Immunology:
Gespeichert in:
| Späterer Titel: | Owen, Judith Immunology |
|---|---|
| Hauptverfasser: | , , |
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
New York
Freeman
2007
|
| Ausgabe: | 6. ed. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Kuby immunology |
| Beschreibung: | Getr. Zählung zahlr. Ill. und graph. Darst. |
| ISBN: | 9780716767640 9781429202114 1429202114 0716785900 9780716785903 |
Internformat
MARC
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| 100 | 1 | |a Kindt, Thomas J. |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Immunology |c Kuby. Thomas J. Kindt ; Richard A. Goldsby ; Barbara A. Osborne |
| 246 | 1 | 3 | |a Kuby Immunology |
| 250 | |a 6. ed. | ||
| 264 | 1 | |a New York |b Freeman |c 2007 | |
| 300 | |a Getr. Zählung |b zahlr. Ill. und graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Kuby immunology | ||
| 650 | 7 | |a Immunité naturelle |2 rasuqam | |
| 650 | 4 | |a Immunologie | |
| 650 | 7 | |a Immunologie |2 gtt | |
| 650 | 7 | |a Immunologie |2 rasuqam | |
| 650 | 7 | |a Système immunitaire |2 rasuqam | |
| 650 | 4 | |a Immune System | |
| 650 | 4 | |a Immunity | |
| 650 | 4 | |a Immunology | |
| 650 | 0 | 7 | |a Immunologie |0 (DE-588)4026637-0 |2 gnd |9 rswk-swf |
| 655 | 7 | |0 (DE-588)4123623-3 |a Lehrbuch |2 gnd-content | |
| 689 | 0 | 0 | |a Immunologie |0 (DE-588)4026637-0 |D s |
| 689 | 0 | |5 DE-604 | |
| 700 | 1 | |a Goldsby, Richard A. |e Verfasser |4 aut | |
| 700 | 1 | |a Osborne, Barbara A. |e Verfasser |4 aut | |
| 700 | 1 | |a Kuby, Janis |e Begründer des Werks |4 oth | |
| 785 | 0 | 0 | |i 7. Aufl u.d.T. |a Owen, Judith |t Immunology |w (DE-604)BV041130775 |
| 856 | 4 | 2 | |m SWB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014968503&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-014968503 | ||
Datensatz im Suchindex
| _version_ | 1804135614661001216 |
|---|---|
| adam_text | IMAGE 1
PART
INTRODUCTION 1 OVERVIEW OF THE IMMUNE SYSTEM 2 CELLS AND ORGANS OF THE
IMMUNE SYSTEM 3 INNATE IMMUNITY
1
23 52
PART GENERATION OF B-CELL AND T-CELL RESPONSES
4 ANTIGENS AND ANTIBODIES 5 ORGANIZATION AND EXPRESSION OF
IMMUNOGLOBULIN GENES 6 ANTIGEN-ANTIBODY INTERACTIONS: PRINCIPLES AND
APPLICATIONS 7 THE COMPLEMENT SYSTEM 8 THE MAJOR HISTOCOMPATIBILITY
COMPLEX AND ANTIGEN PRESENTATION
9 T-CELL RECEPTOR 10 T-CELL MATURATION, ACTIVATION, AND DIFFERENTIATION
11 B-CELL GENERATION, ACTIVATION, AND DIFFERENTIATION
76 111 145 168 189 223
245 271
PART IMMUNE EFFECTOR MECHANISMS 12 CYTOKINES 13 LEUKOCYTE ACTIVATION AND
MIGRATION 14 CELL-MEDIATED CYTOTOXIC RESPONSES 15 HYPERSENSITIVITY
REACTIONS 16 TOLERANCE AND AUTOIMMUNITY
302 327 351
371 401
PART IV THE IMMUNE SYSTEM IN HEALTH AND DISEASE 17 TRANSPLANTATION
IMMUNOLOGY 425
18 IMMUNE RESPONSE TO INFECTIOUS DISEASES 447
19 VACCINES 475
20 AIDS AND OTHER IMMUNODEFICIENCIES 493
21 CANCER AND THE IMMUNE SYSTEM 525
22 EXPERIMENTAL SYSTEMS 546
APPENDIX I: CD ANTIGENS A-1
APPENDIX II: CYTOKINES A-27
GLOSSARY G-1
ANSWERS AN-1
INDEX 1-1
IMAGE 2
PREFACE
VII
CELLS AND ORGANS OF THE
IMMUNE SYSTEM 23
1 OVERVIEW OF THE IMMUNE SYSTEM 1
HISTORICAL PERSPECTIVE 2
EARLY VACCINATION STUDIES LED THE WAY TO IMMUNOLOGY 2
VACCINATION IS AN ONGOING, WORLDWIDE ENTERPRISE 3
EARLY STUDIES OF HUMORAL AND CELLULAR IMMUNITY 4
THEORETICAL CHALLENGES 5
INFECTION AND IMMUNITY 7
INNATE AND ADAPTIVE IMMUNITY 8
PHAGOCYTIC CELLS ARE A BARRIER TO INFECTION 9
SOLUBLE MOLECULES CONTRIBUTE TO INNATE IMMUNITY 9 COLLABORATION BETWEEN
INNATE AND ADAPTIVE IMMUNITY INCREASES IMMUNE RESPONSIVENESS ADAPTIVE
IMMUNITY IS HIGHLY SPECIFIC
LYMPHOCYTES AND ANTIGEN-PRESENTING CELLS COOPERATE IN ADAPTIVE IMMUNITY
ANTIGEN-PRESENTING CELLS INTERACT WITH T CELLS HUMORAL AND CELLULAR
IMMUNE RESPONSES EXHIBIT
DIFFERENT EFFECTOR FUNCTIONS THE ANTIGEN RECEPTORS OF B AND T
LYMPHOCYTES ARE DIVERSE THE MAJOR HISTOCOMPATIBILITY MOLECULES BIND
ANTIGENIC PEPTIDES ANTIGENIC SELECTION OF LYMPHOCYTES CAUSES CLONAL
EXPANSION
IMMUNE DYSFUNCTION AND ITS CONSEQUENCES
CLINICAL FOCUS ALLERGIES AND ASTHMA ARE SERIOUS PUBLIC HEALTH PROBLEMS
9
10
12
14
14
14
16
16
18
20
HEMATOPOIESIS 23
HEMATOPOIESIS IS REGULATED AT THE GENETIC LEVEL 24 HEMATOPOIETIC
HOMEOSTASIS INVOLVES MANY FACTORS 26 PROGRAMMED CELL DEATH IS AN
ESSENTIAL HOMEOSTATIC MECHANISM 26
HEMATOPOIETIC STEM CELLS CAN BE ENRICHED 28
CELLS OF THE IMMUNE SYSTEM 30
LYMPHOID CELLS 30
CLINICAL FOCUS STEM CELLS-CLINICAL USES AND POTENTIAL 32
B LYMPHOCYTES (B CELLS) 34
T LYMPHOCYTES (T CELLS) 34
B- AND T-CELL POPULATIONS COMPRISE SUBPOPULATIONS OF CLONES 35 NATURAL
KILLER CELLS 35
MONONUCLEAR PHAGOCYTES 36
PHAGOCYTOSIS IS FOLLOWED BY DIGESTION AND PRESENTATION OF ANTIGEN 36
GRANULOLYTIC CELLS 37
MAST CELTS 38
DENDRITIC CELLS 38
FOLLICULAR DENDRITIC CELLS 40
ORGANS OF THE IMMUNE SYSTEM 40
PRIMARY LYMPHOID ORGANS 40
SECONDARY LYMPHOID ORGANS 43
LYMPHOID CELLS AND ORGANS-EVOLUTIONARY COMPARISONS 49
3 INNATE IMMUNITY 52
ANATOMICAL BARRIERS 53
CONNECTIONS BETWEEN INNATE AND ADAPTIVE IMMUNITY 55
IMAGE 3
XIV
C O N T E N TS
INFLAMMATION 57
LEUKOCYTE EXTRAVASATION IS A HIGHLY REGULATED, MULTISTEP PROCESS 59
SOLUBLE MOLECULES AND MEMBRANE-ASSOCIATED RECEPTORS 59
ANTIMICROBIAL PEPTIDES CONTRIBUTE TO THE INNATE DEFENSE AGAINST BACTERIA
AND FUNGI 59
PROTEINS OF THE ACUTE PHASE RESPONSE CONTRIBUTE TO INNATE IMMUNITY 61
INNATE IMMUNITY USES A VARIETY OF RECEPTORS TO DETECT INFECTION 61
TOLL-LIKE RECEPTORS 62
CELL TYPES OF INNATE IMMUNITY 65
NEUTROPHILS ARE SPECIALIZED FOR PHAGOCYTOSIS AND KILLING 65
CLINICAL FOCUS C-REACTIVE PROTEIN IS A KEY MARKER OF CARDIOVASCULAR RISK
66
MACROPHAGES DEPLOY A NUMBER OF ANTIPATHOGEN DEVICES 66
NK CELLS ARE AN IMPORTANT FIRST LINE OF DEFENSE AGAINST VIRUSES AND
PROVIDE A KEY ACTIVATING SIGNAL TO OTHER CELLS 68
DENDRITIC CELLS ENGAGE PATHOGENS AND INVOKE ADAPTIVE IMMUNE RESPONSES BY
ACTIVATING T CELLS 68
SIGNAL TRANSDUCTION PATHWAYS 69
TLR SIGNALING IS TYPICAL OF SIGNAL TRANSDUCTION PATHWAYS 69
UBIQUITY OF INNATE IMMUNITY 71
PART II GENERATION OF B-CELL
AND T-CELL RESPONSES
ANTIGENS AND ANTIBODIES 76
IMMUNOGENICITY VERSUS ANTIGENICITY 77
HAPTENS ARE VALUABLE RESEARCH AND DIAGNOSTIC TOOLS 77
PROPERTIES OF THE IMMUNOGEN CONTRIBUTE TO IMMUNOGENICITY 78 THE
BIOLOGICAL SYSTEM CONTRIBUTES TO HETEROGENICITY 80
EPITOPES 81
B-CELL EPITOPES HAVE CHARACTERISTIC PROPERTIES 81
BASIC STRUCTURE OF ANTIBODIES 84
ANTIBODIES ARE HETERODIMERS 85
CHEMICAL AND ENZYMATIC METHODS REVEALED BASIC ANTIBODY STRUCTURE 85
LIGHT-CHAIN SEQUENCES REVEALED CONSTANT AND VARIABLE REGIONS 87
THERE ARE FIVE MAJOR CLASSES OF HEAVY CHAINS 87 IMMUNOGLOBULINS POSSESS
MULTIPLE DOMAINS BASED ON THE IMMUNOGLOBULIN FOLD 87
ANTIBODY BINDING SITE 89
CDRS BIND ANTIGEN 90
CONFORMATIONAL CHANGES MAY BE INDUCED BY ANTIGEN BINDING 92
CONSTANT-REGION DOMAINS 93
ANTIBODY-MEDIATED EFFECTOR FUNCTIONS 94
OPSONIZATION IS PROMOTED BY ANTIBODY 94
ANTIBODIES ACTIVATE COMPLEMENT 95
ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY (ADCC) KILLS CELLS 95
SOME ANTIBODIES CAN CROSS EPITHELIAL LAYERS BY TRANSCYTOSIS 95
ANTIBODY CLASSES AND BIOLOGICAL ACTIVITY 95
IMMUNOGLOBULIN G (IGG) 95
IMMUNOGLOBULIN M (IGM) 96
CLINICAL FOCUS PASSIVE ANTIBODY THERAPY 98
IMMUNOGLOBULIN A (IGA) 99
IMMUNOGLOBULIN E (IGE) 100
IMMUNOGLOBULIN D (IGD) 100
ANTIGENIC DETERMINANTS ON IMMUNOGLOBULINS 100
ISOTYPE 101
ALLOTYPE 101
IDIOTYPE 101
THE B-CELL RECEPTOR 102
FC RECEPTORS BIND TO FC REGIONS OF ANTIBODIES 102
THE IMMUNOGLOBULIN SUPERFAMILY 103
MONOCLONAL ANTIBODIES 105
MONCLONAL ANTIBODIES HAVE IMPORTANT CLINICAL USES 106 ABZYMESARE
MONOCLONAL ANTIBODIES THAT CATALYZE REACTIONS 106
ORGANIZATION AND EXPRESSION OF
IMMUNOGLOBULIN GENES 111
DEVISING A GENETIC MODEL COMPATIBLE WITH IG STRUCTURE 112
GERM-LINE AND SOMATIC-VARIATION MODELS CONTENDED TO EXPLAIN ANTIBODY
DIVERSITY 113
DREYER AND BENNETT PROPOSED A REVOLUTIONARY TWO-GENE ONE-POLYPEPTIDE
MODEL 113
TONEGAWA S BOMBSHELL-IMMUNOGLOBULIN GENES REARRANGE 114
MULTIGENE ORGANIZATION OF IG GENES 115
EACH MULTIGENE FAMILY HAS DISTINCT FEATURES 115 HEAVY-CHAIN MULTIGENE
FAMILY 115
IMAGE 4
C O N T E N TS
XV
VARIABLE-REGION GENE REARRANGEMENTS
LIGHT-CHAIN DNA UNDERGOES V-J REARRANGEMENTS HEAVY-CHAIN DNA UNDERGOES
V-D-J REARRANGEMENTS
MECHANISM OF VARIABLE-REGION
GENE REARRANGEMENTS
RECOMBINATION SIGNAL SEQUENCES DIRECT RECOMBINATION GENE SEGMENTS ARE
JOINED BY RECOMBINASES IG-CENE REARRANGEMENTS MAY BE PRODUCTIVE
OR NONPRODUCTIVE ALLELIC EXCLUSION ENSURES A SINGLE ANTIGENIC
SPECIFICITY
GENERATION OF ANTIBODY DIVERSITY
THERE ARE NUMEROUS GERM-LINE V, D, AND J GENE SEGMENTS COMBINATORIAL V-J
AND V-D-J JOINING GENERATES DIVERSITY JUNCTIONAL FLEXIBILITY ADDS
DIVERSITY
P-ADDITION ADDS DIVERSITY AT PALINDROMIC SEQUENCES N-ADDITION ADDS
CONSIDERABLE DIVERSITY BY ADDITION OF NUCLEOTIDES SOMATIC HYPERMUTATION
ADDS DIVERSITY
IN ALREADY-REARRANGED GENE SEGMENTS A FINAL SOURCE OF DIVERSITY IS
COMBINATORIAL ASSOCIATION OF HEAVY AND LIGHT CHAINS IMMUNOGLOBULIN GENE
DIVERSIFICATION
DIFFERS AMONG SPECIES
CLASS SWITCHING AMONG
CONSTANT-REGION GENES
AID (ACTIVATION-INDUCED CYTIDINE DEAMINASE) MEDIATES BOTH SOMATIC
HYPERMUTATION AND CLASS SWITCHING
EXPRESSION OF IG GENES
HEAVY-CHAIN PRIMARY TRANSCRIPTS UNDERGO DIFFERENTIAL RNA PROCESSING
SYNTHESIS, ASSEMBLY, AND SECRETION
OF IMMUNOGLOBULINS
REGULATION OF IG-GENE TRANSCRIPTION
DNA REARRANGEMENT GREATLY ACCELERATES TRANSCRIPTION IG-GENE EXPRESSION
IS INHIBITED IN T CELLS
ANTIBODY GENES AND ANTIBODY ENGINEERING
CHIMERIC AND HUMANIZED MONOCLONAL ANTIBODIES HAVE POTENT CLINICAL
POTENTIAL MICE HAVE BEEN ENGINEERED WITH HUMAN IMMUNOGLOBULIN LOCI PHAGE
DISPLAY LIBRARIES ALLOW THE DERIVATION
OF MONOCLONAL ANTIBODIES WITHOUT IMMUNIZATION
CLINICAL FOCUS THERAPY FOR NON-HODCKIN S LYMPHOMA AND OTHER DISEASES
WITH GENETICALLY
ENGINEERED ANTIBODIES
6 ANTIGEN-ANTIBODY INTERACTIONS:
117 PRINCIPLES AND APPLICATIONS 145
118
STRENGTH OF ANTIGEN-ANTIBODY INTERACTIONS 145
-|-|9 ANTIBODY AFFINITY IS A QUANTITATIVE MEASURE OF BINDING STRENGTH
145
ANTIBODY AVIDITY INCORPORATES AFFINITY 119 OF MULTIPLE BINDING SITES 148
119
CROSS-REACTIVITY 149
1 21 SURFACE PLASMON RESONANCE (SPR) 149
121 SPR CAN BE USED TO CHARACTERIZE THE EPITOPE SPECIFICITIES OF
COLLECTIONS OF ANTIBODIES 150
123 V
123
123 123 125
125
125
127
127
128
128
130
130
133
133
135 135
136
136
137
137
140
PRECIPITATION REACTIONS 151
PRECIPITATION REACTIONS IN GELS YIELD VISIBLE PRECIPITIN LINES 151
IMMUNOELECTROPHORESIS COMBINES ELECTROPHORESIS AND DOUBLE
IMMUNODIFFUSION 152
AGGLUTINATION REACTIONS 153
HEMAGGLUTINATION IS USED IN BLOOD TYPING 153
BACTERIAL AGGLUTINATION IS USED TO DIAGNOSE INFECTION 154
PASSIVE AGGLUTINATION IS USEFUL WITH SOLUBLE ANTIGENS 154 IN
AGGLUTINATION INHIBITION, ABSENCE OF AGGLUTINATION IS DIAGNOSTIC OF
ANTIGEN 154
RADIOIMMUNOASSAY 154
ENZYME-LINKED IMMUNOSORBENT ASSAY 155
THERE ARE NUMEROUS VARIANTS OF ELIZA 155
WESTERN BLOTTING 158
IMMUNOPRECIPITATION 158
IMMUNOFLUORESCENCE 160
FLOW CYTOMETRY AND FLUORESCENCE 161
CLINICAL FOCUS FLOW CYTOMETRY AND LEUKEMIA TYPING 163
ALTERNATIVES TO ANTIGEN-ANTIBODY REACTIONS 164
IMMUNOELECTRON MICROSCOPY 164
THE COMPLEMENT SYSTEM
THE FUNCTIONS OF COMPLEMENT
THE COMPONENTS OF COMPLEMENT
COMPLEMENT ACTIVATION
THE CLASSICAL PATHWAY BEGINS WITH
ANTIGEN-ANTIBODY BINDING THE ALTERNATIVE PATHWAY IS ANTIBODY-INDEPENDENT
THE LECTIN PATHWAY ORIGINATES WITH HOST PROTEINS BINDING MICROBIAL
SURFACES
168
168
169
169
170 173
175
IMAGE 5
XVI
C O N T E N TS
THE THREE COMPLEMENT PATHWAYS CONVERGE
AT THE MEMBRANE-ATTACK COMPLEX 175
REGULATION OF THE COMPLEMENT SYSTEM 177
BIOLOGICAL CONSEQUENCES OF COMPLEMENT ACTIVATION 180
THE MEMBRANE-ATTACK COMPLEX CAN LYSE A BROAD SPECTRUM OF CELLS 180
CLEAVAGE PRODUCTS OF COMPLEMENT COMPONENTS MEDIATE INFLAMMATION 182
CLINICAL FOCUS PAROXYMAL NOCTURNAL HEMOGLOBINURIA: A DEFECT IN
REGULATION
OF COMPLEMENT LYSIS 183
C3B AND C4B BINDING FACILITATES OPSONIZATION 184
THE COMPLEMENT SYSTEM ALSO NEUTRALIZES VIRAL INFECTIVITY 184
THE COMPLEMENT SYSTEM CLEARS IMMUNE COMPLEXES FROM CIRCULATION 185
COMPLEMENT DEFICIENCIES 185
8 THE MAJOR HISTOCOMPATIBILITY
COMPLEX AND ANTIGEN PRESENTATION 189
GENERAL ORGANIZATION AND INHERITANCE OF THE MHC 190
THE MHC ENCODES THREE MAJOR CLASSES OF MOLECULES 190
ALLELIC FORMS OF MHC GENES ARE INHERITED IN LINKED GROUPS CALLED
HAPLOTYPES 191
INBRED MOUSE STRAINS HAVE AIDED THE STUDY OF THE MHC 193
MHC MOLECULES AND GENES 193
CLASS I MOLECULES HAVE A GLYCOPROTEIN HEAVY CHAIN AND A SMALL PROTEIN
LIGHT CHAIN 193
CLASS II MOLECULES HAVE TWO NONIDENTICAL GLYCOPROTEIN CHAINS 195
THE EXON/LNTRON ARRANGEMENT OF CLASS I AND II GENES REFLECTS THEIR
DOMAIN STRUCTURE 196
CLASS I AND II MOLECULES EXHIBIT POLYMORPHISM IN THE REGION THAT BINDS
TO PEPTIDES 197
CLASS I AND CLASS II MOLECULES EXHIBIT DIVERSITY WITHIN A SPECIES, AND
MULTIPLE FORMS OCCUR IN AN INDIVIDUAL 199
DETAILED GENOMIC MAP OF MHC GENES 201
THE HUMAN CLASS I REGION SPANS ABOUT 2000 KB AT THE TELOMERIC END OF THE
HLA COMPLEX 202
THE CLASS II MHC GENES ARE LOCATED AT THE CENTROMERIC END OF HLA 203
HUMAN MHC CLASS III GENES ARE BETWEEN CLASS I AND II 203
CELLULAR EXPRESSION OF MHC MOLECULES 203
REGULATION OF MHC EXPRESSION 204
MHC AND DISEASE SUSCEPTIBILITY 205
MHC AND IMMUNE RESPONSIVENESS 206
SELF-MHC RESTRICTION OF T CELLS 207
ROLE OF ANTIGEN-PRESENTING CELLS 207
PROCESSING OF ANTIGEN IS REQUIRED FOR RECOGNITION BY T CELLS 208
MOST CELLS CAN PRESENT ANTIGEN WITH CLASS I MHC; PRESENTATION WITH CLASS
II MHC IS RESTRICTED TO APCS 209
EVIDENCE FOR DIFFERENT ANTIGEN-PROCESSING AND PRESENTATION PATHWAYS 2 09
ENDOGENOUS ANTIGENS:
THE CYTOSOLIC PATHWAY 2 10
PEPTIDES FOR PRESENTATION ARE GENERATED BY PROTEASE COMPLEXES CALLED
PROTEASOMES 211 PEPTIDES ARE TRANSPORTED FROM THE CYTOSOL TO THE ROUGH
ENDOPLASMIC RETICULUM 211
PEPTIDES ASSEMBLE WITH CLASS I MHC AIDED BY CHAPERONE MOLECULES 212
CLINICAL FOCUS DEFICIENCY IN TRANSPORTERS ASSOCIATED WITH ANTIGEN
PROCESSING (TAPS) LEADS TO A DIVERSE DISEASE SPECTRUM 213
EXOGENOUS ANTIGENS: THE ENDOCYTIC PATHWAY 214
PEPTIDES ARE GENERATED FROM INTERNALIZED MOLECULES IN ENDOCYTIC VESICLES
214
THE INVARIANT CHAIN GUIDES TRANSPORT OF CLASS II MHC MOLECULES TO
ENDOCYTIC VESICLES 214 PEPTIDES ASSEMBLE WITH CLASS II MHC MOLECULES BY
DISPLACING CLIP 215
CROSS-PRESENTATION OF EXOGENOUS ANTIGENS 2 17
CONTROVERSY EXISTS OVER THE CELL TYPES IN WHICH CROSS-PRESENTATION CAN
OCCUR 217
PRESENTATION OF NONPEPTIDE ANTIGENS 2 17
T-CELL RECEPTOR
EARLY STUDIES OF THE T-CELL RECEPTOR
CLASSIC EXPERIMENTS DEMONSTRATED THE SELF-MHC RESTRICTION OF THE T-CELL
RECEPTOR T-CELL RECEPTORS WERE ISOLATED BY USING CLONOTYPIC ANTIBODIES
THETCR *-CHAIN GENE WAS CLONED BY USE OF SUBTRACTIVE HYBRIDIZATION
AP AND YB T-CELL RECEPTORS:
STRUCTURES AND ROLES
ORGANIZATION AND REARRANGEMENT OF TCR GENES
TCR VARIABLE-REGION GENES REARRANGE IN A MANNER SIMILAR TO ANTIBODY
GENES MECHANISM OF TCR DNA REARRANGEMENTS ALLELIC EXCLUSION OF TCR GENES
223
223
224
224
224
226
228
229 230 231
IMAGE 6
C O N T E N TS
XVII
REARRANGED TCR GENES ARE ASSEMBLED FROM V, J, AND D GENE SEGMENTS 231
CLINICAL FOCUS T-CELL REARRANGEMENTS AS MARKERS FOR CANCEROUS CELLS 232
TCR DIVERSITY IS GENERATED LIKE ANTIBODY DIVERSITY
BUT WITHOUT SOMATIC MUTATION 232
T-CELL RECEPTOR COMPLEX: TCR-CD3 235
T-CELL ACCESSORY MEMBRANE MOLECULES 236
CD4 AND CD8 CORECEPTORS BIND TO CONSERVED
REGIONS OF MHC CLASS II OR I MOLECULES 236
AFFINITY OF TCR FOR PEPTIDE-MHC COMPLEXES IS ENHANCED BY CORECEPTORS 238
THREE-DIMENSIONAL STRUCTURES OF
TCR-PEPTIDE-MHC COMPLEXES 240
TCRS INTERACT DIFFERENTLY WITH CLASS I AND CLASS II MOLECULES 241
ALLOREACTIVITY OF T CELLS 241
10 T-CELL MATURATION, ACTIVATION,
AND DIFFERENTIATION 245
T-CELL MATURATION AND THE THYMUS
THYMIC SELECTION OF THE T-CELL REPERTOIRE
POSITIVE SELECTION ENSURES MHC RESTRICTION NEGATIVE SELECTION ENSURES
SELF-TOLERANCE EXPERIMENTS REVEALED THE ESSENTIAL ELEMENTS OF POSITIVE
AND NEGATIVE SELECTION SOME CENTRAL ISSUES IN THYMIC SELECTION
REMAIN UNRESOLVED
T-CELL ACTIVATION
MULTIPLE SIGNALING PATHWAYS ARE INITIATED BY TCR ENGAGEMENT HOW MANY TCR
COMPLEXES MUST BE ENGAGED TO TRIGGER T-CELL ACTIVATION? COSTIMULATORY
SIGNALS ARE REQUIRED
FOR FULL T-CELL ACTIVATION CLONAL ANERGY ENSUES IF A COSTIMULATORY
SIGNAL IS ABSENT SUPERANTIGENS INDUCE T-CELL ACTIVATION
BY BINDING THE TCR AND MHC II SIMULTANEOUSLY
T-CELL DIFFERENTIATION
ACTIVATED T CELLS GENERATE EFFECTOR AND MEMORY T CELLS ACD4+CD25+
SUBPOPULATION OFT CELLS NEGATIVELY REGULATES IMMUNE RESPONSES
ANTIGEN-PRESENTING CELLS HAVE CHARACTERISTIC COSTIMULATORY PROPERTIES
CELL DEATH AND T-CELL POPULATIONS
CLINICAL FOCUS FAILURE OF APOPTOSIS CAUSES DEFECTIVE LYMPHOCYTE
HOMEOSTASIS
245
248
249 250
250
251
254
254
258
259
259
260
261
262
263
263
264
266
11 B-CELL GENERATION, ACTIVATION, AND DIFFERENTIATION 271
B-CELL MATURATION 271
PROGENITOR B CELLS PROLIFERATE IN BONE MARROW 272 IG-GENE REARRANGEMENT
PRODUCES IMMATURE B CELLS 273
THE PRE-B-CELL RECEPTOR IS ESSENTIAL FOR B-CELL DEVELOPMENT 274
KNOCKOUT EXPERIMENTS IDENTIFIED ESSENTIAL TRANSCRIPTION FACTORS 275
CELL-SURFACE MARKERS IDENTIFY DEVELOPMENTAL STAGES 275
B-1 B CELLS ARE A SELF-RENEWING B-CELL SUBSET 275 SELF-REACTIVE B CELLS
ARE SELECTED AGAINST IN BONE MARROW 276
SELF-REACTIVE B CELLS MAY BE RESCUED BY EDITING OF LIGHT-CHAIN GENES 278
B-CELL ACTIVATION AND PROLIFERATION 278
THYMUS-DEPENDENT AND THYMUS-LNDEPENDENT ANTIGEN HAVE DIFFERENT
REQUIREMENTS FOR RESPONSE 278 TWO TYPES OF SIGNALS DRIVE B CELLS INTO
AND THROUGH THE CELL CYCLE 279
TRANSDUCTION OF ACTIVATING SIGNALS INVOLVES I G - A / L G^ HETERODIMERS
279
B-CELL SIGNALING IS INITIATED BY ANTIGEN BINDING AND INDUCES MANY SIGNAL
TRANSDUCTION PATHWAYS 281
THE B-CELL-CORECEPTOR COMPLEX CAN ENHANCE B-CELL RESPONSES AND CD22 CAN
INHIBIT THEM 281
CLINICAL FOCUS X-LINKED AGAMMAGLOBULINEMIA:
A FAILURE IN SIGNAL TRANSDUCTION AND B-CELL DEVELOPMENT 284
T H CELLS PLAY ESSENTIAL ROLES IN MOST
B-CELL RESPONSES 285
MATURE SELF-REACTIVE B CELLS CAN BE NEGATIVELY SELECTED IN THE PERIPHERY
287
THE HUMORAL RESPONSE 289
PRIMARY AND SECONDARY RESPONSES DIFFER SIGNIFICANTLY 289
T HELPER CELLS PLAY A CRITICAL ROLE IN THE HUMORAL RESPONSE TO
HAPTEN-CARRIER CONJUGATES 290
IN VIVO SITES FOR INDUCTION OF HUMORAL RESPONSES 292
GERMINAL CENTERS AND ANTIGEN-INDUCED B-CELL DIFFERENTIATION 292
AFFINITY MATURATION IS THE RESULT OF REPEATED MUTATION AND SELECTION 293
MEMORY B CELLS AND PLASMA CELLS ARE GENERATED IN GERMINAL CENTERS 296
REGULATION OF THE IMMUNE EFFECTOR RESPONSE 297
DIFFERENT ANTIGENS CAN COMPETE WITH EACH OTHER 297 THE PRESENCE OF
ANTIBODY CAN SUPPRESS THE RESPONSE TO ANTIGEN 297
IMAGE 7
XVIII
C O N T E N TS
PART III IMMUNE EFFECTOR
MECHANISMS
12 CYTOKINES
HIGH-ENDOTHELIAL VENULES ARE SITES
302
PROPERTIES OF CYTOKINES 302
CYTOKINES BELONG TO FOUR FAMILIES 305
CYTOKINES HAVE NUMEROUS BIOLOGICAL FUNCTIONS 306
CYTOKINE RECEPTORS 307
CYTOKINE RECEPTORS FALL WITHIN FIVE FAMILIES 308 SUBFAMILIES OF CLASS I
CYTOKINE RECEPTORS HAVE SIGNALING SUBUNITS IN COMMON 309
IL-2R IS THE MOST THOROUGHLY STUDIED CYTOKINE RECEPTOR 311
CYTOKINE RECEPTORS INITIATE SIGNALING 312
CYTOKINE ANTAGONISTS 314
CYTOKINE SECRETION BY T H1 AND TH2 SUBSETS 314
THE DEVELOPMENT OF T H1 ANDTH2 SUBSETS IS DETERMINED BY THE CYTOKINE
ENVIRONMENT 316 CYTOKINE PROFILES ARE CROSS-REGULATED 317
THET H1/TH2 BALANCE DETERMINES DISEASE OUTCOMES 318
CYTOKINE-RELATED DISEASES 318
SEPTIC SHOCK IS COMMON AND POTENTIALLY LETHAL 318 BACTERIAL TOXIC SHOCK
IS CAUSED BY SUPERANTIGENS 319
CYTOKINE ACTIVITY IS IMPLICATED IN LYMPHOID AND MYELOID CANCERS 319
CHAGAS S DISEASE IS CAUSED BY A PARASITE 320
CYTOKINE-BASED THERAPIES 321
CYTOKINES IN HEMATOPOIESIS 321
CLINICAL FOCUS THERAPY WITH INTERFERONS 322
13 LEUKOCYTE ACTIVATION AND
MIGRATION 327
CELL ADHESION MOLECULES
CHEMOKINES
CHEMOKINE-RECEPTOR PROFILES MEDIATE LEUKOCYTE ACTIVITY
LEUKOCYTE EXTRAVASATION- THE MULTISTEP PARADIGM
LYMPHOCYTE RECIRCULATION
LYMPHOCYTE EXTRAVASATION
327
329
331
332
334
334
OF LYMPHOCYTE EXTRAVASATION 334
LYMPHOCYTE HOMING IS DIRECTED BY RECEPTOR PROFILES AND SIGNALS 336
NAIVE LYMPHOCYTES RECIRCULATE TO SECONDARY LYMPHOID TISSUE 336
EFFECTOR AND MEMORY LYMPHOCYTES ADOPT DIFFERENT TRAFFICKING PATTERNS 337
OTHER MEDIATORS OF INFLAMMATION 338
THE KININ SYSTEM IS ACTIVATED BY TISSUE INJURY 338 THE CLONING SYSTEM
YIELDS FIBRIN-GENERATED MEDIATORS OF INFLAMMATION 338
THE FIBRINOLYTIC SYSTEM YIELDS PLASMIN-GENERATED MEDIATORS OF
INFLAMMATION 338
THE COMPLEMENT SYSTEM PRODUCES ANAPHYLOTOXINS 338 SOME LIPIDS ACT AS
INFLAMMATORY MEDIATORS 339 SOME CYTOKINES ARE IMPORTANT INFLAMMATORY
MEDIATORS 339
THE INFLAMMATORY PROCESS 340
NEUTROPHILS PLAY AN EARLY AND IMPORTANT ROLE IN INFLAMMATION 340
INFLAMMATORY RESPONSES MAY BE LOCALIZED OR SYSTEMIC 340
CLINICAL FOCUS LEUKOCYTE ADHESION DEFICIENCY (LAD) IN HUMANS AND CATTLE
343
CHRONIC INFLAMMATION DEVELOPS
WHEN ANTIGEN PERSISTS 344
ROLES OF IFN-* AND TNF-* IN CHRONIC INFLAMMATION 344
HEV-LIKE STRUCTURES APPEAR IN CHRONIC INFLAMMATORY DISEASE 346
ANTI-INFLAMMATORY AGENTS 346
ANTIBODY THERAPIES REDUCE LEUKOCYTE EXTRAVASATION 346
CORTICOSTEROIDS ARE POWERFUL ANTI-INFLAMMATORY DRUGS 347
NSAIDS COMBAT PAIN AND INFLAMMATION 347
14 CELL-MEDIATED CYTOTOXIC RESPONSES 351
EFFECTOR RESPONSES 351
GENERAL PRINCIPLES OF EFFECTOR T CELLS 352
THE ACTIVATION REQUIREMENTS OFT CELLS DIFFER 352
CELL ADHESION MOLECULES FACILITATE TCR-MEDIATED INTERACTIONS 352
EFFECTOR T CELLS EXPRESS A VARIETY OF EFFECTOR MOLECULES 353
CYTOTOXIC T CELLS 353
EFFECTOR CTLS ARE GENERATED FROM CTL PRECURSORS 353 CD8+ CTLS CAN BE
TRACKED WITH MHCTETRAMERTECHNOLOGY 355
CTLS KILL CELLS IN TWO WAYS 355
IMAGE 8
C O N T E N TS
XIX
NATURAL KILLER CELLS
NK CELLS AND T CELLS SHARE SOME FEATURES KILLING BY NK CELLS IS SIMILAR
TO CTL-MEDIATED KILLING NK CELLS HAVE BOTH ACTIVATION
AND INHIBITION RECEPTORS
CLINICAL FOCUS MHC-KIR GENE COMBINATIONS INFLUENCE HEALTH
NKT CELLS
ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY
EXPERIMENTAL ASSESSMENT OF CELL-MEDIATED CYTOTOXICITY
COCULTURINGT CELLS WITH FOREIGN CELLS STIMULATES MLR CTL ACTIVITY CAN BE
DEMONSTRATED BY CML THE CVH REACTION IS AN INDICATION
OF CELL-MEDIATED CYTOTOXICITY
360
361
361
362
364
364
366
366
366 367
367
15 HYPERSENSITIVITY REACTIONS 371
GELL AND COOMBS CLASSIFICATION
IGE-MEDIATED (TYPE I) HYPERSENSITIVITY
THERE ARE SEVERAL COMPONENTS OF TYPE I REACTIONS IGE-BINDING FC
RECEPTORS IGE CROSS-LINKAGE INITIATES DEGRANULATION INTRACELLULAR EVENTS
TRIGGER MAST-CELL
DEGRANULATION SEVERAL PHARMACOLOGIC AGENTS MEDIATE TYPE I REACTIONS TYPE
I REACTIONS CAN BE SYSTEMIC OR LOCALIZED
LATE-PHASE REACTIONS INDUCE LOCALIZED INFLAMMATORY REACTIONS TYPE I
RESPONSES ARE REGULATED BY MANY FACTORS
CLINICAL FOCUS THE GENETICS OF ASTHMA
SEVERAL CLINICAL METHODS ARE USED
TO DETECT TYPE I HYPERSENSITIVITY REACTIONS TYPE I HYPERSENSITIVITIES
CAN BE CONTROLLED MEDICALLY
ANTIBODY-MEDIATED CYTOTOXIC
(TYPE II) HYPERSENSITIVITY
TRANSFUSION REACTIONS ARE TYPE II REACTIONS HEMOLYTIC DISEASE OF THE
NEWBORN IS CAUSED BY TYPE II REACTIONS DRUG-INDUCED HEMOLYTIC ANEMIA
IS A TYPE II RESPONSE
IMMUNE COMPLEX-MEDIATED (TYPE III) HYPERSENSITIVITY
TYPE III REACTIONS CAN BE LOCALIZED TYPE III REACTIONS CAN ALSO BE
GENERALIZED
TYPE IV OR DELAYED-TYPE HYPERSENSITIVITY (DTH) 393
THERE ARE SEVERAL PHASES OF THE DTH RESPONSE 394 NUMEROUS CYTOKINES
PARTICIPATE IN THE DTH REACTION 395 THE DTH REACTION IS DETECTED WITH A
SKIN TEST 396
CONTACT DERMATITIS IS A TYPE OF DTH RESPONSE 396
16 TOLERANCE AND AUTOIMMUNITY 401
ESTABLISHMENT AND MAINTENANCE OF TOLERANCE 402
CENTRAL TOLERANCE LIMITS DEVELOPMENT OF AUTOREACTIVE T AND B CELLS 403
PERIPHERAL TOLERANCE REGULATES AUTOREACTIVE CELLS IN CIRCULATION 404
REGULATORY T CELLS ARE A COMPONENT OF PERIPHERAL TOLERANCE 406
ANTIGEN SEQUESTRATION IS A MEANS TO PROTECT SELF ANTIGENS 407
FAILURE OF TOLERANCE LEADS TO AUTOIMMUNITY 407
ORGAN-SPECIFIC AUTOIMMUNE DISEASES 407
SOME AUTOIMMUNE DISEASES ARE MEDIATED BY DIRECT CELLULAR DAMAGE 407
SOME AUTOIMMUNE DISEASES ARE MEDIATED
371 OY STIMULATING OR BLOCKING AUTO-ANTIDOCNES 4UY
372 SYSTEMIC AUTOIMMUNE DISEASES 410
SYSTEMIC LUPUS ERYTHEMATOSUS ATTACKS 373 MANY TISSUES 410
376 MULTIPLE SCLEROSIS ATTACKS THE 377 CENTRAL NERVOUS SYSTEM 411
RHEUMATOID ARTHRITIS ATTACKS JOINTS 411
ANIMAL MODELS FOR AUTOIMMUNE DISEASES 411
381 AUTOIMMUNITY CAN DEVELOP SPONTANEOUSLY IN ANIMALS 412
383 AUTOIMMUNITY CAN BE INDUCED EXPERIMENTALLY IN ANIMALS 413
383
EVIDENCE IMPLICATING THE CD4 + T CELL, MHC, AND TCR IN AUTOIMMUNITY 413
386 CD4+ T CELLS AND T H1/TH2 BALANCE PLAY 386 AN IMPORTANT ROLE IN
AUTOIMMUNITY IN SOME ANIMAL MODELS 414
AUTOIMMUNITY CAN BE ASSOCIATED WITH THE 388 MHC OR WITH PARTICULAR
T-CELL RECEPTORS 414
388 PROPOSED MECHANISMS
FOR INDUCTION OF AUTOIMMUNITY 414
389
RELEASE OF SEQUESTERED ANTIGENS 391 CAN INDUCE AUTOIMMUNE DISEASE 415
391
392 392
CLINICAL FOCUS WHY ARE WOMEN MORE SUSCEPTIBLE THAN MEN TO AUTOIMMUNITY?
GENDER DIFFERENCES IN AUTOIMMUNE DISEASE
MOLECULAR MIMICRY MAY CONTRIBUTE
TO AUTOIMMUNE DISEASE
416
416
IMAGE 9
XX
C O N T E N TS
THERE IS EVIDENCE FOR MIMICRY BETWEEN MBP
AND VIRAL PEPTIDES 418
INAPPROPRIATE EXPRESSION OF CLASS II MHC MOLECULES CAN SENSITIZE
AUTOREACTIVE T CELLS 418
POLYCLONAL B-CELL ACTIVATION CAN LEAD TO AUTOIMMUNE DISEASE 419
TREATMENT OF AUTOIMMUNE DISEASES 419
TREATMENT OF HUMAN AUTOIMMUNE DISEASE POSES SPECIAL CHALLENGES 420
INFLAMMATION IS A TARGET FOR TREATMENT OF AUTOIMMUNITY 420 ACTIVATED T
CELLS ARE A POSSIBLE THERAPEUTIC TARGET 421 ORAL ANTIGENS CAN INDUCE
TOLERANCE 421
PART IV THE IMMUNE SYSTEM
IN HEALTH AND DISEASE
CLINICAL TRANSPLANTATION THE MOST COMMONLY TRANSPLANTED ORGAN IS THE
KIDNEY BONE MARROW TRANSPLANTS ARE USED
FOR LEUKEMIA, ANEMIA, AND IMMUNODEFICIENCY HEART TRANSPLANTATION IS A
CHALLENGING OPERATION LUNG TRANSPLANTS ARE ON THE INCREASE LIVER
TRANSPLANTS TREAT CONGENITAL DEFECTS
AND DAMAGE FROM VIRAL OR CHEMICAL AGENTS TRANSPLANTATION OF PANCREATIC
CELLS OFFERS A CURE FOR DIABETES MELLITUS SKIN GRAFTS ARE USED TO TREAT
BURN VICTIMS XENOTRANSPLANTATION MAY BE THE ANSWER
TO THE SHORTAGE OF DONOR ORGANS
18 IMMUNE RESPONSE
TO INFECTIOUS DISEASES
440
441
441 442 442
442
442 443
443
447
17 TRANSPLANTATION IMMUNOLOGY 425
IMMUNOLOGIC BASIS OF GRAFT REJECTION 426
ALLOGRAFT REJECTION DISPLAYS SPECIFICITY AND MEMORY 426
T CELLS PLAY A KEY ROLE IN ALLOGRAFT REJECTION 426
SIMILAR ANTIGENIC PROFILES FOSTER ALLOGRAFT ACCEPTANCE 428
GRAFT DONORS AND RECIPIENTS ARE TYPED FOR RBC AND MHC ANTIGENS 428
CELL-MEDIATED GRAFT REJECTION OCCURS IN TWO STAGES 431
CLINICAL MANIFESTATIONS OF GRAFT REJECTION 433
PREEXISTING RECIPIENT ANTIBODIES MEDIATE HYPERACUTE REJECTION 433
ACUTE REJECTION IS MEDIATED BYT-CELL RESPONSES 434 CHRONIC REJECTION
OCCURS MONTHS OR YEARS POST-TRANSPLANT 434
GENERAL IMMUNOSUPPRESSIVE THERAPY 434
MITOTIC INHIBITORS THWART T-CELL PROLIFERATION 434
CLINICAL FOCUS IS THERE A CLINICAL FUTURE FOR XENOTRANSPLANTATION? 435
CORTICOSTEROIDS SUPPRESS INFLAMMATION 436
CERTAIN FUNGAL METABOLITES ARE IMMUNOSUPPRESSANTS 436
TOTAL LYMPHOID IRRADIATION ELIMINATES LYMPHOCYTES 436
SPECIFIC IMMUNOSUPPRESSIVE THERAPY 436
ANTIBODIES CAN SUPPRESS GRAFT REJECTION RESPONSES 437 BLOCKING
COSTIMULATORY SIGNALS CAN INDUCE ANERGY 438
IMMUNE TOLERANCE TO ALLOGRAFTS 439
PRIVILEGED SITES ACCEPT ANTIGENIC MISMATCHES 439 EARLY EXPOSURE TO
ALLOANTIGENS CAN INDUCE SPECIFIC TOLERANCE 439
VIRAL INFECTIONS 448
MANY VIRUSES ARE NEUTRALIZED BY ANTIBODIES 449
CELL-MEDIATED IMMUNITY IS IMPORTANT FOR VIRAL CONTROL AND CLEARANCE 450
VIRUSES CAN EVADE HOST DEFENSE MECHANISMS 450 INFLUENZA HAS BEEN
RESPONSIBLE FOR SOME OF THE WORST PANDEMICS IN HISTORY 451
THE HUMORAL RESPONSE TO INFLUENZA IS STRAIN SPECIFIC 454 AVIAN H5N1
PRESENTS THE THREAT OF A PANDEMIC 454
BACTERIAL INFECTIONS 454
IMMUNE RESPONSES TO EXTRACELLULAR AND INTRACELLULAR BACTERIA CAN DIFFER
455
BACTERIA CAN EFFECTIVELY EVADE HOST DEFENSE MECHANISMS 455
IMMUNE RESPONSES CAN CONTRIBUTE TO BACTERIAL PATHOGENESIS 457
DIPHTHERIA [CORYNEBACTERIUM DIPHTHERIAE) CAN BE CONTROLLED BY
IMMUNIZATION WITH INACTIVATED TOXOID 458
TUBERCULOSIS (MYCOBACTERIUM TUBERCULOSIS) IS PRIMARILY CONTROLLED BY
CD4+ T CELLS 458
PARASITIC DISEASES 460
PROTOZOAN DISEASES AFFECT MILLIONS WORLDWIDE 460 MALARIA (PLASMODIUM
SPECIES) INFECTS 600 MILLION PEOPLE WORLDWIDE 460
TWO SPECIES OF TRYPANOSOMA CAUSE AFRICAN SLEEPING SICKNESS 462
LEISHMANIASIS IS A USEFUL MODEL FOR DEMONSTRATING DIFFERENCES IN HOST
RESPONSES 462
A VARIETY OF DISEASES ARE CAUSED BY PARASITIC WORMS (HELMINTHS) 462
FUNGAL DISEASES 465
INNATE IMMUNITY CONTROLS MOST FUNGAL INFECTIONS 466 IMMUNITY AGAINST
FUNGAL PATHOGENS CAN BE ACQUIRED 466
IMAGE 10
C O N T E N TS
XXI
EMERGING INFECTIOUS DISEASES
DISEASES MAY RE-EMERGE FOR VARIOUS REASONS
CLINICAL FOCUS THE THREAT OF INFECTION FROM POTENTIAL AGENTS OF
BIOTERRORISM
SOME FATAL DISEASES HAVE APPEARED RECENTLY
THE SARS OUTBREAK TRIGGERED A RAPID INTERNATIONAL RESPONSE
467
467
468
470
470
19 VACCINES 475
CLINICAL FOCUS VACCINATION: CHALLENGES IN THE UNITED STATES AND
DEVELOPING COUNTRIES 476
ACTIVE AND PASSIVE IMMUNIZATION 4 77
PASSIVE IMMUNIZATION INVOLVES TRANSFER OF PREFORMED ANTIBODIES 477
ACTIVE IMMUNIZATION ELICITS LONG-TERM PROTECTION 477
DESIGNING VACCINES FOR ACTIVE IMMUNIZATION 481
LIVE, ATTENUATED VACCINES 481
INACTIVATED OR KILLED VACCINES 4 84
SUBUNIT VACCINES 4 84
TOXOIDS ARE USED AS VACCINES 485
BACTERIAL POLYSACCHARIDE CAPSULES ARE USED AS VACCINES 485 VIRAL
GLYCOPROTEINS ARE CANDIDATE VACCINES 485 PATHOGEN PROTEINS ARE
MANUFACTURED BY RECOMBINANT TECHNIQUES 485
USE OF SYNTHETIC PEPTIDES AS VACCINES HAS PROGRESSED SLOWLY 485
CONJUGATE VACCINES 486
ONE POLYSACCHARIDE CONFERS PROTECTION AGAINST SEVERAL FUNGI 486
MULTIVALENT SUBUNIT VACCINES CONFER BOTH CELLULAR AND HUMORAL IMMUNITY
486
DNA VACCINES 488
RECOMBINANT VECTOR VACCINES 488
20 AIDS AND OTHER
IMMUNODEFICIENCIES
PRIMARY IMMUNODEFICIENCIES
LYMPHOID IMMUNODEFICIENCIES MAY INVOLVE B CELLS, T CELLS, OR BOTH
IMMUNODEFICIENCIES OF THE MYELOID LINEAGE AFFECT INNATE IMMUNITY
COMPLEMENT DEFECTS RESULT IN IMMUNODEFICIENCY
OR IMMUNE-COMPLEX DISEASE IMMUNODEFICIENCY DISORDERS ARE TREATED BY
REPLACEMENT OF THE DEFECTIVE ELEMENT EXPERIMENTAL MODELS OF
IMMUNODEFICIENCY
INCLUDE GENETICALLY ALTERED ANIMALS
493
493
495
500
502
502
503
AIDS AND OTHER ACQUIRED OR SECONDARY IMMUNODEFICIENCIES 504
HIV/AIDS HAS CLAIMED MILLIONS OF LIVES WORLDWIDE 505 HIV-1 SPREADS BY
SEXUAL CONTACT, BY INFECTED BLOOD, AND FROM MOTHER TO INFANT 505
CLINICAL FOCUS PREVENTION OF INFANT HIV INFECTION BY ANTI-RETROVIRAL
TREATMENT 507
THE RETROVIRUS HIV-1 IS THE CAUSATIVE AGENT
OF AIDS 508
IN VITRO STUDIES REVEALED THE HIV-1 REPLICATION CYCLE 509
HIV-1 INFECTION LEADS TO OPPORTUNISTIC INFECTIONS 512 THERAPEUTIC AGENTS
INHIBIT RETROVIRUS REPLICATION 515
A VACCINE MAY BE THE ONLY WAY TO STOP THE HIV/AIDS EPIDEMIC 518
21 CANCER AND THE IMMUNE SYSTEM 525
CANCER: ORIGIN AND TERMINOLOGY 525
MALIGNANT TRANSFORMATION OF CELLS 526
ONCOGENES AND CANCER INDUCTION 527
CANCER-ASSOCIATED GENES HAVE MANY FUNCTIONS 527 PROTO-ONCOGENES CAN BE
CONVERTED TO ONCOGENES 529 THE INDUCTION OF CANCER IS A MULTISTEP
PROCESS 530
TUMORS OF THE IMMUNE SYSTEM 530
TUMOR ANTIGENS 531
SOME ANTIGENS ARE TUMOR-SPECIFIC 532
CLINICAL FOCUS A VACCINE THAT PREVENTS CANCER 534
TUMOR ANTIGENS MAY BE INDUCED BY VIRUSES 535
MOST TUMOR ANTIGENS ARE NOT UNIQUE TO TUMOR CELLS 536
TUMORS CAN INDUCE POTENT IMMUNE RESPONSES 537 NK CELLS AND MACROPHAGES
ARE IMPORTANT IN TUMOR RECOGNITION 537
TUMOR EVASION OF THE IMMUNE SYSTEM 538
ANTITUMOR ANTIBODIES CAN ENHANCE TUMOR GROWTH 538 ANTIBODIES CAN
MODULATE TUMOR ANTIGENS 538
TUMOR CELLS FREQUENTLY EXPRESS LOW LEVELS OF CLASS I MHC MOLECULES 538
TUMOR CELLS MAY PROVIDE POOR COSTIMULATORY SIGNALS 538
CANCER IMMUNOTHERAPY 539
MANIPULATION OF CO-STIMULATORY SIGNALS CAN ENHANCE IMMUNITY 539
ENHANCEMENT OF APC ACTIVITY CAN MODULATE TUMOR IMMUNITY 540
CYTOKINE THERAPY CAN AUGMENT IMMUNE RESPONSES TO TUMORS 540
MONOCLONAL ANTIBODIES ARE EFFECTIVE IN TREATING SOME TUMORS 542
IMAGE 11
XXII
C O N T E N TS
22 EXPERIMENTAL SYSTEMS 546
EXPERIMENTAL ANIMAL METHODS 546
INBRED STRAINS CAN REDUCE EXPERIMENTAL VARIATION 547 ADOPTIVE-TRANSFER
SYSTEMS PERMIT THE IN VIVO EXAMINATION OF ISOLATED CELL POPULATIONS 547
CELL CULTURE SYSTEMS 547
PRIMARY LYMPHOID CELL CULTURES ARE DERIVED FROM BLOOD OR LYMPHOID ORGANS
547
CLONED LYMPHOID CELL LINES ARE IMPORTANT TOOLS IN IMMUNOLOGY 549
PREPARING HYBRID LYMPHOID CELL LINES 550
PROTEIN BIOCHEMISTRY 551
RADIOLABELING TECHNIQUES ALLOW SENSITIVE DETECTION OF ANTIGENS OR
ANTIBODIES 551
BIOTIN LABELS FACILITATE DETECTION OF SMALL AMOUNTS OF PROTEINS 551
GEL ELECTROPHORESIS SEPARATES PROTEINS BY SIZE AND CHARGE 551
X-RAY CRYSTALLOGRAPHY PROVIDES STRUCTURAL INFORMATION 553
RECOMBINANT DNA TECHNOLOGY 555
RESTRICTION ENZYMES CLEAVE DNA AT PRECISE SEQUENCES 555
DNA SEQUENCES ARE CLONED INTO VECTORS 556
CLONING VECTORS ARE USEFUL TO REPLICATE DEFINED SEQUENCES OF DNA 556
CLONING OF CDNA AND GENOMIC DNA ALLOWS THE ISOLATION OF DEFINED
SEQUENCES 556
DNA CLONES ARE SELECTED BY HYBRIDIZATION 558
SOUTHERN BLOTTING DETECTS DNA OF A GIVEN SEQUENCE 559 NORTHERN BLOTTING
DETECTS MRNA 559
THE POLYMERASE CHAIN REACTION AMPLIFIES
SMALL QUANTITIES OF DNA 559
ANALYSIS OF DNA REGULATORY SEQUENCES 560
DNA FOOTPRINTING IDENTIFIES THE SITES
WHERE PROTEINS BIND DNA 560
GEL-SHIFT ANALYSIS IDENTIFIES DNA-PROTEIN COMPLEXES 561 LUCIFERASE
ASSAYS MEASURE TRANSCRIPTIONAL ACTIVITY 562
GENE TRANSFER INTO MAMMALIAN CELLS 562
CLONED GENES TRANSFERRED INTO CULTURED CELLS ALLOW IN VITRO ANALYSIS OF
GENE FUNCTION 562
CLONED GENES TRANSFERRED INTO MOUSE EMBRYOS ALLOW IN VIVO ANALYSIS OF
GENE FUNCTION 563
IN KNOCKOUT MICE, TARGETED GENES ARE DISRUPTED 564 KNOCK-IN TECHNOLOGY
ALLOWS THE REPLACEMENT OF AN ENDOGENOUS GENE 565
INDUCIBLE GENE TARGETING, THE CRE/FOX SYSTEM, TARGETS GENE DELETION 565
MICROARRAYS-AN APPROACH FOR ANALYZING PATTERNS OF GENE EXPRESSION 567
CLINICAL FOCUS MICROARRAY ANALYSIS AS A DIAGNOSTIC TOOL FOR HUMAN
DISEASES 568
TWO-PHOTON MICROSCOPY FOR IN VIVO IMAGING
OF THE IMMUNE SYSTEM 570
ADVANCES IN FLUORESCENT TECHNOLOGY 571
APPENDIX I: CD ANTIGENS A-1
APPENDIX II: CYTOKINES A-27
GLOSSARY G-1
ANSWERS TO STUDY QUESTIONS AN-1
INDEX I-1
|
| adam_txt |
IMAGE 1
PART
INTRODUCTION 1 OVERVIEW OF THE IMMUNE SYSTEM 2 CELLS AND ORGANS OF THE
IMMUNE SYSTEM 3 INNATE IMMUNITY
1
23 52
PART GENERATION OF B-CELL AND T-CELL RESPONSES
4 ANTIGENS AND ANTIBODIES 5 ORGANIZATION AND EXPRESSION OF
IMMUNOGLOBULIN GENES 6 ANTIGEN-ANTIBODY INTERACTIONS: PRINCIPLES AND
APPLICATIONS 7 THE COMPLEMENT SYSTEM 8 THE MAJOR HISTOCOMPATIBILITY
COMPLEX AND ANTIGEN PRESENTATION
9 T-CELL RECEPTOR 10 T-CELL MATURATION, ACTIVATION, AND DIFFERENTIATION
11 B-CELL GENERATION, ACTIVATION, AND DIFFERENTIATION
76 111 145 168 189 223
245 271
PART IMMUNE EFFECTOR MECHANISMS 12 CYTOKINES 13 LEUKOCYTE ACTIVATION AND
MIGRATION 14 CELL-MEDIATED CYTOTOXIC RESPONSES 15 HYPERSENSITIVITY
REACTIONS 16 TOLERANCE AND AUTOIMMUNITY
302 327 351
371 401
PART IV THE IMMUNE SYSTEM IN HEALTH AND DISEASE 17 TRANSPLANTATION
IMMUNOLOGY 425
18 IMMUNE RESPONSE TO INFECTIOUS DISEASES 447
19 VACCINES 475
20 AIDS AND OTHER IMMUNODEFICIENCIES 493
21 CANCER AND THE IMMUNE SYSTEM 525
22 EXPERIMENTAL SYSTEMS 546
APPENDIX I: CD ANTIGENS A-1
APPENDIX II: CYTOKINES A-27
GLOSSARY G-1
ANSWERS AN-1
INDEX 1-1
IMAGE 2
PREFACE
VII
CELLS AND ORGANS OF THE
IMMUNE SYSTEM 23
1 OVERVIEW OF THE IMMUNE SYSTEM 1
HISTORICAL PERSPECTIVE 2
EARLY VACCINATION STUDIES LED THE WAY TO IMMUNOLOGY 2
VACCINATION IS AN ONGOING, WORLDWIDE ENTERPRISE 3
EARLY STUDIES OF HUMORAL AND CELLULAR IMMUNITY 4
THEORETICAL CHALLENGES 5
INFECTION AND IMMUNITY 7
INNATE AND ADAPTIVE IMMUNITY 8
PHAGOCYTIC CELLS ARE A BARRIER TO INFECTION 9
SOLUBLE MOLECULES CONTRIBUTE TO INNATE IMMUNITY 9 COLLABORATION BETWEEN
INNATE AND ADAPTIVE IMMUNITY INCREASES IMMUNE RESPONSIVENESS ADAPTIVE
IMMUNITY IS HIGHLY SPECIFIC
LYMPHOCYTES AND ANTIGEN-PRESENTING CELLS COOPERATE IN ADAPTIVE IMMUNITY
ANTIGEN-PRESENTING CELLS INTERACT WITH T CELLS HUMORAL AND CELLULAR
IMMUNE RESPONSES EXHIBIT
DIFFERENT EFFECTOR FUNCTIONS THE ANTIGEN RECEPTORS OF B AND T
LYMPHOCYTES ARE DIVERSE THE MAJOR HISTOCOMPATIBILITY MOLECULES BIND
ANTIGENIC PEPTIDES ANTIGENIC SELECTION OF LYMPHOCYTES CAUSES CLONAL
EXPANSION
IMMUNE DYSFUNCTION AND ITS CONSEQUENCES
CLINICAL FOCUS ALLERGIES AND ASTHMA ARE SERIOUS PUBLIC HEALTH PROBLEMS
9
10
12
14
14
14
16
16
18
20
HEMATOPOIESIS 23
HEMATOPOIESIS IS REGULATED AT THE GENETIC LEVEL 24 HEMATOPOIETIC
HOMEOSTASIS INVOLVES MANY FACTORS 26 PROGRAMMED CELL DEATH IS AN
ESSENTIAL HOMEOSTATIC MECHANISM 26
HEMATOPOIETIC STEM CELLS CAN BE ENRICHED 28
CELLS OF THE IMMUNE SYSTEM 30
LYMPHOID CELLS 30
CLINICAL FOCUS STEM CELLS-CLINICAL USES AND POTENTIAL 32
B LYMPHOCYTES (B CELLS) 34
T LYMPHOCYTES (T CELLS) 34
B- AND T-CELL POPULATIONS COMPRISE SUBPOPULATIONS OF CLONES 35 NATURAL
KILLER CELLS 35
MONONUCLEAR PHAGOCYTES 36
PHAGOCYTOSIS IS FOLLOWED BY DIGESTION AND PRESENTATION OF ANTIGEN 36
GRANULOLYTIC CELLS 37
MAST CELTS 38
DENDRITIC CELLS 38
FOLLICULAR DENDRITIC CELLS 40
ORGANS OF THE IMMUNE SYSTEM 40
PRIMARY LYMPHOID ORGANS 40
SECONDARY LYMPHOID ORGANS 43
LYMPHOID CELLS AND ORGANS-EVOLUTIONARY COMPARISONS 49
3 INNATE IMMUNITY 52
ANATOMICAL BARRIERS 53
CONNECTIONS BETWEEN INNATE AND ADAPTIVE IMMUNITY 55
IMAGE 3
XIV
C O N T E N TS
INFLAMMATION 57
LEUKOCYTE EXTRAVASATION IS A HIGHLY REGULATED, MULTISTEP PROCESS 59
SOLUBLE MOLECULES AND MEMBRANE-ASSOCIATED RECEPTORS 59
ANTIMICROBIAL PEPTIDES CONTRIBUTE TO THE INNATE DEFENSE AGAINST BACTERIA
AND FUNGI 59
PROTEINS OF THE ACUTE PHASE RESPONSE CONTRIBUTE TO INNATE IMMUNITY 61
INNATE IMMUNITY USES A VARIETY OF RECEPTORS TO DETECT INFECTION 61
TOLL-LIKE RECEPTORS 62
CELL TYPES OF INNATE IMMUNITY 65
NEUTROPHILS ARE SPECIALIZED FOR PHAGOCYTOSIS AND KILLING 65
CLINICAL FOCUS C-REACTIVE PROTEIN IS A KEY MARKER OF CARDIOVASCULAR RISK
66
MACROPHAGES DEPLOY A NUMBER OF ANTIPATHOGEN DEVICES 66
NK CELLS ARE AN IMPORTANT FIRST LINE OF DEFENSE AGAINST VIRUSES AND
PROVIDE A KEY ACTIVATING SIGNAL TO OTHER CELLS 68
DENDRITIC CELLS ENGAGE PATHOGENS AND INVOKE ADAPTIVE IMMUNE RESPONSES BY
ACTIVATING T CELLS 68
SIGNAL TRANSDUCTION PATHWAYS 69
TLR SIGNALING IS TYPICAL OF SIGNAL TRANSDUCTION PATHWAYS 69
UBIQUITY OF INNATE IMMUNITY 71
PART II GENERATION OF B-CELL
AND T-CELL RESPONSES
ANTIGENS AND ANTIBODIES 76
IMMUNOGENICITY VERSUS ANTIGENICITY 77
HAPTENS ARE VALUABLE RESEARCH AND DIAGNOSTIC TOOLS 77
PROPERTIES OF THE IMMUNOGEN CONTRIBUTE TO IMMUNOGENICITY 78 THE
BIOLOGICAL SYSTEM CONTRIBUTES TO HETEROGENICITY 80
EPITOPES 81
B-CELL EPITOPES HAVE CHARACTERISTIC PROPERTIES 81
BASIC STRUCTURE OF ANTIBODIES 84
ANTIBODIES ARE HETERODIMERS 85
CHEMICAL AND ENZYMATIC METHODS REVEALED BASIC ANTIBODY STRUCTURE 85
LIGHT-CHAIN SEQUENCES REVEALED CONSTANT AND VARIABLE REGIONS 87
THERE ARE FIVE MAJOR CLASSES OF HEAVY CHAINS 87 IMMUNOGLOBULINS POSSESS
MULTIPLE DOMAINS BASED ON THE IMMUNOGLOBULIN FOLD 87
ANTIBODY BINDING SITE 89
CDRS BIND ANTIGEN 90
CONFORMATIONAL CHANGES MAY BE INDUCED BY ANTIGEN BINDING 92
CONSTANT-REGION DOMAINS 93
ANTIBODY-MEDIATED EFFECTOR FUNCTIONS 94
OPSONIZATION IS PROMOTED BY ANTIBODY 94
ANTIBODIES ACTIVATE COMPLEMENT 95
ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY (ADCC) KILLS CELLS 95
SOME ANTIBODIES CAN CROSS EPITHELIAL LAYERS BY TRANSCYTOSIS 95
ANTIBODY CLASSES AND BIOLOGICAL ACTIVITY 95
IMMUNOGLOBULIN G (IGG) 95
IMMUNOGLOBULIN M (IGM) 96
CLINICAL FOCUS PASSIVE ANTIBODY THERAPY 98
IMMUNOGLOBULIN A (IGA) 99
IMMUNOGLOBULIN E (IGE) 100
IMMUNOGLOBULIN D (IGD) 100
ANTIGENIC DETERMINANTS ON IMMUNOGLOBULINS 100
ISOTYPE 101
ALLOTYPE 101
IDIOTYPE 101
THE B-CELL RECEPTOR 102
FC RECEPTORS BIND TO FC REGIONS OF ANTIBODIES 102
THE IMMUNOGLOBULIN SUPERFAMILY 103
MONOCLONAL ANTIBODIES 105
MONCLONAL ANTIBODIES HAVE IMPORTANT CLINICAL USES 106 ABZYMESARE
MONOCLONAL ANTIBODIES THAT CATALYZE REACTIONS 106
ORGANIZATION AND EXPRESSION OF
IMMUNOGLOBULIN GENES 111
DEVISING A GENETIC MODEL COMPATIBLE WITH IG STRUCTURE 112
GERM-LINE AND SOMATIC-VARIATION MODELS CONTENDED TO EXPLAIN ANTIBODY
DIVERSITY 113
DREYER AND BENNETT PROPOSED A REVOLUTIONARY TWO-GENE ONE-POLYPEPTIDE
MODEL 113
TONEGAWA'S BOMBSHELL-IMMUNOGLOBULIN GENES REARRANGE 114
MULTIGENE ORGANIZATION OF IG GENES 115
EACH MULTIGENE FAMILY HAS DISTINCT FEATURES 115 HEAVY-CHAIN MULTIGENE
FAMILY 115
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C O N T E N TS
XV
VARIABLE-REGION GENE REARRANGEMENTS
LIGHT-CHAIN DNA UNDERGOES V-J REARRANGEMENTS HEAVY-CHAIN DNA UNDERGOES
V-D-J REARRANGEMENTS
MECHANISM OF VARIABLE-REGION
GENE REARRANGEMENTS
RECOMBINATION SIGNAL SEQUENCES DIRECT RECOMBINATION GENE SEGMENTS ARE
JOINED BY RECOMBINASES IG-CENE REARRANGEMENTS MAY BE PRODUCTIVE
OR NONPRODUCTIVE ALLELIC EXCLUSION ENSURES A SINGLE ANTIGENIC
SPECIFICITY
GENERATION OF ANTIBODY DIVERSITY
THERE ARE NUMEROUS GERM-LINE V, D, AND J GENE SEGMENTS COMBINATORIAL V-J
AND V-D-J JOINING GENERATES DIVERSITY JUNCTIONAL FLEXIBILITY ADDS
DIVERSITY
P-ADDITION ADDS DIVERSITY AT PALINDROMIC SEQUENCES N-ADDITION ADDS
CONSIDERABLE DIVERSITY BY ADDITION OF NUCLEOTIDES SOMATIC HYPERMUTATION
ADDS DIVERSITY
IN ALREADY-REARRANGED GENE SEGMENTS A FINAL SOURCE OF DIVERSITY IS
COMBINATORIAL ASSOCIATION OF HEAVY AND LIGHT CHAINS IMMUNOGLOBULIN GENE
DIVERSIFICATION
DIFFERS AMONG SPECIES
CLASS SWITCHING AMONG
CONSTANT-REGION GENES
AID (ACTIVATION-INDUCED CYTIDINE DEAMINASE) MEDIATES BOTH SOMATIC
HYPERMUTATION AND CLASS SWITCHING
EXPRESSION OF IG GENES
HEAVY-CHAIN PRIMARY TRANSCRIPTS UNDERGO DIFFERENTIAL RNA PROCESSING
SYNTHESIS, ASSEMBLY, AND SECRETION
OF IMMUNOGLOBULINS
REGULATION OF IG-GENE TRANSCRIPTION
DNA REARRANGEMENT GREATLY ACCELERATES TRANSCRIPTION IG-GENE EXPRESSION
IS INHIBITED IN T CELLS
ANTIBODY GENES AND ANTIBODY ENGINEERING
CHIMERIC AND HUMANIZED MONOCLONAL ANTIBODIES HAVE POTENT CLINICAL
POTENTIAL MICE HAVE BEEN ENGINEERED WITH HUMAN IMMUNOGLOBULIN LOCI PHAGE
DISPLAY LIBRARIES ALLOW THE DERIVATION
OF MONOCLONAL ANTIBODIES WITHOUT IMMUNIZATION
CLINICAL FOCUS THERAPY FOR NON-HODCKIN'S LYMPHOMA AND OTHER DISEASES
WITH GENETICALLY
ENGINEERED ANTIBODIES
6 ANTIGEN-ANTIBODY INTERACTIONS:
117 PRINCIPLES AND APPLICATIONS 145
118
STRENGTH OF ANTIGEN-ANTIBODY INTERACTIONS 145
-|-|9 ANTIBODY AFFINITY IS A QUANTITATIVE MEASURE OF BINDING STRENGTH
145
ANTIBODY AVIDITY INCORPORATES AFFINITY 119 OF MULTIPLE BINDING SITES 148
119
CROSS-REACTIVITY 149
1 21 SURFACE PLASMON RESONANCE (SPR) 149
121 SPR CAN BE USED TO CHARACTERIZE THE EPITOPE SPECIFICITIES OF
COLLECTIONS OF ANTIBODIES 150
123 V
123
123 123 125
125
125
127
127
128
128
130
130
133
133
135 135
136
136
137
137
140
PRECIPITATION REACTIONS 151
PRECIPITATION REACTIONS IN GELS YIELD VISIBLE PRECIPITIN LINES 151
IMMUNOELECTROPHORESIS COMBINES ELECTROPHORESIS AND DOUBLE
IMMUNODIFFUSION 152
AGGLUTINATION REACTIONS 153
HEMAGGLUTINATION IS USED IN BLOOD TYPING 153
BACTERIAL AGGLUTINATION IS USED TO DIAGNOSE INFECTION 154
PASSIVE AGGLUTINATION IS USEFUL WITH SOLUBLE ANTIGENS 154 IN
AGGLUTINATION INHIBITION, ABSENCE OF AGGLUTINATION IS DIAGNOSTIC OF
ANTIGEN 154
RADIOIMMUNOASSAY 154
ENZYME-LINKED IMMUNOSORBENT ASSAY 155
THERE ARE NUMEROUS VARIANTS OF ELIZA 155
WESTERN BLOTTING 158
IMMUNOPRECIPITATION 158
IMMUNOFLUORESCENCE 160
FLOW CYTOMETRY AND FLUORESCENCE 161
CLINICAL FOCUS FLOW CYTOMETRY AND LEUKEMIA TYPING 163
ALTERNATIVES TO ANTIGEN-ANTIBODY REACTIONS 164
IMMUNOELECTRON MICROSCOPY 164
THE COMPLEMENT SYSTEM
THE FUNCTIONS OF COMPLEMENT
THE COMPONENTS OF COMPLEMENT
COMPLEMENT ACTIVATION
THE CLASSICAL PATHWAY BEGINS WITH
ANTIGEN-ANTIBODY BINDING THE ALTERNATIVE PATHWAY IS ANTIBODY-INDEPENDENT
THE LECTIN PATHWAY ORIGINATES WITH HOST PROTEINS BINDING MICROBIAL
SURFACES
168
168
169
169
170 173
175
IMAGE 5
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C O N T E N TS
THE THREE COMPLEMENT PATHWAYS CONVERGE
AT THE MEMBRANE-ATTACK COMPLEX 175
REGULATION OF THE COMPLEMENT SYSTEM 177
BIOLOGICAL CONSEQUENCES OF COMPLEMENT ACTIVATION 180
THE MEMBRANE-ATTACK COMPLEX CAN LYSE A BROAD SPECTRUM OF CELLS 180
CLEAVAGE PRODUCTS OF COMPLEMENT COMPONENTS MEDIATE INFLAMMATION 182
CLINICAL FOCUS PAROXYMAL NOCTURNAL HEMOGLOBINURIA: A DEFECT IN
REGULATION
OF COMPLEMENT LYSIS 183
C3B AND C4B BINDING FACILITATES OPSONIZATION 184
THE COMPLEMENT SYSTEM ALSO NEUTRALIZES VIRAL INFECTIVITY 184
THE COMPLEMENT SYSTEM CLEARS IMMUNE COMPLEXES FROM CIRCULATION 185
COMPLEMENT DEFICIENCIES 185
8 THE MAJOR HISTOCOMPATIBILITY
COMPLEX AND ANTIGEN PRESENTATION 189
GENERAL ORGANIZATION AND INHERITANCE OF THE MHC 190
THE MHC ENCODES THREE MAJOR CLASSES OF MOLECULES 190
ALLELIC FORMS OF MHC GENES ARE INHERITED IN LINKED GROUPS CALLED
HAPLOTYPES 191
INBRED MOUSE STRAINS HAVE AIDED THE STUDY OF THE MHC 193
MHC MOLECULES AND GENES 193
CLASS I MOLECULES HAVE A GLYCOPROTEIN HEAVY CHAIN AND A SMALL PROTEIN
LIGHT CHAIN 193
CLASS II MOLECULES HAVE TWO NONIDENTICAL GLYCOPROTEIN CHAINS 195
THE EXON/LNTRON ARRANGEMENT OF CLASS I AND II GENES REFLECTS THEIR
DOMAIN STRUCTURE 196
CLASS I AND II MOLECULES EXHIBIT POLYMORPHISM IN THE REGION THAT BINDS
TO PEPTIDES 197
CLASS I AND CLASS II MOLECULES EXHIBIT DIVERSITY WITHIN A SPECIES, AND
MULTIPLE FORMS OCCUR IN AN INDIVIDUAL 199
DETAILED GENOMIC MAP OF MHC GENES 201
THE HUMAN CLASS I REGION SPANS ABOUT 2000 KB AT THE TELOMERIC END OF THE
HLA COMPLEX 202
THE CLASS II MHC GENES ARE LOCATED AT THE CENTROMERIC END OF HLA 203
HUMAN MHC CLASS III GENES ARE BETWEEN CLASS I AND II 203
CELLULAR EXPRESSION OF MHC MOLECULES 203
REGULATION OF MHC EXPRESSION 204
MHC AND DISEASE SUSCEPTIBILITY 205
MHC AND IMMUNE RESPONSIVENESS 206
SELF-MHC RESTRICTION OF T CELLS 207
ROLE OF ANTIGEN-PRESENTING CELLS 207
PROCESSING OF ANTIGEN IS REQUIRED FOR RECOGNITION BY T CELLS 208
MOST CELLS CAN PRESENT ANTIGEN WITH CLASS I MHC; PRESENTATION WITH CLASS
II MHC IS RESTRICTED TO APCS 209
EVIDENCE FOR DIFFERENT ANTIGEN-PROCESSING AND PRESENTATION PATHWAYS 2 09
ENDOGENOUS ANTIGENS:
THE CYTOSOLIC PATHWAY 2 10
PEPTIDES FOR PRESENTATION ARE GENERATED BY PROTEASE COMPLEXES CALLED
PROTEASOMES 211 PEPTIDES ARE TRANSPORTED FROM THE CYTOSOL TO THE ROUGH
ENDOPLASMIC RETICULUM 211
PEPTIDES ASSEMBLE WITH CLASS I MHC AIDED BY CHAPERONE MOLECULES 212
CLINICAL FOCUS DEFICIENCY IN TRANSPORTERS ASSOCIATED WITH ANTIGEN
PROCESSING (TAPS) LEADS TO A DIVERSE DISEASE SPECTRUM 213
EXOGENOUS ANTIGENS: THE ENDOCYTIC PATHWAY 214
PEPTIDES ARE GENERATED FROM INTERNALIZED MOLECULES IN ENDOCYTIC VESICLES
214
THE INVARIANT CHAIN GUIDES TRANSPORT OF CLASS II MHC MOLECULES TO
ENDOCYTIC VESICLES 214 PEPTIDES ASSEMBLE WITH CLASS II MHC MOLECULES BY
DISPLACING CLIP 215
CROSS-PRESENTATION OF EXOGENOUS ANTIGENS 2 17
CONTROVERSY EXISTS OVER THE CELL TYPES IN WHICH CROSS-PRESENTATION CAN
OCCUR 217
PRESENTATION OF NONPEPTIDE ANTIGENS 2 17
T-CELL RECEPTOR
EARLY STUDIES OF THE T-CELL RECEPTOR
CLASSIC EXPERIMENTS DEMONSTRATED THE SELF-MHC RESTRICTION OF THE T-CELL
RECEPTOR T-CELL RECEPTORS WERE ISOLATED BY USING CLONOTYPIC ANTIBODIES
THETCR *-CHAIN GENE WAS CLONED BY USE OF SUBTRACTIVE HYBRIDIZATION
AP AND YB T-CELL RECEPTORS:
STRUCTURES AND ROLES
ORGANIZATION AND REARRANGEMENT OF TCR GENES
TCR VARIABLE-REGION GENES REARRANGE IN A MANNER SIMILAR TO ANTIBODY
GENES MECHANISM OF TCR DNA REARRANGEMENTS ALLELIC EXCLUSION OF TCR GENES
223
223
224
224
224
226
228
229 230 231
IMAGE 6
C O N T E N TS
XVII
REARRANGED TCR GENES ARE ASSEMBLED FROM V, J, AND D GENE SEGMENTS 231
CLINICAL FOCUS T-CELL REARRANGEMENTS AS MARKERS FOR CANCEROUS CELLS 232
TCR DIVERSITY IS GENERATED LIKE ANTIBODY DIVERSITY
BUT WITHOUT SOMATIC MUTATION 232
T-CELL RECEPTOR COMPLEX: TCR-CD3 235
T-CELL ACCESSORY MEMBRANE MOLECULES 236
CD4 AND CD8 CORECEPTORS BIND TO CONSERVED
REGIONS OF MHC CLASS II OR I MOLECULES 236
AFFINITY OF TCR FOR PEPTIDE-MHC COMPLEXES IS ENHANCED BY CORECEPTORS 238
THREE-DIMENSIONAL STRUCTURES OF
TCR-PEPTIDE-MHC COMPLEXES 240
TCRS INTERACT DIFFERENTLY WITH CLASS I AND CLASS II MOLECULES 241
ALLOREACTIVITY OF T CELLS 241
10 T-CELL MATURATION, ACTIVATION,
AND DIFFERENTIATION 245
T-CELL MATURATION AND THE THYMUS
THYMIC SELECTION OF THE T-CELL REPERTOIRE
POSITIVE SELECTION ENSURES MHC RESTRICTION NEGATIVE SELECTION ENSURES
SELF-TOLERANCE EXPERIMENTS REVEALED THE ESSENTIAL ELEMENTS OF POSITIVE
AND NEGATIVE SELECTION SOME CENTRAL ISSUES IN THYMIC SELECTION
REMAIN UNRESOLVED
T-CELL ACTIVATION
MULTIPLE SIGNALING PATHWAYS ARE INITIATED BY TCR ENGAGEMENT HOW MANY TCR
COMPLEXES MUST BE ENGAGED TO TRIGGER T-CELL ACTIVATION? COSTIMULATORY
SIGNALS ARE REQUIRED
FOR FULL T-CELL ACTIVATION CLONAL ANERGY ENSUES IF A COSTIMULATORY
SIGNAL IS ABSENT SUPERANTIGENS INDUCE T-CELL ACTIVATION
BY BINDING THE TCR AND MHC II SIMULTANEOUSLY
T-CELL DIFFERENTIATION
ACTIVATED T CELLS GENERATE EFFECTOR AND MEMORY T CELLS ACD4+CD25+
SUBPOPULATION OFT CELLS NEGATIVELY REGULATES IMMUNE RESPONSES
ANTIGEN-PRESENTING CELLS HAVE CHARACTERISTIC COSTIMULATORY PROPERTIES
CELL DEATH AND T-CELL POPULATIONS
CLINICAL FOCUS FAILURE OF APOPTOSIS CAUSES DEFECTIVE LYMPHOCYTE
HOMEOSTASIS
245
248
249 250
250
251
254
254
258
259
259
260
261
262
263
263
264
266
11 B-CELL GENERATION, ACTIVATION, AND DIFFERENTIATION 271
B-CELL MATURATION 271
PROGENITOR B CELLS PROLIFERATE IN BONE MARROW 272 IG-GENE REARRANGEMENT
PRODUCES IMMATURE B CELLS 273
THE PRE-B-CELL RECEPTOR IS ESSENTIAL FOR B-CELL DEVELOPMENT 274
KNOCKOUT EXPERIMENTS IDENTIFIED ESSENTIAL TRANSCRIPTION FACTORS 275
CELL-SURFACE MARKERS IDENTIFY DEVELOPMENTAL STAGES 275
B-1 B CELLS ARE A SELF-RENEWING B-CELL SUBSET 275 SELF-REACTIVE B CELLS
ARE SELECTED AGAINST IN BONE MARROW 276
SELF-REACTIVE B CELLS MAY BE RESCUED BY EDITING OF LIGHT-CHAIN GENES 278
B-CELL ACTIVATION AND PROLIFERATION 278
THYMUS-DEPENDENT AND THYMUS-LNDEPENDENT ANTIGEN HAVE DIFFERENT
REQUIREMENTS FOR RESPONSE 278 TWO TYPES OF SIGNALS DRIVE B CELLS INTO
AND THROUGH THE CELL CYCLE 279
TRANSDUCTION OF ACTIVATING SIGNALS INVOLVES I G - A / L G^ HETERODIMERS
279
B-CELL SIGNALING IS INITIATED BY ANTIGEN BINDING AND INDUCES MANY SIGNAL
TRANSDUCTION PATHWAYS 281
THE B-CELL-CORECEPTOR COMPLEX CAN ENHANCE B-CELL RESPONSES AND CD22 CAN
INHIBIT THEM 281
CLINICAL FOCUS X-LINKED AGAMMAGLOBULINEMIA:
A FAILURE IN SIGNAL TRANSDUCTION AND B-CELL DEVELOPMENT 284
T H CELLS PLAY ESSENTIAL ROLES IN MOST
B-CELL RESPONSES 285
MATURE SELF-REACTIVE B CELLS CAN BE NEGATIVELY SELECTED IN THE PERIPHERY
287
THE HUMORAL RESPONSE 289
PRIMARY AND SECONDARY RESPONSES DIFFER SIGNIFICANTLY 289
T HELPER CELLS PLAY A CRITICAL ROLE IN THE HUMORAL RESPONSE TO
HAPTEN-CARRIER CONJUGATES 290
IN VIVO SITES FOR INDUCTION OF HUMORAL RESPONSES 292
GERMINAL CENTERS AND ANTIGEN-INDUCED B-CELL DIFFERENTIATION 292
AFFINITY MATURATION IS THE RESULT OF REPEATED MUTATION AND SELECTION 293
MEMORY B CELLS AND PLASMA CELLS ARE GENERATED IN GERMINAL CENTERS 296
REGULATION OF THE IMMUNE EFFECTOR RESPONSE 297
DIFFERENT ANTIGENS CAN COMPETE WITH EACH OTHER 297 THE PRESENCE OF
ANTIBODY CAN SUPPRESS THE RESPONSE TO ANTIGEN 297
IMAGE 7
XVIII
C O N T E N TS
PART III IMMUNE EFFECTOR
MECHANISMS
12 CYTOKINES
HIGH-ENDOTHELIAL VENULES ARE SITES
302
PROPERTIES OF CYTOKINES 302
CYTOKINES BELONG TO FOUR FAMILIES 305
CYTOKINES HAVE NUMEROUS BIOLOGICAL FUNCTIONS 306
CYTOKINE RECEPTORS 307
CYTOKINE RECEPTORS FALL WITHIN FIVE FAMILIES 308 SUBFAMILIES OF CLASS I
CYTOKINE RECEPTORS HAVE SIGNALING SUBUNITS IN COMMON 309
IL-2R IS THE MOST THOROUGHLY STUDIED CYTOKINE RECEPTOR 311
CYTOKINE RECEPTORS INITIATE SIGNALING 312
CYTOKINE ANTAGONISTS 314
CYTOKINE SECRETION BY T H1 AND TH2 SUBSETS 314
THE DEVELOPMENT OF T H1 ANDTH2 SUBSETS IS DETERMINED BY THE CYTOKINE
ENVIRONMENT 316 CYTOKINE PROFILES ARE CROSS-REGULATED 317
THET H1/TH2 BALANCE DETERMINES DISEASE OUTCOMES 318
CYTOKINE-RELATED DISEASES 318
SEPTIC SHOCK IS COMMON AND POTENTIALLY LETHAL 318 BACTERIAL TOXIC SHOCK
IS CAUSED BY SUPERANTIGENS 319
CYTOKINE ACTIVITY IS IMPLICATED IN LYMPHOID AND MYELOID CANCERS 319
CHAGAS'S DISEASE IS CAUSED BY A PARASITE 320
CYTOKINE-BASED THERAPIES 321
CYTOKINES IN HEMATOPOIESIS 321
CLINICAL FOCUS THERAPY WITH INTERFERONS 322
13 LEUKOCYTE ACTIVATION AND
MIGRATION 327
CELL ADHESION MOLECULES
CHEMOKINES
CHEMOKINE-RECEPTOR PROFILES MEDIATE LEUKOCYTE ACTIVITY
LEUKOCYTE EXTRAVASATION- THE MULTISTEP PARADIGM
LYMPHOCYTE RECIRCULATION
LYMPHOCYTE EXTRAVASATION
327
329
331
332
334
334
OF LYMPHOCYTE EXTRAVASATION 334
LYMPHOCYTE HOMING IS DIRECTED BY RECEPTOR PROFILES AND SIGNALS 336
NAIVE LYMPHOCYTES RECIRCULATE TO SECONDARY LYMPHOID TISSUE 336
EFFECTOR AND MEMORY LYMPHOCYTES ADOPT DIFFERENT TRAFFICKING PATTERNS 337
OTHER MEDIATORS OF INFLAMMATION 338
THE KININ SYSTEM IS ACTIVATED BY TISSUE INJURY 338 THE CLONING SYSTEM
YIELDS FIBRIN-GENERATED MEDIATORS OF INFLAMMATION 338
THE FIBRINOLYTIC SYSTEM YIELDS PLASMIN-GENERATED MEDIATORS OF
INFLAMMATION 338
THE COMPLEMENT SYSTEM PRODUCES ANAPHYLOTOXINS 338 SOME LIPIDS ACT AS
INFLAMMATORY MEDIATORS 339 SOME CYTOKINES ARE IMPORTANT INFLAMMATORY
MEDIATORS 339
THE INFLAMMATORY PROCESS 340
NEUTROPHILS PLAY AN EARLY AND IMPORTANT ROLE IN INFLAMMATION 340
INFLAMMATORY RESPONSES MAY BE LOCALIZED OR SYSTEMIC 340
CLINICAL FOCUS LEUKOCYTE ADHESION DEFICIENCY (LAD) IN HUMANS AND CATTLE
343
CHRONIC INFLAMMATION DEVELOPS
WHEN ANTIGEN PERSISTS 344
ROLES OF IFN-* AND TNF-* IN CHRONIC INFLAMMATION 344
HEV-LIKE STRUCTURES APPEAR IN CHRONIC INFLAMMATORY DISEASE 346
ANTI-INFLAMMATORY AGENTS 346
ANTIBODY THERAPIES REDUCE LEUKOCYTE EXTRAVASATION 346
CORTICOSTEROIDS ARE POWERFUL ANTI-INFLAMMATORY DRUGS 347
NSAIDS COMBAT PAIN AND INFLAMMATION 347
14 CELL-MEDIATED CYTOTOXIC RESPONSES 351
EFFECTOR RESPONSES 351
GENERAL PRINCIPLES OF EFFECTOR T CELLS 352
THE ACTIVATION REQUIREMENTS OFT CELLS DIFFER 352
CELL ADHESION MOLECULES FACILITATE TCR-MEDIATED INTERACTIONS 352
EFFECTOR T CELLS EXPRESS A VARIETY OF EFFECTOR MOLECULES 353
CYTOTOXIC T CELLS 353
EFFECTOR CTLS ARE GENERATED FROM CTL PRECURSORS 353 CD8+ CTLS CAN BE
TRACKED WITH MHCTETRAMERTECHNOLOGY 355
CTLS KILL CELLS IN TWO WAYS 355
IMAGE 8
C O N T E N TS
XIX
NATURAL KILLER CELLS
NK CELLS AND T CELLS SHARE SOME FEATURES KILLING BY NK CELLS IS SIMILAR
TO CTL-MEDIATED KILLING NK CELLS HAVE BOTH ACTIVATION
AND INHIBITION RECEPTORS
CLINICAL FOCUS MHC-KIR GENE COMBINATIONS INFLUENCE HEALTH
NKT CELLS
ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY
EXPERIMENTAL ASSESSMENT OF CELL-MEDIATED CYTOTOXICITY
COCULTURINGT CELLS WITH FOREIGN CELLS STIMULATES MLR CTL ACTIVITY CAN BE
DEMONSTRATED BY CML THE CVH REACTION IS AN INDICATION
OF CELL-MEDIATED CYTOTOXICITY
360
361
361
362
364
364
366
366
366 367
367
15 HYPERSENSITIVITY REACTIONS 371
GELL AND COOMBS CLASSIFICATION
IGE-MEDIATED (TYPE I) HYPERSENSITIVITY
THERE ARE SEVERAL COMPONENTS OF TYPE I REACTIONS IGE-BINDING FC
RECEPTORS IGE CROSS-LINKAGE INITIATES DEGRANULATION INTRACELLULAR EVENTS
TRIGGER MAST-CELL
DEGRANULATION SEVERAL PHARMACOLOGIC AGENTS MEDIATE TYPE I REACTIONS TYPE
I REACTIONS CAN BE SYSTEMIC OR LOCALIZED
LATE-PHASE REACTIONS INDUCE LOCALIZED INFLAMMATORY REACTIONS TYPE I
RESPONSES ARE REGULATED BY MANY FACTORS
CLINICAL FOCUS THE GENETICS OF ASTHMA
SEVERAL CLINICAL METHODS ARE USED
TO DETECT TYPE I HYPERSENSITIVITY REACTIONS TYPE I HYPERSENSITIVITIES
CAN BE CONTROLLED MEDICALLY
ANTIBODY-MEDIATED CYTOTOXIC
(TYPE II) HYPERSENSITIVITY
TRANSFUSION REACTIONS ARE TYPE II REACTIONS HEMOLYTIC DISEASE OF THE
NEWBORN IS CAUSED BY TYPE II REACTIONS DRUG-INDUCED HEMOLYTIC ANEMIA
IS A TYPE II RESPONSE
IMMUNE COMPLEX-MEDIATED (TYPE III) HYPERSENSITIVITY
TYPE III REACTIONS CAN BE LOCALIZED TYPE III REACTIONS CAN ALSO BE
GENERALIZED
TYPE IV OR DELAYED-TYPE HYPERSENSITIVITY (DTH) 393
THERE ARE SEVERAL PHASES OF THE DTH RESPONSE 394 NUMEROUS CYTOKINES
PARTICIPATE IN THE DTH REACTION 395 THE DTH REACTION IS DETECTED WITH A
SKIN TEST 396
CONTACT DERMATITIS IS A TYPE OF DTH RESPONSE 396
16 TOLERANCE AND AUTOIMMUNITY 401
ESTABLISHMENT AND MAINTENANCE OF TOLERANCE 402
CENTRAL TOLERANCE LIMITS DEVELOPMENT OF AUTOREACTIVE T AND B CELLS 403
PERIPHERAL TOLERANCE REGULATES AUTOREACTIVE CELLS IN CIRCULATION 404
REGULATORY T CELLS ARE A COMPONENT OF PERIPHERAL TOLERANCE 406
ANTIGEN SEQUESTRATION IS A MEANS TO PROTECT SELF ANTIGENS 407
FAILURE OF TOLERANCE LEADS TO AUTOIMMUNITY 407
ORGAN-SPECIFIC AUTOIMMUNE DISEASES 407
SOME AUTOIMMUNE DISEASES ARE MEDIATED BY DIRECT CELLULAR DAMAGE 407
SOME AUTOIMMUNE DISEASES ARE MEDIATED
371 OY STIMULATING OR BLOCKING AUTO-ANTIDOCNES 4UY
372 SYSTEMIC AUTOIMMUNE DISEASES 410
SYSTEMIC LUPUS ERYTHEMATOSUS ATTACKS 373 MANY TISSUES 410
376 MULTIPLE SCLEROSIS ATTACKS THE 377 CENTRAL NERVOUS SYSTEM 411
RHEUMATOID ARTHRITIS ATTACKS JOINTS 411
ANIMAL MODELS FOR AUTOIMMUNE DISEASES 411
381 AUTOIMMUNITY CAN DEVELOP SPONTANEOUSLY IN ANIMALS 412
383 AUTOIMMUNITY CAN BE INDUCED EXPERIMENTALLY IN ANIMALS 413
383
EVIDENCE IMPLICATING THE CD4 + T CELL, MHC, AND TCR IN AUTOIMMUNITY 413
386 CD4+ T CELLS AND T H1/TH2 BALANCE PLAY 386 AN IMPORTANT ROLE IN
AUTOIMMUNITY IN SOME ANIMAL MODELS 414
AUTOIMMUNITY CAN BE ASSOCIATED WITH THE 388 MHC OR WITH PARTICULAR
T-CELL RECEPTORS 414
388 PROPOSED MECHANISMS
FOR INDUCTION OF AUTOIMMUNITY 414
389
RELEASE OF SEQUESTERED ANTIGENS 391 CAN INDUCE AUTOIMMUNE DISEASE 415
391
392 392
CLINICAL FOCUS WHY ARE WOMEN MORE SUSCEPTIBLE THAN MEN TO AUTOIMMUNITY?
GENDER DIFFERENCES IN AUTOIMMUNE DISEASE
MOLECULAR MIMICRY MAY CONTRIBUTE
TO AUTOIMMUNE DISEASE
416
416
IMAGE 9
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C O N T E N TS
THERE IS EVIDENCE FOR MIMICRY BETWEEN MBP
AND VIRAL PEPTIDES 418
INAPPROPRIATE EXPRESSION OF CLASS II MHC MOLECULES CAN SENSITIZE
AUTOREACTIVE T CELLS 418
POLYCLONAL B-CELL ACTIVATION CAN LEAD TO AUTOIMMUNE DISEASE 419
TREATMENT OF AUTOIMMUNE DISEASES 419
TREATMENT OF HUMAN AUTOIMMUNE DISEASE POSES SPECIAL CHALLENGES 420
INFLAMMATION IS A TARGET FOR TREATMENT OF AUTOIMMUNITY 420 ACTIVATED T
CELLS ARE A POSSIBLE THERAPEUTIC TARGET 421 ORAL ANTIGENS CAN INDUCE
TOLERANCE 421
PART IV THE IMMUNE SYSTEM
IN HEALTH AND DISEASE
CLINICAL TRANSPLANTATION THE MOST COMMONLY TRANSPLANTED ORGAN IS THE
KIDNEY BONE MARROW TRANSPLANTS ARE USED
FOR LEUKEMIA, ANEMIA, AND IMMUNODEFICIENCY HEART TRANSPLANTATION IS A
CHALLENGING OPERATION LUNG TRANSPLANTS ARE ON THE INCREASE LIVER
TRANSPLANTS TREAT CONGENITAL DEFECTS
AND DAMAGE FROM VIRAL OR CHEMICAL AGENTS TRANSPLANTATION OF PANCREATIC
CELLS OFFERS A CURE FOR DIABETES MELLITUS SKIN GRAFTS ARE USED TO TREAT
BURN VICTIMS XENOTRANSPLANTATION MAY BE THE ANSWER
TO THE SHORTAGE OF DONOR ORGANS
18 IMMUNE RESPONSE
TO INFECTIOUS DISEASES
440
441
441 442 442
442
442 443
443
447
17 TRANSPLANTATION IMMUNOLOGY 425
IMMUNOLOGIC BASIS OF GRAFT REJECTION 426
ALLOGRAFT REJECTION DISPLAYS SPECIFICITY AND MEMORY 426
T CELLS PLAY A KEY ROLE IN ALLOGRAFT REJECTION 426
SIMILAR ANTIGENIC PROFILES FOSTER ALLOGRAFT ACCEPTANCE 428
GRAFT DONORS AND RECIPIENTS ARE TYPED FOR RBC AND MHC ANTIGENS 428
CELL-MEDIATED GRAFT REJECTION OCCURS IN TWO STAGES 431
CLINICAL MANIFESTATIONS OF GRAFT REJECTION 433
PREEXISTING RECIPIENT ANTIBODIES MEDIATE HYPERACUTE REJECTION 433
ACUTE REJECTION IS MEDIATED BYT-CELL RESPONSES 434 CHRONIC REJECTION
OCCURS MONTHS OR YEARS POST-TRANSPLANT 434
GENERAL IMMUNOSUPPRESSIVE THERAPY 434
MITOTIC INHIBITORS THWART T-CELL PROLIFERATION 434
CLINICAL FOCUS IS THERE A CLINICAL FUTURE FOR XENOTRANSPLANTATION? 435
CORTICOSTEROIDS SUPPRESS INFLAMMATION 436
CERTAIN FUNGAL METABOLITES ARE IMMUNOSUPPRESSANTS 436
TOTAL LYMPHOID IRRADIATION ELIMINATES LYMPHOCYTES 436
SPECIFIC IMMUNOSUPPRESSIVE THERAPY 436
ANTIBODIES CAN SUPPRESS GRAFT REJECTION RESPONSES 437 BLOCKING
COSTIMULATORY SIGNALS CAN INDUCE ANERGY 438
IMMUNE TOLERANCE TO ALLOGRAFTS 439
PRIVILEGED SITES ACCEPT ANTIGENIC MISMATCHES 439 EARLY EXPOSURE TO
ALLOANTIGENS CAN INDUCE SPECIFIC TOLERANCE 439
VIRAL INFECTIONS 448
MANY VIRUSES ARE NEUTRALIZED BY ANTIBODIES 449
CELL-MEDIATED IMMUNITY IS IMPORTANT FOR VIRAL CONTROL AND CLEARANCE 450
VIRUSES CAN EVADE HOST DEFENSE MECHANISMS 450 INFLUENZA HAS BEEN
RESPONSIBLE FOR SOME OF THE WORST PANDEMICS IN HISTORY 451
THE HUMORAL RESPONSE TO INFLUENZA IS STRAIN SPECIFIC 454 AVIAN H5N1
PRESENTS THE THREAT OF A PANDEMIC 454
BACTERIAL INFECTIONS 454
IMMUNE RESPONSES TO EXTRACELLULAR AND INTRACELLULAR BACTERIA CAN DIFFER
455
BACTERIA CAN EFFECTIVELY EVADE HOST DEFENSE MECHANISMS 455
IMMUNE RESPONSES CAN CONTRIBUTE TO BACTERIAL PATHOGENESIS 457
DIPHTHERIA [CORYNEBACTERIUM DIPHTHERIAE) CAN BE CONTROLLED BY
IMMUNIZATION WITH INACTIVATED TOXOID 458
TUBERCULOSIS (MYCOBACTERIUM TUBERCULOSIS) IS PRIMARILY CONTROLLED BY
CD4+ T CELLS 458
PARASITIC DISEASES 460
PROTOZOAN DISEASES AFFECT MILLIONS WORLDWIDE 460 MALARIA (PLASMODIUM
SPECIES) INFECTS 600 MILLION PEOPLE WORLDWIDE 460
TWO SPECIES OF TRYPANOSOMA CAUSE AFRICAN SLEEPING SICKNESS 462
LEISHMANIASIS IS A USEFUL MODEL FOR DEMONSTRATING DIFFERENCES IN HOST
RESPONSES 462
A VARIETY OF DISEASES ARE CAUSED BY PARASITIC WORMS (HELMINTHS) 462
FUNGAL DISEASES 465
INNATE IMMUNITY CONTROLS MOST FUNGAL INFECTIONS 466 IMMUNITY AGAINST
FUNGAL PATHOGENS CAN BE ACQUIRED 466
IMAGE 10
C O N T E N TS
XXI
EMERGING INFECTIOUS DISEASES
DISEASES MAY RE-EMERGE FOR VARIOUS REASONS
CLINICAL FOCUS THE THREAT OF INFECTION FROM POTENTIAL AGENTS OF
BIOTERRORISM
SOME FATAL DISEASES HAVE APPEARED RECENTLY
THE SARS OUTBREAK TRIGGERED A RAPID INTERNATIONAL RESPONSE
467
467
468
470
470
19 VACCINES 475
CLINICAL FOCUS VACCINATION: CHALLENGES IN THE UNITED STATES AND
DEVELOPING COUNTRIES 476
ACTIVE AND PASSIVE IMMUNIZATION 4 77
PASSIVE IMMUNIZATION INVOLVES TRANSFER OF PREFORMED ANTIBODIES 477
ACTIVE IMMUNIZATION ELICITS LONG-TERM PROTECTION 477
DESIGNING VACCINES FOR ACTIVE IMMUNIZATION 481
LIVE, ATTENUATED VACCINES 481
INACTIVATED OR "KILLED" VACCINES 4 84
SUBUNIT VACCINES 4 84
TOXOIDS ARE USED AS VACCINES 485
BACTERIAL POLYSACCHARIDE CAPSULES ARE USED AS VACCINES 485 VIRAL
GLYCOPROTEINS ARE CANDIDATE VACCINES 485 PATHOGEN PROTEINS ARE
MANUFACTURED BY RECOMBINANT TECHNIQUES 485
USE OF SYNTHETIC PEPTIDES AS VACCINES HAS PROGRESSED SLOWLY 485
CONJUGATE VACCINES 486
ONE POLYSACCHARIDE CONFERS PROTECTION AGAINST SEVERAL FUNGI 486
MULTIVALENT SUBUNIT VACCINES CONFER BOTH CELLULAR AND HUMORAL IMMUNITY
486
DNA VACCINES 488
RECOMBINANT VECTOR VACCINES 488
20 AIDS AND OTHER
IMMUNODEFICIENCIES
PRIMARY IMMUNODEFICIENCIES
LYMPHOID IMMUNODEFICIENCIES MAY INVOLVE B CELLS, T CELLS, OR BOTH
IMMUNODEFICIENCIES OF THE MYELOID LINEAGE AFFECT INNATE IMMUNITY
COMPLEMENT DEFECTS RESULT IN IMMUNODEFICIENCY
OR IMMUNE-COMPLEX DISEASE IMMUNODEFICIENCY DISORDERS ARE TREATED BY
REPLACEMENT OF THE DEFECTIVE ELEMENT EXPERIMENTAL MODELS OF
IMMUNODEFICIENCY
INCLUDE GENETICALLY ALTERED ANIMALS
493
493
495
500
502
502
503
AIDS AND OTHER ACQUIRED OR SECONDARY IMMUNODEFICIENCIES 504
HIV/AIDS HAS CLAIMED MILLIONS OF LIVES WORLDWIDE 505 HIV-1 SPREADS BY
SEXUAL CONTACT, BY INFECTED BLOOD, AND FROM MOTHER TO INFANT 505
CLINICAL FOCUS PREVENTION OF INFANT HIV INFECTION BY ANTI-RETROVIRAL
TREATMENT 507
THE RETROVIRUS HIV-1 IS THE CAUSATIVE AGENT
OF AIDS 508
IN VITRO STUDIES REVEALED THE HIV-1 REPLICATION CYCLE 509
HIV-1 INFECTION LEADS TO OPPORTUNISTIC INFECTIONS 512 THERAPEUTIC AGENTS
INHIBIT RETROVIRUS REPLICATION 515
A VACCINE MAY BE THE ONLY WAY TO STOP THE HIV/AIDS EPIDEMIC 518
21 CANCER AND THE IMMUNE SYSTEM 525
CANCER: ORIGIN AND TERMINOLOGY 525
MALIGNANT TRANSFORMATION OF CELLS 526
ONCOGENES AND CANCER INDUCTION 527
CANCER-ASSOCIATED GENES HAVE MANY FUNCTIONS 527 PROTO-ONCOGENES CAN BE
CONVERTED TO ONCOGENES 529 THE INDUCTION OF CANCER IS A MULTISTEP
PROCESS 530
TUMORS OF THE IMMUNE SYSTEM 530
TUMOR ANTIGENS 531
SOME ANTIGENS ARE TUMOR-SPECIFIC 532
CLINICAL FOCUS A VACCINE THAT PREVENTS CANCER 534
TUMOR ANTIGENS MAY BE INDUCED BY VIRUSES 535
MOST TUMOR ANTIGENS ARE NOT UNIQUE TO TUMOR CELLS 536
TUMORS CAN INDUCE POTENT IMMUNE RESPONSES 537 NK CELLS AND MACROPHAGES
ARE IMPORTANT IN TUMOR RECOGNITION 537
TUMOR EVASION OF THE IMMUNE SYSTEM 538
ANTITUMOR ANTIBODIES CAN ENHANCE TUMOR GROWTH 538 ANTIBODIES CAN
MODULATE TUMOR ANTIGENS 538
TUMOR CELLS FREQUENTLY EXPRESS LOW LEVELS OF CLASS I MHC MOLECULES 538
TUMOR CELLS MAY PROVIDE POOR COSTIMULATORY SIGNALS 538
CANCER IMMUNOTHERAPY 539
MANIPULATION OF CO-STIMULATORY SIGNALS CAN ENHANCE IMMUNITY 539
ENHANCEMENT OF APC ACTIVITY CAN MODULATE TUMOR IMMUNITY 540
CYTOKINE THERAPY CAN AUGMENT IMMUNE RESPONSES TO TUMORS 540
MONOCLONAL ANTIBODIES ARE EFFECTIVE IN TREATING SOME TUMORS 542
IMAGE 11
XXII
C O N T E N TS
22 EXPERIMENTAL SYSTEMS 546
EXPERIMENTAL ANIMAL METHODS 546
INBRED STRAINS CAN REDUCE EXPERIMENTAL VARIATION 547 ADOPTIVE-TRANSFER
SYSTEMS PERMIT THE IN VIVO EXAMINATION OF ISOLATED CELL POPULATIONS 547
CELL CULTURE SYSTEMS 547
PRIMARY LYMPHOID CELL CULTURES ARE DERIVED FROM BLOOD OR LYMPHOID ORGANS
547
CLONED LYMPHOID CELL LINES ARE IMPORTANT TOOLS IN IMMUNOLOGY 549
PREPARING HYBRID LYMPHOID CELL LINES 550
PROTEIN BIOCHEMISTRY 551
RADIOLABELING TECHNIQUES ALLOW SENSITIVE DETECTION OF ANTIGENS OR
ANTIBODIES 551
BIOTIN LABELS FACILITATE DETECTION OF SMALL AMOUNTS OF PROTEINS 551
GEL ELECTROPHORESIS SEPARATES PROTEINS BY SIZE AND CHARGE 551
X-RAY CRYSTALLOGRAPHY PROVIDES STRUCTURAL INFORMATION 553
RECOMBINANT DNA TECHNOLOGY 555
RESTRICTION ENZYMES CLEAVE DNA AT PRECISE SEQUENCES 555
DNA SEQUENCES ARE CLONED INTO VECTORS 556
CLONING VECTORS ARE USEFUL TO REPLICATE DEFINED SEQUENCES OF DNA 556
CLONING OF CDNA AND GENOMIC DNA ALLOWS THE ISOLATION OF DEFINED
SEQUENCES 556
DNA CLONES ARE SELECTED BY HYBRIDIZATION 558
SOUTHERN BLOTTING DETECTS DNA OF A GIVEN SEQUENCE 559 NORTHERN BLOTTING
DETECTS MRNA 559
THE POLYMERASE CHAIN REACTION AMPLIFIES
SMALL QUANTITIES OF DNA 559
ANALYSIS OF DNA REGULATORY SEQUENCES 560
DNA FOOTPRINTING IDENTIFIES THE SITES
WHERE PROTEINS BIND DNA 560
GEL-SHIFT ANALYSIS IDENTIFIES DNA-PROTEIN COMPLEXES 561 LUCIFERASE
ASSAYS MEASURE TRANSCRIPTIONAL ACTIVITY 562
GENE TRANSFER INTO MAMMALIAN CELLS 562
CLONED GENES TRANSFERRED INTO CULTURED CELLS ALLOW IN VITRO ANALYSIS OF
GENE FUNCTION 562
CLONED GENES TRANSFERRED INTO MOUSE EMBRYOS ALLOW IN VIVO ANALYSIS OF
GENE FUNCTION 563
IN KNOCKOUT MICE, TARGETED GENES ARE DISRUPTED 564 "KNOCK-IN" TECHNOLOGY
ALLOWS THE REPLACEMENT OF AN ENDOGENOUS GENE 565
INDUCIBLE GENE TARGETING, THE CRE/FOX SYSTEM, TARGETS GENE DELETION 565
MICROARRAYS-AN APPROACH FOR ANALYZING PATTERNS OF GENE EXPRESSION 567
CLINICAL FOCUS MICROARRAY ANALYSIS AS A DIAGNOSTIC TOOL FOR HUMAN
DISEASES 568
TWO-PHOTON MICROSCOPY FOR IN VIVO IMAGING
OF THE IMMUNE SYSTEM 570
ADVANCES IN FLUORESCENT TECHNOLOGY 571
APPENDIX I: CD ANTIGENS A-1
APPENDIX II: CYTOKINES A-27
GLOSSARY G-1
ANSWERS TO STUDY QUESTIONS AN-1
INDEX I-1 |
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| author | Kindt, Thomas J. Goldsby, Richard A. Osborne, Barbara A. |
| author_facet | Kindt, Thomas J. Goldsby, Richard A. Osborne, Barbara A. |
| author_role | aut aut aut |
| author_sort | Kindt, Thomas J. |
| author_variant | t j k tj tjk r a g ra rag b a o ba bao |
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| bvnumber | BV021755338 |
| callnumber-first | Q - Science |
| callnumber-label | QR181 |
| callnumber-raw | QR181 |
| callnumber-search | QR181 |
| callnumber-sort | QR 3181 |
| callnumber-subject | QR - Microbiology |
| classification_rvk | WF 9800 |
| classification_tum | CHE 880f |
| ctrlnum | (OCoLC)68207318 (DE-599)BVBBV021755338 |
| 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 | Biologie Chemie Medizin |
| discipline_str_mv | Biologie Chemie Medizin |
| edition | 6. ed. |
| format | Book |
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| genre | (DE-588)4123623-3 Lehrbuch gnd-content |
| genre_facet | Lehrbuch |
| id | DE-604.BV021755338 |
| illustrated | Illustrated |
| index_date | 2024-07-02T15:33:17Z |
| indexdate | 2024-07-09T20:43:18Z |
| institution | BVB |
| isbn | 9780716767640 9781429202114 1429202114 0716785900 9780716785903 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-014968503 |
| oclc_num | 68207318 |
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| owner | DE-19 DE-BY-UBM DE-29T DE-29 DE-70 DE-91G DE-BY-TUM DE-578 |
| owner_facet | DE-19 DE-BY-UBM DE-29T DE-29 DE-70 DE-91G DE-BY-TUM DE-578 |
| physical | Getr. Zählung zahlr. Ill. und graph. Darst. |
| publishDate | 2007 |
| publishDateSearch | 2007 |
| publishDateSort | 2007 |
| publisher | Freeman |
| record_format | marc |
| spelling | Kindt, Thomas J. Verfasser aut Immunology Kuby. Thomas J. Kindt ; Richard A. Goldsby ; Barbara A. Osborne Kuby Immunology 6. ed. New York Freeman 2007 Getr. Zählung zahlr. Ill. und graph. Darst. txt rdacontent n rdamedia nc rdacarrier Kuby immunology Immunité naturelle rasuqam Immunologie Immunologie gtt Immunologie rasuqam Système immunitaire rasuqam Immune System Immunity Immunology Immunologie (DE-588)4026637-0 gnd rswk-swf (DE-588)4123623-3 Lehrbuch gnd-content Immunologie (DE-588)4026637-0 s DE-604 Goldsby, Richard A. Verfasser aut Osborne, Barbara A. Verfasser aut Kuby, Janis Begründer des Werks oth 7. Aufl u.d.T. Owen, Judith Immunology (DE-604)BV041130775 SWB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014968503&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Kindt, Thomas J. Goldsby, Richard A. Osborne, Barbara A. Immunology Immunité naturelle rasuqam Immunologie Immunologie gtt Immunologie rasuqam Système immunitaire rasuqam Immune System Immunity Immunology Immunologie (DE-588)4026637-0 gnd |
| subject_GND | (DE-588)4026637-0 (DE-588)4123623-3 |
| title | Immunology |
| title_alt | Kuby Immunology |
| title_auth | Immunology |
| title_exact_search | Immunology |
| title_exact_search_txtP | Immunology |
| title_full | Immunology Kuby. Thomas J. Kindt ; Richard A. Goldsby ; Barbara A. Osborne |
| title_fullStr | Immunology Kuby. Thomas J. Kindt ; Richard A. Goldsby ; Barbara A. Osborne |
| title_full_unstemmed | Immunology Kuby. Thomas J. Kindt ; Richard A. Goldsby ; Barbara A. Osborne |
| title_new | Owen, Judith Immunology |
| title_short | Immunology |
| title_sort | immunology |
| topic | Immunité naturelle rasuqam Immunologie Immunologie gtt Immunologie rasuqam Système immunitaire rasuqam Immune System Immunity Immunology Immunologie (DE-588)4026637-0 gnd |
| topic_facet | Immunité naturelle Immunologie Système immunitaire Immune System Immunity Immunology Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014968503&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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