCES 1000
E. MECHANISMS UNDERLYING AID 1001
I. PATHOGEN RELATED MECHANISMS 1002
II. INHERENT DEFECTS IN IMMUNE SYSTEM CELLS 1006
III. ALTERATIONS TO CYTOKINE EXPRESSION 1010
IV. DEFECTS IN THE COMPLEMENT SYSTEM 1011
V. EPITOPE SPREADING 1011
F. THERAPY OF AID 1012
I. CONVENTIONAL TREATMENTS 1012
II. IMMUNOTHERAPEUTICS 1014
G. RELATIONSHIP BETWEEN AID AND CANCER 1020
Chapter 30: Hematopoietic Cancers 1025
A. HISTORICAL NOTES 1026
B. OVERVIEW OF HEMATOPOIETIC CANCER BIOLOGY 1027
I. WHAT ARE HEMATOPOIETIC CANCERS? 1027
II. HEMATOPOIETIC CANCER CARCINOGENESIS 1029
C. TERMS USED IN CLINICAL ASSESSMENT AND
TREATMENT OF HC 1030
D. LEUKEMIAS 1035
I. ACUTE MYELOID LEUKEMIA (AML) 1035
II. CHRONIC MYELOGENOUS LEUKEMIA (CML) 1039
III. ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) 1041
IV. CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) 1044
V. OTHER LEUKEMIAS 1045
E. PLASMA CELL DYSCRASIAS 1046
I. MONOCLONAL GAMMOPATHY OF UNDETERMINED
SIGNIFICANCE (MGUS) 1047
II. WALDENSTROM S MACROGLOBULINEMIA (WM) 1047
III. MYELOMA 1047
F. LYMPHOMAS 1050
I. HODGKIN S LYMPHOMA (HL) 1050
II. NON HODGKIN S LYMPHOMAS 1054
Appendix: CD Molecules 1065
Glossary 1119
Index 1179
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| adam_txt |
Contents
Preface VIII
Biographies IX
Acknowledgments XI
PARTI: BASIC IMMUNOLOGY 1
Chapter 1: Perspective on Immunity
and Immunology 3
A. WHAT IS IMMUNOLOGY? 4
B. WHY HAVE AN IMMUNE SYSTEM AND WHAT DOES IT DO? 7
C. TYPES OF IMMUNE RESPONSES: INNATE AND ADAPTIVE 7
D. WHAT IS "INFECTION"? 10
E. PHASES OF HOST DEFENSE 11
F. HOW ARE ADAPTIVE AND INNATE IMMUNITY RELATED? 12
G. LEUKOCYTES: CELLULAR MEDIATORS OF IMMUNITY 13
H. WHERE DO IMMUNE RESPONSES OCCUR? 14
I. CLINICAL IMMUNOLOGY: WHEN THE IMMUNE SYSTEM
DOES NOT WORK PROPERLY 15
Chapter 2: Introduction to the Immune Response 17
A. GENERAL FEATURES OF INNATE IMMUNITY 18
B. GENERAL FEATURES OF ADAPTIVE IMMUNITY 19
I. SPECIFICITY 19
II. IMMUNOLOGIC MEMORY 19
III. DIVERSITY 20
IV. TOLERANCE 21
V. DIVISION OF LABOR 21
C. ELEMENTS OF IMMUNITY COMMON TO THE INNATE
AND ADAPTIVE RESPONSES 22
I. INTRODUCING CYTOKINES 22
II. INTRODUCING INTRACELLULAR SIGNALING 23
D. ELEMENTS OF IMMUNITY EXCLUSIVE TO THE
ADAPTIVE RESPONSE 24
I. ANTIGENS VERSUS IMMUNOGENS 24
II. INTRODUCING SPECIFIC ANTIGEN RECOGNITION: B CELLS 26
III. INTRODUCING SPECIFIC ANTIGEN RECOGNITION: T CELLS
AND THE MAJOR HISTOCOMPATIBILITY COMPLEX 26
IV. INTRODUCING ANTIGEN PROCESSING 27
V. INTRODUCING CORECEPTORS AND COSTIMULATORY MOLECULES 29
VI. INTRODUCING B CELL EFFECTOR FUNCTIONS 29
VII. INTRODUCING T CELL EFFECTOR FUNCTIONS 30
VIII. INTRODUCING PRIMARY AND SECONDARY ADAPTIVE
IMMUNE RESPONSES 31
Chapter 3: Cells and Tissues of the Immune Response 35
A. CELLS OF THE IMMUNE SYSTEM 36
I. TYPES OF HEMATOPOIETIC CELLS 36
II. CELLS OF THE MYELOID LINEAGE 36
III. CELLS OF THE LYMPHOID LINEAGE 41
IV. DENDRITIC CELLS 46
V. HEMATOPOIESIS 47
B. LYMPHOID TISSUES 51
I. PRIMARY LYMPHOID TISSUES 53
II. SECONDARY LYMPHOID TISSUES 56
Chapter 4: Innate Immunity 69
A. MECHANISMS OF INNATE IMMUNITY 70
I. ANATOMICAL AND PHYSIOLOGICAL BARRIERS TO INFECTION 70
II. CELLULAR INTERNALIZATION MECHANISMS THAT
FIGHT INFECTION 73
III. INFLAMMATION AS A RESPONSE TO INFECTION OR INJURY 78
B. PATTERN RECOGNITION IN INNATE IMMUNITY 84
I. PATTERN RECOGNITION BY PRRs 85
II. PATTERN RECOGNITION BY RECEPTORS OF NK, NKT,
AND yhJ CELLS 88
III. PATTERN RECOGNITION BY SOLUBLE MOLECULES 89
Chapter 5: B Cell Receptor Structure
and Effector Function 93
A. HISTORICAL NOTES 94
B. THE STRUCTURE OF IMMUNOGLOBUUNS 97
I. GENERAL STRUCTURAL PROPERTIES OF IMMUNOGLOBULIN
MOLECULES 97
II. CHANGES TO Ig STRUCTURE ASSOCIATED WITH FUNCTION 103
III. THE B CELL ANTIGEN RECEPTOR COMPLEX 108
IV. Fc RECEPTORS 108
C. EFFECTOR FUNCTIONS OF ANTIBODIES 113
I. NEUTRALIZATION 113
II. OPSONIZATION 113
III. ANTIBODY DEPENDENT CELL MEDIATED CYTOTOXICITY 114
IV. COMPLEMENT MEDIATED CLEARANCE OF ANTIGEN 115
D. IMMUNOGLOBULIN ISOTYPES IN BIOLOGICAL CONTEXT 116
I. NATURAL DISTRIBUTION OF ANTIBODIES IN THE BODY 116
II. MORE ABOUT IgM 116
III. MORE ABOUT IgD 118
IV. MORE ABOUT IgG 118
V. MORE ABOUT IgA 118
VI. MORE ABOUT IgE 119
Chapter 6: The Nature of Antigen Antibody
Interaction 121
A. THE NATURE OF B CELL IMMUNOGENS 122
I. WHAT MOLECULES CAN FUNCTION AS IMMUNOGENS? 122
II. IMMUNOGENS IN THE HUMORAL RESPONSE 122
III. PROPERTIES OF Td IMMUNOGENS 125
B. B CELL T CELL COOPERATION IN THE HUMORAL
IMMUNE RESPONSE 130
I. THE DISCOVERY OF B T COOPERATION: RECONSTITUTE
EXPERIMENTS 130
II. THE MOLECULAR BASIS OF B T COOPERATION: THE
HAPTEN CARRIER EXPERIMENTS 131
III. HAPTEN CARRIER COMPLEXES in vivo 134
IV. THE RATIONALE FOR LINKED RECOGNITION 136
C. THE MECHANICS OF ANTIGEN ANTIBODY INTERACTION 137
I. IDENTIFICATION OF B EPITOPE STRUCTURAL REQUIREMENTS 137
II. WHERE ANTIBODY AND ANTIGEN INTERACT: THE
COMPLEMENTARITY DETERMINING REGIONS 137
III. FORCES AT WORK IN SPECIFIC ANTIGEN ANTIBODY BINDING 139
IV. AFFINITY AND AVIDITY OF ANTIBODY BINDING 140
V. ANTIBODY CROSS REACTIVITY 143
Chapter 7: Exploiting Antigen Antibody
Interaction 147
A. SOURCES OF ANTIBODIES 149
I. ANTISERA 149
II. HYBRIDOMAS AND MONOCLONAL ANTIBODIES 150
B. TECHNIQUES BASED ON IMMUNE COMPLEX FORMATION 155
I. CROSS LINKING AND THE FORMATION OF
IMMUNE COMPLEXES 155
II. TECHNIQUES BASED ON THE PRECIPITIN REACTION 156
III. TECHNIQUES BASED ON AGGLUTINATION 159
IV. TECHNIQUES BASED ON COMPLEMENT FIXATION 159
C. ASSAYS BASED ON UNITARY ANTIGEN ANTIBODY
PAIR FORMATION 162
I. GENERAL CONCEPTS 162
II. DETECTION OF ANTIGEN BY TAG ASSAYS 167
III. ISOLATION AND CHARACTERIZATION OF ANTIGEN USING
ANTIBODIES 172
Chapter 8: The Immunoglobulin Genes 179
A. HISTORICAL NOTES 180
B. CHROMOSOMAL ORGANIZATION OF Ig GENES 183
I. THE Ig LOCI 183
II. GENERAL STRUCTURE OF Ig LOCI 184
III. FINE STRUCTURE OF LIGHT CHAIN GENES 185
IV. FINE STRUCTURE OF HEAVY CHAIN GENES 186
C. Ig GENE REARRANGEMENT 188
I. THE ROLE OF V(D)J RECOMBINATION 188
II. VDJ JOINING IN THE Igh LOCUS 188
III. VJ JOINING IN THE Igl AND Igk LOCI 190
IV. PRODUCTIVITY TESTING 191
V. ALLELIC EXCLUSION 192
VI. KAPPA/LAMBDA EXCLUSION 193
VII. INTRODUCING KNOCKOUT MICE 194
D. MOLECULAR MECHANISMS OF Ig GENE REARRANGEMENT 196
I. HOW DO VDJ SEGMENTS JOIN IN THE RIGHT ORDER? THE RSS 196
II. THE RECOMBINASE ENZYMES: RAG 1 AND RAG 2 197
III. SYNAPSIS, SIGNAL JOINTS, AND CODING JOINTS 198
IV. MUTATIONS OF V(D)J RECOMBINATION 200
E. ANTIBODY DIVERSITY GENERATED BY GENE
REARRANGEMENT 201
I. MULTIPLICITY OF GERM LINE GENE SEGMENTS 201
II. COMBINATORIAL DIVERSITY 201
III. JUNCTIONAL DIVERSITY 202
IV. HEAVY LIGHT Ig CHAIN PAIRING 204
F. CONTROL SEQUENCES IN THE Ig LOCI 204
I. ENHANCERS 204
II. DNA BINDING MOTIFS AND NUCLEAR TRANSCRIPTION
FACTORS 206
Chapter 9: The Humoral Response: B Cell
Development and Activation 209
A. THE MATURATION PHASE OF B CELL DEVELOPMENT 211
I. PRO B CELLS 211
II. PRE B CELLS 213
B. THE DIFFERENTIATION PHASE OF B CELL DEVELOPMENT 217
I. THE THREE SIGNAL MODEL OF B CELL ACTIVATION 218
II. CELLULAR INTERACTIONS DURING B CELL ACTIVATION 229
III. PROLIFERATION AND SOMATIC HYPERMUTATION 231
IV. AFFINITY MATURATION 234
V. ISOTYPE SWITCHING: GENERATING FUNCTIONAL DIVERSITY 235
VI. DIFFERENTIATION OF MEMORY B CELLS AND PLASMA CELLS 239
Chapter 10: MHC: The Major
Histocompatibility Complex 247
A. HISTORICAL NOTES 248
I. DISCOVERY OF THE MHC 248
II. MHC INVOLVEMENT INT CELL RECOGNITION 249
III. ELUCIDATION OF THE ANTIGEN PRESENTING FUNCTION
OF THE MHC 249
B. GENERAL ASPECTS OF THE MHC IN HUMANS AND MICE 254
I. OVERVIEW OF THE MHC PROTEINS 254
II. OVERVIEW OF THE MHC LOCI 255
III. INTRODUCING MULTIPLICITY AND POLYMORPHISM IN
THE MHC LOCI 255
IV. INTRODUCING HAPLOTYPES 259
C. MHC PROTEINS 260
I. MHC CLASS I PROTEINS 260
II. MHC CLASS II PROTEINS 262
D. MHC GENES 264
I. DETAILED ORGANIZATION OF THE H 2 COMPLEX 264
II. DETAILED ORGANIZATION OF THE HLA COMPLEX 267
E. EXPRESSION OF MHC MOLECULES 269
I. THE SXY CIITA REGULATORY SYSTEM 270
II. TNF AND IFN7 INDUCED EXPRESSION OF MHC CLASS I 271
III. EXPRESSION OF MHC CLASS Ib GENES 272
IV. OTHER REGULATORY PATHWAYS GOVERNING MHC
CLASS II GENE EXPRESSION 272
F. PHYSIOLOGY OF THE MHC 272
I. POLYMORPHISM AND THE BIOLOGICAL ROLE OF THE MHC 272
II. ALLOREACTIVITY 273
III. MHC AND IMMUNE RESPONSIVENESS 273
IV. INTRODUCING MHC AND DISEASE PREDISPOSITION 274
Chapter 11: Antigen Processing
and Presentation 279
A. THE EXOGENOUS OR ENDOCYTIC ANTIGEN PROCESSING
PATHWAY 281
I. HISTORICAL NOTES 281
II. CELLS THAT CAN FUNCTION AS APCs 282
III. MECHANISM OF ANTIGEN PROCESSING BY APCs 289
IV. FACTORS AFFECTING ANTIGEN PROCESSING AND
PRESENTATION BY APCs 294
B. THE ENDOGENOUS OR CYTOSOUC ANTIGEN
PROCESSING PATHWAY 295
I. HISTORICAL NOTES 295
II. CELLS THAT CAN FUNCTION AS TARGET CELLS 295
III. MECHANISM OF ANTIGEN PROCESSING BY TARGET CELLS 296
C. OTHER PATHWAYS OF ANTIGEN PRESENTATION 302
I. CROSS PRESENTATION 302
II. ANTIGEN PRESENTATION BY NON CLASSICAL AND
MHC LIKE MOLECULES 305
Chapter 12: The T Cell Receptor:
Structure of Its Proteins and Genes 311
A. HISTORICAL NOTES 312
I. INTRODUCTION 312
II. DISCOVERY OF THE GENES AND PROTEINS OF THE TCR 313
III. A SECOND T CELL RECEPTOR 315
B. THE STRUCTURE OFT CELL RECEPTOR PROTEINS 317
I. OVERVIEW 317
C. GENOMIC ORGANIZATION OF THE TCR AND CD3 LOCI 319
I. THE TCRa LOCUS 319
II. THE TCRp LOCUS 320
III. THE TCR /LOCUS 321
IV. THE TCR8 LOCUS 321
V. THE CD3 GENES 322
D. EXPRESSION OF TCR GENES 322
I. MECHANISM OF V(D)J RECOMBINATION IN THE TCR LOCI 322
II. TCR GENE TRANSCRIPTION AND PROTEIN ASSEMBLY 324
E. DEVELOPMENTAL ASPECTS OF V(D)J RECOMBINATION
IN THE TCR LOCI 325
I. TCRp LOCUS REARRANGEMENT 325
II. TCRa LOCUS REARRANGEMENT 326
III. TCR y AND 5 LOCUS REARRANGEMENT 327
IV. TCR LOCUS KNOCKOUT MICE 327
F. GENERATION OF DIVERSITY OF THE T CELL
RECEPTOR REPERTOIRE 327
I. MULTIPLICITY OF GERMLINE GENE SEGMENTS 327
II. COMBINATORIAL DIVERSITY 328
Contents
III. JUNCTIONAL DIVERSITY 328
IV. CHAIN PAIRING 329
G. REGULATION OF TCR GENE EXPRESSION 329
H. STRUCTURE AND FUNCTION OF THE CD3 COMPLEX 330
I. CD3 PROTEIN STRUCTURE 330
II. FUNCTIONS OF THE CD3 COMPLEX 331
III. CD3 KNOCKOUT MICE 331
I. THE CD4 AND CD8 CORECEPTORS 332
I. DISCOVERY OF CD4 AND CD8 332
II. WHATISA"CORECEPTOR"? 332
III. STRUCTURE OF CD4 334
IV. STRUCTURE OF CD8 334
V. FUNCTIONS OF CD4 AND CD8 334
J. PHYSICAL ASPECTS OF THE INTERACTION OF THE
TCR WITH ANTIGEN 336
I. STUDYING TCR PEPTIDE MHC INTERACTION 336
II. BINDING AFFINITY OF TCRap FOR ITS LIGAND 336
III. X RAY CRYSTAL STRUCTURE OFT CELL RECEPTORS 337
Chapter 13: T Cell Development 341
A. HISTORICAL NOTES 342
B. CONTEXT AND OVERVIEW 344
I. COMPARISON OF B AND T CELL ONTOGENY 344
II. OVERVIEW OFT CELL DEVELOPMENT 346
C. T CELL DEVELOPMENT IN THE BONE MARROW 347
D. T CELL DEVELOPMENT IN THE THYMUS 347
I. OVERVIEW 347
II. DN (TN) PHASE (TCR~CD4 CD8') 351
III. THE DP PHASE (CD4+CD8+) 356
IV. THE SP PHASE: CD4/CD8 LINEAGE COMMITMENT 364
E. MATURE SPTHYMOCYTES IN THE PERIPHERY 368
F. T CELL DEVELOPMENT IN AN EMBRYOLOGICAL CONTEXT 368
Chapter 14: T Cell Activation 373
A. BRINGING T CELLS AND APCs TOGETHER 375
I. L SELECTIN 376
II. LFA l 376
B. SIGNAL ONE: BINDING OF PEPTIDE MHC TO THE TCR 378
I. MODELS OF TCR TRIGGERING 378
II. FORMATION OF THE IMMUNOLOGICAL SYNAPSE (SMAC) 380
III. TCR DOWNREGULATION 382
IV. TCR SIGNAL TRANSDUaiON 383
C. SIGNAL TWO: COSTIMULATION 392
I. CD28 B7 393
II. ICOS ICOSL 396
III. PD 1 PDL1/PDL2 397
IV. 7?? B7 H3 397
V. THE TNF/TNFR RELATED COSTIMULATORY MOLECULES 397
VI. CD27/CD70 398
VII. OTHER MINOR COSTIMULATORY CONTACTS 398
D. SIGNAL THREE: CYTOKINES 398
I. THE IL 2/IL 2R SYSTEM 399
II. CONTROL OF TRANSCRIPTION OF THE IL 2 GENE 399
Chapter 15: T Cell Differentiation
and Effector Function 403
A. HISTORICAL NOTES 404
B. Th CELL DIFFERENTIATION AND EFFECTOR FUNCTION 405
I. WHAT ARE "Thl AND Th2 RESPONSES"? 405
II. PROCESS OF Th CELL DIFFERENTIATION 406
III. ACTIVATION OF EFFECTOR Thl AND Th2 CELLS 413
IV. EFFECTOR FUNCTIONS OF Th CELLS 415
C. Tc CELL DIFFERENTIATION AND CTL EFFECTOR FUNCTION 417
I. GENERATION OF EFFECTOR CTLs 418
II. MECHANISMS OF TARGET CELL DESTRUCTION BY CD8+ CTLs 419
D. COMPARISON OF NAIVE AND EFFECTOR T CELLS 422
I. TRAFFICKING AND ADHESION 422
II. ACTIVATION 423
III. FUNCTIONS AND PRODUCTS 424
E. ELIMINATION OF EFFECTOR T CELLS 424
I. ACTIVATION INDUCED CELL DEATH (AICD) 424
II. T CELL EXHAUSTION 427
F. MEMORY T CELLS 427
I. GENERATION OF MEMORY T CELLS 428
II. MEMORY T CELL MARKERS 428
III. MEMORY T CELL DISTRIBUTION 429
IV. MEMORY T CELL ACTIVATION 429
V. MEMORY T CELL DIFFERENTIATION AND EFFECTOR
FUNCTION 430
VI. MEMORY T CELL LIFE SPAN 430
Chapter 16: Immune Tolerance in the
Periphery 433
A. CONTEXT OF PERIPHERAL TOLERANCE 434
I. HISTORICAL NOTES 434
II. EVIDENCE FOR PERIPHERAL SELF TOLERANCE MECHANISMS 436
B. T CELL PERIPHERAL SELF TOLERANCE 437
I. THE IMPORTANCE OF DCs AND "DANGER SIGNALS" 437
II. MECHANISMS OF PERIPHERAL T CELL SELF TOLERANCE 439
C. B CELL PERIPHERAL SELF TOLERANCE 447
I. DEMONSTRATION OF B CELL ANERGY 447
II. MECHANISMS OF PERIPHERAL B CELL TOLERANCE 448
D. REGULATORY T CELLS 450
I. CD4+CD25+Treg CELLS 450
II. Th3 AND Trl CELLS 452
III. CD8+TS CELLS 452
IV. INFECTIOUS TOLERANCE AND LINKED SUPPRESSION 453
E. EXPERIMENTAL TOLERANCE 454
I. CHARACTERISTICS OF EXPERIMENTAL TOLERANCE 454
II. CHARACTERISTICS OF TOLEROGENS 454
III. DEGREE AND PERSISTENCE OF TOLERANCE 457
III. C2 559
IV. C3 559
D. THE ALTERNATIVE PATHWAY OF COMPLEMENT
ACTIVATION 561
I. C3 AND FACTOR B 562
II. FACTOR D AND THE ALTERNATIVE C3
CONVERTASE 562
III. PROPERDIN AND THE ALTERNATIVE C5
CONVERTASE 562
E. THE LECTIN PATHWAY OF COMPLEMENT
ACTIVATION 562
I. MBL 562
II. CRP 563
F. TERMINAL COMPONENTS OF THE COMPLEMENT
CASCADE AND FORMATION OF THE MAC 564
I. C5 564
II. C6ANDC7 564
III. C8ANDC9 565
IV. TARGETS OF THE MAC 566
G. REGULATION OF THE COMPLEMENT SYSTEM 566
I. REGULATION OF THE CLASSICAL PATHWAY 567
II. REGULATION OF THE ALTERNATIVE PATHWAY 570
III. REGULATION OF THE LECTIN PATHWAY 571
IV. REGULATION OF TERMINAL COMPONENTS 571
H. COMPLEMENT RECEPTORS AND THEIR
BIOLOGICAL ROLES 572
I. CRl 573
II. CR2 574
III. CR3 574
IV. CR4 575
V. Ciq "RECEPTORS" 575
VI. RECEPTORS FOR C3a, C4a, AND C5a 575
I. COMPLEMENT DEFICIENCIES 575
I. DEFICIENCY OF C1,C4, OR C2 576
II. DEFICIENCY OF O 577
III. DEFICIENCY OF ALTERNATIVE PATHWAY
COMPONENTS 578
IV. DEFICIENCY OF LECTIN PATHWAY COMPONENTS 578
V. DEFICIENCY OF TERMINAL COMPONENTS (C5 C9) 578
VI. DEFICIENCY OF REGULATORY PROTEINS 578
VII. DEFICIENCY OF COMPLEMENT RECEPTORS 579
J. NEW ROLES FOR COMPLEMENT? 579
Chapter 20: Mucosal and Cutaneous Immunity 583
A. MUCOSAL IMMUNITY 584
I. GALT 586
II. BALT/NALT 591
III. IMMUNE RESPONSES IN THE MAJOR MALT 593
IV. IMMUNE RESPONSES IN THE MINOR MALT 599
B. CUTANEOUS IMMUNITY 600
I. COMPONENTS OF SALT 600
II. IMMUNE RESPONSES IN SALT 605
Chapter 21: Comparative Immunology 611
A. OVERVIEW 612
I. REPRISE OF THE ANIMAL KINGDOM 612
II. FORCES SHAPING THE EVOLUTION OF IMMUNE
RECOGNITION 614
B. ELEMENTS OF INNATE IMMUNITY 618
I. ANATOMICAL AND PHYSIOLOGICAL BARRIERS 618
II. INNATE IMMUNE RESPONSE CELLS AND THEIR
RECOGNITION STRUCTURES 618
III. CYTOKINES 620
IV. PATHOGEN ELIMINATION 621
C. ELEMENTS OF ADAPTIVE IMMUNITY 626
I. LYMPHOID TISSUES 626
II. BCR 628
III. MHC 632
IV. TCR 634
PART II: CLINICAL IMMUNOLOGY 629
Chapter 22: Immunity to Pathogens 641
A. OVERVIEW 642
I. WHAT IS A "PATHOGEN" 642
II. WHAT IS "DISEASE" 644
III. INNATE DEFENSE AGAINST PATHOGENS 645
B. IMMUNITY TO EXTRACELLULAR BACTERIA 647
I. WHAT ARE EXTRACELLULAR BACTERIA? 647
II. EFFECTOR MECHANISMS 652
III. EVASION STRATEGIES 654
C. IMMUNITY TO INTRACELLULAR BACTERIA 656
I. WHAT ARE INTRACELLULAR BACTERIA? 656
II. EFFECTOR MECHANISMS 658
III. EVASION STRATEGIES 662
D. IMMUNITY TO VIRUSES 664
I. WHAT ARE VIRUSES? 664
II. EFFECTOR MECHANISMS 669
III. EVASION STRATEGIES 672
E. IMMUNITY TO PARASITES 680
I. WHAT ARE PARASITES? 680
II. EFFECTOR MECHANISMS 683
III. EVASION STRATEGIES 686
F. IMMUNITY TO FUNGI 688
I. WHAT ARE FUNGI? 688
II. EFFECTOR MECHANISMS 689
III. EVASION STRATEGIES 690
C. THE MYSTERIOUS PRIONS 691
Chapter 23: Vaccines and Clinical Immunization 695
A. VACCINATION: PUBLIC HEALTH SUCCESSES
AND CHALLENGES 696
B. HISTORICAL NOTES 698
C. GENERAL PRINCIPLES OF VACCINE DESIGN 703
I. BIOLOGICAL PURPOSE OF A VACCINE 703
II. VACCINE EFFICACY AND SAFETY 704
D. TYPES OF VACCINES 705
I. LIVE, ATTENUATED VACCINES 705
II. KILLED VACCINES 708
III. TOXOIDS 709
IV. SUBUNIT VACCINES 709
V. PEPTIDE VACCINES 710
VI. RECOMBINANT VECTOR DNA VACCINES 711
VII. "NAKED DNA" VACCINES 713
VIII. ANTI IDIOTYPIC VACCINES 716
E. FACTORS AFFECTING VACCINATION 718
I. SCHEDULING OF VACCINE ADMINISTRATION AND BOOSTING 718
II. ROUTES OF VACCINE ADMINISTRATION 722
III. ADJUVANTS AND DELIVERY VEHICLES 722
F. PROPHYLACTIC VACCINES 727
I. ANTHRAX 727
II. CHOLERA 729
III. DIPHTHERIA, TETANUS, AND PERTUSSIS 729
IV. HAEMOPHILUSINFLUENZAETYPEb 730
V. HEPATITIS A 731
VI. HEPATITIS B 731
VII. INFLUENZA VIRUS 731
VIII. JAPANESE B ENCEPHALITIS 732
IX. MEASLES, MUMPS, AND RUBELLA 732
X. MENINGOCOCCUS 734
XL PLAGUE 734
XII. POLIO 734
XIII. RABIES 735
XIV. STREPTOCOCCUS PNEUMONIAE 735
XV. TUBERCULOSIS 735
XVI. TYPHOID FEVER 736
XVII. VARICELLA ZOSTER (CHICKEN POX) 738
XVIII. VARIOLA (SMALLPOX) 738
XIX. YELLOW FEVER 739
G. THE "DARK SIDE" OF VACCINES 739
I. ADVERSE EFFECTS OF VACCINES 739
II. FAILURE TO VACCINATE AND OPPOSITION TO
VACCINATION 740
H. PROPHYLACTIC VACCINES OF THE FUTURE 740
I. PASSIVE IMMUNIZATION 741
J. THERAPEUTIC VACCINES 744
I. VACCINES TO COMBAT TUMORS 744
II. VACCINES TO CURE CHRONIC VIRAL
DISEASES 745
III. VACCINES TO MITIGATE INDIRECT EFFECTS OF
INFECTIOUS DISEASE 745
IV. VACCINES TO MITIGATE AUTOIMMUNITY 745
V. VACCINES TO MITIGATE ALLERGY 746
VI. VACCINES TO SUPPRESS FERTILITY 746
VII. VACCINES TO SUPPRESS ADDICTION 747
Chapter 24: Primary Immunodeficiencies 751
A. GENERAL CONCEPTS 752
I. DIAGNOSIS OF Pis 752
II. TREATMENT OF Pis 753
III. FOCUS OF PI RESEARCH 754
B. PRIMARY IMMUNODEFICIENCIES DUE TO DEFECTS
IN ADAPTIVE IMMUNE RESPONSES 754
I. COMBINED IMMUNODEFICIENCIES 754
II. T CELL SPECIFIC IMMUNODEFICIENCIES 763
III. B CELL SPECIFIC IMMUNODEFICIENCIES 765
IV. ADAPTIVE IMMUNODEFICIENCIES DUE TO DEFECTS IN
DNA REPAIR 768
V. LYMPHOPROLIFERAT1VE IMMUNODEFICIENCY SYNDROMES 773
VI. OTHER ADAPTIVE IMMUNODEFICIENCIES 774
C. PRIMARY IMMUNODEFICIENCIES DUE TO DEFECTS
IN THE INNATE IMMUNE RESPONSE 776
I. IMMUNODEFICIENCIES AFFECTING PHAGOCYTE
RESPONSES 776
II. COMPLEMENT DEFICIENCIES 780
Chapter 25: HIV and Acquired
Immunodeficiency Syndrome 785
A. HISTORICAL NOTES 786
B. WHAT IS HIV? 788
I. OVERVIEW OF THE HIV 1 LIFE CYCLE 788
II. OVERVIEW OF HIV STRUCTURE 789
C. STRUCTURE AND FUNCTION OF HIV PROTEINS 791
I. VIRAL PROTEINS DERIVED FROM THE gag GENE 792
II. VIRAL PROTEINS DERIVED FROM THE pol GENE 792
III. VIRAL PROTEINS DERIVED FROM THE em GENE 793
IV. REGULATORY PROTEINS 794
V. ACCESSORY PROTEINS 795
D. HIV INFECTION AND AIDS 796
I. CLINICAL VIEW OF HIV INFECTION 796
II. MOLECULAR EVENTS UNDERLYING HIV INFECTION 798
E. THE IMMUNE RESPONSE DURING HIV INFECTION 802
I. Th RESPONSES 802
II. CTL RESPONSES 803
III. ANTIBODY RESPONSES 803
IV. CYTOKINES 804
V. CEM 15 (APOBEC3G) 805
VI. NK CELLS 805
VII. COMPLEMENT 805
F. HOST FACTORS INFLUENCING THE COURSE OF HIV
INFECTION 805
I. RESISTANCE TO HIV INFECTION 806
II. CLINICAL COURSE VARIABILITY 806
G. EPIDEMIOLOGY AND SOCIOLOGY OF HIV INFECTION 808
I. TRANSMISSION OF HIV 808
II. EPIDEMIOLOGY 808
III. SOCIETAL AND ECONOMIC IMPACT OF AIDS 812
H. ANIMAL MODELS OF AIDS 813
I. PRIMATE MODELS OF AIDS 813
II. MOUSE MODELS OF AIDS 814
I. HIV VACCINES 815
I. BARRIERS TO HIV VACCINE DEVELOPMENT 815
II. EXPERIMENTAL AIDS VACCINES IN ANIMALS 816
III. EXPERIMENTAL AIDS VACCINES IN HUMANS 818
IV. PASSIVE IMMUNIZATION 819
J. TREATMENT OF HIV INFECTION WITH
ANTI RETROVIRAL DRUGS 819
I. PROTEASE INHIBITORS 820
II. NUCLEOSIDE RT INHIBITORS 820
III. NON NUCLEOSIDE RT INHIBITORS 820
IV. FUSION INHIBITORS 820
V. IMMUNE RESPONSES AND ANTI RETROVIRAL THERAPY 821
VI. OTHER DRUG THERAPY ISSUES 821
Chapter 26: Tumor Immunology 825
A. HISTORICAL NOTES 826
B. TUMOR BIOLOGY 829
I. WHAT IS A TUMOR AND WHAT IS A CANCER? 829
II. CARCINOGENESIS 832
III. TUMORIGENIC GENETIC ALTERATIONS 834
IV. CARCINOGENS 839
C. IMMUNE RESPONSES TO CANCER 842
I. THE CONCEPT OF IMMUNOSURVE1LLANCE 842
II. TUMOR ANTIGENS 842
III. IMMUNE RESPONSES TO TUMOR CELLS 845
IV. HURDLES TO EFFECTIVE ANTI TUMOR IMMUNITY 849
D. CANCER THERAPY 851
I. RADIATION THERAPY 851
II. CHEMOTHERAPY 852
III. TUMOR HYPOXIA 853
IV. IMMUNOTHERAPY 856
Chapter 27: Transplantation 873
A. HISTORICAL NOTES 874
B. THE MOLECULAR BASIS OF
ALLORECOGNITION 880
I. DIRECT ALLORECOGNITION 881
II. INDIRECT ALLORECOGNITION 881
C. MINOR HISTOCOMPATIBILITY ANTIGENS 881
D. TYPES OF CLINICAL REJECTION AND THEIR MECHANISMS 885
I. HYPERACUTE GRAFT REJECTION 885
II. ACUTE GRAFT REJECTION 886
III. CHRONIC GRAFT REJECTION 888
IV. THEROLEOFCYTOKINESANDCHEMOKINESIN
GRAFT REJECTION 888
V A ROLE FOR TLRs IN GRAFT REJECTION? 888
VI. GRAFT VERSUS HOST DISEASE (GvHD) IN SOLID
ORGAN TRANSPLANTS 890
E. HLA TYPING 890
I. SEROLOGICAL TECHNIQUES 891
II. TYPING BY CELLULAR RESPONSE: MLR 892
III. TYPING AT THE DNA LEVEL 893
F. IMMUNOSUPPRESSION 896
I. AZATHIOPRINE 896
II. CYCLOSPORINE A 896
III. TACROLIMUS 897
IV. MYCOPHENOLATE MOFETIL 897
V. SIROLIMUS 897
VI. MALONONITRILAMIDES (MNAs) 898
VII. FTY720 898
VIII. FLUDARABINE 898
IX. ANTI LYMPHOCYTE ANTIBODIES 898
X. CYTOKINES 899
C. INDUCTION OF GRAFT TOLERANCE 899
I. BONE MARROW MANIPULATION 900
II. THYMIC MANIPULATION 901
III. COSTIMULATORY BLOCKADE 901
IV. REGULATORY T CELLS 903
V. REGULATION BY NKT CELLS 904
VI. TOLEROGENIC DCs 905
VII. CAVEATS 905
H. XENOTRANSPLANTATION 906
I. CHOICE OF SPECIES FOR XENOTRANSPLANTATION 907
II. XENOGRAFT REJECTION 907
III. TRANSMISSION OF ZOONOTIC DISEASES 909
IV. REGULATORY AND LEGAL OBSTACLES 910
V. ETHICAL AND MORAL CONSIDERATIONS 910
I. BLOOD TRANSFUSIONS 910
I. ALLOREACTIVITY IN BLOOD TRANSFUSIONS 910
II. ENSURING THE SAFETY OF THE BLOOD SUPPLY 913
J. HEMATOPOIETIC CELL TRANSPLANTATION (HCT) 913
I. GRAFT REJECTION IN HQ 914
II. GRAFT VERSUS HOST DISEASE (GvHD) IN Ha 915
III. GRAFT VERSUS LEUKEMIA (GvL) EFFEa 916
IV. BENEFICIAL EFFEaS OF ALLOGENEICNK CELLS 916
V. INFECTION CONTROL 917
K. GENE THERAPY IN TRANSPLANTATION 917
Chapter 28: Allergy and Hypersensitivity 923
A. HISTORICAL NOTES 924
B. TYPE I HYPERSENSITIVITY: IMMEDIATE OR
IgE MEDIATED 925
I. WHAT IS TYPE I HS? 925
II. MECHANISMS UNDERLYING TYPE I HS 927
III. EXAMPLES OF TYPE I HS 930
IV. ROLESOFFceRANDIgEINTYPEIHS 934
V. ALLERGEN BIOLOGY 937
VI. DIAGNOSIS AND THERAPY OF TYPE I HS 940
Contents
C. TYPE II HYPERSENSITIVITY: DIRECT ANTIBODY MEDIATED
CYTOTOXICITY 949
I. WHAT IS TYPE II HS? 949
II. MECHANISMS UNDERLYING TYPE II HS 949
III. EXAMPLES OF TYPE II HS: CYTOTOXICITY AGAINST
MOBILE CELLS 949
IV. EXAMPLES OF TYPE II HS: CYTOTOXICITY AGAINST
FIXED TISSUES 953
D. TYPE III HYPERSENSITIVITY: IMMUNE
COMPLEX MEDIATED INJURY 954
I. WHAT IS TYPE III HS? 954
II. MECHANISM UNDERLYING TYPE III HS 954
III. EXAMPLES OF TYPE III HS 956
E. TYPE IV HYPERSENSITIVITY: DELAYED TYPE OR
CELL MEDIATED HYPERSENSITIVITY 957
I. WHAT IS TYPE IV HS? 957
II. CHRONIC DTH REACTIONS 957
III. CONTACT HYPERSENSITIVITY (CHS) 958
IV. HYPERSENSITIVITY PNEUMONITIS (HP) 960
Chapter 29: Autoimmune Disease 963
A. OVERVIEW 964
I. HISTORICAL NOTES 964
II. WHAT CHARACTERIZES AN AUTOIMMUNE DISEASE? 965
III. OUR APPROACH TO DISCUSSING AUTOIMMUNITY 969
B. EXAMPLES OF HUMAN AUTOIMMUNE DISEASES 969
I. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) 970
II. RHEUMATOID ARTHRITIS (RA) 971
III. RHEUMATIC FEVER (RF) 972
IV. TYPE 1 DIABETES MELLITUS (T1 DM) 973
V. MULTIPLE SCLEROSIS (MS) 974
VI. ANKYLOSING SPONDYLITIS (AS) 977
VII. SJOGREN SYNDROME (SS) 977
VIII. AUTOIMMUNE THYROIDITIS 978
IX. AUTOIMMUNE THROMBOCYTOPENIC PURPURA 980
X. SCLERODERMA (SD) 981
XI. MYASTHENIA GRAVIS (MG) 982
XII. KAWASAKI DISEASE (KD) 982
XIII. POLYMYOSITIS (PM) 983
XIV. GUILLAIN BARRE SYNDROME (GBS) 984
XV. PSORIASIS (PS) 984
XVI. ANT1 PHOSPHOLIPID SYNDROME (APS) 985
XVII. INFLAMMATORY BOWEL DISEASE (IBD): CROHN'S
DISEASE (CD) AND ULCERATIVE COLITIS (UC) 985
XVIII. PEMPHIGUS (PG) 986
XIX. GOODPASTURE'S SYNDROME (GS) 986
XX. IMMUNODYSREGULATION, POLYENDOCRINOPATHY,
ENTEROPATHY X LINKED (IPEX) SYNDROME 986
C. ANIMAL MODELS OF AUTOIMMUNE DISEASE 986
I. NZB/W Fl MICE 988
II. MRL/lpr AND gld MICE 988
III. NOD MICE 989
IV. Scurfy M\Ct. 990
V. THYMECTOMY OF NEONATAL MICE 991
VI. IBD MODELS 991
VII. EXPERIMENTAL AUTOIMMUNE ENCEPHALITIS (EAE) 991
VIII. COLLAGEN INDUCED ARTHRITIS (CIA) 992
IX. EXPERIMENTAL AUTOIMMUNE MYASTHENIA CRAVIS (EAMG) 992
X. EXPERIMENTAL AUTOIMMUNE THYROIDITIS (EAT) 993
XI. EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU) 993
XII. EXPERIMENTAL AUTOIMMUNE MYOCARDITIS (EAM) 994
XIII. OTHER POTENTIAL AID MODELS 994
D. DETERMINANTS OF AUTOIMMUNE DISEASE 995
I. GENETIC PREDISPOSITION 995
II. ENVIRONMENTAL TRIGGERS 998
III. HORMONAL INFLUENCES 1000
IV. REGIONAL/ETHNIC DIFFERENCES 1000
E. MECHANISMS UNDERLYING AID 1001
I. PATHOGEN RELATED MECHANISMS 1002
II. INHERENT DEFECTS IN IMMUNE SYSTEM CELLS 1006
III. ALTERATIONS TO CYTOKINE EXPRESSION 1010
IV. DEFECTS IN THE COMPLEMENT SYSTEM 1011
V. EPITOPE SPREADING 1011
F. THERAPY OF AID 1012
I. CONVENTIONAL TREATMENTS 1012
II. IMMUNOTHERAPEUTICS 1014
G. RELATIONSHIP BETWEEN AID AND CANCER 1020
Chapter 30: Hematopoietic Cancers 1025
A. HISTORICAL NOTES 1026
B. OVERVIEW OF HEMATOPOIETIC CANCER BIOLOGY 1027
I. WHAT ARE HEMATOPOIETIC CANCERS? 1027
II. HEMATOPOIETIC CANCER CARCINOGENESIS 1029
C. TERMS USED IN CLINICAL ASSESSMENT AND
TREATMENT OF HC 1030
D. LEUKEMIAS 1035
I. ACUTE MYELOID LEUKEMIA (AML) 1035
II. CHRONIC MYELOGENOUS LEUKEMIA (CML) 1039
III. ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) 1041
IV. CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) 1044
V. OTHER LEUKEMIAS 1045
E. PLASMA CELL DYSCRASIAS 1046
I. MONOCLONAL GAMMOPATHY OF UNDETERMINED
SIGNIFICANCE (MGUS) 1047
II. WALDENSTROM'S MACROGLOBULINEMIA (WM) 1047
III. MYELOMA 1047
F. LYMPHOMAS 1050
I. HODGKIN'S LYMPHOMA (HL) 1050
II. NON HODGKIN'S LYMPHOMAS 1054
Appendix: CD Molecules 1065
Glossary 1119
Index 1179 |
| any_adam_object | 1 |
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| author | Mak, Tak W. 1945- Saunders, Mary E. |
| author_GND | (DE-588)131833316 |
| author_facet | Mak, Tak W. 1945- Saunders, Mary E. |
| author_role | aut aut |
| author_sort | Mak, Tak W. 1945- |
| author_variant | t w m tw twm m e s me mes |
| building | Verbundindex |
| bvnumber | BV021755250 |
| callnumber-first | Q - Science |
| callnumber-label | QR181 |
| callnumber-raw | QR181 |
| callnumber-search | QR181 |
| callnumber-sort | QR 3181 |
| callnumber-subject | QR - Microbiology |
| classification_rvk | XD 3000 |
| ctrlnum | (OCoLC)635199304 (DE-599)BVBBV021755250 |
| dewey-full | 616.07/9 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 616 - Diseases |
| dewey-raw | 616.07/9 |
| dewey-search | 616.07/9 |
| dewey-sort | 3616.07 19 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| discipline_str_mv | Medizin |
| format | Book |
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| id | DE-604.BV021755250 |
| illustrated | Illustrated |
| index_date | 2024-07-02T15:33:16Z |
| indexdate | 2024-07-09T20:43:18Z |
| institution | BVB |
| isbn | 0120884518 9780120884513 |
| language | English |
| lccn | 2005024292 |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-014968415 |
| oclc_num | 635199304 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-526 |
| owner_facet | DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-526 |
| physical | XX, 1216 S. Ill., graph. Darst. 1 CD-ROM (12 cm) |
| publishDate | 2006 |
| publishDateSearch | 2006 |
| publishDateSort | 2006 |
| publisher | Elsevier Acad. Press |
| record_format | marc |
| spelling | Mak, Tak W. 1945- Verfasser (DE-588)131833316 aut The immune response basic and clinical principles ; [CD-ROM included] Tak W. Mak and Mary E. Saunders Amsterdam [u.a.] Elsevier Acad. Press 2006 XX, 1216 S. Ill., graph. Darst. 1 CD-ROM (12 cm) txt rdacontent n rdamedia nc rdacarrier Immunology Immunity Immune System Immune System Diseases Immunreaktion (DE-588)4133841-8 gnd rswk-swf Immunreaktion (DE-588)4133841-8 s b DE-604 Saunders, Mary E. Verfasser aut http://www.loc.gov/catdir/toc/ecip0518/2005024292.html Table of contents only http://www.loc.gov/catdir/enhancements/fy0623/2005024292-d.html Publisher description HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014968415&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Mak, Tak W. 1945- Saunders, Mary E. The immune response basic and clinical principles ; [CD-ROM included] Immunology Immunity Immune System Immune System Diseases Immunreaktion (DE-588)4133841-8 gnd |
| subject_GND | (DE-588)4133841-8 |
| title | The immune response basic and clinical principles ; [CD-ROM included] |
| title_auth | The immune response basic and clinical principles ; [CD-ROM included] |
| title_exact_search | The immune response basic and clinical principles ; [CD-ROM included] |
| title_exact_search_txtP | The immune response basic and clinical principles ; [CD-ROM included] |
| title_full | The immune response basic and clinical principles ; [CD-ROM included] Tak W. Mak and Mary E. Saunders |
| title_fullStr | The immune response basic and clinical principles ; [CD-ROM included] Tak W. Mak and Mary E. Saunders |
| title_full_unstemmed | The immune response basic and clinical principles ; [CD-ROM included] Tak W. Mak and Mary E. Saunders |
| title_short | The immune response |
| title_sort | the immune response basic and clinical principles cd rom included |
| title_sub | basic and clinical principles ; [CD-ROM included] |
| topic | Immunology Immunity Immune System Immune System Diseases Immunreaktion (DE-588)4133841-8 gnd |
| topic_facet | Immunology Immunity Immune System Immune System Diseases Immunreaktion |
| url | http://www.loc.gov/catdir/toc/ecip0518/2005024292.html http://www.loc.gov/catdir/enhancements/fy0623/2005024292-d.html http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014968415&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT maktakw theimmuneresponsebasicandclinicalprinciplescdromincluded AT saundersmarye theimmuneresponsebasicandclinicalprinciplescdromincluded |