Stress Proteins in Medicine

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Stress Proteins in Medicine

edited by Willem van Eden

University of Utrecht Utrecht, The Netherlands

Douglas B. Young

St. Mary's Hospital Medical School Imperial College of Science, Technology and Medicine London, England

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ISBN: 0-8247-9623-3

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Preface

All living cells, from the simplest prokaryote to the most complex multicellular organism, contain stress proteins-molecular chaperones that are responsible for management of unfolded polypeptides within the cell. Unfolded polypeptides are generated during protein synthesis, and also as a result of breakdown associated with protein turnover. Interaction of polypeptides with the chaperone proteins plays an essential role in their folding and assembly into functionally mature oligomers and regulates trafficking between intracellular compartments. Particularly high levels of molecular chaperones are required to maintain protein homeostasis in cells subjected to stress conditions-such as heat shock, nutrient deprivation, malignant transformation, and anoxia-when intracellular proteins are destabilized, or when a major alteration is required in overall cell protein composition. The major molecular chaperones were, in fact, initially identified by the dramatic induction of their expression level in stressed cells and are consequently often referred to as "heat shock proteins" or "stress proteins." It is important to realize that stress proteins are critical to the maintenance of cell integrity during normal physiological growth as well as in response to the stressful event of imminent loss of normal physiology. The stress proteins discussed in this book belong for the most part to two major protein classes, commonly referred to as hsp 70 and hsp 60, in reference to their approximate molecular weight and their initial identification as heat shock proteins. Generally, bacteria express one or at most two homologues from each of these families, while eukaryotic cells have multiple homologues localized in different intracellular compartments and regulated in response to differing signals. Homologues within each family share a high degree of sequence homology, with almost 50% amino acid identity between corresponding bacterial and mammalian proteins.

In view of the fundamental role of stress proteins in maintenance of protein homeostasis, it seems likely that malfunctions associated with members of stress protein families would have pathological effects. Such effects might be minimal under normal physiological conditions, but could be exacerbated at times

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when other disease stimuli trigger the requirement for local alterations in stress protein function, in particular afflicted cells or tissues. During infection, it can be anticipated that the requirement of stress proteins for cell viability will be equally essential for the pathogen and for the infected host. Just as stress proteins are essential in "normal" as well as stressed cells, it is clear that changes in stress protein expression will be associated with physiologically normal events accompanying infection as well as with any subsequent pathological events. In studying the role of stress proteins in medicine it is important to understand the normal physiology of stress proteins in order to detect and characterize aberrations associated with disease.

In addition to the direct role of stress proteins in cell physiology, their potential medical influence is compounded by their ability to act as potent immunogens. Responses to microbial stress proteins are a prominent feature of the immune repertoire in patients and in experimental animals, and there has been wide discussion of the possibility that recognition of conserved, self-like, epitopes on such antigens could influence infectious and other diseases. Three broad hypotheses have been proposed concerning the relevance of autoreactivity to stress proteins. In some instances, this can be seen as an example of "mimicry" in which an initial response against a pathogen component cross-reacts with a self-protein, triggering autoimmune pathology. Alternatively, the detection of autoreactive responses in individuals without disease suggests they may be integral to normal immune function-possibly with a role in "immune surveillance," acting as a generalized recognition system for cells stressed by infection, malignancy, or other factors. Finally, responses to stress proteins can be viewed as a secondary event, reflecting tissue breakdown and release of intracellular proteins following any pathological disturbance. This book provides a stateof-the-art overview from experts in a wide range of disciplines, setting out currently available evidence on the role of stress proteins in medicine. The reader is invited to consider whether the involvement of stress proteins can be described by a single set of general principles or is best viewed within the specific context of each individual disease, and to evaluate the potential contribution of such research to the development of novel diagnostic, prophylactic, and therapeutic approaches to control of human disease.

The book opens with introductory chapters providing an overview of the cell biology and immunology of stress proteins. This is followed by 15 chapters focusing predominantly on immunological responses to stress proteins in a range of immune-mediated diseases, such as arthritis, lupus, Crohn's disease, and multiple sclerosis, and in infectious diseases including tuberculosis, leishmaniasis, and fungal infection. Three chapters deal with infertility, experimental studies of tumor immunology, and organ transplantation. The next section contains 12 chapters that focus on local expression of stress proteins in diseased tissues. In addition to diseases covered in the immunological section, this sec-

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tion includes sarcoidosis, liver diseases, gastritis, celiac disease, artherosclerosis, allergic asthma, and muscular diseases. One chapter is devoted to myocardial protection in heart disease. A final section focuses on some exciting new aspects of stress proteins, including their use as carrier molecules for vaccines and their relationship with the gamma/delta subset of T cells.

The book is the first comprehensive compilation of the wide variety of observations made on the topic of stress proteins in disease. It is intended to provide a useful resource for readers as diverse as medical doctors, pathologists, cell biologists, immunologists, microbiologists, and all who wish to stay informed in this rapidly evolving field.

WILLEM VAN EDEN DOUGLAS B. YOUNG [DP]1996[/DP]End of Citation

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Contents

Preface

iii

Overview

1. Stress Proteins as Molecular Chaperones 1 R. John Ellis

2. The Unique Role of Heat Shock Proteins in Infections 27 Bernd Schoel and Stefan H. E. Kaufmann

3. Clinical Implications of the Stress Response 53 George Minowada and William J. Welch

4. T-Lymphocyte Recognition of Hsp 60 in Experimental Arthritis 73 Stephen M. Anderton and Willem Van Eden

5. Heat Shock Protein 60 and the Regulation of Autoimmunity 93 Irun R. Cohen

Stress Proteins and Specific Immune Responses

6. Immune Responses to Heat Shock Proteins in Reactive Arthritis 103 J. S. H. Gaston and J. H. Pearce

7. Juvenile Chronic Arthritis and Heat Shock Proteins E. R. De Graeff-Meeder, G. T. Rijkers, A. B. J. Prakken, W. Kuis, B. J. M. Zegers, R. Van Der Zee, and Willem Van Eden

119

8. T-Cell Responses to Heat Shock Proteins in Rheumatoid Arthritis 131 Harald G. Wiker, Morten Harboe, and Jacob B. Natvig

9. Heat Shock Protein 60 Autoimmunity in Lyme Disease

147

Zhizhong Dai, Stanley Stein, Stephanie Williams, and Leonard H. Sigal

10. Stress Proteins in Behçet's Disease and Experimental Uveitis

163

T. Lehner, A. Childerstone, K. Pervin, A. Hasan, H. Direskeneli, M. R. Stanford, R. Whiston, E. Kasp, D. C. Dumonde, T. Shinnick, R. van der Zee, and Y. Mizushima

11. Stress Proteins in Systemic Lupus Erythematosus

187

John B. Winfield and Wael N. Jarjour

12. Expression of and Immune Response to Heat Shock Protein 65 in Crohn's Disease

197

Willy E. Peetermans

13. Stress Proteins in Multiple Sclerosis and Other Central Nervous System Diseases Gary Birnbaum

213

14. Heat Shock Protein 60 and Insulin-Dependent Diabetes Mellitus

227

David B. Jones and Nigel W. Armstrong

15. Protection against Tumors by Stress Protein Gene Transfer

249

Katalin V. Lukacs, Douglas B. Lowrie, and M. Joseph Colston

16. Immune Responses to Stress Proteins in Mycobacterial Infections

265

Juraj Ivanyi, Pamela M. Norton, and Goro Matsuzaki

17. Heat Shock Proteins in Fungal Infections

287

Bruno Maresca and George S. Kobayashi

18. Stress Proteins and Infertility

301

Steven S. Witkin

19. Heat Shock Proteins in Visceral Leishmaniasis

307

Paulo Paes de Andrade and Cynthia Rayol de Andrade

20. Role of Heat Shock Protein Immunity in Transplantation

327

Rene J. Duquesnoy and Ricardo Moliterno

Stress Proteins and Expression in Diseased Tissue

21. Lupus and Heat Shock Proteins Breda N. Twomey, Veena B. Dhillon, David S. Latchman, and David Isenberg

345

22. Stress Protein Expression in Sarcoidosis

359

H. Bielefeldt-Ohmann, Janelle M. Staton, and Joanne E. Dench

23. Stress Proteins in Inflammatory Liver Disease

383

Ansgar W. Lohse and Hans Peter Dienes

24. Helicobacter pylori–Associated Chronic Gastritis

391

Lars Engstrand

25. Jejunal Epithelial Cell Stress Protein Expression in Gluten-Induced Enteropathy (Celiac Disease)

399

Markku Mäki and Immo Rantala

26. Identification of Endogenous Heat Shock Protein 60 as an Autoantigen in Autoimmune NOD Mouse Diabetes

407

Katrina Brudzynski

27. Expression of Stress Proteins in Diabetes Mellitus: Detection of a Heat Shock Protein 60–like Protein in Pancreatic RINm5F β-Cell Plasma Membranes

427

Burkhard Göke, Brigitte Lankat-Buttgereit, Hanna Steffen, Rüdiger Göke, and Friedrich Lottspeich

28. Stress Proteins in Atherogenesis

445

Qingbo Xu and Georg Wick

29. Stress Proteins and Myocardial Protection Michael R. Gralinski, Benedict R. Lucchesi, and Shawn C. Black

465

30. Heat Shock Proteins in Eosinophilic Inflammation

479

Pandora Christie, Muriel R. Jacquier-Sarlin, Anne Janin, Jean Bousquet, and Barbara S. Polla

31. Heat Shock Proteins in Duchenne Muscular Dystrophy and Other Muscular Diseases

495

Liza Bornman and Barbara S. Polla

32. Mitochondrial Neuromuscular Disease Associated with Partial Deficiency of Heat Shock Protein 60

509

Etienne Agsteribbe and Anke Huckriede

Stress Proteins and Interactions with Proteins or Cells in Immunity

33. Heat Shock Proteins as Chaperones of Unique and Shared Antigenic Epitopes of Human Cancers: A Novel Approach to Vaccination

519

Pramod K. Srivastava

22. Stress Protein Expression in Sarcoidosis

359

H. Bielefeldt-Ohmann, Janelle M. Staton, and Joanne E. Dench

23. Stress Proteins in Inflammatory Liver Disease

383

Ansgar W. Lohse and Hans Peter Dienes

24. Helicobacter pylori–Associated Chronic Gastritis

391

Lars Engstrand

25. Jejunal Epithelial Cell Stress Protein Expression in Gluten-Induced Enteropathy (Celiac Disease)

399

Markku Mäki and Immo Rantala

26. Identification of Endogenous Heat Shock Protein 60 as an Autoantigen in Autoimmune NOD Mouse Diabetes

407

Katrina Brudzynski

27. Expression of Stress Proteins in Diabetes Mellitus: Detection of a Heat Shock Protein 60–like Protein in Pancreatic RINm5F β-Cell Plasma Membranes

427

Burkhard Göke, Brigitte Lankat-Buttgereit, Hanna Steffen, Rüdiger Göke, and Friedrich Lottspeich

28. Stress Proteins in Atherogenesis

445

Qingbo Xu and Georg Wick

29. Stress Proteins and Myocardial Protection

465

Michael R. Gralinski, Benedict R. Lucchesi, and Shawn C. Black

30. Heat Shock Proteins in Eosinophilic Inflammation

479

Pandora Christie, Muriel R. Jacquier-Sarlin, Anne Janin, Jean Bousquet, and Barbara S. Polla

31. Heat Shock Proteins in Duchenne Muscular Dystrophy and Other Muscular Diseases

495

Liza Bornman and Barbara S. Polla

32. Mitochondrial Neuromuscular Disease Associated with Partial Deficiency of Heat Shock Protein 60 Etienne Agsteribbe and Anke Huckriede

Stress Proteins and Interactions with Proteins or Cells in Immunity

509

33. Heat Shock Proteins as Chaperones of Unique and Shared Antigenic Epitopes of Human Cancers: A Novel Approach to Vaccination Pramod K. Srivastava

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Index A Acetone-precipitable fraction, 133 Actin, 498 Adjuvant arthritis, 74 Adjuvants, 67 Alcoholic hepatitis, 388 Alpha-b-cystallin, 12, 55, 502 a-Crystallin, 268, 269 Allograft, 327 Allograft-infiltrating cells, 330 Alzheimer's disease, 215 Ankylosing spondylitis, 190 Antibodies, 158 Anticardiolipin antibody (ACL), 350 Antigenic mimicry, 266, 418 Antioxidant therapy, 497 Antisense oligonucleotides, 39 Apoptosis, 353 Apo-1/Fas antigen, 352 Arterial wall, 455 Artherogenesis, 446 Artherosclerotic plaques, 446, 447, 487 Arthritis inflammatory, 103 models, 77 pathogenesis, 87 Asbestosis, 369 Aspergillus fumigatus, 289 Asthma, 489 Astrocytes, 217 Atherogenesis, 456 Atherosclerosis, 445, 456 Atypical mycobacteria, 198 Autoantigens, 87 Autoimmune, 39 Autoimmune hepatitis, 383 Autoimmunity, 32, 539 Avridine, 126 B Bannwarth's syndrome, 151 Bacille Calmette-Guérin, 534 BCG, 67, 103, 534 Behçet's disease (BD), 163 Bile ducts, 386 Biliary cirrhosis, 385, 387 Biobreeding (BB) rat, 227 BiP, 7, 31 Bladder Cancer, 103 Blastomyces dermatitidis, 291

Bleomycin, 490 B lymphoma, 563 Bordetella pertussis, 168 Borrelia burgdorferi, 65, 147 Bronchoalveolar lavage (BAL), 362 Bullous pemphigoid, 190 Bursitis, 152 Bystander suppression, 98 B27, 110 B7-positive cells, 202 C Calnexin (calreticulin), 420 Cancer immunotherapy, 520 Candida, 287 Candida albicans, 36, 38, 369 Candidosis, 36 Cardiovascular system, 465 Carotid atherosclerosis, 449 Carrier, 534 Carrier effect, 539 Carrier-specific T cells, 538 Carrington's disease, 482 Cartilage, 131 Cartilage proteoglycans, 75 CD1, 106 Celiac disease, 399 Cell surface expression, 123 Cell surface localization, 347 Central nervous system (CNS), 213 Cereal proteins, 399 Cerebrospinal fluid, 151 Chagas' disease, 308, 313 Chaperone, 13 Chaperone disease, 20 Chaperones, 2, 31, 58 Chest pains, 345 Chinese hamster fibroblast (HA-1), 465 Chinese hamster ovary cells (CHO), 413, 432 Chlamydia, 104, 369 Chlamydial, 65 Chlamydial 57-kDa hsp, 304 Chlamydia pneumoniae, 454 Chlamydia trachomatis, 301 Chloroplast, 9, 14 Cholangitis, 385 Cholesterol, 489 Cholestrol-rich diet, 456 Chronic rejection, 328 Citric acid cycle, 511

Class Ib molecules, 547 Class I MCH-like, 106 Clathrin, 2 Clathrin-uncoating ATPase, 7 Clonal selection theory, 94 Cognitive theory, 97 Collagen type II, 126 Common antigen, 9 Conjugation procedure, 541 Connective tissue disease, 500 Cord blood, 95 Coronary atherosclerosis, 454 Coronary disease, 329 Coxsackie B4 virus, 239 Cpn 10, 10 Cpn 60, 10 CP20961, 86, 126 CP20961-induced arthritis, 79 Crohn's disease, 197 Cryptic epitope, 80 CTL epitope, 522 Cutaneous leishmaniasis, 313 Cytokeratin, 132, 266 Cytokines, 557 Cytolytic cells, 30 Cytomegalovirus (CMV) hepatitis, 336 Cytotoxic T-lymphocytes, 521 D Daudi B-cell line, 123 Daudi cells, 560 Daudi lymphoma, 564 Demyelinating disease, 215 Deoxyspergulain, 63 Dermatitis herpetiformis, 403 Diabetes, 409, 427 DnaJ, 12 DnaK, 7, 537 Double donut, 408 Drosophila, 214, 307 Drosophila melanogaster, 53 Duchenne, 495 Dystrophin gene, 496 E E. coli, 107 Ectopic pregnancy, 302 Enolase, 56 Environmental pollutants, 67 Eosinophilia, 480

Eosinophil cationic proteins (ECPs), 480 Eosinophilic inflammation, 479 Epidermolysis bullosa acquisita, 190 Epitheloid, 361 Epitopes, 524 Epitope spreading, 82 Erythema migrans, 150 Experimental autoimmune encephalo-myelitis (EAE), 215 Eye lens, 12 F Fallopian tube occlusion, 302 Fallopian tubes, 301 Fatty streaks, 446 Feedback, 98 Fertility, 301 Fibromyalgia, 151 Fisher rats, 81 FK506, 55, 63 Flagellin, 147, 152 Foamy macrophages, 216 Fonsecae pedrosoi, 289 Freund's adjuvant, 74 Fungal diseases, 289 G gd T cell receptor, 346, 557 gd T cells, 30, 64, 138, 218, 271, 318, 361, 363, 400, 447, 547, 557 Gastric epithelial cells, 394 Gastritis, 391 Gastroduodenal disease, 391 Gene hsp 70 transcription, 351 Genital ulcers, 163 Germ-free conditions, 78, 81 Gliadin, 399 Glucocorticosteroid receptor, 6 Glucose regulated protein(Grp) 94, 6 Glutamate, 215 Glutamic acid decarboxylase (GAD 65), 228 Glutathione peroxidase, 496 Gluten, 399 Gluten-induced enteropathy, 399 Glyceraldehyde 3-phosphate dehydrogenase, 57 Gp 96, 420 Graft-infiltrating lymphocytes, 331 Graft injury, 327 Gram-negative bacteria, 111 Granulomas, 361 Granulomatous diseases, 364 Granulomatous inflammation, 361

GrpE, 12 Grp 78, 486 GroE, 9 GroEL, 9, 63, 269, 429, 537 GroES, 9, 58 Grp 75, 57 Gro 94, 31 Gullain-Barré syndrome, 152 Gut flora, 86 H Heat, 465 Heart attack, 445 Heart failure, 151 Heart transplants, 328 Heat shock consensus element (HSE), 352 Heat shock element (HSE), 54, 288 Heat shock factor (HSF-1), 54 Heat shock cognate genes, hsc, 288 HeLa cells, 432 Helicobacter pylori, 108, 391 Heme oxygenase (HO), 496 Hepatitis, 388 alcoholic, 388 Hepatocytes, 384 HER2/neu oncogene, 522 Histone-like protein, 109 Histoplasma capsulatum, 37, 64, 289 Histone H2A, 190 Histones, 13 HLA, 350 HLA-B27, 103, 347 HLA-DR, 266 HSF-2, 55 Homunculus, 389 H. pylori, 395 hsp-bound peptides, 524 hsp 10, 267 hsp 104, 12 hsp 110, 12 hsp 28, 11, 60 hsp 60, 9, 57, 147, 216, 227, 231, 347, 413, 429, 502, 559 hsp 65, 75, 199, 252 hsp 70, 7, 57, 536 hsp 70/72, 217 hsp 72, 57, 188, 217, 473 hsp 73, 57 hsp 90, 6, 59, 188, 192, 347 hsp 65, 536 hsp 65, gene, 251 hsp 65-transfected cells, 258

hsp 70 family, 192 hsp 70 gene, 346 hsp 70-2 gene, 193 Human immunodeficiency virus (HIV), 37 Hypercholesterolemia, 452 Hyperglycemia, 429 Hyperthermia, 61, 334 Hyperthermic stress, 465 Hypothalamic-pituitary axis, 62 I Immune complexes, 131 Immunization, 540 Immunoblot, 170 Immunogenic particles, 192 Immunological homunculus, 96 Immunotherapy, 86, 103 Infarction, 61 Infections, 27 Infertility, 301 Inflammation, 479 Inflammatory bowel disease, 190, 197 Inflammatory responses, 86 Insulin-dependent diabetes, 66 Insulin-dependent diabetes mellitus, 95, 148, 227, 409 Insulinoma RINm5F, 431 Insulin-secreting b cells, 409 Insulitis, 227, 409, 429, 431 Interferon gamma (ING-g), 217 Interleukin-1 (IL-1), 217, 486 Interleukin-1 b, 188 Intestinal mucus, 65 Intraepithelial lymphocytes (IELs), 561 Ischemia, 61, 333, 466 Islet inflammation, 413 J JCA, 66, 86, 119 Johne's disease, 198 Joints, 119 Juvenile chronic arthritis (JCA), 66, 86, 119 K Kala-azar, 308 canine, 311 Keratinocytes, 191, 552 Kidney inflammation, 345 Kupffer cells, 384

L Lactoferrin, 132 human, 266 L. donovani, 318 Legionella pneumophila, 36, 64 Leishmania, 37 Leishmania chagasi, 311 Leishmania major, 307, 487 Leishmania mexicana, 307 Leishmaniasis, 307, 561 Leishmania tropica, 536 Lepromatous leprosy, 313 Leprosy, 275 Lewis rats, 177 Limiting dilution, 138 Link protein, 75 Liver, 383, 559 Liver diseases, 383 LK-1, 122, 200, 364, 384 LK-2, 122, 200, 364, 384 Low-density lipoprotein (LDL), 445, 448, 487 Low-molecular-weight hsps, 59 Luciferase, 296 Lupus, 345 Lupus anticoagulant (LAC), 350 Lyme disease, 65, 147 Lymphoproliferation, 353 M Macrophage cell line, 251 Macrophages, 276 Major histocompatibility complex (MHC), 29, 63, 428, 547 Malabsorption, 402 Malaria, 37, 64, 313 Malasezzia furfur, 287 Mammalian hsp 60, 75 Mannoproteins, 294 Marek's disease virus (MDV), 453 Mastocytoma P815, 526 Melanoma, 522, 525 Melanoma antigen MAG, 526 Meningitis, 151 Meningopolyneuritis, 151 Metabolism, 511 Metallothionines, cytochrome 450 system, 67 Methylcholanthrene-induced murine sarcomas, 332 Methylcholanthrene-induced sarcoma, 257 Mimicry, 99 Minor histocompatibility antigens, 328 Mitochondria, 509

Mitochondrial diseases, 509 Mitochondrial encephalomyopathy, 511 Mitochondrial metabolism, 509 Mitochondrial myopathies, 501 Mitogens, 188 Mixed connective tissue disease, 190, 354 MHC, 193 MHC restriction, 30, 533 M. kansasii, 132 M. leprae, 38, 268 MLR augmentation, 330 ML-30, 122, 401, 451 Molecular chaperone, 14, 15 Molecular mimicry, 148, 231, 360, 418 Molecules, 266 Monoclonal antibody, 122 Monomyelocytic line HL60, 189 Mouse, 66 MRL/lpr, 353 MRL/lpr mouse strain, 346 M. tuberculosis, 74, 133, 268, 360 Mucosa, 197 Mucocutaneous candidiasis, 294 Multidrug resistance protein (MDR), 62 Multiple drug-resistant gene product, 55 Multiple sclerosis, 215 Murine EAE, 80 Murine gd T cells, 563 Muscle fibers, 497 Muscular diseases, 495 Muscular dystrophy, 495 Mycobacteria, 360 atypical, 198 Mycobacterial heat shock protein 65, 74 Mycobacterial hsp 70, 561 Mycobacterium avium, 360 Mycobacterium bovi, Mycobacterium leprae, 132 Mycobacterium paratuberculosis, 198 Mycobacterium tuberculosis, 36, 107 Mycobacterium tuberculosis, extracts (MTEs), 328 Myocardium, 465 Myelin, 221 Myelin sheaths, 214 Myopathies, 496 N NANP40, 535 Negative selection, 94, 100

Nervous system, 214 Network, 389 Neurodegenerative diseases, 215 Neuroendocrine mechanisms, 62 Neuropathy, 151 NOD, 148 NOD mouse, 66 NOD mice, 407 NOD strain, 95 Non-insulin-dependent diabetes (NIDDM), 235 Nonobese diabetic, 65 Nonobese diabetic (NOD) mouse, 227, 428 Nucleoplasmin, 3, 13 O Oligoarticular onset, 119 Oligodendrocytes, 214, 216 Oral tolerance, 33 Oral ulcers, 164 Organ transplants, 327 Oxidative injury, 496 Oxidative phosphorylation, 511 Oxidative stress, 496 Oxygen depletion (hypoxia), 467 P P815 Parasite, 560 Paracoccidioides brasiliensis, 291 PBP 72/74, 36 PBP-74, 63 Peptide, 523, 533, 551 Peptide binding, 63 Peptide-binding protein, 188 Peptide p277, 96, 419, 430 Peri-insulitis, 409 Peripheral nerves, 151 P-glycoprotein, 55 Phage lambda, 12 Phase transiti, 291 Phorbol esters, 189 Placenta, 559 Plasmodium falciparum, 64, 312, 535 Polyarthralgia, 151 Polyarticular onset, 119 Polyendocrine autoimmune syndrome, 227 Polymyositis/dermatomyositis, 189, 190, 496, 500 Polymyxin B, 330 Polyoma virus T antigens, 38 PPD, 133, 221

PPD-responsive T cells, 134 Primary biliary cirrhosis, 383 Primary sclerosing cholangitis, 383 Priming to hsp, 540 Pristane arthritis, 78, 81, 126 Prostaglandins, 187 Proteoglycan, 99, 266 Proteoglycan link protein, 132 Psoriatic arthritis, 190 P. yoellii, 560 Pyruvate, 511 Q Qa-2 molecule, 548 Querecetin, 62 R Radiculoneuropathy, 151 Rapamycin, 55 Reactive arthritis, 103, 110, 134 Reactive oxygen species (ROS), 479, 496 Recombinant vaccinia virus, 81 Regulation of autoimmunity, 93 Regulatory cells, 97 Rejection, 327 Remission, 128 Reperfusion, 466 Rhabdomyolysis, 503 Rheumatoid arthritis, 106, 131, 189, 560 RMA-S cell line, 550 Rotamase, 55 Rubella virus infection, 127 Rubisco, 14 S Saccharomyces cerevisiae, 288 Salmonella, 104, 107 Salmonella typhimurium, 37, 65, 536 Salpingitis, 302, 303 Sarcoidosis, 359 Sarcomere hypercontraction, 500 Schwann cells, 38, 275 Schistosoma mansoni, 292 Schistosomiasis, 313 SCW arthritis, 77 Secretory granules, 411 Self-assembly, 13 Self-hsp 60, 82 Self-tolerance, 94 Sexually transmitted disease (STD), 301

Shared epitope, 139 Shigella, 104 Sjögren's syndrome, 189 Skin rashes, 559 Small intestine, 559 Steroid hormone receptors, 6, 348 Steroid receptors, 498 Streptococcal cell wall-induced arthritis, 126 Streptococci, 164 Streptococcus sanguis, 164 Streptozotocine, 95 Superoxide dismutase, 496 Surface expression, 189, 347 Synovial membrane, 121 Synovial T cells, 66 Synovial tissue, 131, 133 Synovium, 74 Systemic lupus erythematosus (SLE), 187, 345 Systemic onset, 119 Systemic sclerosis, 189 T Tailless complex polypeptide (TCP), 10 TB-78, 122 TCP-1, 9, 58 TCP-1 complex, 408 T-cell, 396 T-cell clones, 135 T-cell hybridomas, 559 T-cell lines, 83 T-cell recognition, 86 T-cell responsiveness, 86 Tendonitis, 151 T helper cells, 30 thermotolerance, 54, 61, 289, 465 thymic selection, 100 Thymus, 94 Thoracic ganglion, 214 Thrombocytopaenia, 350 TH1, 487 TH2, 487 Tick borne, 151 T-lymphocyte, 74 T-lymphocyte response, 128 Toroidal complex (TRiC), 409 Toxicology, 67 Toxoplasma gondii, 275 Trachoma, 108 Transcriptional factors, 7 Transcription regulatory regions, 352

Transferrin, 266 Transforming growth factor b (TGF- b), 486 transgenic mice, 97 Transgenic stress reporter organisms, 67 Transplantation, 327 Transplant immunity, 334 Transplant rejection, 334 Trophoblast cell line, 563 Trypanosoma, 292 Trypanosoma brucei, 307 Trypanosoma cruzi, 308 Tubulin, 498 Tuberculin, 204 Tuberculosis, 135, 275 Tumor, 250, 520 Tumor antigens, 521 Tumor-associated antigens, 250, 257 Tumor cell lines, 347 Tumorigenicity, 249, 252 Tumor necrosis factor alpha (TNF-a), 217 Tumor rejection, 525 Tumorrejection antigens, 66 Tyrosine kinases, 6, 498 U Ubiquitin, 12, 15, 502 Ulcerative colitis, 190 Urease, 108, 392 Uveitis, 163 chronic, 121 V Vaccination, 82, 520 Vaccine, 533 Vaccines, 67, 540 V genes, 138 Visceral leishmaniasis, 311 V-region usage, 346 W Whole-body hyperthermia, 469, 472 Y Yeast, 8, 289 Yersinia, 104, 107 Yersinia enterocolitica, 36 Yersinia-infected cells, 106

About the Editors

WILLEM VAN EDEN is a Full Professor of Immunology and Head of the Immunology Section of the Faculty of Veterinary Medicine at Utrecht University, The Netherlands. The author, coauthor, editor, or coeditor of over 100 professional publications, Dr. van Eden is a member of the Dutch Society of Immunology, the Society for Infectious Diseases, the American Society for Microbiology, and the Immunocompromised Host Society, among others. He received the M.D. degree (1978) from the University of Groningen, The Netherlands, and the Ph.D. degree (1983) in immunogenetics from Leiden University, The Netherlands.

DOUGLAS B. YOUNG is the Fleming Professor of Medical Microbiology at St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, England. The author or coauthor of over 100 journal articles and book chapters, Professor Young is currently chairman of the World Health Organization's Steering Committee responsible for the coordination of molecular and immunological research on tuberculosis and leprosy. He received the B.Sc. degree (1975) in biochemistry from the University of Edinburgh, Scotland, and the D.Phil. degree (1978) in biochemistry from the University of Oxford, England.