Janeway's immunobiology:
Gespeichert in:
| Hauptverfasser: | , , |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
New York [u.a.]
Garland Science
2008
|
| Ausgabe: | 7. ed. |
| Schlagworte: | |
| Online-Zugang: | Table of contents only Inhaltsverzeichnis |
| Beschreibung: | Bis 6. Aufl. u.d.T.: Janeway, Charles: Immunobiology. - Ab 8. Aufl. u.d.T.: Janeway's immunobiology |
| Beschreibung: | XXI, 887 S. Ill., graph. Darst. 1 CD-ROM (12 cm) |
| ISBN: | 0815341237 |
Internformat
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| 100 | 1 | |a Murphy, Kenneth M. |e Verfasser |0 (DE-588)1089816251 |4 aut | |
| 245 | 1 | 0 | |a Janeway's immunobiology |c Kenneth Murphy ; Paul Travers ; Mark Walport |
| 246 | 1 | 3 | |a Immunobiology |
| 250 | |a 7. ed. | ||
| 264 | 1 | |a New York [u.a.] |b Garland Science |c 2008 | |
| 300 | |a XXI, 887 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 | ||
| 500 | |a Bis 6. Aufl. u.d.T.: Janeway, Charles: Immunobiology. - Ab 8. Aufl. u.d.T.: Janeway's immunobiology | ||
| 650 | 4 | |a Immunology | |
| 650 | 0 | 7 | |a Immunbiologie |0 (DE-588)4072743-9 |2 gnd |9 rswk-swf |
| 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 Immunbiologie |0 (DE-588)4072743-9 |D s |
| 689 | 0 | |5 DE-604 | |
| 689 | 1 | 0 | |a Immunologie |0 (DE-588)4026637-0 |D s |
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| 700 | 1 | |a Travers, Paul |d 1956- |e Verfasser |0 (DE-588)1145896154 |4 aut | |
| 700 | 1 | |a Walport, Mark |e Verfasser |4 aut | |
| 700 | 1 | |a Janeway, Charles A. |c Jr. |d 1943-2003 |e Sonstige |0 (DE-588)123088178 |4 oth | |
| 856 | 4 | |u http://www.loc.gov/catdir/toc/ecip079/2007002499.html |3 Table of contents only | |
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| 999 | |a oai:aleph.bib-bvb.de:BVB01-016261838 | ||
Datensatz im Suchindex
| _version_ | 1804137294827880448 |
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| adam_text | JANEWAY S IMMUNO IOLOGY SEVENTH EDITION KENNETH MURPHY WASHINGTON
UNIVERSITY SCHOOL OF MEDICINE, ST. LOUIS PAUL TRAVERS ANTHONY NOLAN
RESEARCH INSTITUTE, LONDON MARK WALPORT THE WELLCOME TRUST, LONDON WITH
CONTRIBUTIONS BY: MICHAEL EHRENSTEIN UNIVERSITY COLLEGE LONDON, DIVISION
OF MEDICINE CLAUDIA MAURI UNIVERSITY COLLEGE LONDON, DIVISION OF
MEDICINE ALLAN MOWAT - UNIVERSITY OF GLASGOW ANDREYSHAW WASHINGTON
UNIVERSITY SCHOOL OF MEDICINE, ST. LOUIS GARLAND SCIENCE TAYLOR &
FRANCIS CROUP NEW YORK AND LONDON DETAILED CONTENTS PARTI AN
INTRODUCTION TO IMMUNO- BIOLOGY AND INNATE IMMUNITY CHAPTER 1 BASIC
CONCEPTS IN IMMUNOLOGY 1 PRINCIPLES OF INNATE AND ADAPTIVE IMMUNITY. 3
1-1 FUNCTIONS OF THE IMMUNE RESPONSE. 3 1 -2 THE CELLS OF THE IMMUNE
SYSTEM DERIVE FROM PRECURSORS IN THE BONE MARROW. 5 1 -3 THE MYELOID
LINEAGE COMPRISES MOST OF THE CELLS OF THE INNATE IMMUNE SYSTEM. 5 1-4
THE LYMPHOID LINEAGE COMPRISES THE LYMPHOCYTES OF THE ADAPTIVE IMMUNE
SYSTEM AND THE NATURAL KILLER CELLS OF INNATE IMMUNITY. 8 1 -5
LYMPHOCYTES MATURE IN THE BONE MARROW OR THE THYMUS AND THEN CONGREGATE
IN LYMPHOID TISSUES THROUGHOUT THE BODY. 9 1 -6 MOST INFECTIOUS AGENTS
ACTIVATE THE INNATE IMMUNE SYSTEM AND INDUCE AN INFLAMMATORY RESPONSE.
10 1-7 ACTIVATION OF SPECIALIZED ANTIGEN-PRESENTING CELLS IS A NECESSARY
FIRST STEP FOR INDUCTION OF ADAPTIVE IMMUNITY. 12 1-8 THE INNATE IMMUNE
SYSTEM PROVIDES AN INITIAL DISCRIMINATION BETWEEN SELF AND NONSELF. 13 1
-9 LYMPHOCYTES ACTIVATED BY ANTIGEN GIVE RISE TO CLONES OF
ANTIGEN-SPECIFIC EFFECTOR CELLS THAT MEDIATE ADAPTIVE IMMUNITY. 13 1-10
CLONAL SELECTION OF LYMPHOCYTES IS THE CENTRAL PRINCIPLE OF ADAPTIVE
IMMUNITY. 14 1-11 THE STRUCTURE OF THE ANTIBODY MOLECULE ILLUSTRATES THE
CENTRAL PUZZLE OF ADAPTIVE IMMUNITY. 15 1-12 EACH DEVELOPING LYMPHOCYTE
GENERATES A UNIQUE ANTIGEN RECEPTOR BY REARRANGING ITS RECEPTOR GENE
SEGMENTS. 16 1 -13 IMMUNOGLOBULINS BIND A WIDE VARIETY OF CHEMICAL
STRUCTURES, WHEREAS THE T-CELL RECEPTOR IS SPECIALIZED TO RECOGNIZE
FOREIGN ANTIGENS AS PEPTIDE FRAGMENTS BOUND TO PROTEINS OF THE MAJOR
HISTOCOMPATIBILITY COMPLEX. 17 1-14 THE DEVELOPMENT AND SURVIVAL OF
LYMPHOCYTES IS DETERMINED BY SIGNALS RECEIVED THROUGH THEIR ANTIGEN
RECEPTORS. 18 1-15 LYMPHOCYTES ENCOUNTER AND RESPOND TO ANTIGEN IN THE
PERIPHERAL LYMPHOID ORGANS. 18 1-16 INTERACTION WITH OTHER CELLS AS WELL
AS WITH ANTIGEN IS NECESSARY FOR LYMPHOCYTE ACTIVATION. 23 1-17
LYMPHOCYTES ACTIVATED BY ANTIGEN PROLIFERATE IN THE PERIPHERAL LYMPHOID
ORGANS, GENERATING EFFECTOR CELLS AND IMMUNOLOGICAL MEMORY. - 23
SUMMARY. 27 THE EFFECTOR MECHANISMS OF ADAPTIVE IMMUNITY. 27 1-18
ANTIBODIES DEAL WITH EXTRACELLULAR FORMS OF PATHOGENS AND THEIR TOXIC
PRODUCTS. 28 1-19 T CELLS ARE NEEDED TO CONTROL INTRACELLULAR PATHOGENS
AND TO ACTIVATE B-CELL RESPONSES TO MOST ANTIGENS. 30 1 -20 CD4 AND CD8
T CELLS RECOGNIZE PEPTIDES BOUND TO TWO DIFFERENT CLASSES OF MHC
MOLECULES. 32 1 -21 DEFECTS IN THE IMMUNE SYSTEM RESULT IN INCREASED
SUSCEPTIBILITY TO INFECTION. 34 1-22 UNDERSTANDING ADAPTIVE IMMUNE
RESPONSES IS IMPORTANT FOR THE CONTROL OF ALLERGIES, AUTOIMMUNE DISEASE,
AND ORGAN GRAFT REJECTION. 34 1 -23 VACCINATION IS THE MOST EFFECTIVE
MEANS OF CONTROLLING INFECTIOUS DISEASES. 36 SUMMARY. 37 SUMMARY TO
CHAPTER 1. 37 CHAPTER 2 INNATE IMMUNITY 39 THE FRONT LINE OF HOST
DEFENSE. 40 2-1 INFECTIOUS DISEASES ARE CAUSED BY DIVERSE LIVING AGENTS
THAT REPLICATE IN THEIR HOSTS. 41 2-2 INFECTIOUS AGENTS MUST OVERCOME
INNATE HOST DEFENSES TO ESTABLISH A FOCUS OF INFECTION. - 44 2-3 THE
EPITHELIAL SURFACES OF THE BODY MAKE UP THE FIRST LINES OF DEFENSE
AGAINST INFECTION. 46 2-4 AFTER ENTERING TISSUES, MANY PATHOGENS ARE
RECOGNIZED, INGESTED, AND KILLED BY PHAGOCYTES. 48 2-5 PATHOGEN
RECOGNITION AND TISSUE DAMAGE INITIATE AN INFLAMMATORY RESPONSE. 50
SUMMARY. 52 PATTERN RECOGNITION IN THE INNATE IMMUNE SYSTEM. 53 2-6
RECEPTORS WITH SPECIFICITY FOR PATHOGEN MOLECULES RECOGNIZE PATTERNS OF
REPEATING STRUCTURAL MOTIFS. 54 2-7 THE TOLL-LIKE RECEPTORS ARE
SIGNALING RECEPTORS THAT DISTINGUISH DIFFERENT TYPES OF PATHOGEN AND
HELP DIRECT AN APPROPRIATE IMMUNE RESPONSE. 56 2-8 THE EFFECTS OF
BACTERIAL LIPOPOLYSACCHARIDE ON MACROPHAGES ARE MEDIATED BY CD14 BINDING
TO TLR-4. 57 2-9 THE NOD PROTEINS ACT AS INTRACELLULAR SENSORS OF
BACTERIAL INFECTION. 58 2-10 ACTIVATION OF TOLL-LIKE RECEPTORS AND NOD
PROTEINS TRIGGERS THE PRODUCTION OF PRO-INFLAMMATORY CYTOKINES AND
CHEMOKINES, AND THE EXPRESSION OF CO-STIMULATORY MOLECULES. 58 SUMMARY.-
59 THE COMPLEMENT SYSTEM AND INNATE IMMUNITY. 61 2-11 COMPLEMENT IS A
SYSTEM OF PLASMA PROTEINS THAT IS ACTIVATED BY THE PRESENCE OF
PATHOGENS. 61 2-12 COMPLEMENT INTERACTS WITH PATHOGENS TO MARK THEM FOR
DESTRUCTION BY PHAGOCYTES. 62 2-13 THE CLASSICAL PATHWAY IS INITIATED BY
ACTIVATION OF THE C1 COMPLEX. 64 2-14 THE LECTIN PATHWAY IS HOMOLOGOUS
TO THE CLASSICAL PATHWAY. 65 2-15 COMPLEMENT ACTIVATION IS LARGELY
CONFINED TO THE SURFACE ON WHICH IT IS INITIATED. 67 2-16 HYDROLYSIS OF
C3 CAUSES INITIATION OF THE ALTERNATIVE PATHWAY OF COMPLEMENT. 69 XIII
2-17 MEMBRANE AND PLASMA PROTEINS THAT REGULATE THE FORMATION AND
STABILITY OF C3 CONVERTASES DETERMINE THE EXTENT OF COMPLEMENT
ACTIVATION UNDER DIFFERENT CIRCUMSTANCES. 69 2-18 SURFACE-BOUND C3
CONVERTASE DEPOSITS LARGE NUMBERS OF C3B FRAGMENTS ON PATHOGEN SURFACES
AND GENERATES P5 CONVERTASE ACTIVITY. 73 2-19 INGESTION OF
COMPLEMENT-TAGGED PATHOGENS BY PHAGOCYTES IS MEDIATED BY RECEPTORS FOR
THE BOUND COMPLEMENT PROTEINS. 73 2-20 SMALL FRAGMENTS OF SOME
COMPLEMENT PROTEINS CAN INITIATE A LOCAL INFLAMMATORY RESPONSE. 75 2-21
THE TERMINAL COMPLEMENT PROTEINS POLYMERIZE TO FORM PORES IN MEMBRANES
THAT CAN KILL CERTAIN PATHOGENS. 75 2-22 COMPLEMENT CONTROL PROTEINS
REGULATE ALL THREE PATHWAYS OF COMPLEMENT ACTIVATION AND PROTECT THE
HOST FROM ITS DESTRUCTIVE EFFECTS. 78 SUMMARY. INDUCED INNATE
RESPONSES TO INFECTION. 2-23 ACTIVATED MACROPHAGES SECRETE A RANGE OF
CYTOKINES THAT 81 82 83 HAVE A VARIETY OF LOCAL AND DISTANT EFFECTS.
2-24 CHEMOKINES RELEASED BY PHAGOCYTES AND DENDRITIC CELLS RECRUIT CELLS
TO SITES OF INFECTION. , 83 2-25 CELL-ADHESION MOLECULES CONTROL
INTERACTIONS BETWEEN LEUKOCYTES AND ENDOTHELIAL CELLS DURING AN
INFLAMMATORY RESPONSE. 87 2-26 NEUTROPHILS MAKE UP THE FIRST WAVE OF
CELLS THAT CROSS THE BLOOD VESSEL WALL TO ENTER INFLAMMATORY SITES. 88
2-27 TNF-A IS AN IMPORTANT CYTOKINE THAT TRIGGERS LOCAL CONTAINMENT OF
INFECTION BUT INDUCES SHOCK WHEN RELEASED SYSTEMICALLY. 90 2-28
CYTOKINES RELEASED BY PHAGOCYTES ACTIVATE THE ACUTE-PHASE RESPONSE. 92
2-29 INTERTERONS INDUCED BY VIRAL INFECTION MAKE SEVERAL CONTRIBUTIONS
TO HOST DEFENSE. 94 2-30 NK CELLS ARE ACTIVATED BY INTERFERONS AND
MACROPHAGE-DERIVED CYTOKINES TO SERVE AS AN EARLY DEFENSE AGAINST
CERTAIN INTRACELLULAR INFECTIONS. 95 2-31 NK CELLS POSSESS RECEPTORS FOR
SELF MOLECULES THAT PREVENT THEIR ACTIVATION BY UNINFECTED CELLS. 96
2-32 NK CELLS BEAR RECEPTORS THAT ACTIVATE THEIR KILLER FUNCTION IN
RESPONSE TO LIGANDS EXPRESSED ON INFECTED CELLS OR TUMOR CELLS. 99 2-33
THE NKG2D RECEPTOR ACTIVATES A DIFFERENT SIGNALING PATHWAY FROM THAT OF
THE OTHER ACTIVATING NK RECEPTORS. 100 2-34 SEVERAL LYMPHOCYTE
SUBPOPULATIONS BEHAVE AS INNATE-LIKE LYMPHOCYTES. 100 SUMMARY. 102
SUMMARY TO CHAPTER 2. 103 IRTLL THE RECOGNITION OF ANTIGEN CHAPTER 3
ANTIGEN RECOGNITION BY B-CELL AND T-CELL RECEPTORS 111 THE STRUCTURE OF
A TYPICAL ANTIBODY MOLECULE. 112 3-1 IGG ANTIBODIES CONSIST OF FOUR
POLYPEPTIDE CHAINS. 113 3-2 IMMUNOGLOBULIN HEAVY AND LIGHT CHAINS ARE
COMPOSED OF CONSTANT AND VARIABLE REGIONS. 113 3-3 THE ANTIBODY MOLECULE
CAN READILY BE CLEAVED INTO FUNCTIONALLY DISTINCT FRAGMENTS. 114 3-4 THE
IMMUNOGLOBULIN MOLECULE IS FLEXIBLE, ESPECIALLY AT THE HINGE REGION.
115 3-5 THE DOMAINS OF AN IMMUNOGLOBULIN MOLECULE HAVE SIMILAR.
STRUCTURES. 116 SUMMARY. 118 THE INTERACTION OF THE ANTIBODY MOLECULE
WITH SPECIFIC ANTIGEN. 118 3-6 LOCALIZED REGIONS OF HYPERVARIABLE
SEQUENCE FORM THE ANTIGEN-BINDING SITE. 118 3-7 ANTIBODIES BIND ANTIGENS
VIA CONTACTS WITH AMINO ACIDS IN CDRS, BUT THE DETAILS OF BINDING DEPEND
UPON THE SIZE AND SHAPE OF THE ANTIGEN. 119 3-8 ANTIBODIES BIND TO
CONFORMATIONAL SHAPES ON THE SURFACES OF ANTIGENS. 120 3-9
ANTIGEN-ANTIBODY INTERACTIONS INVOLVE A VARIETY OF FORCES. 121 SUMMARY.
122 ANTIGEN RECOGNITION BY T CELLS. 123 3-10 THE T-CELL RECEPTOR IS VERY
SIMILAR TO A FAB FRAGMENT OF IMMUNOGLOBULIN. 123 3-11 A T-CELL RECEPTOR
RECOGNIZES ANTIGEN IN THE FORM OF A COMPLEX OF A FOREIGN PEPTIDE BOUND
TO AN MHC MOLECULE. 125 3-12 THERE ARE TWO CLASSES OF MHC MOLECULES WITH
DISTINCT SUBUNIT COMPOSITION BUT SIMILAR THREE-DIMENSIONAL STRUCTURES.
126 3-13 PEPTIDES ARE STABLY BOUND TO MHC MOLECULES, AND ALSO SERVE TO
STABILIZE THE MHC MOLECULE ON THE CELL SURFACE. 128 3-14 MHC CLASS I
MOLECULES BIND SHORT PEPTIDES OF 8-10 AMINO ACIDS BY BOTH ENDS. 129 3-15
THE LENGTH OF THE PEPTIDES BOUND BY MHC CLASS II MOLECULES IS NOT
CONSTRAINED. 130 3-16 THE CRYSTAL STRUCTURES OF SEVERAL
MHC:PEPTIDE:T-CELL RECEPTOR COMPLEXES SHOW A SIMILAR T-CELL RECEPTOR
ORIENTATION OVER THE MHC:PEPTIDE COMPLEX. 132 3-17 THE CD4 AND CD8
CELL-SURFACE PROTEINS OF T CELLS ARE REQUIRED TO MAKE AN EFFECTIVE
RESPONSE TO ANTIGEN. 133 3-18 THE TWO CLASSES OF MHC MOLECULES ARE
EXPRESSED DIFFERENTIALLY ON CELLS. 135 3-19 A DISTINCT SUBSET OF T CELLS
BEARS AN ALTERNATIVE RECEPTOR MADE UP OF Y AND 5 CHAINS. 137 SUMMARY.
137 SUMMARY TO CHAPTER 3. 138 CHAPTER 4 THE GENERATION OF LYMPHOCYTE
ANTIGEN RECEPTORS 143 PRIMARY IMMUNOGLOBULIN GENE REARRANGEMENT 144 4-1
IMMUNOGLOBULIN GENES ARE REARRANGED IN * ANTJBODY-PRODUCING CELLS. 144
4-2 _ COMPLETE GENES THAT ENCODE A VARIABLE REGION ARE GENERATED BY THE
SOMATIC RECOMBINATION OF SEPARATE GENE SEGMENTS. 145 4-3 MULTIPLE
CONTIGUOUS V GENE SEGMENTS ARE PRESENT AT EACH IMMUNOGLOBULIN LOCUS. 146
4-4 REARRANGEMENT OF V, D, AND J GENE SEGMENTS IS GUIDED BY FLANKING DNA
SEQUENCES. 148 4-5 THE REACTION THAT RECOMBINES V, D, AND J GENE
SEGMENTS INVOLVES BOTH LYMPHOCYTE-SPECIFIC AND UBIQUITOUS DNA-MODIFYING
ENZYMES. 150 4-6 THE DIVERSITY OF THE IMMUNOGLOBULIN REPERTOIRE IS
GENERATED BY FOUR MAIN PROCESSES. 153 4-7 THE MULTIPLE INHERITED GENE
SEGMENTS ARE USED IN DIFFERENT COMBINATIONS. 153 [IV THE GENERATION OF
T-CELL RECEPTOR LIGANDS. 154 155 4-8 VARIABLE ADDITION AND SUBTRACTION
OF NUCLEOTIDES AT THE JUNCTIONS BETWEEN GENE SEGMENTS CONTRIBUTES TO THE
DIVERSITY OF THE THIRD HYPERVARIABLE REGION. SUMMARY. S T-CELL RECEPTOR
GENE REARRANGEMENT. 4-9 THE T-CELL RECEPTOR GENE SEGMENTS ARE ARRANGED
IN A SIMILAR PATTERN TO IMMUNOGLOBULIN GENE SEGMENTS AND ARE REARRANGED
BY THE SAME ENZYMES. 4-10 T-CELL RECEPTORS CONCENTRATE DIVERSITY IN THE
THIRD HYPERVARIABLE REGION. 4-11 Y.H T-CELL RECEPTORS ARE ALSO GENERATED
BY GENE REARRANGEMENT. SUMMARY. STRUCTURAL VARIATION IN IMMUNOGLOBULIN
CONSTANT REGIONS. 160 4-12 DIFFERENT CLASSES OF IMMUNOGLOBULINS ARE
DISTINGUISHED BY THE STRUCTURE OF THEIR HEAVY-CHAIN CONSTANT REGIONS.
4-13 THE CONSTANT REGION CONFERS FUNCTIONAL SPECIALIZATION ON THE
ANTIBODY. 161 4-14 MATURE NAIVE B CELLS EXPRESS BOTH IGM AND IGD AT
THEIR SURFACE. - 163 4-15 TRANSMEMBRANE AND SECRETED FORMS OF
IMMUNOGLOBULIN ARE GENERATED FROM ALTERNATIVE HEAVY-CHAIN TRANSCRIPTS.
IGM AND IGA CAN FORM POLYMERS. 163 164 166 4-16 SUMMARY. SECONDARY
DIVERSIFICATION OF THE ANTIBODY REPERTOIRE. 167 4-17 ACTIVATION-INDUCED
CYTIDINE DEAMINASE INTRODUCES MUTATIONS IN GENES TRANSCRIBED IN B CELLS.
168 4-18 REARRANGED V-REGION GENES ARE FURTHER DIVERSIFIED BY SOMATIC
HYPERMUTATION. 4-19 IN SOME SPECIES, MOST IMMUNOGLOBULIN GENE
DIVERSIFICATION OCCURS AFTER GENE REARRANGEMENT. 4-20 CLASS SWITCHING
ENABLES THE SAME ASSEMBLED VH EXON TO BE ASSOCIATED WITH DIFFERENT CH
GENES IN THE COURSE OF AN IMMUNE RESPONSE. SUMMARY. SUMMARY TO CHAPTER
4. CHAPTER 5 ANTIGEN PRESENTATION TO T LYMPHOCYTES 181 182 5-1 THE MHC
CLASS I AND CLASS II MOLECULES DELIVER PEPTIDES TO THE CELL SURFACE FROM
TWO INTRACELLULAR COMPARTMENTS. 182 5-2 PEPTIDES THAT BIND TO MHC CLASS
I MOLECULES ARE ACTIVELY TRANSPORTED FROM THE CYTOSOL TO THE ENDOPLASMIC
RETICULUM. 183 5-3 PEPTIDES FOR TRANSPORT INTO THE ENDOPLASMIC RETICULUM
ARE GENERATED IN THE CYTOSOL. 184 5-4 RETROGRADE TRANSPORT FROM THE
ENDOPLASMIC RETICULUM TO THE - CYTOSOL ENABLES EXOGENOUS PROTEINS TO BE
PROCESSED FPR-CROSS- PRESENTATION BY MHC CLASS I MOLECULES. ** 186 5-5
NEWLY SYNTHESIZED MHC CLASS I MOLECULES ARE RETAINED IN THE ENDOPLASMIC
RETICULUM UNTIL THEY BIND A PEPTIDE. . 187 5-6 MANY VIRUSES PRODUCE
IMMUNOEVASINS THAT INTERFERE WITH ANTIGEN PRESENTATION BY MHC CLASS I
MOLECULES. . 189 5-7 PEPTIDES PRESENTED BY MHC CLASS II MOLECULES ARE
GENERATED IN ACIDIFIED ENDOCYTIC VESICLES. 190 5-8 THE INVARIANT CHAIN
DIRECTS NEWLY SYNTHESIZED MHC CLASS II MOLECULES TO ACIDIFIED
INTRACELLULAR VESICLES. 192 5-9 A SPECIALIZED MHC CLASS LL-LIKE MOLECULE
CATALYZES LOADING OF MHC CLASS II MOLECULES WITH PEPTIDES. 193 5-10 -
STABLE BINDING OF PEPTIDES BY MHC MOLECULES PROVIDES EFFECTIVE ANTIGEN
PRESENTATION AT THE CELL SURFACE. 194 SUMMARY. 195 155 THE MAJOR
HISTOCOMPATIBILITY COMPLEX AND ITS FUNCTIONS. 196 156 157 158 159 160
160 5-12 5-13 5-14 5-15 5-16 5-11 MANY PROTEINS INVOLVED IN ANTIGEN
PROCESSING AND PRESENTATION ARE ENCODED BY GENES WITHIN THE MAJOR
HISTOCOMPATIBILITY COMPLEX. 197 THE PROTEIN PRODUCTS OF MHC CLASS I ARID
CLASS II GENES ARE HIGHLY POLYMORPHIC. 199 MHC POLYMORPHISM AFFECTS
ANTIGEN RECOGNITION BY T CELLS BY INFLUENCING BOTH PEPTIDE BINDING AND
THE CONTACTS BETWEEN T-CELL RECEPTOR AND MHC MOLECULE. , 201
ALLOREACTIVE T CELLS RECOGNIZING NONSELF MHC MOLECULES ARE VERY
ABUNDANT. 204 MANY T CELLS RESPOND TO SUPERANTIGENS. 206 MHC
POLYMORPHISM EXTENDS THE RANGE OF ANTIGENS TO WHICH THE IMMUNE SYSTEM
CAN RESPOND. 207 5-17 A VARIETY OF GENES WITH SPECIALIZED FUNCTIONS IN
IMMUNITY ARE ALSO ENCODED IN THE MHC. 208 5-18 SPECIALIZED MHC CLASS I
MOLECULES ACT AS LIGANDSFOR THE ACTIVATION AND INHIBITION OF NK CELLS.
209 5-19 THE CD1 FAMILY OF MHC CLASS L-LIKE MOLECULES IS ENCODED OUTSIDE
THE MHC AND PRESENTS MICROBIAL LIPIDS TO CD1-RESTRICTED T CELLS. 211
SUMMARY. 212 SUMMARY TO CHAPTER 5. 212 THE DEVELOPMENT OF MATURE
LYMPHOCYTE RECEPTOR REPERTOIRES 169 171 171 175 175 FILIFF CHAPTER I 6
SIGNALING THROUGH IMMUNE SYSTEM RECEPTORS GENERAL PRINCIPLES OF SIGNAL
TRANSDUCTION. 6-1 TRANSMEMBRANE RECEPTORS CONVERT EXTRACELLULAR SIGNALS
INTO INTRACELLULAR BIOCHEMICAL EVENTS. 6-2 INTRACELLULAR SIGNAL
TRANSDUCTION OFTEN TAKES PLACE IN LARGE MULTIPROTEIN SIGNALING
COMPLEXES. 6-3 THE ACTIVATION OF SOME RECEPTORS.GENERATES SMALL-MOLECULE
SECOND MESSENGERS. 6-4 SMALL G PROTEINS ACT AS MOLECULAR SWITCHES IN
MANY DJFFERENT SIGNALING PATHWAYS. 6-5 SIGNALING PROTEINS ARE RECRUITED
TO THE MEMBRANE BY A VARIETY OF MECHANISMS. 6-6 SIGNAL TRANSDUCTION
PROTEINS ARE ORGANIZED IN THE PLASMA MEMBRANE IN STRUCTURES CALLED LIPID
RAFTS. 6-7 PROTEIN DEGRADATION HAS AN IMPORTANT ROLE IN TERMINATING
SIGNALING RESPONSES. SUMMARY. 219 220 220^ 221 222 224 224 225 226 227
ANTIGEN RECEPTOR SIGNALING AND LYMPHOCYTE ACTIVATION. 227 6-8 THE
VARIABLE CHAINS OF ANTIGEN RECEPTORS ARE ASSOCIATED WITH INVARIANT
ACCESSORY CHAINS THAT CARRY OUT THE SIGNALING FUNCTION OF THE RECEPTOR.
228 6-9 LYMPHOCYTES ARE EXTREMELY SENSITIVE TO THEIR SPECIFIC ANTIGENS.
229 XV 6-10 ANTIGEN BINDING LEADS TO PHOSPHORYLATION OF THE IT AM
SEQUENCES ASSOCIATED WITH THE ANTIGEN RECEPTORS. 231 6-11 IN T CELLS,
FULLY PHOSPHORYLATED ITAMS BIND THE KINASE ZAP-70 AND ENABLE IT TO BE
ACTIVATED. 233 6-12 ACTIVATED SYK AND ZAP-70 PHOSPHORYLATE SCAFFOLD
PROTEINS THAT MEDIATE MANY OF THE DOWNSTREAM EFFECTS OF ANTIGEN RECEPTOR
SIGNALING. . 233 6-13 PLC-Y IS ACTIVATED BY TEC TYROSINE KINASES. 234
6-14 ACTIVATION OF THE SMALL G PROTEIN RAS ACTIVATES A MAP KINASE
CASCADE, RESULTING IN THE PRODUCTION OF THE TRANSCRIPTION FACTOR AP-1.
235 6-15 THE TRANSCRIPTION FACTOR NFAT IS INDIRECTLY ACTIVATED BY CA 2+
. 236 6-16 THE TRANSCRIPTION FACTOR NFKB IS ACTIVATED BY THE ACTIONS OF
PROTEIN KINASE C. 237 6-17 THE LOGIC OF B-CELL RECEPTOR SIGNALING IS
SIMILAR TO THAT OF T-CELL RECEPTOR SIGNALING BUT SOME OF THE SIGNALING
COMPONENTS ARE SPECIFIC TO B CELLS. 239 6-18 ITAMS ARE ALSO FOUND IN
OTHER RECEPTORS ON LEUKOCYTES THAT SIGNAL FOR CELL ACTIVATION. 240 6-19
THE CELL-SURFACE PROTEIN CD28 IS A CO-STIMULATORY RECEPTOR FOR NAIVE T
CELLS. 240 6-20 INHIBITORY RECEPTORS ON LYMPHOCYTES HELP REGULATE IMMUNE
RESPONSES. 242 SUMMARY. . 244 OTHER RECEPTORS AND SIGNALING PATHWAYS.
244 6-21 CYTOKINES TYPICAJLY ACTIVATE FAST SIGNALING PATHWAYS THAT END
IN THE NUCLEUS. 245 6-22 CYTOKINE RECEPTORS FORM DIMERS OR TRIMERS ON
LIGAND BINDING. 245 6-23 CYTOKINE RECEPTORS ARE ASSOCIATED WITH THE JAK
FAMILY OF TYROSINE KINASES WHICH ACTIVATE STAT TRANSCRIPTION FACTORS.
245 6-24 CYTOKINE SIGNALING IS TERMINATED BY A NEGATIVE FEEDBACK
MECHANISM. 246 6-25 THE RECEPTORS THAT INDUCE APOPTOSIS ACTIVATE
SPECIALIZED INTRACELLULAR PROTEASES CALLED CASPASES. 247 6-26 THE
INTRINSIC PATHWAY OF APOPTOSIS IS MEDIATED BY RELEASE OF CYTOCHROME C
FROM MITOCHONDRIA. 249 6-27 MICROBES AND THEIR PRODUCTS ACT VIA
TOLL-LIKE RECEPTORS TO ACTIVATE NFKB. 249 6-28 BACTERIAL PEPTIDES,
MEDIATORS OF INFLAMMATORY RESPONSES, AND CHEMOKINES SIGNAL THROUGH
MEMBERS OF THE G-PROTEIN-COUPLED RECEPTOR FAMILY. 251 SUMMARY. 253
SUMMARY TO CHAPTER 6. 3 253 CHAPTER 7 THE DEVELOPMENT AND SURVIVAL OF
LYMPHOCYTES 257 DEVELOPMENT OF B LYMPHOCYTES 259 7-1 LYMPHOCYTES DERIVE
FROM HEMATOPOIETIC STEM CELLS IN THE BONE MARROW. - 259 7-2 B-CELL
DEVELOPMENT BEGINS BY REARRANGEMENT OF THE . - HEAVY-CHAIN LOCUS. -^
262 7-3 THE PRE-B-CELL RECEPTOR TESTS FOR SUCCESSFUL PRODUCTION OF A
COMPLETE HEAVY CHAIN AND SIGNALS FOR PROLIFERATION OF PRO-B CELLS. ;
264 7-4 PRE-B-CELL RECEPTOR SIGNALING INHIBITS FURTHER HEAVY-CHAIN LOCUS
REARRANGEMENT AND ENFORCES ALLELIC EXCLUSION. 266 7-5 PRE-B CELLS
REARRANGE THE LIGHT-CHAIN LOCUS AND EXPRESS CELL-SURFACE IMMUNOGLOBULIN.
266 7-6 IMMATURE B CELLS ARE TESTED FOR AUTOREACTIVITY BEFORE THEY LEAVE
THE BONE MARROW. 268 SUMMARY. 272 T-CELL DEVELOPMENT IN THE THYMUS. 273
7-7 T-CELL PROGENITORS ORIGINATE IN THE BONE MARROW, BUT ALL THE
IMPORTANT EVENTS IN THEIR DEVELOPMENT OCCUR IN THE THYMUS. 274 7-8
T-CELL PRECURSORS PROLIFERATE EXTENSIVELY IN THE THYMUS BUT ~ J MOST DIE
THERE. 275 7-9 SUCCESSIVE STAGES IN THE DEVELOPMENTS THYMOCYTES ARE
MARKED BY CHANGES IN CELL-SURFACE MOLECULES. 277 7-10 THYMOCYTES AT
DIFFERENT DEVELOPMENTAL STAGES ARE FOUND IN DISTINCT PARTS OF THE
THYMUS. 279 7-11 T CELLS WITH A:(3 OR J. 8 RECEPTORS ARISE FROM A COMMON
PROGENITOR. 280 7-12 T CELLS EXPRESSING PARTICULAR Y- AND 5-CHAIN V
REGIONS ARISE IN AN ORDERED SEQUENCE EARLY IN LIFE. 282 7-13 SUCCESSFUL
SYNTHESIS OF A REARRANGED P CHAIN ALLOWS THE PRODUCTION OF A PRE-T-CELL
RECEPTOR THAT TRIGGERS CELL PROLIFERATION AND BLOCKS FURTHER P-CHAIN
GENE REARRANGEMENT. 283 7-14 T-CELL A-CHAIN GENES UNDERGO SUCCESSIVE
REARRANGEMENTS UNTIL POSITIVE SELECTION OR CELL DEATH INTERVENES. 286
SUMMARY. 288 POSITIVE AND NEGATIVE SELECTION OF T CELLS. 288 7-15 THE
MHC TYPE OF THE THYMIC STROMA SELECTS A REPERTOIRE OF MATURE T CELLS
THAT CAN RECOGNIZE FOREIGN ANTIGENS PRESENTED BY THE SAME MHC TYPE. *
289 7-16 ONLY THYMOCYTES WHOSE RECEPTORS INTERACT WITH
SELF-PEPTIDE:SELF-MHC COMPLEXES CAN SURVIVE AND MATURE. 290 7-17
POSITIVE SELECTION ACTS ON A REPERTOIRE OF T-CELL RECEPTORS WITH
INHERENT SPECIFICITY FOR MHC MOLECULES. 291 7-18 POSITIVE SELECTION
COORDINATES THE EXPRESSION OF CD4 OR CD8 WITH THE SPECIFICITY OF THE
T-CELL RECEPTOR AND THE POTENTIAL EFFECTOR FUNCTIONS OF THE T CELL. 292
7-19 THYMIC CORTICAL EPITHELIAL CELLS MEDIATE POSITIVE SELECTION OF
DEVELOPING THYMOCYTES. 293 7-20 T CELLS THAT REACT STRONGLY WITH
UBIQUITOUS SELF ANTIGENS ARE DELETED IN THE THYMUS. 294 7-21 NEGATIVE
SELECTION IS DRIVEN MOST EFFICIENTLY BY BONE MARROW DERIVED
ANTIGEN-PRESENTING CELLS. 296 7-22 THE SPECIFICITY AND/OR THE STRENGTH
OF SIGNALS FOR NEGATIVE AND POSITIVE SELECTION MUST DIFFER. 297 SUMMARY.
298 SURVIVAL AND MATURATION OF LYMPHOCYTES IN PERIPHERAL LYMPHOID
TISSUES. 299 7-23 DIFFERENT LYMPHOCYTE SUBSETS ARE FOUND IN PARTICULAR
LOCATIONS IN PERIPHERAL LYMPHOID TISSUES. 299 * - 7-24 THE-DEVELOPMENT
AND ORGANIZATION OF PERIPHERAL LYMPHOID TISSUES ARE CONTROLLED BY
PROTEINS OF THE TUMOR NECROSIS FACTOR FAMILY. 300 7-25 THE HOMING OF
LYMPHOCYTES TO SPECIFIC REGIONS OF PERIPHERAL LYMPHOID TISSUES IS
MEDIATED BY CHEMOKINES. 302 7-26 LYMPHOCYTES THAT ENCOUNTER SUFFICIENT
QUANTITIES OF SELF ANTIGENS FOR THE FIRST TIME IN THE PERIPHERY ARE
ELIMINATED OR INACTIVATED. 303 7-27 MOST IMMATURE B CELLS ARRIVING IN
THE SPLEEN ARE SHORT-LIVED AND REQUIRE CYTOKINES AND POSITIVE SIGNALS
THROUGH THE B-CELL RECEPTOR FOR MATURATION AND SURVIVAL. 304 7-28 B-1
CELLS AND MARGINAL ZONE B CELLS ARE DISTINCT B-CELL SUBTYPES WITH UNIQUE
ANTIGEN RECEPTOR SPECIFICITY. 306 7-29 T-CELL HOMEOSTASIS IN THE
PERIPHERY IS REGULATED BY CYTOKINES AND SELF-MHC INTERACTIONS. 307
SUMMARY. 307 XVI LYMPHOID TUMORS. 308 7-30 B-CELL TUMORS OFTEN OCCUPY
THE SAME SITE AS THEIR NORMAL COUNTERPARTS. 308 7-31 T-CELL TUMORS
CORRESPOND TO A SMALL NUMBER OF STAGES OF T-CELL DEVELOPMENT. S 311 7-32
B-CELL LYMPHOMAS FREQUENTLY CARRY CHROMOSOMAL TRANSLOCATIONS THAT JOIN
IMMUNOGLOBULIN LOCI TO GENES THAT REGULATE CELL GROWTH. 312 SUMMARY. 312
SUMMARY TO CHAPTER 7. 313 PART IV THE ADAPTIVE IMMUNE RESPONSE CHAPTER 8
T CELL-MEDIATED IMMUNITY 323 ENTRY OF NAIVE T CELLS AND
ANTIGEN-PRESENTING CELLS INTO PERIPHERAL LYMPHOID ORGANS. 325 8-1 NAIVE
T CELLS MIGRATE THROUGH PERIPHERAL LYMPHOID TISSUES, SAMPLING THE
PEPTIDE:MHC COMPLEXES ON DENDRITIC CELL SURFACES. 325 8-2 LYMPHOCYTE
ENTRY INTO LYMPHOID TISSUES DEPENDS ON CHEMOKINES AND ADHESION
MOLECULES. 326 8-3 ACTIVATION OF INTEGRINS BY CHEMOKINES IS RESPONSIBLE
FOR THE ENTRY OF NAIVE T CELLS INTO LYMPH NODES. 327 8-4 T-CELL
RESPONSES ARE INITIATED IN PERIPHERAL LYMPHOID ORGANS BY ACTIVATED
DENDRITIC CELLS. ^ 331 8-5 THERE ARE TWO DIFFERENT FUNCTIONAL CLASSES OF
DENDRITIC CELLS. 332 8-6 DENDRITIC CELLS PROCESS ANTIGENS FROM A WIDE
ARRAY OF PATHOGENS. 334 8-7 PATHOGEN-INDUCED TLR SIGNALING IN IMMATURE
DENDRITIC CELLS INDUCES THEIR MIGRATION TO LYMPHOID ORGANS AND ENHANCES
ANTIGEN PROCESSING. 336 8-8 PLASMACYTOID DENDRITIC CELLS DETECT VIRAL
INFECTIONS AND GENERATE ABUNDANT TYPE I INTERFERONS AND PRO-INFLAMMATORY
CYTOKINES. 338 8-9 MACROPHAGES ARE SCAVENGER CELLS THAT CAN BE INDUCED
BY PATHOGENS TO PRESENT FOREIGN ANTIGENS TO NAIVE T CELLS. 339 8-10 B
CELLS ARE HIGHLY EFFICIENT AT PRESENTING ANTIGENS THAT BIND TO THEIR
SURFACE IMMUNOGLOBULIN. 340 SUMMARY. 342 PRIMING OF NAIVE T CELLS BY
PATHOGEN-ACTIVATED DENDRITIC CELLS. 343. 8 : 11 CELL-ADHESION MOLECULES
MEDIATE THE INITIAL INTERACTION OF NAIVE T CELLS WITH ANTIGEN-PRESENTING
CELLS. 343 8-12 ANTIGEN-PRESENTING CELLS DELIVER THREE KINDS OF SIGNALS
_ FOR CLONAL EXPANSION AND DIFFERENTIATION OF NAIVE T,CELLSL 344 8-13
CD28-DEPENDENT CO-STIMULATION OF ACTIVATED T CELLS INDUCES EXPRESSION OF
THE T-CELL GROWTH FACTOR INTERLEUKIN-2 AND THE HIGH-AFFINITY IL-2
RECEPTOR. 345 8-14 SIGNAL 2 CAN BE MODIFIED BY ADDITIONAL CO-STIMULATORY
PATHWAYS. . * 346 8-15 ANTIGEN RECOGNITION IN THE ABSENCE OF
CO-STIMULATION I EADS TO FUNCTIONAL INACTIVATION OR CLONAL DELETION OF
PERIPHERAL T CELLS. 347 8-16 PROLIFERATING T CELLS DIFFERENTIATE INTO
EFFECTOR T CELLS THAT DO NOT REQUIRE CO-STIMULATION TO ACT. 349 8-17
8-18 T CELLS DIFFERENTIATE INTO SEVERAL SUBSETS OF FUNCTIONALLY
DIFFERENT EFFECTOR CELLS. 349 CD8 T CELLS CAN-BE ACTIVATED IN DIFFERENT
WAYS TO BECOME CYTOTOXIC EFFECTOR CELLS. 352 8-19 VARIOUS FORMS OF
SIGNAL 3 INDUCE THE DIFFERENTIATION OF NAIVE CD4 T CELLS DOWN DISTINCT
EFFECTOR PATHWAYS. 352 8-20 REGULATORY CD4 T CELLS ARE INVOLVED IN
CONTROLLING ADAPTIVE IMMUNE RESPONSES. - 354 SUMMARY. 356 GENERAL
PROPERTIES OF EFFECTOR T CELLS AND THEIR CYTOKINES. 356 8-21 EFFECTOR
T-CELL INTERACTIONS WITH TARGET CELLS ARE INITIATED BY
ANTIGEN-NONSPECIFIC CELL-ADHESION MOLECULES. 357 8-22 BINDING OF THE
T-CELL RECEPTOR COMPLEX DIRECTS THE RELEASE OF EFFECTOR MOLECULES AND
FOCUSES THEM ON THE TARGET CELL. 357 8-23 THE EFFECTOR FUNCTIONS OF T
CELLS ARE DETERMINED BY THE ARRAY OF EFFECTOR MOLECULES THAT THEY
PRODUCE. 358 8-24 CYTOKINES CAN ACT LOCALLY OR AT A DISTANCE. 359 8-25
CYTOKINES AND THEIR RECEPTORS FALL INTO DISTINCT FAMILIES OF
STRUCTURALLY RELATED PROTEINS. 361 8-26 THE TNF FAMILY OF CYTOKINES ARE
TRIMERIC PROTEINS THAT ARE USUALLY ASSOCIATED WITH THE CELL SURFACE. 362
SUMMARY. 363 T CELL-MEDIATED CYTOTOXICITY. 364 8-27 CYTOTOXIC T CELLS
CAN INDUCE TARGET CELLS TO UNDERGO PROGRAMMED CELL DEATH. 364 8-28
CYTOTOXIC EFFECTOR PROTEINS THAT TRIGGER APOPTOSIS ARE CONTAINED IN THE
GRANULES OF CD8 CYTOTOXIC T CELLS. 365 8-29 CYTOTOXIC T CELLS ARE
SELECTIVE AND SERIAL KILLERS OF TARGETS EXPRESSING A SPECIFIC ANTIGEN.
367 8-30 CYTOTOXIC T CELLS ALSO ACT BY RELEASING CYTOKINES. 368 SUMMARY.
368 MACROPHAGE ACTIVATION BY T H 1 CELLS. 368 8-31 TH1 CELLS HAVE A
CENTRAL ROLE IN MACROPHAGE ACTIVATION. 369 8-32 ACTIVATION OF
MACROPHAGES BY TH1 CELLS PROMOTES MICROBIAL KILLING AND MUST BE TIGHTLY
REGULATED TO AVOID TISSUE DAMAGE. 370 8-33 TH1 CELLS COORDINATE THE HOST
RESPONSE TO INTRACELLULAR PATHOGENS. 371 SUMMARY. 372 SUMMARY TO CHAPTER
8. 372 CHAPTER 9 THE HUMORAL IMMUNE RESPONSE 379 B-CELL ACTIVATION AND
ANTIBODY PRODUCTION. 381 9-1 THE HUMORAL IMMUNE RESPONSE IS INITIATED
WHEN B CELLS THAT BIND ANTIGEN ARE SIGNALED BY HELPER T CELLS OR BYR
CERTAIN MICROBIAL ANTIGENS ALONE. 381 9-2 B-CELL RESPONSES TO ANTIGEN
ARE ENHANCED BY CO-LIGATION OF THE B-CELL CO-RECEPTOR. 382 9-3 HELPER T
CELLS ACTIVATE B CELLS THAT RECOGNIZE THE SAME ANTIGEN. 383 9-4
ANTIGENIC PEPTIDES BOUND TO SELF-MHC CLASS II MOLECULES ON B CELLS
TRIGGER HELPER T CELLS TO MAKE MEMBRANE-BOUND AND SECRETED MOLECULES
THAT CAN ACTIVATE A B CELL. 384 9-5 B CELLS THAT HAVE BOUND ANTIGEN VIA
THEIR B-CELL RECEPTOR ARE TRAPPED IN THE T-CELL ZONES OF SECONDARY
LYMPHOID TISSUES. 386 XVII 9-6 9-7 ANTIBODY-SECRETING PLASMA CELLS
DIFFERENTIATE FROM ACTIVATED B CELLS. 387 THE SECOND PHASE OF A PRIMARY
B-CELL IMMUNE RESPONSE OCCURS WHEN ACTIVATED B CELLS MIGRATE TO
FOLLICLES AND PROLIFERATE TO FORM GERMINAL CENTERS. I 388 9-8 GERMINAL
CENTER B CELLS UNDERGO V-REGION SOMATIC HYPERMUTATION, AND CELLS WITH
MUTATIONS THAT IMPROVE AFFINITY FOR ANTIGEN ARE SELECTED. 390 9-9 CLASS
SWITCHING IN THYMUS-DEPENDENT ANTIBODY RESPONSES REQUIRES EXPRESSION OF
CD40 LIGAND BY THE HELPER T CELL AND IS DIRECTED BY CYTOKINES. 392 9-10
LIGATION OF THE B-CELL RECEPTOR AND CD40, TOGETHER WITH DIRECT CONTACT
WITH T CELLS, ARE ALL REQUIRED TO SUSTAIN GERMINAL CENTER B CELLS. 394
9-11 SURVIVING GERMINAL CENTER B CELLS^DIFFERENTIATE INTO EITHER PLASMA
CELLS OR MEMORY CELLS. 395 9-12 B-CELL RESPONSES TO BACTERIAL ANTIGENS
WITH INTRINSIC ABILITY TO ACTIVATE B CELLS DO NOT REQUIRE T-CELL HELP.
396 9-13 B-CELL RESPONSES TO BACTERIAL POLYSACCHARIDES DO NOT REQUIRE
PEPTIDE-SPECIFIC T-CELL HELP. 397 SUMMARY. 399 THE DISTRIBUTION AND
FUNCTIONS OF IMMUNOGLOBULIN ISOTYPES. 400 9-14 ANTIBODIES OF DIFFERENT
ISOTYPES OPERATE IN DISTINCT PLACES AND HAVE DISTINCT EFFECTOR
FUNCTIONS. 400 9-15 TRANSPORT PROTEINS THAT BIND TO THE FC REGIONS OF
ANTIBODIES CARRY PARTICULAR ISOTYPES ACROSS EPITHELIAL BARRIERS. 402
9-16 HIGH-AFFINITY IGG AND IGA ANTIBODIES CAN NEUTRALIZE BACTERIAL
TOXINS. 404 9-17 HIGH-AFFINITY IGG AND IGA ANTIBODIES CAN INHIBIT THE
INFECTIVITY OF VIRUSES. 405 9-18 ANTIBODIES CAN BLOCK THE ADHERENCE OF
BACTERIA TO HOST CELLS. 406 9-19 ANTIBODY:ANTIGEN COMPLEXES ACTIVATE THE
CLASSICAL PATHWAY OF COMPLEMENT BY BINDING TO C1Q. . 406 9-20 COMPLEMENT
RECEPTORS ARE IMPORTANT IN THE REMOVAL OF IMMUNE COMPLEXES FROM THE
CIRCULATION. , 408 SUMMARY. 409 THE DESTRUCTION OF ANTIBODY-COATED
PATHOGENS VIA FC RECEPTORS. 409 9-21 THE FC RECEPTORS OF ACCESSORY CELLS
ARE SIGNALING RECEPTORS SPECIFIC FOR IMMUNOGLOBULINS OF DIFFERENT
CLASSES. 410 9-22 FC RECEPTORS ON PHAGOCYTES-ARE ACTIVATED BY ANTIBODIES
BOUND TO THE SURFACE OF PATHOGENS AND ENABLE THE PHAGOCYTES TO INGEST
AND DESTROY PATHOGENS. 411 9-23 FC RECEPTORS ACTIVATE NK CELLS TO
DESTROY ANTIBODY-COATED TARGETS. 412 9-24 MAST CELLS, BASOPHILS, AND
ACTIVATED EOSINOPHILS BIND IGE ANTIBODY VIA THE HIGH-AFFINITY FEE
RECEPTOR. 413 - 9-25 IGE-MEDIATED ACTIVATION OF ACCESSORY CELLS HAS AN
IMPORTANT ROLE IN RESISTANCE TO PARASITE INFECTION. ^ 414 SUMMARY. 415
SUMMARY TO CHAPTER 9. 416 CHAPTER 10 DYNAMICS OF ADAPTIVE IMMUNITY 421
THE COURSE OF THE IMMUNE RESPONSE TO INFECTION. 422 10-1 THE COURSE OF
AN INFECTION CAN BE DIVIDED INTO SEVERAL DISTINCT PHASES. 422 10-2 THE
NONSPECIFIC RESPONSES OF INNATE IMMUNITY ARE NECESSARY FOR AN ADAPTIVE
IMMUNE RESPONSE TO BE INITIATED. . 425 10-3 CYTOKINES MADE IN THE
EARLIEST PHASE OF AN INFECTION INFLUENCE DIFFERENTIATION OF CD4 T CELLS
TOWARD THE T H 17 SUBSET. 426 10-4 CYTOKINES MADE IN THE LATER STAGES
OF AN INFECTION INFLUENCE DIFFERENTIATION OF CD4 T CELLS TOWARD TH1 OR T
H 2 CELLS. 427 10-5 THE DISTINCT SUBSETS OF CD4 T CELLS CAN REGULATE
EACH OTHER S DIFFERENTIATION. 430 10-6 EFFECTOR T CELLS ARE GUIDED TO
SITES OF INFECTION BY CHEMOKINES AND NEWLY EXPRESSED ADHESION MOLECULES.
432 10-7 DIFFERENTIATED EFFECTOR T CELLS ARE NOT A STATIC POPULATION BUT
CONTINUE TO RESPOND TO SIGNALS AS THEY CARRY OUT THEIR EFFECTOR
FUNCTIONS. 434 10-8 PRIMARY CD8 T-CELL RESPONSES TO PATHOGENS CAN OCCUR
IN THE ABSENCE OF CD4 HELP. 435 10-9 ANTIBODY RESPONSES DEVELOP IN
LYMPHOID TISSUES UNDER THE DIRECTION OF CD4 HELPER T CELLS. 437 10-10
ANTIBODY RESPONSES ARE SUSTAINED IN MEDULLARY CORDS AND BONE MARROW. 438
10-11 THE EFFECTOR MECHANISMS USED TO CLEAR AN INFECTION DEPEND ON THE
INFECTIOUS AGENT. 439 10-12 RESOLUTION OF AN INFECTION IS ACCOMPANIED BY
THE DEATH OF MOST OF THE EFFECTOR CELLS AND THE GENERATION OF MEMORY
CELIS. - 441 SUMMARY. 441 IMMUNOLOGICAL MEMORY 442 10-13 IMMUNOLOGICAL
MEMORY IS LONG-LIVED AFTER INFECTION OR VACCINATION. 442 10-14 MEMORY
B-CELL RESPONSES DIFFER IN SEVERAL WAYS FROM THOSE OF NAIVE B CELLS. 444
10-15 REPEATED IMMUNIZATION LEADS TO INCREASING AFFINITY OF ANTIBODY DUE
TO SOMATIC HYPERMUTATION AND SELECTION BY ANTIGEN IN GERMINAL CENTERS.
445 10-16 MEMORY T CELLS ARE INCREASED IN FREQUENCY COMPARED WITH NAIVE
T CELLS SPECIFIC FOR THE SAME ANTIGEN AND HAVE DISTINCT ACTIVATION
REQUIREMENTS AND CELL-SURFACE PROTEINS THAT DISTINGUISH THEM FROM
EFFECTOR T CELLS. 446 10-17 MEMORY T CELLS ARE HETEROGENEOUS AND INCLUDE
CENTRAL MEMORY AND EFFECTOR MEMORY SUBSETS. 449 10-18 CD4 T-CELL HELP IS
REQUIRED FOR CD8 T-CELL MEMORY AND INVOLVES CD40 AND IL-2 SIGNALING. 450
10-19 IN IMMUNE INDIVIDUALS, SECONDARY AND SUBSEQUENT RESPONSES ARE
MAINLY ATTRIBUTABLE TO MEMORY LYMPHOCYTES. 452 SUMMARY, ,, 453 SUMMARY
TO CHAPTER 10. 454 CHAPTER 11 THE MUCOSAL IMMUNE SYSTEM 459 THE
ORGANIZATION OF THE MUCOSAL IMMUNE SYSTEM. 459 11-1 THE MUCOSAL IMMUNE
SYSTEM PROTECTS THE INTERNAL SURFACES OF THE BODY. 4459 11-2 THE MUCOSAL
IMMUNE SYSTEM MAY BE THE ORIGINAL VERTEBRATE IMMUNE SYSTEM. 461 11-3
MUCOSA-ASSOCIATED LYMPHOID TISSUE IS LOCATED IN ANATOMICALLY DEFINED
COMPARTMENTS IN THE GUT. 462 11-4 THE INTESTINE HAS DISTINCTIVE ROUTES
AND MECHANISMS OF ANTIGEN UPTAKE. 464 CVIII 11 -5 THE MUCOSAL IMMUNE
SYSTEM CONTAINS LARGE NUMBERS OF EFFECTOR LYMPHOCYTES EVEN IN THE
ABSENCE OF DISEASE. 466 11 -6 THE CIRCULATION OF LYMPHOCYTES WITHIN THE
MUCOSAL IMMUNE SYSTEM IS CONTROLLED BY TISSUE-SPECIFIC ADHESION
MOLECULES AND CHEMOKINE RECEPTORS. T 467 11-7 PRIMING OF LYMPHOCYTES IN
ONE MUCOSAL TISSUE CAN INDUCE PROTECTIVE IMMUNITY AT OTHER MUCOSAL
SURFACES. 469 11 -8 SECRETORY IGA IS THE CLASS OF ANTIBODY ASSOCIATED
WITH THE MUCOSAL IMMUNE SYSTEM. 469 11-9 IGA DEFICIENCY IS COMMON IN
HUMANS BUT MAY BE OVERCOME BY SECRETORY IGM. 472 11-10 THE MUCOSAL
IMMUNE SYSTEM CONTAINS UNUSUAL T LYMPHOCYTES. 472 SUMMARY. 475 THE
MUCOSAL RESPONSE TO INFECTION AND REGULATION OF MUCOSAL IMMUNE
RESPONSES. THE IMMUNE SYSTEM IN HEALTH AND DISEASE CHAPTER 12 FAILURES
OF HOST DEFENSE MECHANISMS 476 11-11 ENTERIC PATHOGENS CAUSE A LOCAL
INFLAMMATORY RESPONSE AND THE DEVELOPMENT OF PROTECTIVE IMMUNITY. 476
11-12 THE OUTCOME OF INFECTION BY INTESTINAL PATHOGENS IS DETERMINED BY
A COMPLEX INTERPLAY BETWEEN THE MICROORGANISM AND THE HOST IMMUNE
RESPONSE. 478 11-13 THE MUCOSAL IMMUNE SYSTEM MUST MAINTAIN A BALANCE
BETWEEN PROTECTIVE IMMUNITY AND HOMEOSTASIS TO A LARGE NUMBER OF
DIFFERENT FOREIGN ANTIGENS. 480 11-14 THE HEALTHY INTESTINE CONTAINS
LARGE QUANTITIES OF BACTERIA BUT DOES NOT GENERATE PRODUCTIVE IMMUNITY
AGAINST THEM. 482 11-15 FULL IMMUNE RESPONSES TO COMMENSAL BACTERIA
PROVOKE INTESTINAL DISEASE. ^ 485 11-16 INTESTINAL HELMINTHS PROVOKE
STRONG ^-MEDIATED IMMUNE RESPONSES. 485 11-17 OTHER EUKARYOTIC PARASITES
PROVOKE PROTECTIVE IMMUNITY AND PATHOLOGY IN THE GUT. 488 11-18
DENDRITIC CELLS AT MUCOSAL SURFACES FAVOR THE INDUCTION OF TOLERANCE
UNDER PHYSIOLOGICAL CONDITIONS AND MAINTAIN THE PRESENCE OF
PHYSIOLOGICAL INFLAMMATION. 488 SUMMARY. 489 SUMMARY TO CHAPTER 11. 490
497 EVASION AND SUBVERSION OF IMMUNE DEFENSES 498 12-1 ANTIGENIC
VARIATION ALLOWS PATHOGENS TO ESCAPE FROM IMMUNITY. 498 12-2 SOME
VIRUSES PERSIST IN VIVO BY CEASING TO REPLICATE UNTIL IMMUNITY WANES.
.,-- 501 12-3 SOME PATHOGENS RESIST DESTRUCTION BY HOST DEFENSE
MECHANISMS OR EXPLOIT THEM FOR THEIR OWN PURPOSES. 502 12-4
IMMUNOSUPPRESSION OR INAPPROPRIATE IMMUNE RESPONSES CAN CONTRIBUTE TO
PERSISTENT DISEASE. 504 12-5 IMMUNE RESPONSES CAN CONTRIBUTE DIRECTLY TO
PATHOGENESIS. 506 12-6 REGULATORY T CELLS CAN AFFECT THE 1 OUTCOME OF
INFECTIOUS DISEASE. 506 SUMMARY. 507 IMMUNODEFICIENCY DISEASES. 507 12-7
A HISTORY OF REPEATED INFECTIONS SUGGESTS A DIAGNOSIS OF
IMMUNODEFICIENCY. 507 12-8 INHERITED IMMUNODEFICIENCY DISEASES ARE
CAUSED BY RECESSIVE GENE DEFECTS. * 508 12-9 THE MAIN EFFECT OF LOW
LEVELS OF ANTIBODY IS AN INABILITY TO CLEAR EXTRACELLULAR BACTERIA. 509
12-10 SOME ANTIBODY DEFICIENCIES CAN BE DUE TO DEFECTS IN EITHER B-CELL
OR T-CELL FUNCTION. 12-11 DEFECTS IN COMPLEMENT COMPONENTS CAUSE
DEFECTIVE HUMORAL IMMUNE FUNCTION. 512 514 12-12 DEFECTS IN PHAGOCYTIC
CELLS PERMIT WIDESPREAD BACTERIAL INFECTIONS. 515 12-13 DEFECTS IN
T-CELL DIFFERENTIATION CAN RESULT IN SEVERE COMBINED IMMUNODEFICIENCIES.
517 12-14 DEFECTS IN ANTIGEN RECEPTOR GENE REARRANGEMENT RESULT INSCID.
519 12-15 DEFECTS IN SIGNALING FROM T-CELL ANTIGEN RECEPTORS CAN CAUSE
SEVERE IMMUNODEFICIENCY. 520 12-16 GENETIC DEFECTS IN THYMIC FUNCTION
THAT BLOCK T-CELL DEVELOPMENT RESULT IN SEVERE IMMUNODEFICIENCIES. 520
12-17 THE NORMAL PATHWAYS FOR HOST DEFENSE AGAINST INTRACELLULAR
BACTERIA ARE PINPOINTED BY GENETIC DEFICIENCIES OF IFN-Y AND IL-12 AND
THEIR RECEPTORS. 522 12-18 X-LINKED LYMPHOPROLIFERATIVE SYNDROME IS
ASSOCIATED WITH FATAL INFECTION BY EPSTEIN-BARR VIRUS AND WITH THE
DEVELOPMENT OF LYMPHOMAS. 523 12-19 GENETIC ABNORMALITIES IN THE
SECRETORY CYTOTOXIC PATHWAY OF LYMPHOCYTES CAUSE UNCONTROLLED
LYMPHOPROLIFERATION AND INFLAMMATORY RESPONSES TO VIRAL INFECTIONS. 523
12-20 BONE MARROW TRANSPLANTATION OR GENE THERAPY CAN BE USEFUL TO
CORRECT GENETIC DEFECTS. 525 12-21 SECONDARY IMMUNODEFICIENCIES ARE
MAJOR PREDISPOSING CAUSES OF INFECTION AND DEATH. 526 SUMMARY. 527
ACQUIRED IMMUNE DEFICIENCY SYNDROME. 527 12-22 MOST INDIVIDUALS INFECTED
WITH HIV PROGRESS OVER TIME TO AIDS. 528 12-23 HIV IS A RETROVIRUS THAT
INFECTS CD4 T CELLS, DENDRITIC ^ CELLS, AND MACROPHAGES. 530 12-24
GENETIC VARIATION IN THE HOST CAN ALTER THE RATE OF PROGRESSION OF
DISEASE. 532 12-25 A GENETIC DEFICIENCY OF THE CO-RECEPTOR CCR5 CONFERS
RESISTANCE TO HIV INFECTION IN VIVO. 532 12-26 HIV RNA IS TRANSCRIBED BY
VIRAL REVERSE TRANSCRIPTASE INTO DNA THAT INTEGRATES INTO THE HOST-CELL
GENOME. 534 12-27 REPLICATION OF HIV OCCURS ONLY IN ACTIVATED T CELLS.
536 12-28 LYMPHOID TISSUE IS THE MAJOR RESERVOIR OF HIV INFECTION. 537
12-29 AN IMMUNE RESPONSE CONTROLS BUT DOES NOT ELIMINATE HIV. 538 12-30
THE DESTRUCTION OF IMMUNE FUNCTION AS A RESULT OF HIV INFECTION LEADS TO
INCREASED SUSCEPTIBILITY TO OPPORTUNISTIC INFECTION AND EVENTUALLY TO
DEATH. 540 12-31 DRUGS THAT BLOCK HIV REPLICATION LEAD TO A RAPID
DECREASE IN TITER OF INFECTIOUS VIRUS AND AN INCREASE IN CD4T CELLS. 540
12-32 HIV ACCUMULATES MANY MUTATIONS IN THE COURSE OF INFECTION, AND
DRUG TREATMENT IS SOON FOLLOWED BY THE OUTGROWTH OF DRUG-RESISTANT
VARIANTS. 542 12-33 VACCINATION AGAINST HIV IS AN ATTRACTIVE SOLUTION
BUT POSES MANY DIFFICULTIES. 543 XIX 12-34 PREVENTION AND EDUCATION ARE
ONE WAY IN WHICH THE SPREAD OF HIV AND AIDS CAN BE CONTROLLED. SUMMARY.
SUMMARY TO CHAPTER 12. CHAPTER 13 ALLERGY AND HYPERSENSITIVITY
SENSITIZATION AND THE PRODUCTION OF IGE. ALLERGENS ARE OFTEN DELIVERED
TRANSMUCOSALLY AT LOW DOSE, A ROUTE THAT FAVORS IGE PRODUCTION. ENZYMES
ARE FREQUENT TRIGGERS OF ALLERGY. CLASS SWITCHING TO IGE IN B
LYMPHOCYTES IS FAVORED BY SPECIFIC SIGNALS. BOTH GENETIC AND
ENVIRONMENTAL FACTORS CONTRIBUTE TO THE DEVELOPMENT OF IGE-MEDIATED
ALLERGY. REGULATORY T CELLS CAN CONTROL ALLERGIC RESPONSES. 13-1 13-2
13-3 13-4 13-5 SUMMARY. EFFECTOR MECHANISMS IN ALLERGIC REACTIONS. 13-6
MOST IGE IS CELL-BOUND AND ENGAGES EFFECTOR MECHANISMS OF THE IMMUNE
SYSTEM BY DIFFERENT PATHWAYS FROM OTHER ANTIBODY ISOTYPES. 13-7 MAST
CELLS RESIDE IN TISSUES AND ORCHESTRATE ALLERGIC REACTIONS. 13-8
EOSINOPHILS ARE NORMALLY UNDER TIGHT CONTROL TO PREVENT INAPPROPRIATE
TOXIC RESPONSES. 13-9 EOSINOPHILS AND BASOPHILS CAUSE INFLAMMATIONLND
TISSUE DAMAGE IN ALLERGIC REACTIONS. 13-10 ALLERGIC REACTIONS CAN BE
DIVIDED INTO IMMEDIATE AND LATE-PHASE RESPONSES. 13-11 THE CLINICAL
EFFECTS OF ALLERGIC REACTIONS VARY ACCORDING TO THE SITE OF MAST-CELL
ACTIVATION. 13-12 ALLERGEN INHALATION IS ASSOCIATED WITH THE
DEVELOPMENT OF RHINITIS AND ASTHMA. 13-13 SKIN ALLERGY IS MANIFESTED AS
URTICARIA OR CHRONIC ECZEMA. 13-14 ALLERGY TO FOODS CAUSES SYSTEMIC
REACTIONS AS WELF AS SYMPTOMS LIMITED TO THE GUT. *** 13-15 CELIAC
DISEASE IS A MODEL OF ANTIGEN-SPECIFIC * IMMUNOPATHOLOGY. H 13-16
ALLERGY CAN BE TREATED BY INHIBITING EITHER IGE PRODUCTION OR THE
EFFECTOR PATHWAYS ACTIVATED BY THE CROSS-LINKING OF CELL-SURFACE IGE. V
SUMMARY. I HYPERSENSITIVITY DISEASES. 13-17 INNOCUOUS ANTIGENS CAN CAUSE
TYPE II HYPERSENSITIVITY REACTIONS IN SUSCEPTIBLE INDIVIDUALS BY BINDING
TO THE SURFACES OF CIRCULATING BLOOD CELLS. 13-18 SYSTEMIC DISEASE
CAUSED BY IMMUNE-COMPLEX FORMATION CAN FOLLOW THE ADMINISTRATION OF
LARGE QUANTITIES OF POORLY CATABOLIZED ANTIGENS. 13-19 DELAYED-TYPE
HYPERSENSITIVITY REACTIONS ARE MEDIATED BY TH1 CELLS AND CD8 CYTOTOXIC
T CELLS. 13-20 MUTATION IN THE MOLECULAR REGULATORS OF INFLAMMATION CAN
CAUSE HYPERSENSITIVE INFLAMMATORY RESPONSES RESULTING IN
AUTOINFLAMMATORY DISEASE. R Y 13-21 CROHN S DISEASE IS A RELATIVELY
COMMON INFLAMMATORY DISEASE WITH A COMPLEX ETIOLOGY. SUMMARY. SUMMARY TO
CHAPTER 13. 545 545 546 555 557 557 558 559 560 565 565 566 567 567 569
571 571 572 574 576 577 578 580 583 583 583 583 585 588 590 591 591
CHAPTER 14 AUTOIMMUNITY AND TRANSPLANTATION 599 THE MAKING AND BREAKING
OF SELF-TOLERANCE 14-1 600 A CRITICAL FUNCTION OF THE IMMUNE SYSTEM IS
TO DISCRIMINATE SELF FROM NONSELF. 14-2 MULTIPLE TOLERANCE MECHANISMS
NORMALLY PREVENT AUTOIMMUNITY. CENTRAL DELETION OR INACTIVATION OF NEWLY
FORMED LYMPHOCYTES IS THE FIRST CHECKPOINT OF SELF-TOLERANCE.
LYMPHOCYTES THAT BIND SELF ANTIGENS WITH RELATIVELY LOW AFFINITY USUALLY
IGNORE THEM BUT IN SOME CIRCUMSTANCES BECOME ACTIVATED. ANTIGENS IN
IMMUNOLOGICALLY PRIVILEGED SITES DO NOT INDUCE IMMUNE ATTACK BUT CAN
SERVE AS TARGETS. AUTOREACTIVE T CELLS THAT EXPRESS PARTICULAR CYTOKINES
MAY BE NONPATHOGENIC OR MAY SUPPRESS PATHOGENIC LYMPHOCYTES. AUTOIMMUNE
RESPONSES CAN BE CONTROLLED AT VARIOUS STAGES BY REGULATORY T CELLS.
SUMMARY. 14-3 14-4 14-5 14-6 14-7 AUTOIMMUNE DISEASES AND PATHOGENIC
MECHANISMS. 14-8 SPECIFIC ADAPTIVE IMMUNE RESPONSES TO SELF ANTIGENS CAN
CAUSE AUTOIMMUNE DISEASE. 14-9 AUTOIMMUNE DISEASES CAN BE CLASSIFIED
INTO CLUSTERS THAT ARE TYPICALLY EITHER ORGAN-SPECIFIC OR SYSTEMIC.
14-10 MULTIPLE ASPECTS OF THE IMMUNE SYSTEM ARE TYPICALLY RECRUITED IN
AUTOIMMUNE DISEASE. 14-11 CHRONIC AUTOIMMUNE DISEASE DEVELOPS THROUGH
POSITIVE FEEDBACK FROM INFLAMMATION, INABILITY TO CLEAR THE SELF
ANTIGEN, AND A BROADENING OF THE AUTOIMMUNE RESPONSE. 14-12 BOTH
ANTIBODY AND EFFECTOR T CELLS CAN CAUSE TISSUE DAMAGE IN AUTOIMMUNE
DISEASE. 14-13 AUTOANTIBODIES AGAINST BLOOD CELLS PROMOTE THEIR
DESTRUCTION. 14-14 THE FIXATION OF SUBLYTIC DOSES OF COMPLEMENT TO CELLS
IN TISSUES STIMULATES A POWERFUL INFLAMMATORY RESPONSE. 14-15
AUTOANTIBODIES AGAINST RECEPTORS CAUSE DISEASE BY STIMULATING OR
BLOCKING RECEPTOR FUNCTION. 14-16 AUTOANTIBODIES AGAINST EXTRACELLULAR
ANTIGENS CAUSE INFLAMMATORY INJURY BY MECHANISMS AKIN TO TYPE II AND
TYPE III HYPERSENSITIVITY REACTIONS. 14-17 T CELLS SPECIFIC FOR SELF
ANTIGENS CAN CAUSE DIRECT TISSUE INJURY AND SUSTAIN AUTOANTIBODY
RESPONSES. SUMMARY. THE GENETIC AND ENVIRONMENTAL BASIS OF AUTOIMMUNITY.
14-18 AUTOIMMUNE DISEASES HAVE A STRONG GENETIC COMPONENT. 14-19 A
DEFECT IN A SINGLE GENE CAN CAUSE AUTOIMMUNE DISEASE. 14-20 SEVERAL
APPROACHES HAVE GIVEN US INSIGHT INTO THE GENETIC BASIS OF AUTOIMMUNITY.
14-21 GENES THAT PREDISPOSE TO AUTOIMMUNITY FALL INTO CATEGORIES THAT
AFFECT ONE OR MORE OF THE MECHANISMS OF TOLERANCE. 14-22 MHC GENES HAVE
AN IMPORTANT ROLE IN CONTROLLING SUSCEPTIBILITY TO AUTOIMMUNE DISEASE.
14-23 EXTERNAL EVENTS CAN INITIATE AUTOIMMUNITY. 14-24 INFECTION CAN
LEAD TO AUTOIMMUNE DISEASE BY PROVIDING AN ENVIRONMENT THAT PROMOTES
LYMPHOCYTE ACTIVATION. 14-25 CROSS-REACTIVITY BETWEEN FOREIGN MOLECULES
ON PATHOGENS AND SELF MOLECULES CAN LEAD TO ANTI-SELF RESPONSES AND
AUTOIMMUNE DISEASE. 600 602 603 603 605 606 607 609 610 610 611 612 615
617 617 619 620 621 622 625 626 626» 627 628 631 631 634 634 635 14-26
DRUGS AND TOXINS CAN CAUSE AUTOIMMUNE SYNDROMES. 14-27 RANDOM EVENTS MAY
BE REQUIRED FOR THE INITIATION OF AUTOIMMUNITY. SUMMARY. RESPONSES TO
ALLOANTIGENS AND TRANSPLANT REJECTION. 14-28 GRAFT REJECTION IS AN
IMMUNOLOGICAL RESPONSE MEDIATED PRIMARILY BY T CELLS. 14-29 MATCHING
DONOR AND RECIPIENT AT THE MHC IMPROVES THE OUTCOME OF TRANSPLANTATION.
14-30 IN MHC-IDENTICAL GRAFTS, REJECTION IS CAUSED BY PEPTIDES FROM
OTHER ALLOANTIGENS BOUND TO GRAFT MHC MOLECULES. 14-31 THERE ARE TWO
WAYS OF PRESENTING ALLOANTIGENS ON THE TRANSPLANT TO THE RECIPIENT S T
LYMPHOCYTES. 14-32 ANTIBODIES REACTING WITH ENDOTHELIUM CAUSE HYPERACUTE
GRAFT REJECTION. 14-33 CHRONIC ORGAN REJECTION IS CAUSED BY INFLAMMATORY
VASCULAR INJURY TO THE GRAFT. 14-34 A VARIETY OF ORGANS ARE TRANSPLANTED
ROUTINELY IN CLINICAL MEDICINE. 14-35 14-36 THE CONVERSE OF GRAFT
REJECTION IS GRAFT-VERSUS-HOST DISEASE. REGULATORY T CELLS ARE INVOLVED
IN ALLOREACTIVE IMMUNE RESPONSES. 14-37 THE FETUS IS AN ALLOGRAFT THAT
IS TOLERATED REPEATEDLY. SUMMARY. SUMMARY TO CHAPTER 14. 636 637 637 637
638 639 640 641 642 643 644 645 646 647 648 648 CHAPTER 15 MANIPULATION
OF THE IMMUNE RESPONSE 655 1525 EXTRINSIC REGULATION OF UNWANTED IMMUNE
RESPONSES. 15-1 CORTICOSTEROIDS ARE POWERFUL ANTI-INFLAMMATORY DRUGS
THAT ALTER THE TRANSCRIPTION OF MANY GENES. 15-2 CYTOTOXIC DRUGS CAUSE
IMMUNOSUPPRESSION BY KILLING DIVIDING CELLS AND HAVE SERIOUS
SIDE-EFFECTS. 15-3 CYCLOSPORIN A, TACROLIMUS (FK506) R AND RAPAMYCIN
(SIROLIMUS) ARE POWERFUL IMMUNOSUPPRESSIVE AGENTS THAT INTERFERE WITH
T-CELL SIGNALING. 15-4 IMMUNOSUPPRESSIVE DRUGS ARE VALUABLE PROBES OF
INTRACELLULAR SIGNALING PATHWAYS IN LYMPHOCYTES. 15-5 ANTIBODIES AGAINST
CELL-SURFACE MOLECULES HAVE BEEN USED TO REMOVE SPECIFIC LYMPHOCYTE
SUBSETS OR TO INHIBIT CELL FUNCTION. 15-6 ANTIBODIES CAN BE ENGINEEREDTO
REDUCE THEIR IMMUNOGENICITY IN HUMANS. 15-7 MONOCLONAL ANTIBODIES CAN BE
USED TO PREVENT ALLOGRAFT REJECTION. 15-8 BIOLOGICAL AGENTS CAN BE USED
TO ALLEVIATE AND SUPPRESS AUTOIMMUNE DISEASE. 15-9 15-10 15-11 15-12
DEPLETION OR INHIBITION OF AUTOREACTIVE LYMPHOCYTES^CAN TREAT AUTOIMMUNE
DISEASE. INTERFERENCE WITH CO-STIMULATORY PATHWAYS FOR THE ^
ACTIVATION OF LYMPHOCYTES COULD BE A TREATMENT FOR ^ AUTOIMMUNE DISEASE.
INDUCTION OF REGULATORY T CELLS BY ANTIBODY THERAPY CAN INHIBIT
AUTOIMMUNE DISEASE. A NUMBER OF COMMONLY USED DRUGS HAVE
IMMUNOMODULATORY PROPERTIES. 15-13 CONTROLLED ADMINISTRATION OF ANTIGEN
CAN BE USED TO MANIPULATE THE NATURE OF AN ANTIGEN-SPECIFIC RESPONSE.
SUMMARY. 655 656 657 658 659 661 661 662 664 666 668 668 669 671 672
USING THE IMMUNE RESPONSE TO ATTACK TUMORS. 15-14 THE DEVELOPMENT OF
TRANSPLANTABLE TUMORS IN MICE LED TO THE DISCOVERY OF PROTECTIVE IMMUNE
RESPONSES TO TUMORS. 15-15 TUMORS CAN ESCAPE REJECTION IN MANY WAYS.
15-16 T LYMPHOCYTES CAN RECOGNIZE SPECIFIC ANTIGENS ON HUMAN TUMORS, AND
ADOPTIVE T-CELL TRANSFER IS BEING TESTED IN CANCER PATIENTS. 15-17
MONOCLONAL ANTIBODIES AGAINST TUMOR ANTIGENS, ALONE OR LINKED TO TOXINS,
CAN CONTROL TUMOR GROWTH] 15-18 ENHANCING THE IMMUNE RESPONSE TO TUMORS
BY VACCINATION HOLDS PROMISE FOR CANCER PREVENTION AND THERAPY. SUMMARY.
MANIPULATING THE IMMUNE RESPONSE TO FIGHT INFECTION. 15-19 THERE ARE
SEVERAL REQUIREMENTS FOR AN EFFECTIVE VACCINE. 15-20 THE HISTORY OF
VACCINATION AGAINST BORDETELLA PERTUSSIS ILLUSTRATES THE IMPORTANCE OF
DEVELOPING AN EFFECTIVE VACCINE THAT IS PERCEIVED TO BE SAFE. 15-21
CONJUGATE VACCINES HAVE BEEN DEVELOPED AS A RESULT OF UNDERSTANDING HOW
T AND B CELLS COLLABORATE IN AN IMMUNE RESPONSE. 15-22 THE USE OF
ADJUVANTS IS ANOTHER IMPORTANT APPROACH TO ENHANCING THE IMMUNOGENICITY
OF VACCINES. 15-23 LIVE-ATTENUATED VIRAL VACCINES ARE USUALLY MORE
POTENT THAN KILLED VACCINES AND CAN BE MADE SAFER BY THE USE OF
RECOMBINANT DNA TECHNOLOGY. 15-24 LIVE-ATTENUATED BACTERIAL VACCINES CAN
BE DEVELOPED BY SELECTING NONPATHOGENIC OR DISABLED MUTANTS. SYNTHETIC
PEPTIDES OF PROTECTIVE ANTIGENS CAN ELICIT PROTECTIVE IMMUNITY. 15-26
THE ROUTE OF VACCINATION IS AN IMPORTANT DETERMINANT OF SUCCESS. 15-27
PROTECTIVE IMMUNITY CAN BE INDUCED BY INJECTING DNA ENCODING MICROBIAL
ANTIGENS AND HUMAN CYTOKINES INTO MUSCLE. 15-28 THE EFFECTIVENESS OF A
VACCINE CAN BE ENHANCED BY TARGETING IT TO SITES OF ANTIGEN
PRESENTATION. 15-29 AN IMPORTANT QUESTION IS WHETHER VACCINATION CAN BE
USED THERAPEUTICALLY TO CONTROL EXISTING CHRONIC INFECTIONS. 15-30
MODULATION OF THE IMMUNE SYSTEM MIGHT BE USED TO INHIBIT
IMMUNOPATHOLOGICAL RESPONSES TO INFECTIOUS AGENTS. SUMMARY. SUMMARY TO
CHAPTER 15. PART VI THE ORIGINS OF IMMUNE RESPONSES CHAPTER 16 EVOLUTION
OF THE IMMUNE SYSTEM EVOLUTION OF THE INNATE IMMUNE SYSTEM. THE
EVOLUTION OF THE IMMUNE SYSTEM CAN BE STUDIED BY COMPARING THE GENES
EXPRESSED BY DIFFERENT SPECIES. ANTIMICROBIAL PEPTIDES ARE LIKELY TO BE
THE MOST ANCIENT IMMUNE DEFENSES. TOLL-LIKE RECEPTORS MAY REPRESENT THE
MOST ANCIENT PATHOGEN-RECOGNITION SYSTEM. TOLL-LIKE RECEPTOR GENES HAVE
UNDERGONE EXTENSIVE DIVERSIFICATION IN SOME INVERTEBRATE SPECIES. 16-1
16-2 16-3 16-4 672 673 674 678 682 684 687 687 689 690 691 693 . 695 696
696 697 698 699 700 701 702 703 711 712 712 713 714 716 XXI 16-5 A
SECOND RECOGNITION SYSTEM IN DROSOPHILA HOMOLOGOUS TO THE MAMMALIAN TNF
RECEPTOR PATHWAY PROVIDES PROTECTION FROM GRAM-NEGATIVE BACTERIA. 717
16-6 AN ANCESTRAL COMPLEMENT SYSTEM OPSONIZES PATHOGENS FOR UPTAKE BY
PHAGOCYTIC CELLS. { 16-7 THE LECTIN PATHWAY OF COMPLEMENT ACTIVATION
EVOLVED IN INVERTEBRATES. SUMMARY. EVOLUTION OF THE ADAPTIVE IMMUNE
RESPONSE. 720 16-8 SOME INVERTEBRATES GENERATE EXTENSIVE DIVERSITY IN A
REPERTOIRE OF IMMUNOGLOBULIN-LIKE GENES. 721 16-9 AGNATHANS POSSESS AN
ADAPTIVE IMMUNE SYSTEM THAT USES SOMATIC GENE REARRANGEMENT TO DIVERSIFY
RECEPTORS BUILT FROM LRR DOMAINS. 722 16-10 ADAPTIVE IMMUNITY BASED ON A
DIVERSIFIED REPERTOIRE OF IMMUNOGLOBULIN-LIKE GENES APPEARED ABRUPTLY IN
THE CARTILAGINOUS FISH. 724 16-11 THE TARGET OF THE TRANSPOSON IS LIKELY
TO HAVE BEEN A GENE ENCODING A CELL-SURFACE RECEPTOR CONTAINING AN
IMMUNOGLOBULIN-LIKE V DOMAIN. 725 16-12 DIFFERENT SPECIES GENERATE
IMMUNOGLOBULIN DIVERSITY IN DIFFERENT WAYS. 726 16-13 BOTH OC:P AND Y.H
T-CELL RECEPTORS ARE PRESENT IN CARTILAGINOUS FISH. 16-14 MHC CLASS I
AND CLASS II MOLECULES ARE ALSO FIRST FOUND IN THE CARTILAGINOUS FISHES.
SUMMARY. SUMMARY TO CHAPTER 16. APPENDIX I IMMUNOLOGISTS TOOLBOX
IMMUNIZATION. A-1 HAPTENS. A-2 ROUTES OF IMMUNIZATION. A-3 EFFECTS OF
ANTIGEN DOSE. A-4 ADJUVANTS. THE DETECTION, MEASUREMENT, AND
CHARACTERIZATION OF ANTIBODIES AND THEIR USE AS RESEARCH AND DIAGNOSTIC
TOOLS. 740 A-5 AFFINITY CHROMATOGRAPHY. 741 A-6 RADIOIMMUNOASSAY
(RIA), ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA), AND
COMPETITIVE-INHIBITION ASSAY. 741 A-7 HEMAGGLUTINATION AND BLOOD
TYPING. 743 ^*8 PRECIPITIN REACTION. 744 A-9 EQUILIBRIUM DIALYSIS:
MEASUREMENT OF ANTIBODY AFFINITY AND AVIDITY. 745 A-10
ANTI-IMMUNOGLOBULIN ANTIBODIES. . 746 A-11 COOMBS TESTS AND THE
DETECTION OF RHESUS INCOMPATIBILITY. 747 A-12 MONOCLONAL ANTIBODIES. 749
- A-13 PHAGE DISPLAY LIBRARIES FOR ANTIBODY V-REGION PRODUCTION. ^- 750
A-14 IMMUNOFLUORESCENCE MICROSCOPY. ^ 751 A-15 IMMUNOELECTRON
MICROSCOPY. 753 A-16 IMMUNOHISTOCHEMISTRY. - 753 A-17
IMMUNOPRECIPITATION AND CO-IMMUNOPRECIPITATION. 754 A-18 IMMUNOBLOTTING
(WESTERN BLOTTING). 755 A-19 USE OF ANTIBODIES IN THE ISOLATION AND
IDENTIFICATION OF GENES AND THEIR PRODUCTS. 756 717 719 720 A-21 A-22
A-23 728 729 729 735 735 736 738 738 738 A-32 A-33 A-34 A-35 DETC A-36
A-37 A-38 A-39 A-40 A-41 ISOLATION OF LYMPHOCYTES. 758 A-20 ISOLATION OF
PERIPHERAL BLOOD LYMPHOCYTES BY FICOLL-HYPAQUE* GRADIENT. 758 ISOLATION
OF LYMPHOCYTES FROM TISSUES OTHER THAN BLOOD. 758 FLOW CYTOMETRY AND
FACS ANALYSIS. 759 LYMPHOCYTE ISOLATION USING ANTIBODY-COATED MAGNETIC
BEADS. 761 A-24 ISOLATION OF HOMOGENEOUS T-CELL LINES. 761
CHARACTERIZATION OF LYMPHOCYTE SPECIFICITY, FREQUENCY, AND FUNCTION. 762
A-25 LIMITING-DILUTION CULTURE. 763 A-26 ELISPOT ASSAYS. 763 A-27
IDENTIFICATION OF FUNCTIONAL SUBSETS OF T CELLS BY STAINING FOR
CYTOKINES. 764 A-28 IDENTIFICATION OF T-CELL RECEPTOR SPECIFICITY USING
MHC: PEPTIDE TETRAMERS. 765 A-29 ASSESSING THE DIVERSITY OF THE T-CELL
REPERTOIRE BY SPECTRATYPING. 766 A-30 BIOSENSOR ASSAYS FOR MEASURING
THE RATES OF ASSOCIATION AND DISASSOCIATION OF ANTIGEN RECEPTORS FOR
THEIR LIGANDS. 767 A-31 STIMULATION OF LYMPHOCYTE PROLIFERATION BY
TREATMENT WITH POLYCLONAL MITOGENS OR SPECIFIC ANTIGEN. 769 MEASUREMENTS
OF APOPTOSIS BY THE TUNEL ASSAY. 770 ASSAYS FOR CYTOTOXIC T CELLS. 770
ASSAYS FOR CD4 T CELLS. 770 DNA MICROARRAYS. 772 DETECTION OF IMMUNITY
IN VIVO. 772 ASSESSMENT OF PROTECTIVE IMMUNITY. 772 TRANSFER OF
PROTECTIVE IMMUNITY. 773 THE TUBERCULIN TEST. 774 TESTING FOR ALLERGIC
RESPONSES. 774 ASSESSMENT OF IMMUNE RESPONSES AND IMMUNOLOGICAL
COMPETENCE IN HUMANS. 775 THE ARTHUS REACTION. 776 MANIPULATION OF THE
IMMUNE SYSTEM. 777 A-42 ADOPTIVE TRANSFER OF LYMPHOCYTES. 777 A-43
HEMATOPOIETIC STEM-CELL TRANSFERS. 777 A-44 IN VIVO DEPLETIO N OF T
CELLS. 777 A-45 IN VIVO DEPLETION OF B CELLS. 778 A-46 TRANSGENIC MICE.
778 A-47 GENE KNOCKOUT BY TARGETED DISRUPTION. 779 APPENDIX II CD
ANTIGENS 783 APPENDIX III CYTOKINES AND THEIR RECEPTORS 799 APPENDIX IV
CHEMOKINES AND THEIR RECEPTORS 802 APPENDIX V IMMUNOLOGICAL CONSTANTS
804 BIOGRAPHIES 805 GLOSSARY 806 INDEX 835
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JANEWAY'S IMMUNO IOLOGY SEVENTH EDITION KENNETH MURPHY WASHINGTON
UNIVERSITY SCHOOL OF MEDICINE, ST. LOUIS PAUL TRAVERS ANTHONY NOLAN
RESEARCH INSTITUTE, LONDON MARK WALPORT THE WELLCOME TRUST, LONDON WITH
CONTRIBUTIONS BY: MICHAEL EHRENSTEIN UNIVERSITY COLLEGE LONDON, DIVISION
OF MEDICINE CLAUDIA MAURI UNIVERSITY COLLEGE LONDON, DIVISION OF
MEDICINE ALLAN MOWAT - UNIVERSITY OF GLASGOW ANDREYSHAW WASHINGTON
UNIVERSITY SCHOOL OF MEDICINE, ST. LOUIS GARLAND SCIENCE TAYLOR &
FRANCIS CROUP NEW YORK AND LONDON DETAILED CONTENTS PARTI AN
INTRODUCTION TO IMMUNO- BIOLOGY AND INNATE IMMUNITY CHAPTER 1 BASIC
CONCEPTS IN IMMUNOLOGY 1 PRINCIPLES OF INNATE AND ADAPTIVE IMMUNITY. 3
1-1 FUNCTIONS OF THE IMMUNE RESPONSE. 3 1 -2 THE CELLS OF THE IMMUNE
SYSTEM DERIVE FROM PRECURSORS IN THE BONE MARROW. 5 1 -3 THE MYELOID
LINEAGE COMPRISES MOST OF THE CELLS OF THE INNATE IMMUNE SYSTEM. 5 1-4
THE LYMPHOID LINEAGE COMPRISES THE LYMPHOCYTES OF THE ADAPTIVE IMMUNE
SYSTEM AND THE NATURAL KILLER CELLS OF INNATE IMMUNITY. 8 1 -5
LYMPHOCYTES MATURE IN THE BONE MARROW OR THE THYMUS AND THEN CONGREGATE
IN LYMPHOID TISSUES THROUGHOUT THE BODY. 9 1 -6 MOST INFECTIOUS AGENTS
ACTIVATE THE INNATE IMMUNE SYSTEM AND INDUCE AN INFLAMMATORY RESPONSE.
10 1-7 ACTIVATION OF SPECIALIZED ANTIGEN-PRESENTING CELLS IS A NECESSARY
FIRST STEP FOR INDUCTION OF ADAPTIVE IMMUNITY. 12 1-8 THE INNATE IMMUNE
SYSTEM PROVIDES AN INITIAL DISCRIMINATION BETWEEN SELF AND NONSELF. 13 1
-9 LYMPHOCYTES ACTIVATED BY ANTIGEN GIVE RISE TO CLONES OF
ANTIGEN-SPECIFIC EFFECTOR CELLS THAT MEDIATE ADAPTIVE IMMUNITY. 13 1-10
CLONAL SELECTION OF LYMPHOCYTES IS THE CENTRAL PRINCIPLE OF ADAPTIVE
IMMUNITY. 14 1-11 THE STRUCTURE OF THE ANTIBODY MOLECULE ILLUSTRATES THE
CENTRAL PUZZLE OF ADAPTIVE IMMUNITY. 15 1-12 EACH DEVELOPING LYMPHOCYTE
GENERATES A UNIQUE ANTIGEN RECEPTOR BY REARRANGING ITS RECEPTOR GENE
SEGMENTS. 16 1 -13 IMMUNOGLOBULINS BIND A WIDE VARIETY OF CHEMICAL
STRUCTURES, WHEREAS THE T-CELL RECEPTOR IS SPECIALIZED TO RECOGNIZE
FOREIGN ANTIGENS AS PEPTIDE FRAGMENTS BOUND TO PROTEINS OF THE MAJOR
HISTOCOMPATIBILITY COMPLEX. 17 1-14 THE DEVELOPMENT AND SURVIVAL OF
LYMPHOCYTES IS DETERMINED BY SIGNALS RECEIVED THROUGH THEIR ANTIGEN
RECEPTORS. 18 1-15 LYMPHOCYTES ENCOUNTER AND RESPOND TO ANTIGEN IN THE
PERIPHERAL LYMPHOID ORGANS. 18 1-16 INTERACTION WITH OTHER CELLS AS WELL
AS WITH ANTIGEN IS NECESSARY FOR LYMPHOCYTE ACTIVATION. 23 1-17
LYMPHOCYTES ACTIVATED BY ANTIGEN PROLIFERATE IN THE PERIPHERAL LYMPHOID
ORGANS, GENERATING EFFECTOR CELLS AND IMMUNOLOGICAL MEMORY. -' 23
SUMMARY. " 27 THE EFFECTOR MECHANISMS OF ADAPTIVE IMMUNITY. 27 1-18
ANTIBODIES DEAL WITH EXTRACELLULAR FORMS OF PATHOGENS AND THEIR TOXIC
PRODUCTS. 28 1-19 T'CELLS ARE NEEDED TO CONTROL INTRACELLULAR PATHOGENS
AND TO ACTIVATE B-CELL RESPONSES TO MOST ANTIGENS. 30 1 -20 CD4 AND CD8
T CELLS RECOGNIZE PEPTIDES BOUND TO TWO DIFFERENT CLASSES OF MHC
MOLECULES. 32 1 -21 DEFECTS IN THE IMMUNE SYSTEM RESULT IN INCREASED
SUSCEPTIBILITY TO INFECTION. 34 1-22 UNDERSTANDING ADAPTIVE IMMUNE
RESPONSES IS IMPORTANT FOR THE CONTROL OF ALLERGIES, AUTOIMMUNE DISEASE,
AND ORGAN GRAFT REJECTION. 34 1 -23 VACCINATION IS THE MOST EFFECTIVE
MEANS OF CONTROLLING INFECTIOUS DISEASES. 36 SUMMARY. 37 SUMMARY TO
CHAPTER 1. 37 CHAPTER 2 INNATE IMMUNITY 39 THE FRONT LINE OF HOST
DEFENSE. 40 2-1 INFECTIOUS DISEASES ARE CAUSED BY DIVERSE LIVING AGENTS
THAT REPLICATE IN THEIR HOSTS. 41 2-2 INFECTIOUS AGENTS MUST OVERCOME
INNATE HOST DEFENSES TO ESTABLISH A FOCUS OF INFECTION. - 44 2-3 THE
EPITHELIAL SURFACES OF THE BODY MAKE UP THE FIRST LINES OF DEFENSE
AGAINST INFECTION. 46 2-4 AFTER ENTERING TISSUES, MANY PATHOGENS ARE
RECOGNIZED, INGESTED, AND KILLED BY PHAGOCYTES. 48 2-5 PATHOGEN
RECOGNITION AND TISSUE DAMAGE INITIATE AN INFLAMMATORY RESPONSE. 50
SUMMARY. 52 PATTERN RECOGNITION IN THE INNATE IMMUNE SYSTEM. 53 2-6
RECEPTORS WITH SPECIFICITY FOR PATHOGEN MOLECULES RECOGNIZE PATTERNS OF
REPEATING STRUCTURAL MOTIFS. 54 2-7 THE TOLL-LIKE RECEPTORS ARE
SIGNALING RECEPTORS THAT DISTINGUISH DIFFERENT TYPES OF PATHOGEN AND
HELP DIRECT AN APPROPRIATE IMMUNE RESPONSE. 56 2-8 THE EFFECTS OF
BACTERIAL LIPOPOLYSACCHARIDE ON MACROPHAGES ARE MEDIATED BY CD14 BINDING
TO TLR-4. 57 2-9 THE NOD PROTEINS ACT AS INTRACELLULAR SENSORS OF
BACTERIAL INFECTION. 58 2-10 ACTIVATION OF TOLL-LIKE RECEPTORS AND NOD
PROTEINS TRIGGERS THE PRODUCTION OF PRO-INFLAMMATORY CYTOKINES AND
CHEMOKINES, AND THE EXPRESSION OF CO-STIMULATORY MOLECULES. 58 SUMMARY.-
59 THE COMPLEMENT SYSTEM AND INNATE IMMUNITY. 61 2-11 ' COMPLEMENT IS A
SYSTEM OF PLASMA PROTEINS THAT IS ACTIVATED BY THE PRESENCE OF
PATHOGENS. 61 2-12 COMPLEMENT INTERACTS WITH PATHOGENS TO MARK THEM FOR
DESTRUCTION BY PHAGOCYTES. 62 2-13 THE CLASSICAL PATHWAY IS INITIATED BY
ACTIVATION OF THE C1 COMPLEX. 64 2-14 THE LECTIN PATHWAY IS HOMOLOGOUS
TO THE CLASSICAL PATHWAY. 65 2-15 COMPLEMENT ACTIVATION IS LARGELY
CONFINED TO THE SURFACE ON WHICH IT IS INITIATED. 67 2-16 HYDROLYSIS OF
C3 CAUSES INITIATION OF THE ALTERNATIVE PATHWAY OF COMPLEMENT. 69 XIII
2-17 MEMBRANE AND PLASMA PROTEINS THAT REGULATE THE FORMATION AND
STABILITY OF C3 CONVERTASES DETERMINE THE EXTENT OF COMPLEMENT
ACTIVATION UNDER DIFFERENT CIRCUMSTANCES. 69 2-18 SURFACE-BOUND C3
CONVERTASE DEPOSITS LARGE NUMBERS OF C3B FRAGMENTS ON PATHOGEN SURFACES
AND GENERATES P5 CONVERTASE ACTIVITY. 73 2-19 INGESTION OF
COMPLEMENT-TAGGED PATHOGENS BY PHAGOCYTES IS MEDIATED BY RECEPTORS FOR
THE BOUND COMPLEMENT PROTEINS. ' 73 2-20 SMALL FRAGMENTS OF SOME
COMPLEMENT PROTEINS CAN INITIATE A LOCAL INFLAMMATORY RESPONSE. 75 2-21
THE TERMINAL COMPLEMENT PROTEINS POLYMERIZE TO FORM PORES IN MEMBRANES
THAT CAN KILL CERTAIN PATHOGENS. 75 2-22 COMPLEMENT CONTROL PROTEINS
REGULATE ALL THREE PATHWAYS OF COMPLEMENT ACTIVATION AND PROTECT THE
HOST FROM ITS DESTRUCTIVE EFFECTS. ' 78 SUMMARY. INDUCED INNATE
RESPONSES TO INFECTION. 2-23 ACTIVATED MACROPHAGES SECRETE A RANGE OF
CYTOKINES THAT 81 82 83 HAVE A VARIETY OF LOCAL AND DISTANT EFFECTS.
2-24 CHEMOKINES RELEASED BY PHAGOCYTES AND DENDRITIC CELLS RECRUIT CELLS
TO SITES OF INFECTION. , 83 2-25 CELL-ADHESION MOLECULES CONTROL
INTERACTIONS BETWEEN LEUKOCYTES AND ENDOTHELIAL CELLS DURING AN
INFLAMMATORY RESPONSE. 87 2-26 NEUTROPHILS MAKE UP THE FIRST WAVE OF
CELLS THAT CROSS THE BLOOD VESSEL WALL TO ENTER INFLAMMATORY SITES. 88
2-27 TNF-A IS AN IMPORTANT CYTOKINE THAT TRIGGERS LOCAL CONTAINMENT OF
INFECTION BUT INDUCES SHOCK WHEN RELEASED SYSTEMICALLY. 90 2-28
CYTOKINES RELEASED BY PHAGOCYTES ACTIVATE THE ACUTE-PHASE RESPONSE. 92
2-29 INTERTERONS INDUCED BY VIRAL INFECTION MAKE SEVERAL CONTRIBUTIONS
TO HOST DEFENSE. 94 2-30 NK CELLS ARE ACTIVATED BY INTERFERONS AND
MACROPHAGE-DERIVED CYTOKINES TO SERVE AS AN EARLY DEFENSE AGAINST
CERTAIN INTRACELLULAR INFECTIONS. 95 2-31 NK CELLS POSSESS RECEPTORS FOR
SELF MOLECULES THAT PREVENT THEIR ACTIVATION BY UNINFECTED CELLS. 96
2-32 NK CELLS BEAR RECEPTORS THAT ACTIVATE THEIR KILLER FUNCTION IN
RESPONSE TO LIGANDS EXPRESSED ON INFECTED CELLS OR TUMOR CELLS. 99 2-33
THE NKG2D RECEPTOR ACTIVATES A DIFFERENT SIGNALING PATHWAY FROM THAT OF
THE OTHER ACTIVATING NK RECEPTORS. 100 2-34 SEVERAL LYMPHOCYTE
SUBPOPULATIONS BEHAVE AS INNATE-LIKE LYMPHOCYTES. 100 SUMMARY. 102
SUMMARY TO CHAPTER 2. 103 IRTLL THE RECOGNITION OF ANTIGEN CHAPTER 3
ANTIGEN RECOGNITION BY B-CELL AND T-CELL RECEPTORS 111 THE STRUCTURE OF
A TYPICAL ANTIBODY MOLECULE. 112 3-1 IGG ANTIBODIES CONSIST OF FOUR
POLYPEPTIDE CHAINS. 113 3-2 IMMUNOGLOBULIN HEAVY AND LIGHT CHAINS ARE
COMPOSED OF CONSTANT AND VARIABLE REGIONS. 113 3-3 THE ANTIBODY MOLECULE
CAN READILY BE CLEAVED INTO FUNCTIONALLY DISTINCT FRAGMENTS. 114 3-4 THE
IMMUNOGLOBULIN MOLECULE IS FLEXIBLE, ESPECIALLY AT THE HINGE REGION. "
115 3-5 THE DOMAINS OF AN IMMUNOGLOBULIN MOLECULE HAVE SIMILAR.
STRUCTURES. 116 SUMMARY. 118 THE INTERACTION OF THE ANTIBODY MOLECULE
WITH SPECIFIC ANTIGEN. 118 3-6' LOCALIZED REGIONS OF HYPERVARIABLE
SEQUENCE FORM THE ANTIGEN-BINDING SITE. 118 3-7 ANTIBODIES BIND ANTIGENS
VIA CONTACTS WITH AMINO ACIDS IN CDRS, BUT THE DETAILS OF BINDING DEPEND
UPON THE SIZE AND SHAPE OF THE ANTIGEN. 119 3-8 ANTIBODIES BIND TO
CONFORMATIONAL SHAPES ON THE SURFACES OF ANTIGENS. 120 3-9
ANTIGEN-ANTIBODY INTERACTIONS INVOLVE A VARIETY OF FORCES. 121 SUMMARY.
122 ANTIGEN RECOGNITION BY T CELLS. 123 3-10 THE T-CELL RECEPTOR IS VERY
SIMILAR TO A FAB FRAGMENT OF IMMUNOGLOBULIN. 123 3-11 A T-CELL RECEPTOR
RECOGNIZES ANTIGEN IN THE FORM OF A COMPLEX OF A FOREIGN PEPTIDE BOUND
TO AN MHC MOLECULE. 125 3-12 THERE ARE TWO CLASSES OF MHC MOLECULES WITH
DISTINCT SUBUNIT COMPOSITION BUT SIMILAR THREE-DIMENSIONAL STRUCTURES.
126 3-13 PEPTIDES ARE STABLY BOUND TO MHC MOLECULES, AND ALSO SERVE TO
STABILIZE THE MHC MOLECULE ON THE CELL SURFACE. 128 3-14 MHC CLASS I
MOLECULES BIND SHORT PEPTIDES OF 8-10 AMINO ACIDS BY BOTH ENDS. 129 3-15
THE LENGTH OF THE PEPTIDES BOUND BY MHC CLASS II MOLECULES IS NOT
CONSTRAINED. 130 3-16 THE CRYSTAL STRUCTURES OF SEVERAL
MHC:PEPTIDE:T-CELL RECEPTOR COMPLEXES SHOW A SIMILAR T-CELL RECEPTOR
ORIENTATION OVER THE MHC:PEPTIDE COMPLEX. 132 3-17 THE CD4 AND CD8
CELL-SURFACE PROTEINS OF T CELLS ARE REQUIRED TO MAKE AN EFFECTIVE
RESPONSE TO ANTIGEN. 133 3-18 THE TWO CLASSES OF MHC MOLECULES ARE
EXPRESSED DIFFERENTIALLY ON CELLS. 135 3-19 A DISTINCT SUBSET OF T CELLS
BEARS AN ALTERNATIVE RECEPTOR MADE UP OF Y AND 5 CHAINS. 137 SUMMARY.
137 SUMMARY TO CHAPTER 3. 138 CHAPTER 4 THE GENERATION OF LYMPHOCYTE
ANTIGEN RECEPTORS 143 PRIMARY IMMUNOGLOBULIN GENE REARRANGEMENT 144 4-1
IMMUNOGLOBULIN GENES ARE REARRANGED IN * ANTJBODY-PRODUCING CELLS. 144
4-2 _ COMPLETE GENES THAT ENCODE A VARIABLE REGION ARE GENERATED BY THE
SOMATIC RECOMBINATION OF SEPARATE GENE SEGMENTS. 145 4-3 MULTIPLE
CONTIGUOUS V GENE SEGMENTS ARE PRESENT AT EACH IMMUNOGLOBULIN LOCUS. 146
4-4 REARRANGEMENT OF V, D, AND J GENE SEGMENTS IS GUIDED BY FLANKING DNA
SEQUENCES. 148 4-5 THE REACTION THAT RECOMBINES V, D, AND J GENE
SEGMENTS INVOLVES BOTH LYMPHOCYTE-SPECIFIC AND UBIQUITOUS DNA-MODIFYING
ENZYMES. 150 4-6 THE DIVERSITY OF THE IMMUNOGLOBULIN REPERTOIRE IS
GENERATED BY FOUR MAIN PROCESSES. 153 4-7 THE MULTIPLE INHERITED GENE
SEGMENTS ARE USED IN DIFFERENT COMBINATIONS. 153 [IV THE GENERATION OF
T-CELL RECEPTOR LIGANDS. 154 155 4-8 VARIABLE ADDITION AND SUBTRACTION
OF NUCLEOTIDES AT THE JUNCTIONS BETWEEN GENE SEGMENTS CONTRIBUTES TO THE
DIVERSITY OF THE THIRD HYPERVARIABLE REGION. SUMMARY. S T-CELL RECEPTOR
GENE REARRANGEMENT. 4-9 THE T-CELL RECEPTOR GENE SEGMENTS ARE ARRANGED
IN A SIMILAR PATTERN TO IMMUNOGLOBULIN GENE SEGMENTS AND ARE REARRANGED
BY THE SAME ENZYMES. 4-10 T-CELL RECEPTORS CONCENTRATE DIVERSITY IN THE
THIRD HYPERVARIABLE REGION. 4-11 Y.H T-CELL RECEPTORS ARE ALSO GENERATED
BY GENE REARRANGEMENT. SUMMARY. STRUCTURAL VARIATION IN IMMUNOGLOBULIN
CONSTANT REGIONS. 160 4-12 DIFFERENT CLASSES OF IMMUNOGLOBULINS ARE
DISTINGUISHED BY THE STRUCTURE OF THEIR HEAVY-CHAIN CONSTANT REGIONS.
4-13 THE CONSTANT REGION CONFERS FUNCTIONAL SPECIALIZATION ON THE
ANTIBODY. 161 4-14 MATURE NAIVE B CELLS EXPRESS BOTH IGM AND IGD AT
THEIR SURFACE. - 163 4-15 TRANSMEMBRANE AND SECRETED FORMS OF
IMMUNOGLOBULIN ARE GENERATED FROM ALTERNATIVE HEAVY-CHAIN TRANSCRIPTS.
IGM AND IGA CAN FORM POLYMERS. 163 164 166 4-16 SUMMARY. SECONDARY
DIVERSIFICATION OF THE ANTIBODY REPERTOIRE. 167 4-17 ACTIVATION-INDUCED
CYTIDINE DEAMINASE INTRODUCES MUTATIONS IN GENES TRANSCRIBED IN B CELLS.
168 4-18 REARRANGED V-REGION GENES ARE FURTHER DIVERSIFIED BY SOMATIC
HYPERMUTATION. 4-19 IN SOME SPECIES, MOST IMMUNOGLOBULIN GENE
DIVERSIFICATION OCCURS AFTER GENE REARRANGEMENT. 4-20 CLASS SWITCHING
ENABLES THE SAME ASSEMBLED VH EXON TO BE ASSOCIATED WITH DIFFERENT CH
GENES IN THE COURSE OF AN IMMUNE RESPONSE. SUMMARY. SUMMARY TO CHAPTER
4. CHAPTER 5 ANTIGEN PRESENTATION TO T LYMPHOCYTES 181 182 5-1 THE MHC
CLASS I AND CLASS II MOLECULES DELIVER PEPTIDES TO THE CELL SURFACE FROM
TWO INTRACELLULAR COMPARTMENTS. 182 5-2 PEPTIDES THAT BIND TO MHC CLASS
I MOLECULES ARE ACTIVELY TRANSPORTED FROM THE CYTOSOL TO THE ENDOPLASMIC
RETICULUM. 183 5-3 PEPTIDES FOR TRANSPORT INTO THE ENDOPLASMIC RETICULUM
ARE GENERATED IN THE CYTOSOL. 184 5-4 RETROGRADE TRANSPORT FROM THE
ENDOPLASMIC RETICULUM TO THE -' CYTOSOL ENABLES EXOGENOUS PROTEINS TO BE
PROCESSED FPR-CROSS- PRESENTATION BY MHC CLASS I MOLECULES. ** 186 5-5
NEWLY SYNTHESIZED MHC CLASS I MOLECULES ARE RETAINED IN THE ENDOPLASMIC
RETICULUM UNTIL THEY BIND A PEPTIDE. . 187 5-6 MANY VIRUSES PRODUCE
IMMUNOEVASINS THAT INTERFERE WITH ANTIGEN PRESENTATION BY MHC CLASS I
MOLECULES. . 189 5-7 PEPTIDES PRESENTED BY MHC CLASS II MOLECULES ARE
GENERATED IN ACIDIFIED ENDOCYTIC VESICLES. 190 5-8 THE INVARIANT CHAIN
DIRECTS NEWLY SYNTHESIZED MHC CLASS II MOLECULES TO ACIDIFIED
INTRACELLULAR VESICLES. 192 5-9 A SPECIALIZED MHC CLASS LL-LIKE MOLECULE
CATALYZES LOADING OF MHC CLASS II MOLECULES WITH PEPTIDES. 193 5-10 -
STABLE BINDING OF PEPTIDES BY MHC MOLECULES PROVIDES EFFECTIVE ANTIGEN
PRESENTATION AT THE CELL SURFACE. 194 SUMMARY. ' 195 155 THE MAJOR
HISTOCOMPATIBILITY COMPLEX AND ITS FUNCTIONS. 196 156 157 158 159 160
160 5-12 5-13 5-14 5-15 5-16 5-11 MANY PROTEINS INVOLVED IN ANTIGEN
PROCESSING AND PRESENTATION ARE ENCODED BY GENES WITHIN THE MAJOR
HISTOCOMPATIBILITY COMPLEX. 197 THE PROTEIN PRODUCTS OF MHC CLASS I ARID
CLASS II GENES ARE HIGHLY POLYMORPHIC. 199 MHC POLYMORPHISM AFFECTS
ANTIGEN RECOGNITION BY T CELLS BY INFLUENCING BOTH PEPTIDE BINDING AND
THE CONTACTS BETWEEN T-CELL RECEPTOR AND MHC MOLECULE. , 201
ALLOREACTIVE T CELLS RECOGNIZING NONSELF MHC MOLECULES ARE VERY
ABUNDANT. 204 MANY T CELLS RESPOND TO SUPERANTIGENS. 206 MHC
POLYMORPHISM EXTENDS THE RANGE OF ANTIGENS TO WHICH THE IMMUNE SYSTEM
CAN RESPOND. 207 5-17 A VARIETY OF GENES WITH SPECIALIZED FUNCTIONS IN
IMMUNITY ARE ALSO ENCODED IN THE MHC. 208 5-18 SPECIALIZED MHC CLASS I
MOLECULES ACT AS LIGANDSFOR THE ACTIVATION AND INHIBITION OF NK CELLS.
209 5-19 THE CD1 FAMILY OF MHC CLASS L-LIKE MOLECULES IS ENCODED OUTSIDE
THE MHC AND PRESENTS MICROBIAL LIPIDS TO CD1-RESTRICTED T CELLS. 211
SUMMARY. 212 SUMMARY TO CHAPTER 5. 212 THE DEVELOPMENT OF MATURE
LYMPHOCYTE RECEPTOR REPERTOIRES 169 171 171 175 175 FILIFF CHAPTER I 6
SIGNALING THROUGH IMMUNE SYSTEM RECEPTORS GENERAL PRINCIPLES OF SIGNAL
TRANSDUCTION. 6-1 TRANSMEMBRANE RECEPTORS CONVERT EXTRACELLULAR SIGNALS
INTO INTRACELLULAR BIOCHEMICAL EVENTS. 6-2 INTRACELLULAR SIGNAL
TRANSDUCTION OFTEN TAKES PLACE IN LARGE MULTIPROTEIN SIGNALING
COMPLEXES. 6-3 THE ACTIVATION OF SOME RECEPTORS.GENERATES SMALL-MOLECULE
SECOND MESSENGERS. 6-4 SMALL G PROTEINS ACT AS MOLECULAR SWITCHES IN
MANY DJFFERENT SIGNALING PATHWAYS. 6-5 SIGNALING PROTEINS ARE RECRUITED
TO THE MEMBRANE BY A VARIETY OF MECHANISMS. 6-6 SIGNAL TRANSDUCTION
PROTEINS ARE ORGANIZED IN THE PLASMA MEMBRANE IN STRUCTURES CALLED LIPID
RAFTS. 6-7 PROTEIN DEGRADATION HAS AN IMPORTANT ROLE IN TERMINATING
SIGNALING RESPONSES. SUMMARY. 219 220 220^ 221 222 224 224 225 226 227
ANTIGEN RECEPTOR SIGNALING AND LYMPHOCYTE ACTIVATION. 227 6-8 THE
VARIABLE CHAINS OF ANTIGEN RECEPTORS ARE ASSOCIATED WITH INVARIANT
ACCESSORY CHAINS THAT CARRY OUT THE SIGNALING FUNCTION OF THE RECEPTOR.
228 6-9 LYMPHOCYTES ARE EXTREMELY SENSITIVE TO THEIR SPECIFIC ANTIGENS.
229 XV 6-10 ANTIGEN BINDING LEADS TO PHOSPHORYLATION OF THE IT AM
SEQUENCES ASSOCIATED WITH THE ANTIGEN RECEPTORS. 231 6-11 IN T CELLS,
FULLY PHOSPHORYLATED ITAMS BIND THE KINASE ZAP-70 AND ENABLE IT TO BE
ACTIVATED. 233 6-12 ACTIVATED SYK AND ZAP-70 PHOSPHORYLATE SCAFFOLD
PROTEINS THAT MEDIATE MANY OF THE DOWNSTREAM EFFECTS OF ANTIGEN RECEPTOR
SIGNALING. . 233 6-13 PLC-Y IS ACTIVATED BY TEC TYROSINE KINASES. 234
6-14 ACTIVATION OF THE SMALL G PROTEIN RAS ACTIVATES A MAP KINASE
CASCADE, RESULTING IN THE PRODUCTION OF THE TRANSCRIPTION FACTOR AP-1.
235 6-15 THE TRANSCRIPTION FACTOR NFAT IS INDIRECTLY ACTIVATED BY CA 2+
. 236 6-16 THE TRANSCRIPTION FACTOR NFKB IS ACTIVATED BY THE ACTIONS OF
PROTEIN KINASE C. 237 6-17 THE LOGIC OF B-CELL RECEPTOR SIGNALING IS
SIMILAR TO THAT OF T-CELL RECEPTOR SIGNALING BUT SOME OF THE SIGNALING
COMPONENTS ARE SPECIFIC TO B CELLS. 239 6-18 ITAMS ARE ALSO FOUND IN
OTHER RECEPTORS ON LEUKOCYTES THAT SIGNAL FOR CELL ACTIVATION. 240 6-19
THE CELL-SURFACE PROTEIN CD28 IS A CO-STIMULATORY RECEPTOR FOR NAIVE T
CELLS. 240 6-20 INHIBITORY RECEPTORS ON LYMPHOCYTES HELP REGULATE IMMUNE
RESPONSES. 242 SUMMARY. . 244 OTHER RECEPTORS AND SIGNALING PATHWAYS.
244 6-21 CYTOKINES TYPICAJLY ACTIVATE FAST'SIGNALING PATHWAYS THAT END
IN THE NUCLEUS. 245 6-22 CYTOKINE RECEPTORS FORM DIMERS OR TRIMERS ON
LIGAND BINDING. 245 6-23 CYTOKINE RECEPTORS ARE ASSOCIATED WITH THE JAK
FAMILY OF TYROSINE KINASES WHICH ACTIVATE STAT TRANSCRIPTION FACTORS.
245 6-24 CYTOKINE SIGNALING IS TERMINATED BY A NEGATIVE FEEDBACK
MECHANISM. 246 6-25 THE RECEPTORS THAT INDUCE APOPTOSIS ACTIVATE
SPECIALIZED INTRACELLULAR PROTEASES CALLED CASPASES. 247 6-26 THE
INTRINSIC PATHWAY OF APOPTOSIS IS MEDIATED BY RELEASE OF CYTOCHROME C
FROM MITOCHONDRIA. 249 6-27 MICROBES AND THEIR PRODUCTS ACT VIA
TOLL-LIKE RECEPTORS TO ACTIVATE NFKB. 249 6-28 BACTERIAL PEPTIDES,
MEDIATORS OF INFLAMMATORY RESPONSES, AND CHEMOKINES SIGNAL THROUGH
MEMBERS OF THE G-PROTEIN-COUPLED RECEPTOR FAMILY. 251 SUMMARY. 253
SUMMARY TO CHAPTER 6. 3 253 CHAPTER 7 THE DEVELOPMENT AND SURVIVAL OF
LYMPHOCYTES 257 DEVELOPMENT OF B LYMPHOCYTES 259 7-1 LYMPHOCYTES DERIVE
FROM HEMATOPOIETIC STEM CELLS IN THE BONE MARROW. - 259 ' 7-2 B-CELL
DEVELOPMENT BEGINS BY REARRANGEMENT OF THE . -"' HEAVY-CHAIN LOCUS. -^
262 7-3 THE PRE-B-CELL RECEPTOR TESTS FOR SUCCESSFUL PRODUCTION OF A
COMPLETE HEAVY CHAIN AND SIGNALS FOR PROLIFERATION OF PRO-B CELLS. ; '
264 7-4 PRE-B-CELL RECEPTOR SIGNALING INHIBITS FURTHER HEAVY-CHAIN LOCUS
REARRANGEMENT AND ENFORCES ALLELIC EXCLUSION. 266 7-5 PRE-B CELLS
REARRANGE THE LIGHT-CHAIN LOCUS AND EXPRESS CELL-SURFACE IMMUNOGLOBULIN.
266 7-6 IMMATURE B CELLS ARE TESTED FOR AUTOREACTIVITY BEFORE THEY LEAVE
THE BONE MARROW. 268 SUMMARY. 272 T-CELL DEVELOPMENT IN THE THYMUS. 273
7-7 T-CELL PROGENITORS ORIGINATE IN THE BONE MARROW, BUT ALL THE
IMPORTANT EVENTS IN THEIR DEVELOPMENT OCCUR IN THE THYMUS. 274 7-8
T-CELL PRECURSORS PROLIFERATE EXTENSIVELY IN THE THYMUS BUT ~ J MOST DIE
THERE. 275 7-9 SUCCESSIVE STAGES IN THE DEVELOPMENTS THYMOCYTES ARE
MARKED BY CHANGES IN CELL-SURFACE MOLECULES. 277 7-10 THYMOCYTES AT
DIFFERENT DEVELOPMENTAL STAGES ARE FOUND IN DISTINCT PARTS OF THE
THYMUS. 279 7-11 T CELLS WITH A:(3 OR J. 8 RECEPTORS ARISE FROM A COMMON
PROGENITOR. 280 7-12 T CELLS EXPRESSING PARTICULAR Y- AND 5-CHAIN V
REGIONS ARISE IN AN ORDERED SEQUENCE EARLY IN LIFE. 282 7-13 SUCCESSFUL
SYNTHESIS OF A REARRANGED P CHAIN ALLOWS THE PRODUCTION OF A PRE-T-CELL
RECEPTOR THAT TRIGGERS CELL PROLIFERATION AND BLOCKS FURTHER P-CHAIN
GENE REARRANGEMENT. 283 7-14 T-CELL A-CHAIN GENES UNDERGO SUCCESSIVE
REARRANGEMENTS UNTIL POSITIVE SELECTION OR CELL DEATH INTERVENES. 286
SUMMARY. 288 POSITIVE AND NEGATIVE SELECTION OF T CELLS. 288 7-15 THE
MHC TYPE OF THE THYMIC STROMA SELECTS A REPERTOIRE OF MATURE T CELLS
THAT CAN RECOGNIZE FOREIGN ANTIGENS PRESENTED BY THE SAME MHC TYPE. *
289 7-16 ONLY THYMOCYTES WHOSE RECEPTORS INTERACT WITH
SELF-PEPTIDE:SELF-MHC COMPLEXES CAN SURVIVE AND MATURE. 290 7-17
POSITIVE SELECTION ACTS ON A REPERTOIRE OF T-CELL RECEPTORS WITH
INHERENT SPECIFICITY FOR MHC MOLECULES. 291 7-18 POSITIVE SELECTION
COORDINATES THE EXPRESSION OF CD4 OR CD8 WITH THE SPECIFICITY OF THE
T-CELL RECEPTOR AND THE POTENTIAL EFFECTOR FUNCTIONS OF THE T CELL. 292
7-19 THYMIC CORTICAL EPITHELIAL CELLS MEDIATE POSITIVE SELECTION OF
DEVELOPING THYMOCYTES. 293 7-20 T CELLS THAT REACT STRONGLY WITH
UBIQUITOUS SELF ANTIGENS ARE DELETED IN THE THYMUS. 294 7-21 NEGATIVE
SELECTION IS DRIVEN MOST EFFICIENTLY BY BONE MARROW DERIVED
ANTIGEN-PRESENTING CELLS. 296 7-22 THE SPECIFICITY AND/OR THE STRENGTH
OF SIGNALS FOR NEGATIVE AND POSITIVE SELECTION MUST DIFFER. 297 SUMMARY.
298 SURVIVAL AND MATURATION OF LYMPHOCYTES IN PERIPHERAL LYMPHOID
TISSUES. 299 7-23 DIFFERENT LYMPHOCYTE SUBSETS ARE FOUND IN PARTICULAR
LOCATIONS IN PERIPHERAL LYMPHOID TISSUES. 299 * - 7-24 THE-DEVELOPMENT
AND ORGANIZATION OF PERIPHERAL LYMPHOID TISSUES ARE CONTROLLED BY
PROTEINS OF THE TUMOR NECROSIS FACTOR FAMILY. 300 7-25 THE HOMING OF
LYMPHOCYTES TO SPECIFIC REGIONS OF PERIPHERAL LYMPHOID TISSUES IS
MEDIATED BY CHEMOKINES. 302 7-26 LYMPHOCYTES THAT ENCOUNTER SUFFICIENT
QUANTITIES OF SELF ANTIGENS FOR THE FIRST TIME IN THE PERIPHERY ARE
ELIMINATED OR INACTIVATED. 303 7-27 MOST IMMATURE B CELLS ARRIVING IN
THE SPLEEN ARE SHORT-LIVED AND REQUIRE CYTOKINES AND POSITIVE SIGNALS
THROUGH THE B-CELL RECEPTOR FOR MATURATION AND SURVIVAL. 304 7-28 B-1
CELLS AND MARGINAL ZONE B CELLS ARE DISTINCT B-CELL SUBTYPES WITH UNIQUE
ANTIGEN RECEPTOR SPECIFICITY. 306 7-29 T-CELL HOMEOSTASIS IN THE
PERIPHERY IS REGULATED BY CYTOKINES AND SELF-MHC INTERACTIONS. 307
SUMMARY. 307 XVI LYMPHOID TUMORS. 308 7-30 B-CELL TUMORS OFTEN OCCUPY
THE SAME SITE AS THEIR NORMAL COUNTERPARTS. 308 7-31 T-CELL TUMORS
CORRESPOND TO A SMALL NUMBER OF STAGES OF T-CELL DEVELOPMENT. S 311 7-32
B-CELL LYMPHOMAS FREQUENTLY CARRY CHROMOSOMAL TRANSLOCATIONS THAT JOIN
IMMUNOGLOBULIN LOCI TO GENES THAT REGULATE CELL GROWTH. 312 SUMMARY. 312
SUMMARY TO CHAPTER 7. 313 PART IV THE ADAPTIVE IMMUNE RESPONSE CHAPTER 8
T CELL-MEDIATED IMMUNITY 323 ENTRY OF NAIVE T CELLS AND
ANTIGEN-PRESENTING CELLS INTO PERIPHERAL LYMPHOID ORGANS. 325 8-1 NAIVE
T CELLS MIGRATE THROUGH PERIPHERAL LYMPHOID TISSUES, SAMPLING THE
PEPTIDE:MHC COMPLEXES ON DENDRITIC CELL SURFACES. 325 8-2 LYMPHOCYTE
ENTRY INTO LYMPHOID TISSUES DEPENDS ON CHEMOKINES AND ADHESION
MOLECULES. 326 8-3 ACTIVATION OF INTEGRINS BY CHEMOKINES IS RESPONSIBLE
FOR THE ENTRY OF NAIVE T CELLS INTO LYMPH NODES. 327 8-4 T-CELL
RESPONSES ARE INITIATED IN PERIPHERAL LYMPHOID ORGANS BY ACTIVATED
DENDRITIC CELLS. ^ 331 8-5 THERE ARE TWO DIFFERENT FUNCTIONAL CLASSES OF
DENDRITIC CELLS. 332 8-6 DENDRITIC CELLS PROCESS ANTIGENS FROM A WIDE
ARRAY OF PATHOGENS. 334 8-7 PATHOGEN-INDUCED TLR SIGNALING IN IMMATURE
DENDRITIC CELLS INDUCES THEIR MIGRATION TO LYMPHOID ORGANS AND ENHANCES
ANTIGEN PROCESSING. 336 8-8 PLASMACYTOID DENDRITIC CELLS DETECT VIRAL
INFECTIONS AND GENERATE ABUNDANT TYPE I INTERFERONS AND PRO-INFLAMMATORY
CYTOKINES. 338 8-9 MACROPHAGES ARE SCAVENGER CELLS THAT CAN BE " INDUCED
BY PATHOGENS TO PRESENT FOREIGN ANTIGENS TO NAIVE T CELLS. 339 8-10 B
CELLS ARE HIGHLY EFFICIENT AT PRESENTING ANTIGENS THAT BIND TO THEIR
SURFACE IMMUNOGLOBULIN. 340 SUMMARY. 342 PRIMING OF NAIVE T CELLS BY
PATHOGEN-ACTIVATED DENDRITIC CELLS. 343. 8 : 11 CELL-ADHESION MOLECULES
MEDIATE THE INITIAL INTERACTION OF NAIVE T CELLS WITH ANTIGEN-PRESENTING
CELLS. 343 8-12 ANTIGEN-PRESENTING CELLS DELIVER THREE KINDS OF SIGNALS
_ FOR CLONAL EXPANSION AND DIFFERENTIATION OF NAIVE T,CELLSL 344 8-13
CD28-DEPENDENT CO-STIMULATION OF ACTIVATED T CELLS INDUCES EXPRESSION OF
THE T-CELL GROWTH FACTOR INTERLEUKIN-2 AND THE HIGH-AFFINITY IL-2
RECEPTOR. 345 8-14 SIGNAL 2 CAN BE MODIFIED BY ADDITIONAL CO-STIMULATORY
PATHWAYS. . * 346 8-15 ANTIGEN RECOGNITION IN THE ABSENCE OF
CO-STIMULATION I EADS TO FUNCTIONAL INACTIVATION OR CLONAL DELETION OF
PERIPHERAL T CELLS. 347 8-16 PROLIFERATING T CELLS DIFFERENTIATE INTO
EFFECTOR T CELLS THAT DO NOT REQUIRE CO-STIMULATION TO ACT. 349 8-17
8-18 T CELLS DIFFERENTIATE INTO SEVERAL SUBSETS OF FUNCTIONALLY
DIFFERENT EFFECTOR CELLS. 349 CD8 T CELLS CAN-BE ACTIVATED IN DIFFERENT
WAYS TO BECOME CYTOTOXIC EFFECTOR CELLS. 352 8-19 VARIOUS FORMS OF
SIGNAL 3 INDUCE THE DIFFERENTIATION OF NAIVE CD4 T CELLS DOWN DISTINCT
EFFECTOR PATHWAYS. 352 8-20 REGULATORY CD4 T CELLS ARE INVOLVED IN
CONTROLLING ADAPTIVE IMMUNE RESPONSES. - 354 SUMMARY. 356 GENERAL
PROPERTIES OF EFFECTOR T CELLS AND THEIR CYTOKINES. 356 8-21 EFFECTOR
T-CELL INTERACTIONS WITH TARGET CELLS ARE INITIATED BY
ANTIGEN-NONSPECIFIC CELL-ADHESION MOLECULES. 357 8-22 BINDING OF THE
T-CELL RECEPTOR COMPLEX DIRECTS THE RELEASE OF EFFECTOR MOLECULES AND
FOCUSES THEM ON THE TARGET CELL. 357 8-23 THE EFFECTOR FUNCTIONS OF T
CELLS ARE DETERMINED BY THE ARRAY OF EFFECTOR MOLECULES THAT THEY
PRODUCE. 358 8-24 CYTOKINES CAN ACT LOCALLY OR AT A DISTANCE. 359 8-25
CYTOKINES AND THEIR RECEPTORS FALL INTO DISTINCT FAMILIES OF
STRUCTURALLY RELATED PROTEINS. 361 8-26 THE TNF FAMILY OF CYTOKINES ARE
TRIMERIC PROTEINS THAT ARE USUALLY ASSOCIATED WITH THE CELL SURFACE. 362
SUMMARY. 363 T CELL-MEDIATED CYTOTOXICITY. 364 8-27 CYTOTOXIC T CELLS
CAN INDUCE TARGET CELLS TO UNDERGO PROGRAMMED CELL DEATH. ' 364 8-28
CYTOTOXIC EFFECTOR PROTEINS THAT TRIGGER APOPTOSIS ARE CONTAINED IN THE
GRANULES OF CD8 CYTOTOXIC T CELLS. 365 8-29 CYTOTOXIC T CELLS ARE
SELECTIVE AND SERIAL KILLERS OF TARGETS EXPRESSING A SPECIFIC ANTIGEN.
367 8-30 CYTOTOXIC T CELLS ALSO ACT BY RELEASING CYTOKINES. 368 SUMMARY.
368 MACROPHAGE ACTIVATION BY T H 1 CELLS. 368 8-31 TH1 CELLS HAVE A
CENTRAL ROLE IN MACROPHAGE ACTIVATION. 369 8-32 ACTIVATION OF
MACROPHAGES BY TH1 CELLS PROMOTES MICROBIAL KILLING AND MUST BE TIGHTLY
REGULATED TO AVOID TISSUE DAMAGE. 370 8-33 TH1 CELLS COORDINATE THE HOST
RESPONSE TO INTRACELLULAR PATHOGENS. 371 SUMMARY. 372 SUMMARY TO CHAPTER
8. 372 CHAPTER 9 THE HUMORAL IMMUNE RESPONSE 379 B-CELL ACTIVATION AND
ANTIBODY PRODUCTION. 381 9-1 THE HUMORAL IMMUNE RESPONSE IS INITIATED
WHEN B CELLS THAT BIND ANTIGEN ARE SIGNALED BY HELPER T CELLS OR BYR
CERTAIN MICROBIAL ANTIGENS ALONE. 381 9-2 B-CELL RESPONSES TO ANTIGEN
ARE ENHANCED BY CO-LIGATION OF THE B-CELL CO-RECEPTOR. 382 9-3 HELPER T
CELLS ACTIVATE B CELLS THAT RECOGNIZE THE SAME ANTIGEN. 383 9-4
ANTIGENIC PEPTIDES BOUND TO SELF-MHC CLASS II MOLECULES ON B CELLS
TRIGGER HELPER T CELLS TO MAKE MEMBRANE-BOUND AND SECRETED MOLECULES
THAT CAN ACTIVATE A B CELL. 384 9-5 B CELLS THAT HAVE BOUND ANTIGEN VIA
THEIR B-CELL RECEPTOR ARE TRAPPED IN THE T-CELL ZONES OF SECONDARY
LYMPHOID TISSUES. 386 XVII 9-6 9-7 ANTIBODY-SECRETING PLASMA CELLS
DIFFERENTIATE FROM ACTIVATED B CELLS. 387 THE SECOND PHASE OF A PRIMARY
B-CELL IMMUNE RESPONSE OCCURS WHEN ACTIVATED B CELLS MIGRATE TO
FOLLICLES AND PROLIFERATE TO FORM GERMINAL CENTERS. I 388 9-8 GERMINAL
CENTER B CELLS UNDERGO V-REGION SOMATIC HYPERMUTATION, AND CELLS WITH
MUTATIONS THAT IMPROVE AFFINITY FOR ANTIGEN ARE SELECTED. 390 9-9 CLASS
SWITCHING IN THYMUS-DEPENDENT ANTIBODY RESPONSES REQUIRES EXPRESSION OF
CD40 LIGAND BY THE HELPER T CELL AND IS DIRECTED BY CYTOKINES. 392 9-10
LIGATION OF THE B-CELL RECEPTOR AND CD40, TOGETHER WITH DIRECT CONTACT
WITH T CELLS, ARE ALL REQUIRED TO SUSTAIN GERMINAL CENTER B CELLS. 394
9-11 SURVIVING GERMINAL CENTER B CELLS^DIFFERENTIATE INTO EITHER PLASMA
CELLS OR MEMORY CELLS. 395 9-12 B-CELL RESPONSES TO BACTERIAL ANTIGENS
WITH INTRINSIC ABILITY TO ACTIVATE B CELLS DO NOT REQUIRE T-CELL HELP.
396 9-13 B-CELL RESPONSES TO BACTERIAL POLYSACCHARIDES DO NOT REQUIRE
PEPTIDE-SPECIFIC T-CELL HELP. 397 SUMMARY. 399 THE DISTRIBUTION AND
FUNCTIONS OF IMMUNOGLOBULIN ISOTYPES. 400 9-14 ANTIBODIES OF DIFFERENT
ISOTYPES OPERATE IN DISTINCT PLACES AND HAVE DISTINCT EFFECTOR
FUNCTIONS. 400 9-15 TRANSPORT PROTEINS THAT BIND TO THE FC REGIONS OF
ANTIBODIES CARRY PARTICULAR ISOTYPES ACROSS EPITHELIAL BARRIERS. 402
9-16 HIGH-AFFINITY IGG AND IGA ANTIBODIES CAN NEUTRALIZE BACTERIAL
TOXINS. 404 9-17 HIGH-AFFINITY IGG AND IGA ANTIBODIES CAN INHIBIT THE
INFECTIVITY OF VIRUSES. 405 9-18 ANTIBODIES CAN BLOCK THE ADHERENCE OF
BACTERIA TO HOST CELLS. 406 9-19 ANTIBODY:ANTIGEN COMPLEXES ACTIVATE THE
CLASSICAL PATHWAY OF COMPLEMENT BY BINDING TO C1Q. . 406 9-20 COMPLEMENT
RECEPTORS ARE IMPORTANT IN THE REMOVAL OF IMMUNE COMPLEXES FROM THE
CIRCULATION. , 408 SUMMARY. 409 THE DESTRUCTION OF ANTIBODY-COATED
PATHOGENS VIA FC RECEPTORS. 409 9-21 THE FC RECEPTORS OF ACCESSORY CELLS
ARE SIGNALING RECEPTORS SPECIFIC FOR IMMUNOGLOBULINS OF DIFFERENT
CLASSES. 410 9-22 FC RECEPTORS ON PHAGOCYTES-ARE ACTIVATED BY ANTIBODIES
BOUND TO THE SURFACE OF PATHOGENS AND ENABLE THE PHAGOCYTES TO INGEST
AND DESTROY PATHOGENS. 411 9-23 FC RECEPTORS ACTIVATE NK CELLS TO
DESTROY ANTIBODY-COATED TARGETS. 412 9-24 MAST CELLS, BASOPHILS, AND
ACTIVATED EOSINOPHILS BIND IGE ANTIBODY VIA THE HIGH-AFFINITY FEE
RECEPTOR. 413 - 9-25 IGE-MEDIATED ACTIVATION OF ACCESSORY CELLS HAS AN
IMPORTANT ROLE IN RESISTANCE TO PARASITE INFECTION. ^ 414 SUMMARY. 415
SUMMARY TO CHAPTER 9. 416 CHAPTER 10 DYNAMICS OF ADAPTIVE IMMUNITY 421
THE COURSE OF THE IMMUNE RESPONSE TO INFECTION. 422 10-1 THE COURSE OF
AN INFECTION CAN BE DIVIDED INTO SEVERAL DISTINCT PHASES. 422 10-2 THE
NONSPECIFIC RESPONSES OF INNATE IMMUNITY ARE NECESSARY FOR AN ADAPTIVE
IMMUNE RESPONSE TO BE INITIATED. . 425 10-3 CYTOKINES MADE IN THE
EARLIEST PHASE OF AN INFECTION INFLUENCE DIFFERENTIATION OF CD4 T CELLS
TOWARD THE T H 17 SUBSET. ' 426 10-4' CYTOKINES MADE IN THE LATER STAGES
OF AN INFECTION INFLUENCE DIFFERENTIATION OF CD4 T CELLS TOWARD TH1 OR T
H 2 CELLS. 427 10-5 THE DISTINCT SUBSETS OF CD4 T CELLS CAN REGULATE
EACH OTHER'S DIFFERENTIATION. 430 10-6 EFFECTOR T CELLS ARE GUIDED TO
SITES OF INFECTION BY CHEMOKINES AND NEWLY EXPRESSED ADHESION MOLECULES.
432 10-7 DIFFERENTIATED EFFECTOR T CELLS ARE NOT A STATIC POPULATION BUT
CONTINUE TO RESPOND TO SIGNALS AS THEY CARRY OUT THEIR EFFECTOR
FUNCTIONS. 434 10-8 PRIMARY CD8 T-CELL RESPONSES TO PATHOGENS CAN OCCUR
IN THE ABSENCE OF CD4 HELP. 435 10-9 ANTIBODY RESPONSES DEVELOP IN
LYMPHOID TISSUES UNDER THE DIRECTION OF CD4 HELPER T CELLS. 437 10-10
ANTIBODY RESPONSES ARE SUSTAINED IN MEDULLARY CORDS AND BONE MARROW. 438
10-11 THE EFFECTOR MECHANISMS USED TO CLEAR AN INFECTION DEPEND ON THE
INFECTIOUS AGENT. 439 10-12 RESOLUTION OF AN INFECTION IS ACCOMPANIED BY
THE DEATH OF MOST OF THE EFFECTOR CELLS AND THE GENERATION OF MEMORY
CELIS. - 441 SUMMARY. 441 IMMUNOLOGICAL MEMORY 442 10-13 IMMUNOLOGICAL
MEMORY IS LONG-LIVED AFTER INFECTION OR VACCINATION. 442 10-14 MEMORY
B-CELL RESPONSES DIFFER IN SEVERAL WAYS FROM THOSE OF NAIVE B CELLS. 444
10-15 REPEATED IMMUNIZATION LEADS TO INCREASING AFFINITY OF ANTIBODY DUE
TO SOMATIC HYPERMUTATION AND SELECTION BY ANTIGEN IN GERMINAL CENTERS.
445 10-16 MEMORY T CELLS ARE INCREASED IN FREQUENCY COMPARED WITH NAIVE
T CELLS SPECIFIC FOR THE SAME ANTIGEN AND HAVE DISTINCT ACTIVATION
REQUIREMENTS AND CELL-SURFACE PROTEINS THAT DISTINGUISH THEM FROM
EFFECTOR T CELLS. 446 10-17 MEMORY T CELLS ARE HETEROGENEOUS AND INCLUDE
CENTRAL MEMORY AND EFFECTOR MEMORY SUBSETS. 449 10-18 CD4 T-CELL HELP IS
REQUIRED FOR CD8 T-CELL MEMORY AND INVOLVES CD40 AND IL-2 SIGNALING. 450
10-19 IN IMMUNE INDIVIDUALS, SECONDARY AND SUBSEQUENT RESPONSES ARE
MAINLY ATTRIBUTABLE TO MEMORY LYMPHOCYTES. 452 SUMMARY, ,, 453 SUMMARY
TO CHAPTER 10. 454 CHAPTER 11 THE MUCOSAL IMMUNE SYSTEM 459 THE
ORGANIZATION OF THE MUCOSAL IMMUNE SYSTEM. 459 11-1 THE MUCOSAL IMMUNE
SYSTEM PROTECTS THE INTERNAL SURFACES OF THE BODY. 4459 11-2 THE MUCOSAL
IMMUNE SYSTEM MAY BE THE ORIGINAL VERTEBRATE IMMUNE SYSTEM. 461 11-3
MUCOSA-ASSOCIATED LYMPHOID TISSUE IS LOCATED IN ANATOMICALLY DEFINED
COMPARTMENTS IN THE GUT. 462 11-4 THE INTESTINE HAS DISTINCTIVE ROUTES
AND MECHANISMS OF ANTIGEN UPTAKE. 464 CVIII 11 -5 THE MUCOSAL IMMUNE
SYSTEM CONTAINS LARGE NUMBERS OF EFFECTOR LYMPHOCYTES EVEN IN THE
ABSENCE OF DISEASE. 466 11 -6 THE CIRCULATION OF LYMPHOCYTES WITHIN THE
MUCOSAL IMMUNE SYSTEM IS CONTROLLED BY TISSUE-SPECIFIC ADHESION
MOLECULES AND CHEMOKINE RECEPTORS. T 467 11-7 PRIMING OF LYMPHOCYTES IN
ONE MUCOSAL TISSUE CAN INDUCE PROTECTIVE IMMUNITY AT OTHER MUCOSAL
SURFACES. 469 11 -8 SECRETORY IGA IS THE CLASS OF ANTIBODY ASSOCIATED
WITH THE MUCOSAL IMMUNE SYSTEM. 469 11-9 IGA DEFICIENCY IS COMMON IN
HUMANS BUT MAY BE OVERCOME BY SECRETORY IGM. 472 11-10 THE MUCOSAL
IMMUNE SYSTEM CONTAINS UNUSUAL T LYMPHOCYTES. 472 SUMMARY. 475 THE
MUCOSAL RESPONSE TO INFECTION AND REGULATION OF MUCOSAL IMMUNE
RESPONSES. THE IMMUNE SYSTEM IN HEALTH AND DISEASE CHAPTER 12 FAILURES
OF HOST DEFENSE MECHANISMS 476 11-11 ENTERIC PATHOGENS CAUSE A LOCAL
INFLAMMATORY RESPONSE AND THE DEVELOPMENT OF PROTECTIVE IMMUNITY. 476
11-12 THE OUTCOME OF INFECTION BY INTESTINAL PATHOGENS IS DETERMINED BY
A COMPLEX INTERPLAY BETWEEN THE MICROORGANISM AND THE HOST IMMUNE
RESPONSE. 478 11-13 THE MUCOSAL IMMUNE SYSTEM MUST MAINTAIN A BALANCE
BETWEEN PROTECTIVE IMMUNITY AND HOMEOSTASIS TO A LARGE NUMBER OF
DIFFERENT FOREIGN ANTIGENS. 480 11-14 THE HEALTHY INTESTINE CONTAINS
LARGE QUANTITIES OF BACTERIA BUT DOES NOT GENERATE PRODUCTIVE IMMUNITY
AGAINST THEM. 482 11-15 FULL IMMUNE RESPONSES TO COMMENSAL BACTERIA
PROVOKE INTESTINAL DISEASE. ^ 485 11-16 INTESTINAL HELMINTHS PROVOKE
STRONG ^-MEDIATED IMMUNE RESPONSES. 485 11-17 OTHER EUKARYOTIC PARASITES
PROVOKE PROTECTIVE IMMUNITY AND PATHOLOGY IN THE GUT. 488 11-18
DENDRITIC CELLS AT MUCOSAL SURFACES FAVOR THE INDUCTION OF TOLERANCE
UNDER PHYSIOLOGICAL CONDITIONS AND MAINTAIN THE PRESENCE OF
PHYSIOLOGICAL INFLAMMATION. 488 SUMMARY. 489 SUMMARY TO CHAPTER 11. 490
497 EVASION AND SUBVERSION OF IMMUNE DEFENSES 498' 12-1 ANTIGENIC
VARIATION ALLOWS PATHOGENS TO ESCAPE FROM IMMUNITY. 498 12-2 SOME
VIRUSES PERSIST IN VIVO BY CEASING TO REPLICATE UNTIL IMMUNITY WANES.
.,-- 501 12-3 SOME PATHOGENS RESIST DESTRUCTION BY HOST DEFENSE
MECHANISMS OR EXPLOIT THEM FOR THEIR OWN PURPOSES. 502 12-4
IMMUNOSUPPRESSION OR INAPPROPRIATE IMMUNE RESPONSES CAN CONTRIBUTE TO
PERSISTENT DISEASE. 504 12-5 IMMUNE RESPONSES CAN CONTRIBUTE DIRECTLY TO
PATHOGENESIS. 506 12-6 REGULATORY T CELLS CAN AFFECT THE 1 OUTCOME OF
INFECTIOUS DISEASE. 506 SUMMARY. 507 IMMUNODEFICIENCY DISEASES. 507 12-7
A HISTORY OF REPEATED INFECTIONS SUGGESTS A DIAGNOSIS OF
IMMUNODEFICIENCY. ' 507 12-8 INHERITED IMMUNODEFICIENCY DISEASES ARE
CAUSED BY RECESSIVE GENE DEFECTS. * 508 12-9 THE MAIN EFFECT OF LOW
LEVELS OF ANTIBODY IS AN INABILITY TO CLEAR EXTRACELLULAR BACTERIA. 509
12-10 SOME ANTIBODY DEFICIENCIES CAN BE DUE TO DEFECTS IN EITHER B-CELL
OR T-CELL FUNCTION. 12-11 DEFECTS IN COMPLEMENT COMPONENTS CAUSE
DEFECTIVE HUMORAL IMMUNE FUNCTION. 512 514 12-12 DEFECTS IN PHAGOCYTIC
CELLS PERMIT WIDESPREAD BACTERIAL INFECTIONS. 515 12-13 DEFECTS IN
T-CELL DIFFERENTIATION CAN RESULT IN SEVERE COMBINED IMMUNODEFICIENCIES.
517 12-14 DEFECTS IN ANTIGEN RECEPTOR GENE REARRANGEMENT RESULT INSCID.
519 12-15 DEFECTS IN SIGNALING FROM T-CELL ANTIGEN RECEPTORS CAN CAUSE
SEVERE IMMUNODEFICIENCY. 520 12-16 GENETIC DEFECTS IN THYMIC FUNCTION
THAT BLOCK T-CELL DEVELOPMENT RESULT IN SEVERE IMMUNODEFICIENCIES. 520
12-17 THE NORMAL PATHWAYS FOR HOST DEFENSE AGAINST INTRACELLULAR
BACTERIA ARE PINPOINTED BY GENETIC DEFICIENCIES OF IFN-Y AND IL-12 AND
THEIR RECEPTORS. 522 12-18 X-LINKED LYMPHOPROLIFERATIVE SYNDROME IS
ASSOCIATED WITH FATAL INFECTION BY EPSTEIN-BARR VIRUS AND WITH THE
DEVELOPMENT OF LYMPHOMAS. 523 12-19 GENETIC ABNORMALITIES IN THE
SECRETORY CYTOTOXIC PATHWAY OF LYMPHOCYTES CAUSE UNCONTROLLED
LYMPHOPROLIFERATION AND INFLAMMATORY RESPONSES TO VIRAL INFECTIONS. 523
12-20 BONE MARROW TRANSPLANTATION OR GENE THERAPY CAN BE USEFUL TO
CORRECT GENETIC DEFECTS. 525 12-21 SECONDARY IMMUNODEFICIENCIES ARE
MAJOR PREDISPOSING CAUSES OF INFECTION AND DEATH. 526 SUMMARY. 527
ACQUIRED IMMUNE DEFICIENCY SYNDROME. 527 12-22 MOST INDIVIDUALS INFECTED
WITH HIV PROGRESS OVER TIME TO AIDS. 528 12-23 HIV IS A RETROVIRUS THAT
INFECTS CD4 T CELLS, DENDRITIC ^ CELLS, AND MACROPHAGES. 530 12-24
GENETIC VARIATION IN THE HOST CAN ALTER THE RATE OF PROGRESSION OF
DISEASE. 532 12-25 A GENETIC DEFICIENCY OF THE CO-RECEPTOR CCR5 CONFERS
RESISTANCE TO HIV INFECTION IN VIVO. 532 12-26 HIV RNA IS TRANSCRIBED BY
VIRAL REVERSE TRANSCRIPTASE INTO DNA THAT INTEGRATES INTO THE HOST-CELL
GENOME. 534 12-27 REPLICATION OF HIV OCCURS ONLY IN ACTIVATED T CELLS.
536 12-28 LYMPHOID TISSUE IS THE MAJOR RESERVOIR OF HIV INFECTION. 537
12-29 AN IMMUNE RESPONSE CONTROLS BUT DOES NOT ELIMINATE HIV. 538 12-30
THE DESTRUCTION OF IMMUNE FUNCTION AS A RESULT OF HIV INFECTION LEADS TO
INCREASED SUSCEPTIBILITY TO OPPORTUNISTIC INFECTION AND EVENTUALLY TO
DEATH. 540 12-31 DRUGS THAT BLOCK HIV REPLICATION LEAD TO A RAPID
DECREASE IN TITER OF INFECTIOUS VIRUS AND AN INCREASE IN CD4T CELLS. 540
12-32 HIV ACCUMULATES MANY MUTATIONS IN THE COURSE OF INFECTION, AND
DRUG TREATMENT IS SOON FOLLOWED BY THE OUTGROWTH OF DRUG-RESISTANT
VARIANTS. 542 12-33 VACCINATION AGAINST HIV IS AN ATTRACTIVE SOLUTION
BUT POSES MANY DIFFICULTIES. 543 XIX 12-34 PREVENTION AND EDUCATION ARE
ONE WAY IN WHICH THE SPREAD OF HIV AND AIDS CAN BE CONTROLLED. SUMMARY.
SUMMARY TO CHAPTER 12. CHAPTER 13 ALLERGY AND HYPERSENSITIVITY
SENSITIZATION AND THE PRODUCTION OF IGE. ALLERGENS ARE OFTEN DELIVERED
TRANSMUCOSALLY AT LOW DOSE, A ROUTE THAT FAVORS IGE PRODUCTION. ENZYMES
ARE FREQUENT TRIGGERS OF ALLERGY. CLASS SWITCHING TO IGE IN B
LYMPHOCYTES IS FAVORED BY SPECIFIC SIGNALS. BOTH GENETIC AND
ENVIRONMENTAL FACTORS CONTRIBUTE TO THE DEVELOPMENT OF IGE-MEDIATED
ALLERGY. REGULATORY T CELLS CAN CONTROL ALLERGIC RESPONSES. 13-1 13-2
13-3 13-4 13-5 SUMMARY. EFFECTOR MECHANISMS IN ALLERGIC REACTIONS. 13-6
MOST IGE IS CELL-BOUND AND ENGAGES EFFECTOR MECHANISMS OF THE IMMUNE
SYSTEM BY DIFFERENT PATHWAYS FROM OTHER ANTIBODY ISOTYPES. 13-7 MAST
CELLS RESIDE IN TISSUES AND ORCHESTRATE ALLERGIC REACTIONS. 13-8
EOSINOPHILS ARE NORMALLY UNDER TIGHT CONTROL TO PREVENT INAPPROPRIATE
TOXIC RESPONSES. 13-9 EOSINOPHILS AND BASOPHILS CAUSE INFLAMMATIONLND
TISSUE DAMAGE IN ALLERGIC REACTIONS. 13-10 ALLERGIC REACTIONS CAN BE
DIVIDED INTO IMMEDIATE AND LATE-PHASE RESPONSES. 13-11 THE CLINICAL
EFFECTS OF ALLERGIC REACTIONS VARY ACCORDING TO THE SITE OF MAST-CELL
ACTIVATION. 13-12 ALLERGEN INHALATION IS ASSOCIATED WITH THE
DEVELOPMENT' OF RHINITIS AND ASTHMA. 13-13 SKIN ALLERGY IS MANIFESTED AS
URTICARIA OR CHRONIC ECZEMA. 13-14 ALLERGY TO FOODS CAUSES SYSTEMIC
REACTIONS AS WELF' AS SYMPTOMS LIMITED TO THE GUT. *** 13-15 CELIAC
DISEASE IS A MODEL OF ANTIGEN-SPECIFIC * IMMUNOPATHOLOGY. H 13-16
ALLERGY CAN BE TREATED BY INHIBITING EITHER IGE PRODUCTION OR THE
EFFECTOR PATHWAYS ACTIVATED BY THE CROSS-LINKING OF CELL-SURFACE IGE. V
SUMMARY. I HYPERSENSITIVITY DISEASES. 13-17 INNOCUOUS ANTIGENS CAN CAUSE
TYPE II HYPERSENSITIVITY REACTIONS IN SUSCEPTIBLE INDIVIDUALS BY BINDING
TO THE SURFACES OF CIRCULATING BLOOD CELLS. 13-18 SYSTEMIC DISEASE
CAUSED BY IMMUNE-COMPLEX FORMATION CAN FOLLOW THE ADMINISTRATION OF
LARGE QUANTITIES OF POORLY CATABOLIZED ANTIGENS. 13-19 DELAYED-TYPE
HYPERSENSITIVITY REACTIONS ARE MEDIATED' BY TH1 CELLS AND CD8 CYTOTOXIC
T CELLS. 13-20 MUTATION IN THE MOLECULAR REGULATORS OF INFLAMMATION CAN
CAUSE HYPERSENSITIVE INFLAMMATORY RESPONSES RESULTING IN
'AUTOINFLAMMATORY DISEASE.' R Y 13-21 CROHN'S DISEASE IS A RELATIVELY
COMMON INFLAMMATORY DISEASE WITH A COMPLEX ETIOLOGY. SUMMARY. SUMMARY TO
CHAPTER 13. 545 545 546 555 557 557 558 559 560 565 565 566 567 567 569
571 571 572 574 576 577 578 580 583 583 583 583 585 588 590 591 591
CHAPTER 14 AUTOIMMUNITY AND TRANSPLANTATION 599 THE MAKING AND BREAKING
OF SELF-TOLERANCE 14-1 600 A CRITICAL FUNCTION OF THE IMMUNE SYSTEM IS
TO DISCRIMINATE SELF FROM NONSELF. 14-2 MULTIPLE TOLERANCE MECHANISMS
NORMALLY PREVENT AUTOIMMUNITY. CENTRAL DELETION OR INACTIVATION OF NEWLY
FORMED LYMPHOCYTES IS THE FIRST CHECKPOINT OF SELF-TOLERANCE.
LYMPHOCYTES THAT BIND SELF ANTIGENS WITH RELATIVELY LOW AFFINITY USUALLY
IGNORE THEM BUT IN SOME CIRCUMSTANCES BECOME ACTIVATED. ANTIGENS IN
IMMUNOLOGICALLY PRIVILEGED SITES DO NOT INDUCE IMMUNE ATTACK BUT CAN
SERVE AS TARGETS. AUTOREACTIVE T CELLS THAT EXPRESS PARTICULAR CYTOKINES
MAY BE NONPATHOGENIC OR MAY SUPPRESS PATHOGENIC LYMPHOCYTES. AUTOIMMUNE
RESPONSES CAN BE CONTROLLED AT VARIOUS STAGES BY REGULATORY T CELLS.
SUMMARY. 14-3 14-4 14-5 14-6 14-7 AUTOIMMUNE DISEASES AND PATHOGENIC
MECHANISMS. 14-8 SPECIFIC ADAPTIVE IMMUNE RESPONSES TO SELF ANTIGENS CAN
CAUSE AUTOIMMUNE DISEASE. 14-9 AUTOIMMUNE DISEASES CAN BE CLASSIFIED
INTO CLUSTERS THAT ARE TYPICALLY EITHER ORGAN-SPECIFIC OR SYSTEMIC.
14-10 MULTIPLE ASPECTS OF THE IMMUNE SYSTEM ARE TYPICALLY RECRUITED IN
AUTOIMMUNE DISEASE. 14-11 CHRONIC AUTOIMMUNE DISEASE DEVELOPS THROUGH
POSITIVE FEEDBACK FROM INFLAMMATION, INABILITY TO CLEAR THE SELF
ANTIGEN, AND A BROADENING OF THE AUTOIMMUNE RESPONSE. 14-12 BOTH
ANTIBODY AND EFFECTOR T CELLS CAN CAUSE TISSUE DAMAGE IN AUTOIMMUNE
DISEASE. 14-13 AUTOANTIBODIES AGAINST BLOOD CELLS PROMOTE THEIR
DESTRUCTION. 14-14 THE FIXATION OF SUBLYTIC DOSES OF COMPLEMENT TO CELLS
IN TISSUES STIMULATES A POWERFUL INFLAMMATORY RESPONSE. 14-15
AUTOANTIBODIES AGAINST RECEPTORS CAUSE DISEASE BY STIMULATING OR
BLOCKING RECEPTOR FUNCTION. 14-16 AUTOANTIBODIES AGAINST EXTRACELLULAR
ANTIGENS CAUSE INFLAMMATORY INJURY BY MECHANISMS AKIN TO TYPE II AND
TYPE III HYPERSENSITIVITY REACTIONS. 14-17 T CELLS SPECIFIC FOR SELF
ANTIGENS CAN CAUSE DIRECT TISSUE INJURY AND SUSTAIN AUTOANTIBODY
RESPONSES. SUMMARY. THE GENETIC AND ENVIRONMENTAL BASIS OF AUTOIMMUNITY.
14-18 AUTOIMMUNE DISEASES HAVE A STRONG GENETIC COMPONENT. 14-19 A
DEFECT IN A SINGLE GENE CAN CAUSE AUTOIMMUNE DISEASE. 14-20 SEVERAL
APPROACHES HAVE GIVEN US INSIGHT INTO THE GENETIC BASIS OF AUTOIMMUNITY.
14-21 GENES THAT PREDISPOSE TO AUTOIMMUNITY FALL INTO CATEGORIES THAT
AFFECT ONE OR MORE OF THE MECHANISMS OF TOLERANCE. 14-22 MHC GENES HAVE
AN IMPORTANT ROLE IN CONTROLLING SUSCEPTIBILITY TO AUTOIMMUNE DISEASE.
14-23 EXTERNAL EVENTS CAN INITIATE AUTOIMMUNITY. 14-24 INFECTION CAN
LEAD TO AUTOIMMUNE DISEASE BY PROVIDING AN ENVIRONMENT THAT PROMOTES
LYMPHOCYTE ACTIVATION. 14-25 CROSS-REACTIVITY BETWEEN FOREIGN MOLECULES
ON PATHOGENS AND SELF MOLECULES CAN LEAD TO ANTI-SELF RESPONSES AND
AUTOIMMUNE DISEASE. 600 602 603 603 605 606 607 609 610 610 611 612 615
617 617 619 620 621 622 625 626 626» 627 628 631 631 634 634 635 14-26
DRUGS AND TOXINS CAN CAUSE AUTOIMMUNE SYNDROMES. 14-27 RANDOM EVENTS MAY
BE REQUIRED FOR THE INITIATION OF AUTOIMMUNITY. SUMMARY. RESPONSES TO
ALLOANTIGENS AND TRANSPLANT REJECTION. 14-28 GRAFT REJECTION IS AN
IMMUNOLOGICAL RESPONSE MEDIATED PRIMARILY BY T CELLS. 14-29 MATCHING
DONOR AND RECIPIENT AT THE MHC IMPROVES THE OUTCOME OF TRANSPLANTATION.
14-30 IN MHC-IDENTICAL GRAFTS, REJECTION IS CAUSED BY PEPTIDES FROM
OTHER ALLOANTIGENS BOUND TO GRAFT MHC MOLECULES. 14-31 THERE ARE TWO
WAYS OF PRESENTING ALLOANTIGENS ON THE TRANSPLANT TO THE RECIPIENT'S T
LYMPHOCYTES. 14-32 ANTIBODIES REACTING WITH ENDOTHELIUM CAUSE HYPERACUTE
GRAFT REJECTION. 14-33 CHRONIC ORGAN REJECTION IS CAUSED BY INFLAMMATORY
VASCULAR INJURY TO THE GRAFT. 14-34 A VARIETY OF ORGANS ARE TRANSPLANTED
ROUTINELY IN CLINICAL MEDICINE. 14-35 14-36 THE CONVERSE OF GRAFT
REJECTION IS GRAFT-VERSUS-HOST DISEASE. REGULATORY T CELLS ARE INVOLVED
IN ALLOREACTIVE IMMUNE RESPONSES. 14-37 THE FETUS IS AN ALLOGRAFT THAT
IS TOLERATED REPEATEDLY. SUMMARY. SUMMARY TO CHAPTER 14. 636 637 637 637
638 639 640 641 642 643 644 645 646 647 648 648 CHAPTER 15 MANIPULATION
OF THE IMMUNE RESPONSE 655 1525 EXTRINSIC REGULATION OF UNWANTED IMMUNE
RESPONSES. 15-1 CORTICOSTEROIDS ARE POWERFUL ANTI-INFLAMMATORY DRUGS
THAT ALTER THE TRANSCRIPTION OF MANY GENES. 15-2 CYTOTOXIC DRUGS CAUSE
IMMUNOSUPPRESSION BY KILLING DIVIDING CELLS AND HAVE SERIOUS
SIDE-EFFECTS. 15-3 CYCLOSPORIN A, TACROLIMUS (FK506) R AND RAPAMYCIN
(SIROLIMUS) ARE POWERFUL IMMUNOSUPPRESSIVE AGENTS THAT INTERFERE WITH
T-CELL SIGNALING. 15-4 IMMUNOSUPPRESSIVE DRUGS ARE VALUABLE PROBES OF
INTRACELLULAR SIGNALING PATHWAYS IN LYMPHOCYTES. 15-5 ANTIBODIES AGAINST
CELL-SURFACE MOLECULES HAVE BEEN USED TO REMOVE SPECIFIC LYMPHOCYTE
SUBSETS OR TO INHIBIT CELL FUNCTION. 15-6 ANTIBODIES CAN BE ENGINEEREDTO
REDUCE THEIR IMMUNOGENICITY IN HUMANS. 15-7 MONOCLONAL ANTIBODIES CAN BE
USED TO PREVENT ALLOGRAFT REJECTION. 15-8 BIOLOGICAL AGENTS CAN BE USED
TO ALLEVIATE AND SUPPRESS AUTOIMMUNE DISEASE. 15-9 15-10 15-11 15-12
DEPLETION OR INHIBITION OF AUTOREACTIVE LYMPHOCYTES^CAN TREAT AUTOIMMUNE
DISEASE. INTERFERENCE WITH CO-STIMULATORY PATHWAYS FOR THE ^ '
ACTIVATION OF LYMPHOCYTES COULD BE A TREATMENT FOR"^ AUTOIMMUNE DISEASE.
INDUCTION OF REGULATORY T CELLS BY ANTIBODY THERAPY CAN INHIBIT
AUTOIMMUNE DISEASE. A NUMBER OF COMMONLY USED DRUGS HAVE
IMMUNOMODULATORY PROPERTIES. 15-13 CONTROLLED ADMINISTRATION OF ANTIGEN
CAN BE USED TO MANIPULATE THE NATURE OF AN ANTIGEN-SPECIFIC RESPONSE.
SUMMARY. 655 656 657 658 659 661 661 662 664 666 668 668 669 671 672
USING THE IMMUNE RESPONSE TO ATTACK TUMORS. 15-14 THE DEVELOPMENT OF
TRANSPLANTABLE TUMORS IN MICE LED TO THE DISCOVERY OF PROTECTIVE IMMUNE
RESPONSES TO TUMORS. 15-15 TUMORS CAN ESCAPE REJECTION IN MANY WAYS.
15-16 T LYMPHOCYTES CAN RECOGNIZE SPECIFIC ANTIGENS ON HUMAN TUMORS, AND
ADOPTIVE T-CELL TRANSFER IS BEING TESTED IN CANCER PATIENTS. 15-17
MONOCLONAL ANTIBODIES AGAINST TUMOR ANTIGENS, ALONE OR LINKED TO TOXINS,
CAN CONTROL TUMOR GROWTH] 15-18 ENHANCING THE IMMUNE RESPONSE TO TUMORS
BY VACCINATION HOLDS PROMISE FOR CANCER PREVENTION AND THERAPY. SUMMARY.
MANIPULATING THE IMMUNE RESPONSE TO FIGHT INFECTION. 15-19 THERE ARE
SEVERAL REQUIREMENTS FOR AN EFFECTIVE VACCINE. 15-20 THE HISTORY OF
VACCINATION AGAINST BORDETELLA PERTUSSIS ILLUSTRATES THE IMPORTANCE OF
DEVELOPING AN EFFECTIVE VACCINE THAT IS PERCEIVED TO BE SAFE. 15-21
CONJUGATE VACCINES HAVE BEEN DEVELOPED AS A RESULT OF UNDERSTANDING HOW
T AND B CELLS COLLABORATE IN AN IMMUNE RESPONSE. 15-22 THE USE OF
ADJUVANTS IS ANOTHER IMPORTANT APPROACH TO ENHANCING THE IMMUNOGENICITY
OF VACCINES. 15-23 LIVE-ATTENUATED VIRAL VACCINES ARE USUALLY MORE
POTENT THAN 'KILLED' VACCINES AND CAN BE MADE SAFER BY THE USE OF
RECOMBINANT DNA TECHNOLOGY. 15-24 LIVE-ATTENUATED BACTERIAL VACCINES CAN
BE DEVELOPED BY SELECTING NONPATHOGENIC OR DISABLED MUTANTS. SYNTHETIC
PEPTIDES OF PROTECTIVE ANTIGENS CAN ELICIT PROTECTIVE IMMUNITY. 15-26
THE ROUTE OF VACCINATION IS AN IMPORTANT DETERMINANT OF SUCCESS. 15-27
PROTECTIVE IMMUNITY CAN BE INDUCED BY INJECTING DNA ENCODING MICROBIAL
ANTIGENS AND HUMAN CYTOKINES INTO MUSCLE. 15-28 THE EFFECTIVENESS OF A
VACCINE CAN BE ENHANCED BY TARGETING IT TO SITES OF ANTIGEN
PRESENTATION. 15-29 AN IMPORTANT QUESTION IS WHETHER VACCINATION CAN BE
USED THERAPEUTICALLY TO CONTROL EXISTING CHRONIC INFECTIONS. 15-30
MODULATION OF THE IMMUNE SYSTEM MIGHT BE USED TO INHIBIT
IMMUNOPATHOLOGICAL RESPONSES TO INFECTIOUS AGENTS. SUMMARY. SUMMARY TO
CHAPTER 15. PART VI THE ORIGINS OF IMMUNE RESPONSES CHAPTER 16 EVOLUTION
OF THE IMMUNE SYSTEM EVOLUTION OF THE INNATE IMMUNE SYSTEM. THE
EVOLUTION OF THE IMMUNE SYSTEM CAN BE STUDIED BY COMPARING THE GENES
EXPRESSED BY DIFFERENT SPECIES. ANTIMICROBIAL PEPTIDES ARE LIKELY TO BE
THE MOST ANCIENT IMMUNE DEFENSES. TOLL-LIKE RECEPTORS MAY REPRESENT THE
MOST ANCIENT PATHOGEN-RECOGNITION SYSTEM. TOLL-LIKE RECEPTOR GENES HAVE
UNDERGONE EXTENSIVE DIVERSIFICATION IN SOME INVERTEBRATE SPECIES. 16-1
16-2 16-3 16-4 672 673 674 678 682 684 687 687 689 690 691 693 . 695 696
696 697 698 699 700 701 702 703 711 712 712 713 714 716 XXI 16-5 A
SECOND RECOGNITION SYSTEM IN DROSOPHILA HOMOLOGOUS TO THE MAMMALIAN TNF
RECEPTOR PATHWAY PROVIDES PROTECTION FROM GRAM-NEGATIVE BACTERIA. 717
16-6 AN ANCESTRAL COMPLEMENT SYSTEM OPSONIZES PATHOGENS FOR UPTAKE BY
PHAGOCYTIC CELLS. { 16-7 THE LECTIN PATHWAY OF COMPLEMENT ACTIVATION
EVOLVED IN INVERTEBRATES. SUMMARY. EVOLUTION OF THE ADAPTIVE IMMUNE
RESPONSE. 720 16-8 SOME INVERTEBRATES GENERATE EXTENSIVE DIVERSITY IN A
REPERTOIRE OF IMMUNOGLOBULIN-LIKE GENES. 721 16-9 AGNATHANS POSSESS AN
ADAPTIVE IMMUNE SYSTEM THAT USES SOMATIC GENE REARRANGEMENT TO DIVERSIFY
RECEPTORS BUILT FROM LRR DOMAINS. 722 16-10 ADAPTIVE IMMUNITY BASED ON A
DIVERSIFIED REPERTOIRE OF IMMUNOGLOBULIN-LIKE GENES APPEARED ABRUPTLY IN
THE CARTILAGINOUS FISH. 724 16-11 THE TARGET OF THE TRANSPOSON IS LIKELY
TO HAVE BEEN A GENE ENCODING A CELL-SURFACE RECEPTOR CONTAINING AN '
IMMUNOGLOBULIN-LIKE V DOMAIN. 725 16-12 DIFFERENT SPECIES GENERATE
IMMUNOGLOBULIN DIVERSITY IN DIFFERENT WAYS. 726 16-13 BOTH OC:P AND Y.H
T-CELL RECEPTORS ARE PRESENT IN CARTILAGINOUS FISH. 16-14 MHC CLASS I
AND CLASS II MOLECULES ARE ALSO FIRST FOUND IN THE CARTILAGINOUS FISHES.
SUMMARY. SUMMARY TO CHAPTER 16. APPENDIX I IMMUNOLOGISTS'TOOLBOX
IMMUNIZATION. A-1 HAPTENS. A-2 ROUTES OF IMMUNIZATION. A-3 EFFECTS OF
ANTIGEN DOSE. A-4 ADJUVANTS. THE DETECTION, MEASUREMENT, AND
CHARACTERIZATION OF ANTIBODIES AND THEIR USE AS RESEARCH AND DIAGNOSTIC
TOOLS. 740 A-5 AFFINITY CHROMATOGRAPHY. ' 741 A-6 RADIOIMMUNOASSAY
(RIA), ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA), AND
COMPETITIVE-INHIBITION ASSAY. 741 'A-7 HEMAGGLUTINATION AND BLOOD
TYPING. 743 ^*8 PRECIPITIN REACTION. 744 A-9 EQUILIBRIUM DIALYSIS:
MEASUREMENT OF ANTIBODY AFFINITY AND AVIDITY. 745 A-10
ANTI-IMMUNOGLOBULIN ANTIBODIES. . 746 A-11 COOMBS TESTS AND THE
DETECTION OF RHESUS INCOMPATIBILITY. 747 A-12 MONOCLONAL ANTIBODIES. 749
- A-13 PHAGE DISPLAY LIBRARIES FOR ANTIBODY V-REGION PRODUCTION. ^-' 750
A-14 IMMUNOFLUORESCENCE MICROSCOPY. '^ 751 A-15 IMMUNOELECTRON
MICROSCOPY. 753 A-16 IMMUNOHISTOCHEMISTRY. - 753 A-17
IMMUNOPRECIPITATION AND CO-IMMUNOPRECIPITATION. 754 A-18 IMMUNOBLOTTING
(WESTERN BLOTTING). 755 A-19 USE OF ANTIBODIES IN THE ISOLATION AND
IDENTIFICATION OF GENES AND THEIR PRODUCTS. ' 756 717 719 720 A-21 A-22
A-23 728 729 729 735 735 736 738 738 738 A-32 A-33 A-34 A-35 DETC A-36
A-37 A-38 A-39 A-40 A-41 ISOLATION OF LYMPHOCYTES. 758 A-20 ISOLATION OF
PERIPHERAL BLOOD LYMPHOCYTES BY FICOLL-HYPAQUE* GRADIENT. 758 ISOLATION
OF LYMPHOCYTES FROM TISSUES OTHER THAN BLOOD. 758 FLOW CYTOMETRY AND
FACS ANALYSIS. 759 LYMPHOCYTE ISOLATION USING ANTIBODY-COATED MAGNETIC
BEADS. 761 A-24 ISOLATION OF HOMOGENEOUS T-CELL LINES. 761
CHARACTERIZATION OF LYMPHOCYTE SPECIFICITY, FREQUENCY, AND FUNCTION. 762
A-25 LIMITING-DILUTION CULTURE. ' 763 A-26 ELISPOT ASSAYS. 763 A-27
IDENTIFICATION OF FUNCTIONAL SUBSETS OF T CELLS BY STAINING FOR
CYTOKINES. 764 A-28 IDENTIFICATION OF T-CELL RECEPTOR SPECIFICITY USING
MHC: PEPTIDE TETRAMERS. 765 A-29 ASSESSING THE DIVERSITY OF THE T-CELL
REPERTOIRE BY 'SPECTRATYPING.' 766 A-30 BIOSENSOR ASSAYS FOR MEASURING
THE RATES OF ASSOCIATION AND DISASSOCIATION OF ANTIGEN RECEPTORS FOR
THEIR LIGANDS. 767 A-31 STIMULATION OF LYMPHOCYTE PROLIFERATION BY
TREATMENT WITH POLYCLONAL MITOGENS OR SPECIFIC ANTIGEN. 769 MEASUREMENTS
OF APOPTOSIS BY THE TUNEL ASSAY. 770 ASSAYS FOR CYTOTOXIC T CELLS. 770
ASSAYS FOR CD4 T CELLS. 770 DNA MICROARRAYS. 772 DETECTION OF IMMUNITY
IN VIVO. 772 ASSESSMENT OF PROTECTIVE IMMUNITY. 772 TRANSFER OF
PROTECTIVE IMMUNITY. 773 THE TUBERCULIN TEST. 774 TESTING FOR ALLERGIC
RESPONSES. 774 ASSESSMENT OF IMMUNE RESPONSES AND IMMUNOLOGICAL
COMPETENCE IN HUMANS. 775 THE ARTHUS REACTION. 776 MANIPULATION OF THE
IMMUNE SYSTEM. 777 A-42 ADOPTIVE TRANSFER OF LYMPHOCYTES. 777 A-43
HEMATOPOIETIC STEM-CELL TRANSFERS. 777 A-44 IN VIVO DEPLETIO N OF T
CELLS. 777 A-45 IN VIVO DEPLETION OF B CELLS. 778 A-46 TRANSGENIC MICE.
778 A-47 GENE KNOCKOUT BY TARGETED DISRUPTION. 779 APPENDIX II CD
ANTIGENS 783 APPENDIX III CYTOKINES AND THEIR RECEPTORS 799 APPENDIX IV
CHEMOKINES AND THEIR RECEPTORS 802 APPENDIX V IMMUNOLOGICAL CONSTANTS
804 BIOGRAPHIES 805 GLOSSARY 806 INDEX 835 |
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| author | Murphy, Kenneth M. Travers, Paul 1956- Walport, Mark |
| author_GND | (DE-588)1089816251 (DE-588)1145896154 (DE-588)123088178 |
| author_facet | Murphy, Kenneth M. Travers, Paul 1956- Walport, Mark |
| author_role | aut aut aut |
| author_sort | Murphy, Kenneth M. |
| author_variant | k m m km kmm p t pt m w mw |
| building | Verbundindex |
| bvnumber | BV023058577 |
| 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 XD 2700 |
| classification_tum | CHE 880f MED 450f |
| ctrlnum | (OCoLC)263656239 (DE-599)BVBBV023058577 |
| dewey-full | 616.079 616.07/9 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 616 - Diseases |
| dewey-raw | 616.079 616.07/9 |
| dewey-search | 616.079 616.07/9 |
| dewey-sort | 3616.079 |
| dewey-tens | 610 - Medicine and health |
| discipline | Biologie Chemie Medizin |
| discipline_str_mv | Biologie Chemie Medizin |
| edition | 7. ed. |
| format | Book |
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| genre_facet | Lehrbuch |
| id | DE-604.BV023058577 |
| illustrated | Illustrated |
| index_date | 2024-07-02T19:27:47Z |
| indexdate | 2024-07-09T21:10:01Z |
| institution | BVB |
| isbn | 0815341237 |
| language | English |
| lccn | 2007002499 |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-016261838 |
| oclc_num | 263656239 |
| open_access_boolean | |
| owner | DE-91G DE-BY-TUM DE-29T DE-19 DE-BY-UBM DE-M49 DE-BY-TUM DE-355 DE-BY-UBR DE-20 DE-29 |
| owner_facet | DE-91G DE-BY-TUM DE-29T DE-19 DE-BY-UBM DE-M49 DE-BY-TUM DE-355 DE-BY-UBR DE-20 DE-29 |
| physical | XXI, 887 S. Ill., graph. Darst. 1 CD-ROM (12 cm) |
| publishDate | 2008 |
| publishDateSearch | 2008 |
| publishDateSort | 2008 |
| publisher | Garland Science |
| record_format | marc |
| spelling | Murphy, Kenneth M. Verfasser (DE-588)1089816251 aut Janeway's immunobiology Kenneth Murphy ; Paul Travers ; Mark Walport Immunobiology 7. ed. New York [u.a.] Garland Science 2008 XXI, 887 S. Ill., graph. Darst. 1 CD-ROM (12 cm) txt rdacontent n rdamedia nc rdacarrier Bis 6. Aufl. u.d.T.: Janeway, Charles: Immunobiology. - Ab 8. Aufl. u.d.T.: Janeway's immunobiology Immunology Immunbiologie (DE-588)4072743-9 gnd rswk-swf Immunologie (DE-588)4026637-0 gnd rswk-swf (DE-588)4123623-3 Lehrbuch gnd-content Immunbiologie (DE-588)4072743-9 s DE-604 Immunologie (DE-588)4026637-0 s Travers, Paul 1956- Verfasser (DE-588)1145896154 aut Walport, Mark Verfasser aut Janeway, Charles A. Jr. 1943-2003 Sonstige (DE-588)123088178 oth http://www.loc.gov/catdir/toc/ecip079/2007002499.html Table of contents only HEBIS Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016261838&sequence=000005&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Murphy, Kenneth M. Travers, Paul 1956- Walport, Mark Janeway's immunobiology Immunology Immunbiologie (DE-588)4072743-9 gnd Immunologie (DE-588)4026637-0 gnd |
| subject_GND | (DE-588)4072743-9 (DE-588)4026637-0 (DE-588)4123623-3 |
| title | Janeway's immunobiology |
| title_alt | Immunobiology |
| title_auth | Janeway's immunobiology |
| title_exact_search | Janeway's immunobiology |
| title_exact_search_txtP | Janeway's immunobiology |
| title_full | Janeway's immunobiology Kenneth Murphy ; Paul Travers ; Mark Walport |
| title_fullStr | Janeway's immunobiology Kenneth Murphy ; Paul Travers ; Mark Walport |
| title_full_unstemmed | Janeway's immunobiology Kenneth Murphy ; Paul Travers ; Mark Walport |
| title_short | Janeway's immunobiology |
| title_sort | janeway s immunobiology |
| topic | Immunology Immunbiologie (DE-588)4072743-9 gnd Immunologie (DE-588)4026637-0 gnd |
| topic_facet | Immunology Immunbiologie Immunologie Lehrbuch |
| url | http://www.loc.gov/catdir/toc/ecip079/2007002499.html http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016261838&sequence=000005&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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