CONTENTS
1 Introduction = 1
1.1 General Features of the immune system = 3
1.1.1 Immunity = 3
1.1.2 Innate and adaptive immunity = 6
1.1.3 Receptors, antigens, and lymphocyte antigen receptors = 29
1.1.4 Self and non-self discrimination = 37
1.2 An overview of immune responses = 39
1.2.1 A map of cellular and molecular interactions during immune responses = 39
1.2.2 Innate responses = 39
1.2.3 Adaptive responses = 41
1.3 Lymphoid tissues = 47
1.3.1 Bone marrow origin of cells of the immune system = 47
1.3.2 Primary and secondary lymphoid tissues = 51
1.3.3 Lymphocyte recirculation = 52
1.3.4 The structures of some lymphoid tissus = 55
Futher reading = 61
2 The major histocompatibility complex = 63
2.1 Introduction = 65
2.2 General features of the MHC = 66
2.3 Nomenclature = 66
2.4 Cellular distribution of MHC molecules = 72
2.5 Structure of MHC molecules = 72
2.5.1 Class Ⅰ = 72
2.5.2 Class Ⅱ = 84
2.6 Biosynthesis and surface expression = 88
2.6.1 Class Ⅰ molecules = 88
2.6.2 Class Ⅱ molecules = 89
2.7 Structure and regulation of expression of MHC genes = 93
2.7.1 Class Ⅰ genes = 93
2.7.2 Class Ⅱ genes = 94
2.8 Genomic organization of the MHC = 96
2.8.1 Class Ⅰ loci = 97
2.8.2 Class Ⅱ loci = 101
2.9 Mechanisms for the generation of polymorphisms = 105
2.9.1 Generation of class Ⅰ polymorphisms = 106
2.9.2 Generation of class Ⅱ polymorphisms = 108
2.9.3 Selection pressure = 108
2.10 Disease association = 109
Further reading = 111
Literature cited = 112
3 Antigen-presenting cells = 115
3.1 Historical perspective = 117
3.2 Antigen processing and presentation = 123
3.2.1 T Cell recognition of processed antigens = 123
3.2.2 Presentation of exogenous antigens by macrophocytes = 127
3.2.3 Presentation of exogenous antigens by B lymphocytes = 140
3.2.4 Presentation of endogenous antigens by fibroblasts and other cells = 143
3.3 Peptide-MHC interactions = 145
3.3.1 Presentation of exogenous and endogenous antigens by different MHC molecules = 145
3.3.2 Intracellular sites of peptide-MHC associations = 146
3.3.3 Binding of peptides to MHC molecules = 153
3.4 Dendritic cells = 161
3.4.1 Properties of dendritic cells = 162
3.4.2 Distribution of dendritic cells and related cells = 165
3.4.3 The role of dendritic cells in initiating immune responses = 168
3.4.4 Antigen-presenting cell requirements for resting and activated T cells = 170
3.4.5 Mechanism of dendritic cell stimulation = 172
Further reading = 176
Literature cited = 177
4 The molecular basis of T cell responses = 181
4.1 Introduction = 183
4.2 Membrance molecules in T cell responses = 189
4.2.1 The αβ T cell receptor = 189
4.2.2 The γδ T cell receptor = 192
4.2.3 The CD3 complex = 197
4.2.4 CD4 and CD8: interaction with MHC = 203
4.2.5 CD45, the leukocyte common antigen: regulation of signal transduction = 213
4.2.6 Integrins and selectins: cell adhesion and activation molecules = 218
4.2.7 CD2: an alternative pathway for T cell activation = 227
4.2.8 CD28: regulation of cytokine gene expression = 231
4.2.9 Thy-1 = 233
4.3 Expression of membrane molecules during T cell development = 234
4.4 Cytokines and their receptors in T cell responses = 237
4.4.1 Cytokines = 237
4.4.2 Different T cells can produce different cytokines = 239
4.4.3 Interleukin-2 and its receptor = 242
4.4.4 Effects of other cytokines on T lymphocytes = 248
Further reading = 251
Literature cited = 253
5 The T cell repertoire = 257
5.1 Introduction = 259
5.2 Response of mature peripheral T cells to foreign antigens = 259
5.2.1 Discovery of MHC restriction = 259
5.2.2 Alloreactivity = 263
5.2.3 Self-restriction and mechanisms of positive selection = 268
5.2.4 Allorestriction = 276
5.2.5 Self-tolerance and mechanisms of negative selection = 278
5.2.6 The sequence of positive and negative selection in the thymus = 288
5.3 Selection of the T cell repertoire during development = 291
5.3.1 Introduction = 291
5.3.2 The restriction specificity of T cells is acquired: studies with bone marrow chimeras = 291
5.3.3 The restriction repertoire of helper T cells is determined in the thymus = 304
5.3.4 The restriction repertoire of cytotoxic T cells can be determined outside of the thymus = 308
5.3.5 The cells responsible for positive and negative selection in the thymus = 311
5.4 Unresponsiveness of mature peripheral T cells to antigens under Ir gene control = 316
5.4.1 MHC-linked immune response genes = 316
5.4.2 Non-MHC-linked Ir genes = 320
5.4.3 Function of MHC-linked Ir genes = 320
5.4.4 Summary = 324
Further reading = 325
Literature cited = 326
6 Antigen receptors―structure and function = 329
6.1 Introduction = 331
6.2 Antibodies―B lymphocyte antigen receptors = 334
6.2.1 Structure―an overview = 334
6.2.2 Classification = 340
6.2.3 Fine structure―hypervariable or complementarity determining regions = 346
6.2.4 Functions = 348
6.2.5 Relationship between structure and effector function = 358
6.2.6 Biosynthesis and assembly = 368
6.2.7 Level of expression of light chains in different species = 369
6.2.8 ‘Designer antibodies’ = 370
6.3 T cell antigen receptors = 372
6.3.1 Structure = 372
6.3.2 Function = 374
Further reading = 381
Literature cited = 382
7 Antigen receptor genes and the immunoglobulin superfamily = 385
7.1 Introduction = 387
7.2 Immunoglobulin genes = 388
7.2.1 Organization = 389
7.2.2 Rearrangement = 389
7.2.3 Control of rearrangements and tissue-specific expression of Ig genes = 408
7.2.4 Summary = 411
7.3 T cell receptor genes = 413
7.3.1 Organization = 413
7.3.2 Rearrangement = 419
7.3.3 Generation of T cell receptor diversity = 421
7.3.4 Control of gene rearrangements = 423
7.4 The immunoglobulin gene superfamily = 423
7.4.1 Criteria for inclusion in the immunoglobulin superfamily = 425
7.4.2 Members of the immunoglobulin superfamily = 427
7.4.3 Evolution and possible significance of the immunoglobulin superfamily = 431
Further reading = 433
Literature cited = 434
8 B cells and antibody responses = 437
8.1 Introduction = 439
8.2 B cell development = 442
8.2.1 Expression of antibody molecules during development of B cells = 442
8.2.2 allelic exclusion of Ig genes = 443
8.2.3 Other markers of B cell development = 446
8.2.4 B cell lineages and subsets = 447
8.3 Antibody responses to different types of antigen = 449
8.3.1 T-dependent (TD) responses = 449
8.3.2 T-independent (TI) responses = 464
8.3.3 Responses to mitogens and polyclonal B cell activators = 466
8.3.4 Overlaps in classification of antigens = 466
8.4 B cell activation and B cell responses = 467
8.4.1 Different phases in B cell responses = 467
8.4.2 B cell activation = 469
8.4.3 Control of B cell responses by cytokines = 475
8.4.5 Two types of helper T cells and B cell responses = 489
8.5 CD5-positives B cells = 489
8.5.1 Distribution = 489
8.5.2 Function = 491
8.6 B cell tolerance = 492
8.6.1 Clonal deletion = 493
8.6.2 Clonal anergy = 494
Further reading = 495
Literature cited = 496
9 Inflammatory mediators and soluble effector mechanisms = 499
9.1 Introduction = 501
9.2 Inflammation = 501
9.2.1 The response to injury and infection = 501
9.2.2 The phases of inflammation = 504
9.2.3 Mediators of inflammation = 506
9.3 The plasma enzyme systems = 512
9.3.1 The coagulation mechanism = 512
9.3.2 Fibrinolysis = 517
9.3.3 Kinin formation = 520
9.4 Complement = 522
9.4.1 Overview = 522
9.4.2 Nomenclature = 522
9.4.3 Activators of the complement cascade = 524
9.4.4 The classical pathway―early events = 529
9.4.5 The alternative pathway = 544
9.4.6 Terminal components and formation of the membrance attack complex = 547
9.4.7 Summary of the functions and control of the complement system = 551
9.4.8 Genetics and biosynthesis of complement proteins = 553
9.5 Cytokines mediating inflammatory and effector functions = 554
9.5.1 Interleukin-1 and its receptor = 554
9.5.2 Interleukin-6 and its receptor = 559
9.5.3 Tumour necrosis factors and their receptor = 567
9.5.4 Interferons = 572
Further reading = 578
Literature cited = 579
10 Cellular cytotoxicity = 581
10.1 Introduction = 583
10.2 Natural killer cells = 583
10.2.1 Characteristics = 583
10.2.2 Functions = 584
10.2.3 Origin = 586
10.2.4 Membrane molecules = 587
10.2.5 NK cell lines and clones = 589
10.2.6 Regulation of NK activity by cytokines = 590
10.2.7 Antibody-dependent cellular cytotoxicity = 591
10.3 Mechanisms of killing by NK cells and cytotoxic T cells = 593
10.3.1 Phases of killing = 593
10.3.2 Target cell recognition = 594
10.3.3 Reorganization of cytoplasmic organelles = 598
10.3.4 Delivery of the ‘lethal hit’ = 598
10.3.5 Target cell death = 606
10.3.6 Protection from self-lysis = 607
10.4 Macrophages = 608
10.4.1 Characteristics of macrophages = 609
10.4.2 Resident macrophages = 612
10.4.3 Inflammatory macrophages = 614
10.4.4 Activated macrophages = 615
10.4.5 Some macrophage receptors = 620
10.5 Hypersensitivity = 633
10.5.1 Type Ⅰ hypersensitivity = 634
10.5.2 Type Ⅱ hypersensitivity = 635
10.5.3 Type Ⅲ hypersensitivity = 635
10.5.4 Type Ⅳ hypersensitivity = 635
Further reading = 636
Literature cited = 637
11 Idiotype networks and suppressor pathways = 641
11.1 Idiotypes and idiotypic networks = 643
11.1.1 Idiotypes of antibodies = 643
11.1.2 Idiotypic networks = 654
11.1.3 T cell idiotypes = 659
11.1.4 Idiotypic regulation in vivo = 663
11.2 Suppressor T cells and suppressor pathways = 670
11.2.1 Immune suppression = 670
11.2.2 Suppressor T cells = 671
11.2.3 Suppressor factors = 679
11.2.4 Accessory cells in suppressor pathways = 681
11.2.5 Contrasuppression = 682
11.2.6 Veto cells = 683
11.3 Immune regulation by cytokines = 684
Further reading = 687
Literature cited = 688
Appendix: cellular and molecular techniques = 693
A1 Production and use of antibodies = 695
A1.1 Production and use of antisera = 695
A1.2 Production of monoclonal antibodies = 696
A1.3 Immunoprecipitation = 699
A1.4 Immunocytochemistry = 702
A1.5 Affinity chromatography = 704
A1.6 Western blottin of immunoblotting = 705
A1.7 Antibody-mediated complement-dependent cytotoxicity assay = 706
A2 Cellular techniques = 707
A2.1 Cell proliferation assays = 707
A2.2 Cytotoxic T lymphocyte assay (CTL assay or 51 Cr release assay) = 709
A2.3 Plaque-forming cell (PFC) assay = 711
A3 Molecular techniques = 712
A3.1 southern blotting: DNA-DNA hybridization analysis = 712
A3.2 Northern blotting: RNA-DNA hybridization = 714
A3.3 Polymerase chain reaction (PCR) = 715
A3.4 DNA-mediated gene transfer (DMGT): gene transfection = 716
A3.5 Production of transgenic mice = 717
A3.6 Homologous recombination = 720
Index = 721
