Skin Immune System: Cutaneous Immunology and Clinical Immunodermatology, Third Edition

Front cover......Page 1
Preface to the Third Edition......Page 6
The Editor......Page 8
Contributors......Page 10
Contents......Page 16
Introduction......Page 20
I. The Skin as an Organ of Defense......Page 22
II. Concepts of the Skin as an Immunological Organ......Page 23
A. Resident, Recruited, and Recirculating Cells......Page 25
IV. The Distinction between Cutaneous and Systemic Immunity......Page 26
V. Skin-Specific Recirculating T Cells......Page 27
Bibliography......Page 28
I. Introduction......Page 32
II. Major Shifts in Medical Paradigms......Page 33
IV. Application of Immunological Principles to Dermatology......Page 34
References......Page 35
Comparative Immunology of the Integument......Page 38
I. Introduction......Page 39
C. The Elasmobranchs......Page 40
F. Reptiles......Page 41
A. General Considerations Concerning the Presence of Langerhans Cells......Page 42
C. Co-Expression of MHC Class II Molecules and ATPase in Relation to Putative Langerhans Cells......Page 43
D. Are There LC Subsets Based on Class II Differences?......Page 44
F. An Experimental Model for Demonstrating Putative LC Subsets in Frog Skin......Page 45
H. Ontogeny of Dendritic Cells......Page 46
J. Functional Development of LC......Page 47
L. Cytoplasmic Lectins......Page 48
IV. Langerhans Cells in Reptilian Epidermis......Page 49
A. Rejection of Allografts and Xenografts in Invertebrates......Page 50
E. Graft Rejection in Reptiles......Page 52
B. Skin Lymphocytes Express Immunoglobulin......Page 53
C. Surface Immunoglobulin on Epithelial Cells......Page 54
1. Introduction......Page 56
4. Prostaglandin Biosynthesis......Page 57
1. General Characteristics......Page 58
4. Localized Leukocyte Response to Parasites......Page 59
1. Fish Skin: An Innate Immunity Organ......Page 60
2. Fish Skin and Pro-Inflammatory Cytokines......Page 61
4. Fish Epidermal Langerhans Cells......Page 62
VIII. Summary......Page 64
References......Page 65
The Immunogenetics of Inflammatory Skin Disease......Page 74
B. Psoriasis......Page 75
III. Molecular Genetics......Page 76
5. RANTES......Page 77
1. HLA Association......Page 78
2. Non-HLA Loci......Page 79
1. Epidermal Differentiation Cluster (chromosome 1q21)......Page 80
2. Chromosome 3q21......Page 81
B. Netherton’s Disease......Page 82
VI. Gene-Environment Interactions......Page 83
VIII. Conclusions......Page 84
References......Page 85
Cellular Constituents of the Skin Immune System......Page 94
I. Introduction......Page 96
III. HLA-DR Expression by Keratinocytes......Page 97
V. Other Biological Effects of IFN-g and Other Cytokines on Keratinocytes......Page 98
A. Pro-Inflammatory Cytokines (Table 5.1)......Page 100
C. Chemoattractant Cytokines (Table 5.3)......Page 102
D. Downregulatory Cytokines (Table 5.4)......Page 103
A. Inductive Effect of Keratinocytes on T Cells......Page 105
D. Keratinocytes as Accessory Cells for Superantigen-Driven Responses......Page 106
E. Keratinocytes as Antigen-Presenting Cells......Page 107
F. Keratinocytes as Antigen-Presenting Cells for Allogeneic T Cells......Page 108
A. Toll-Like Receptors......Page 109
B. Antimicrobial Peptides......Page 110
References......Page 112
I. Introduction......Page 120
B. T-Cell Emigration and Positioning in Peripheral Lymphoid Organs......Page 121
A. T-Cell Receptor and Antigen Recognition......Page 122
B. Requirement and Diversity of Co-Stimulatory Signals for T-Cell Activation......Page 123
D. Effector Mechanisms of T Cells: T-Cell-Mediated Cytotoxicity......Page 125
E. Regulatory T Cells......Page 126
F. Natural Killer and Natural Killer T Cells......Page 127
A. T Cells in Healthy Skin......Page 128
B. T Cells in Atopic Dermatitis......Page 129
C. T Cells in Psoriasis......Page 130
D. T Cells in Allergic Contact Dermatitis......Page 131
References......Page 132
I. Introduction......Page 142
A. Origin and Distribution......Page 143
1. Endocytotic Activity......Page 144
2. Antigen Processing......Page 145
3. Dendritic Cell - T-Cell Interaction......Page 147
C. Ontogeny and Subpopulations......Page 149
1. Definition, Localization, and Distribution......Page 153
2. Immature Langerhans Cells......Page 155
3. Mature Langerhans Cells......Page 159
4. Birbeck Granules......Page 161
B. Migration of Langerhans Cells......Page 164
1. The Sensitization Phase......Page 168
2. The Elicitation Phase......Page 170
V. Dermal Dendritic Cells......Page 172
VI. Inflammatory Dendritic Epidermal Cells......Page 175
VII. Cutaneous Plasmacytoid Dendritic Cells......Page 176
VIII. Final Remarks......Page 177
References......Page 180
I. Introduction......Page 202
1. Functional Repertoire in Relation to Cell Surface Molecules......Page 203
2. Functional Repertoire in Relation to Secreted Products......Page 207
C. Challenges to the Isolation of Monocytes/Macrophages......Page 209
A. Stimulus for Cellular Differentiation......Page 210
B. Monocyte Differentiation Utilized in Skin Disease Therapeutic Model......Page 211
1. Role of Mo/Mac in UV-Induced Immunosuppression......Page 212
2. Role of Mo/Mac in UV Tumorigenesis......Page 213
A. Infection......Page 214
1. Cutaneous Leishmaniasis......Page 215
B. Granulomatous Diseases......Page 216
1. Scleroderma - GVHD......Page 217
1. Cutaneous Xanthomatoses......Page 218
V. Concluding Remarks and Perspectives......Page 220
References......Page 221
I. Introduction......Page 230
II. Morphology and Physiology: Vascular Endothelial Cell Receptors......Page 231
III. Pathology......Page 236
IV. Vascular Endothelial Cell Markers......Page 239
References......Page 242
I. Introduction......Page 256
II. Morphology and Heterogeneity......Page 257
A. Mediators Released......Page 258
B. Stimulation and Inhibition Regulate Mast Cell Activation......Page 259
C. Signal Transduction in Mast Cell Activation......Page 260
1. Protein Tyrosine Phosphorylation......Page 261
4. Involvement of G Proteins......Page 263
D. Inhibitors of Mast Cell Activation......Page 264
A. Neurogenic Inflammation......Page 265
C. Priming......Page 266
VI. Mast Cells in Immediate-Type Hypersensitivity Responses......Page 267
VII. Mast Cells in Contact Hypersensitivity and Delayed-Type Hypersensitivity Reactions......Page 268
VIII. Mast Cells in Autoimmune Diseases......Page 269
IX. Mast Cells in Skin Diseases......Page 270
References......Page 271
I. Granulocyte Life Cycle......Page 282
C. Tissue Phase......Page 283
II. Granulocyte Migration......Page 287
A. Adherence......Page 289
B. Diapedesis......Page 292
C. Chemotaxis......Page 293
A. Phagocytosis......Page 294
B. Degranulation......Page 296
C. Production of Oxygen Radicals......Page 297
IV. Granulocytes and Skin Diseases......Page 298
B. Models to Study Granulocyte Migration in Skin......Page 299
D. Modulating Skin Immune Response by Granulocytes......Page 300
References......Page 301
Humoral Constituents of the Skin Immune System......Page 304
Free Radicals......Page 306
A. Singlet Oxygen......Page 307
B. Superoxide Anion......Page 308
F. Lipoperoxides......Page 309
III. Intracellular Generation of ROS......Page 310
IV. Cell Protective System against Oxidative Stress......Page 311
B. Glutathione System......Page 312
D. Superoxide Dismutases......Page 313
ROS as Intracellular Messengers......Page 314
2. From Mitochondria to Nucleus......Page 315
4. Cysteine as Redox Sensor and Signal Transducer......Page 316
5. Nitric Oxide......Page 317
6. Intracellular Pathways......Page 318
7. Transcription Factors......Page 319
A. Lymphocytes......Page 321
D. Neutrophils......Page 323
G. Soluble Factors: Cytokines......Page 324
VII. ROS as Mediators of the Altered Immune Response......Page 325
IX. Antioxidant Supplementation......Page 326
References......Page 327
II. Major Categories of Human Antimicrobial Peptides......Page 334
A. Defensins......Page 335
B. Alpha and Beta Defensins Have Different Patterns of Disulfide Bonding......Page 336
III. Antimicrobial Activities of Human AMP......Page 337
B. Mechanism of Action of Human AMP......Page 338
A. Sweat as a Vehicle for AMP......Page 339
D. Antimicrobial Activities of Chemokines......Page 340
References......Page 341
I. Introduction......Page 346
II. Complement Pathways......Page 347
A. Control of Complement Activation in Fluid Phase by Soluble Regulators......Page 350
B. Control of Complement Activation on Self-Cell by Cell Surface Regulators......Page 351
IV. Mediation of Cell Functions by Complement Receptors......Page 352
1. Expression of Complement Proteins by Keratinocytes......Page 353
2. Synthesis of Complement Proteins by Melanocytes and Langerhans Cells......Page 356
B. Synthesis of Complement in the Dermis......Page 357
C. Contribution of Migrating Cells to Complement Biosynthesis in the Skin......Page 358
B. Soluble Regulators......Page 359
VII. Aberrancy in the Expression of Complement Proteins and Skin Diseases......Page 360
References......Page 361
The Skin Cytokine Network......Page 368
I. Introduction......Page 369
A. Interleukin-1......Page 370
B. Interleukin-6......Page 371
C. Tumor Necrosis Factor......Page 372
D. Interleukin-7......Page 373
H. Interleukin-13......Page 374
M. Interleukin-18......Page 375
IV. Immunosuppressive Cytokines......Page 376
2. Interleukin-19......Page 377
B. IL-1RA and IL-18 RA......Page 378
V. Interferons......Page 379
VI. Hematopoietic Growth Factors......Page 380
A. Colony-Stimulating Factors......Page 381
VII. Conclusion......Page 383
References......Page 384
I. Introduction......Page 392
B. Chemokine Receptors on T-Cell Subsets......Page 393
C. Chemokine Production by Resident Skin Cells......Page 396
A. Allergic Contact Dermatitis......Page 398
B. Psoriasis......Page 400
C. Atopic Dermatitis......Page 402
IV. Chemokines and Chemokine Receptors as Potential Therapeutic Targets in Inflammatory Skin Disorders......Page 404
References......Page 405
I. Introduction......Page 412
II. Neurogenic Inflammation, Capsaicin, and TRP Proteins......Page 413
III. Sensory Nerves......Page 415
V. Calcitonin Gene-Related Peptide......Page 416
VI. Regulation by Peptidases......Page 417
IX. Nerve Distributions and Neuropeptide Localization......Page 418
X. The Triple Response of Lewis Revisited......Page 419
XI. Activation of Sensory Receptors, Nerve Depolarization, and the Axon Response......Page 420
XII. Subtypes of Type C Neurons: Itch, Pain, and Mechanical Sensitivity......Page 422
XIV. Neuropeptides and Immunity......Page 423
XVI. Neuropeptides in Dermatologic Disease......Page 424
Acknowledgments......Page 425
References......Page 426
Response Patterns of the Skin Immune System......Page 432
I. Introduction......Page 434
A. IL-1 Receptor Family......Page 435
C. Hematopoietin Receptor Family (Class I Receptors)......Page 436
F. TGF-b Receptor Family......Page 437
III. JAK/STAT Pathway......Page 438
IV. MAPKs......Page 440
A. ERK1 and 2......Page 441
B. JNK1 to 3......Page 442
C. p38 MAPK......Page 443
A. AP-1......Page 445
B. NF-kB......Page 447
A. PPAR......Page 449
References......Page 451
I. Introduction......Page 458
A. Cellular Effects of Environmental Challenge......Page 459
B. Keratinocyte Responses to Environmental Stimuli......Page 460
III. Epidermal Control of T-Cell Function......Page 461
B. Amplification......Page 462
References......Page 463
I. Introduction......Page 466
A. Rolling......Page 467
C. Transendothelial Migration......Page 468
A. Inflammatory Cell Migration in and out of the Epidermis......Page 469
B. Adhesion Molecule-Mediated Signaling Reactions......Page 470
References......Page 471
I. Introduction......Page 476
II. Immunologic Aspects of Photocarcinogenesis......Page 477
1. UVR-Mediated DNA Damage and Its Relationship to Immunosuppression......Page 478
2. cis-Urocanic Acid......Page 479
B. The Role of Cytokines and Other Soluble Mediators......Page 480
C. T-Suppressor Cells......Page 483
A. Antigen Presenting Cells......Page 484
B. Keratinocytes......Page 485
A. Wavelengths Implicated in UVR-Induced Immunosuppression and Carcinogenesis......Page 486
B. Chemoprevention......Page 487
VI. Conclusion......Page 488
References......Page 489
I. Introduction......Page 494
A. Animal Studies......Page 495
B. Human Studies......Page 496
A. Induction......Page 497
B. Effector Cellular Mechanisms......Page 499
C. Evidence for Antitumor Immunity and Tumor Destruction......Page 500
A. Induction......Page 501
B. Tumor Destruction......Page 503
V. Therapeutic Manipulation of Antitumor Immunity......Page 504
References......Page 505
Immunodermatological Diseases......Page 514
Some Congenital Immunodeficiencies and Their Dermatological Manifestations......Page 516
II. Classification of the Primary Immunodeficiencies......Page 517
1. Introduction......Page 518
3. Erythroderma and Graft vs. Host Disease......Page 519
3. Relation between Atopic Dermatitis and IgA Deficiency......Page 520
1. Introduction......Page 521
3. Skin Lesions in Carriers of X-Linked Cytochrome b Negative CGD......Page 522
1. Introduction......Page 523
1. Introduction......Page 524
2. Characterization of the Defects Involved......Page 525
References......Page 526
I. Introduction......Page 530
II. Cellular Mechanisms......Page 531
A. Autoantibodies......Page 532
C. Proteases......Page 535
A. Pemphigus......Page 536
B. Bullous Pemphigoid (BP)......Page 537
C. Mucous Membrane Pemphigoid......Page 538
E. Linear IgA Disease......Page 539
V. Immunodiagnosis......Page 540
References......Page 542
II. Clinical Features......Page 546
III. Histopathology......Page 547
IV. Immunohistopathological Features......Page 548
V. Pathogenesis......Page 549
VI. Lichen Planus-Like Skin Diseases......Page 552
VIII. Immunotherapy in Lichen Planus......Page 553
References......Page 555
II. Major Clinical Characteristics of Cutaneous LE......Page 564
III. Cellular and Humoral Immunity in LE......Page 565
IV. Models of Cutaneous LE Immunopathogenesis......Page 567
V. Immunodiagnosis of Cutaneous LE......Page 568
VII. Conclusions......Page 569
References......Page 570
I. Introduction and Classification......Page 572
1. Deposition of Immunoglobulins......Page 574
2. Recruitment of Granulocytes and Mechanisms of Granulocyte-Dependent Endothelial Damage......Page 575
C. Pathogenic T-Cell Responses and Granuloma Formation......Page 576
IV. Diagnosis......Page 577
V. Treatment Regimens......Page 578
References......Page 579
II. Clinical Aspects......Page 584
III. Histopathology and Laboratory Changes......Page 585
IV. Pathogenesis......Page 587
V. Treatment......Page 588
References......Page 589
I. Introduction......Page 592
3. Recent Advances in Noncovalent Binding of Drugs to MHC Molecules......Page 593
2. Immunohistological Features of Cutaneous Lesions in ADRs......Page 594
C. Why Drug Allergy Manifests Itself in the Skin......Page 595
C. Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome......Page 596
F. Fixed Drug Eruption......Page 597
References......Page 598
II. Epidemiology......Page 602
V. IgE Antibodies and Atopic Dermatitis......Page 603
VI. The T Lymphocyte System and Atopic Dermatitis......Page 604
VIII. Stationary Skin Cells and Atopic Dermatitis......Page 605
A. The Keratinocyte Hypothesis......Page 606
References......Page 607
Allergic Contact Dermatitis......Page 612
III. Pathophysiology of Contact Sensitivity......Page 613
Phase 1: Sensitization Phase (also referred to as afferent phase or induction phase of CS)......Page 614
A. The Central Role of Cutaneous Dendritic Cells......Page 615
2. Maturation of Cutaneous DC......Page 616
2. Hapten Determinants for T Cells Provide the First Signal......Page 617
4. T-Cell Polarization and Constitution of CD4+ and CD8+ T-Cell Populations......Page 618
5. Need for CD4+ Help in Hapten-Specific CD8+ Responses?......Page 619
1. T-Cell Recruitment......Page 620
4. Cytotoxic Activity of CD8+ T Cells......Page 621
D. Regulation of Contact Sensitivity......Page 622
VI. Diagnosis......Page 623
D. Drug Dermatitis......Page 625
IX. Conclusion......Page 626
References......Page 627
I. Introduction......Page 634
II. Epidemiology and Genetics of Psoriasis......Page 635
B. Gene Expression......Page 636
B. The Psoriatic T-Cell Infiltrate......Page 637
C. Cytokines in Psoriasis......Page 638
B. Analysis of the Lesional Psoriatic T-Cell Receptor Usage: Evidence of Clonal T-Cell Expansion......Page 639
VI. Conclusions......Page 640
References......Page 641
I. Introduction......Page 646
A. Virus Types and Diseases......Page 648
C. Immune Responses......Page 650
1. Local Immunity......Page 651
2. Regression......Page 653
A. The Viruses and Their Diseases......Page 654
B. Immune Responses......Page 655
1. Local Immunity to HSV-1......Page 656
2. The Effects of UVB Radiation on HSV-1 Infection......Page 658
A. The Viruses......Page 659
B. Pityriasis Rosea......Page 660
C. Kaposi’s Sarcoma......Page 662
B. The Involvement of HIV with the Skin......Page 663
A. The Virus and the Disease......Page 664
B. Local Immunity......Page 665
References......Page 666
I. Introduction......Page 674
A. Early Stages of Dermatophytosis......Page 675
B. Immunity and Dermatophytosis......Page 676
III. Cutaneous Candidosis......Page 678
B. Immunological Defects in Chronic Mucocutaneous Candidosis......Page 679
V. Vaginal Candidosis......Page 680
VI. Infections Due to Malassezia spp.......Page 681
VII. Conclusion......Page 682
References......Page 683
I. Introduction......Page 688
II. Protozoal Infections......Page 689
A. Schistosomiasis......Page 692
1. Onchocerciasis......Page 693
A. Arthropod Bites: General Aspects......Page 694
B. Mosquito Bites......Page 695
C. Flea Bites......Page 697
E. Furuncular Cutaneous Myasis......Page 698
F. Scabies......Page 699
References......Page 700
I. Introduction......Page 710
II. Cutaneous Lymphomas: Tumors of Skin-Homing Lymphocytes......Page 711
1. Genetic Factors......Page 712
3. Immunological Factors......Page 713
5. Evasion of Antitumor Immune Response......Page 714
1. Primary Cutaneous CD30+ (anaplastic) Large T-Cell Lymphoma......Page 715
B. Immunopathogenesis and Tumor Progression......Page 716
2. Primary Cutaneous Follicle Center Cell Lymphoma (PCFCCL)......Page 717
B. Immunopathogenesis and Tumor Progression......Page 718
References......Page 719
Immunotherapy in Dermatology......Page 724
Immunomodulatory Drugs......Page 726
II. Adrenocorticosteroids......Page 727
3. Endothelial Cells......Page 728
2. Intralesional GCS......Page 729
3. Systemic GCS......Page 730
B. Dosage and Monitoring......Page 731
IV. Calcineurin Inhibitors......Page 732
B. Tacrolimus......Page 733
C. Pimecrolimus......Page 734
C. Side Effects......Page 735
VII. Mycophenolate Mofetil......Page 736
1. Viral Infections......Page 737
IX. Conclusion......Page 738
References......Page 739
Therapeutic Manipulation of the Complement System in Dermatology......Page 742
II. Low-Molecular-Weight Inhibitors......Page 743
1. Treatment of HANE......Page 744
B. Mannose-Binding Lectin......Page 745
C. Intravenous Immunoglobulin Preparation......Page 746
3. Pemphigoid and Pemphigus......Page 747
6. Epidermolysis Bullosa Acquisita......Page 748
D. Factor I, Factor H, and C4-Binding Protein......Page 749
E. Decay-Accelerating Factor (DAF), Membrane Cofactor Protein (MCP), and CD59......Page 750
2. Inhibition of Hyperacute Rejection Phase of Xenotransplantation......Page 751
3. Purging of Tumor......Page 752
F. Complement Receptor-1 (CR1)......Page 753
2. Inhibition of Immune-Complex-Induced Inflammation......Page 754
IV. Molecules That Can Alter the Expression of Cell- Surface Regulators of the Complement......Page 755
References......Page 756
I. Introduction......Page 764
A. Classification......Page 765
B. Screening for Tumor Antigens......Page 767
2. Screening by Antibodies......Page 768
1. Identification of Melanoma Antigens and Corresponding Epitopes......Page 770
2. Known Melanoma Antigens......Page 771
1. Tumor Antigens Identified by Antibodies......Page 772
E. Targets in Other Skin Cancers......Page 773
A. Specific Immune Responses against Malignant Melanoma......Page 774
B. Requirements for T-Cell-Based Immunotherapies......Page 775
C. Peptide and Protein Vaccines......Page 776
E. Recombinant Viral Vaccines......Page 777
F. DC Vaccines......Page 778
H. Obstacles of T-Cell-Based Immunotherapy......Page 779
I. Antibody-Based Immunotherapies......Page 780
References......Page 782
I. Introduction: Principles of Ultraviolet-Mediated Immunosuppression......Page 790
1. Keratinocytes......Page 792
5. Fibroblasts......Page 793
1. Combination Therapies......Page 794
C. Pruritus and Other Dermatological Disorders......Page 795
A. Principles of PUVA Therapy......Page 796
B. PUVA for Psoriasis......Page 798
4. Miscellaneous......Page 799
VII. Conclusion......Page 800
References......Page 801
Biologicals for the Treatment of Immune-Mediated Skin Disease......Page 808
C. Fusion Proteins......Page 809
II. Mechanism of Action......Page 811
E. T-Cell Adhesion and Migration......Page 812
III. Adverse Events......Page 813
1. T-Cell-Targeted Therapies......Page 814
2. Co-Stimulatory Molecules (accessory cell signals)......Page 815
4. Cytokine-Targeted Therapies......Page 816
B. Atopic Dermatitis......Page 817
2. Anti-CD25-Directed Therapies......Page 818
V. Conclusion......Page 819
References......Page 820
A......Page 824
B......Page 825
C......Page 826
E......Page 829
F......Page 830
H......Page 831
I......Page 832
K......Page 834
L......Page 835
M......Page 836
O......Page 837
P......Page 838
R......Page 839
S......Page 840
T......Page 841
U......Page 842
Z......Page 843