Table of Contents

Introduction: Immunoparasitology: The Making of a Modern Immunological science 1
Alan Sher

Section 1

1 Notes on the Immune System 15
Tracey J. Lamb

1.1 The immune system 15

1.2 Innate immune processes 17

1.3 The complement cascade 19

1.4 Innate recognition 20

1.5 Pattern recognition receptors 21

1.6 Innate immune cells 23

1.7 Communication in the immune system 31

1.8 Adaptive immunity 31

1.9 The role of theMHC in the immune response 34

1.10 T cell activation and cellular-mediated immunity 36

1.11 B cells and the humoral response 43

1.12 Cell trafficking around the body 49

1.13 Cellular immune effector mechanisms 50

1.14 Hypersensitivity reactions 52

References for further reading 54

Section 2

2 Introduction to Protozoan Infections 61
David B. Guiliano and Tracey J. Lamb

2.1 The protozoa 61

2.2 Amoebozoa 62

2.3 Excavata 67

2.4 Harosa 75

2.5 Protozoa that are now fungi 81

2.6 Taxonomy and the evolution of the parasitic protozoa 82

2.7 Genomic and post genomic exploration of protozoan biology 83

2.8 Summary 87

2.9 General information on protozoa 88

References for further reading 88

3 Apicomplexa:Malaria 91
Tracey J. Lamb and Francis M. Ndung’u

3.1 Malaria 91

3.2 Recognition ofmalaria parasites 94

3.3 Innate effector mechanisms 95

3.4 Adaptive immunity 98

3.5 Memory responses 101

3.6 Immune evasion 101

3.7 Immunopathology 103

References for further reading 105

4 Apicomplexa: Toxoplasma gondii 107
EmmaWilson

4.1 Introduction 107

4.2 Life cycle and pathogenesis 107

4.3 Innate immune responses 111

4.4 Evasion strategies 113

4.5 Adaptive immune responses 115

4.6 CNS infection 117

4.7 Conclusions 118

References for further reading 118

5 Apicomplexa: Cryptosporidium 121
Jan R. Mead andMichael J. Arrowood

5.1 Life cycle 122

5.2 Clinical presentation 123

5.3 General immune responses in cryptosporidiosis 124

5.4 Innate effector mechanisms 125

5.5 Adaptive immunity 127

5.6 Memory responses 131

5.7 Antigens eliciting the immune response 132

5.8 Immune evasion 132

5.9 Immunopathology in the gut and intestinal tract 134

References for further reading 134

6 Diplomonadida: Giardia 139
Steven Singer

6.1 The life cycle and pathogenesis of Giardia infection 139

6.2 Recognition of Giardia by the immune system 141

6.3 Innate effector mechanisms against Giardia 142

6.4 Adaptive immunity against Giardia 143

6.5 Memory responses 145

6.6 Antigens eliciting the immune response 146

6.7 Immune evasion 147

6.8 Immunopathology 148

6.9 Summary 150

References for further reading 150

7 Kinetoplastids: Leishmania 153
IngridM¨ uller and Pascale Kropf

7.1 The pathogenesis of Leishmania infection 153

7.2 Life cycle 154

7.3 Parasite transmission and avoidance of immune responses 155

7.4 Innate effector mechanisms: the role of neutrophils in Leishmania infection 157

7.5 Adaptive immunity: lessons from L. major infections of mice 158

7.6 Arginase promotes Leishmania parasite growth 162

7.7 Memory responses 163

References for further reading 164

8 Kinetoplastids: Trypanosomes 165
Jeremy Sternberg

8.1 The African trypanosomes (Trypanosoma brucei ssp.) 165

8.2 Pathogenesis of sleeping sickness 167

8.3 Variant surface glycoprotein – the key to trypanosome-host interactions 168

8.4 The humoral response to African trypanosomes 172

8.5 T cell responses in African trypanosome infections 173

8.6 Innate defence mechanisms: trypanosome lytic factor 173

8.7 Immunopathology and VSG 174

8.8 Summary 175

References for further reading 176

9 Kinetoplastids: Trypanosoma cruzi (Chagas disease) 179
Rick Tarleton

9.1 Life cycle and transmission 180

9.2 Immune control and disease 181

9.3 Innate recognition of T. cruzi 182

9.4 Adaptive immunity 183

9.5 Regulation of immune responses and parasite persistence 186

9.6 Conclusions 189

References for further reading 189

Section 3

10 Introduction to Helminth Infections 195
David B. Guiliano

10.1 Acanthocephala 196

10.2 Nematodes 196

10.3 Pentastomida 203

10.4 Platyhelminthes 203

10.5 The evolution of parasitism within the helminths: divergent phyla with common themes 208

10.6 Genomic and post-genomic exploration of helminth biology 211

10.7 Summary 211

References for further reading 213

11 Nematoda: Filarial Nematodes 217
Sabine Specht and Achim Hoerauf

11.1 The life cycle and pathogenesis of filarial nematode infections 217

11.2 Animal models of filariasis 220

11.3 Immune responsesmounted against filarial nematodes 221

11.4 Innate immunity 221

11.5 Adaptive immunity 224

11.6 Immune evasion 225

11.7 Immunopathology 228

References for further reading 229

12 Nematoda: Ascaris lumbricoides 231
Christina Dold

12.1 Introduction 231

12.2 Ascaris infection displays an over-dispersed frequency distribution 232

12.3 Life cycle 232

12.4 Pathogenesis of infection 233

12.5 Animal models of Ascaris infection 234

12.6 Immune responses generated against the migratory phase of Ascaris 235

12.7 The cytokine response to Ascaris lumbricoides 237

12.8 The humoral response to Ascaris lumbricoides 238

12.9 Antigens eliciting immune responses in Ascaris infection 241

12.10 Conclusions 242

References for further reading 243

13 Nematoda: Hookworms 247
Soraya Gaze, HenryMcSorley and Alex Loukas

13.1 Pathogenesis of hookworminfection 247

13.2 The life cycle of hookworms 248

13.3 Animal models of hookworminfection 249

13.4 Innate immune responses to hookworms 251

13.5 Adaptive immunity 252

13.6 Cytokine responses 253

13.7 Antibody responses 254

13.8 Antigens eliciting the immune response 255

13.9 Memory responses 255

13.10 Immunoregulatory aspects of the anti-hookwormimmune response 256

13.11 Conclusion 258

References for further reading 259

14 Nematoda: Trichuris 263
Colby Zaph

14.1 Trichuris infection 263

14.2 Life cycle and pathogenesis 264

14.3 Immunity to Trichuris 265

14.4 Recognition by the immune system 265

14.5 Innate immune responses 265

14.6 Adaptive immune responses 269

14.7 Immune memory 269

14.8 Vaccines 270

14.9 Trichuris as a therapeutic 270

14.10 Summary 271

References for further reading 271

15 Nematoda: Trichinella 275
Judith A. Appleton, Lisa K. Blum and Nebiat G. Gebreselassie

15.1 Life cycle 275

15.2 Pathogenesis 277

15.3 Adaptive immunity 278

15.4 Immunopathology 282

15.5 Evasion strategies 283

References for further reading 284

16 Trematoda: Schistosomes 287
Mark Wilson

16.1 The schistosome life cycle 287

16.2 Immunological recognition of schistosomes 290

16.3 Innate effector mechanisms 291

16.4 Adaptive immunity 292

16.5 Memory responses 297

16.6 Schistosome antigens eliciting immune responses 298

16.7 Immune evasion 298

16.8 Schistosomiasis and immunopathology 299

References for further reading 303

17 Cestoda: Tapeworm Infection 307
Cèsar A. Terrazas,Miriam Rodríguez-Sosa and Luis I. Terrazas

17.1 The life cycle of tapeworms 307

17.2 Epidemiology 309

17.3 Pathology 310

17.4 Innate immunity 311

17.5 Adaptive immunity 312

17.6 Antigens eliciting the immune responses 315

17.7 Immunomodulation or evasivemechanisms 316

17.8 Echinococcosis 316

17.9 Conclusions 320

References for further reading 320

Section 4

18 Co-infection: Immunological Considerations 325
Joanne Lello

18.1 Co-infection is the rule rather than the exception 325

18.2 Interactions between co-infecting parasites 326

18.3 The Th1/Th2 paradigm in co-infection 327

18.4 Co-infection can alter disease severity 328

18.5 Modelling parasite interactions during co-infection 329

18.6 Co-infection as a therapy? 330

18.7 Consideration of co-infection in an ecological framework 331

18.8 Concluding remarks 332

References for further reading 333

19 HIV and Malaria Co-infection 335
Aubrey Cunnington and EleanorM. Riley

19.1 The endemicity of HIV and malaria 335

19.2 HIV infection 335

19.3 Immunopathogenesis of HIV 341

19.4 Interactions between malaria and HIV 343

19.5 Effect of co-infection on treatment of HIV and malaria infections 347

19.6 Combined effects of HIV and malaria on susceptibility to other diseases 348

19.7 Malaria and HIV vaccines 349

19.8 Summary 351

References for further reading 351

20 HIV and Leishmania Co-infection 353
JavierMoreno

20.1 Leishmania parasitaemia is increased in HIV-Leishmania co-infection 354

20.2 Leishmania infection increases viral replication rate 354

20.3 Cell specific interactions between HIV-1 and Leishmania 355

20.4 Immune response interactions between HIV-1 and Leishmania 357

20.5 Immune reconstitution inflammatory syndrome in HIV-1/Leishmania co-infection 358

References for further reading 359

21 Gastrointestinal Nematodes and Malaria 361
Mathieu Nacher

21.1 Introduction 361

21.2 Results from field studies in humans are conflicting 361

21.3 Immune responses in GI nematode and malaria co-infections 363

21.4 Stereotypical but different 370

21.5 Animal models of GI nematode-malaria co-infection 370

21.6 Conclusions 372

References for further reading 372

22 Malaria and Schistosomes 375
ShonaWilson and Jamal Khalife

22.1 The epidemiology of schistosomiasis and malaria co-infection 375

22.2 Study design for malaria/schistosome co-infection studies 376

22.3 Antibody responses 380

22.4 Cytokine responses 382

22.5 Contribution of experimental models to the understanding of Schistosoma mansoni and Plasmodium co-infection 384

22.6 Conclusions 385

References for further reading 385

Section 5

23 Hygiene and Other Early Childhood Influences on the Subsequent Function of the Immune System 391
Graham A.W. Rook

23.1 Introduction 392

23.2 The Hygiene Hypothesis (or ‘Old Friends’ hypothesis) 392

23.3 Epidemiological transitions 393

23.4 Compensatory genetic variants 394

23.5 The critical organisms and their immunological role 395

23.6 Helminth infections and allergic disorders 395

23.7 Helminths and non-allergic chronic inflammatory disorders: human data 396

23.8 Animal models of helminth infection used to test the Hygiene Hypothesis 397

23.9 Non-helminthic ‘Old Friends’ 397

23.10 Mechanisms of immunoregulation 398

23.11 Conclusions 399

References for further reading 400

24 Nematodes as Therapeutic Organisms 401
William Harnett andMargaretM. Harnett

24.1 Evidence that parasitic nematodes can protect humans from allergy and autoimmunity 401

24.2 Mechanism of action 404

24.3 Nematodemolecules involved in preventing allergic/autoimmune disease 408

24.4 Clinical aspects 412

References for further reading 413

25.1 Vaccination AgainstMalaria 417
AlbertoMoreno

25.1.1 Malaria vaccines: proof of concept 417

25.1.2 Vaccine development 419

25.1.3 Pre-erythrocytic vaccines 420

25.1.4 Erythrocytic vaccines 423

25.1.5 Transmission-blocking vaccines 425

25.1.6 Whole organism vaccines 426

25.1.7 P. vivax vaccines 427

25.1.8 Concluding remarks 429

References for further reading 429

25.2 Current Approaches to the Development of a Vaccine Against Leishmaniasis 431
Yasuyuki Goto and Steven G. Reed

25.2.1 Vaccination against leishmaniasis 432

25.2.2 Anti-amastigote vaccines 432

25.2.3 Anti-saliva vaccines 436

25.2.4 Transmission prevention vaccines 436

25.2.5 Role of an adjuvant in vaccine development 436

25.2.6 Future directions 438

References for further reading 438

25.3 Vaccination Against Hookworms 441
Brent Schneider,Maria Victoria Periago and Jeffrey M. Bethony

25.3.1 The need for a vaccine 441

25.3.2 The Human HookwormVaccine Initiative 442

25.3.3 The history of hookwormvaccines: experiments in dogs 443

25.3.4 Antibody production against canine hookworm 443

25.3.5 Vaccination against hookwormwith irradiated larvae 444

25.3.6 Lessons from vaccination with irradiated larvae 445

25.3.7 Research identifying target proteins for an anti-hookwormvaccine 446

25.3.8 A human hookwormvaccine phase 1 clinical trial based on Na-ASP2 453

25.3.9 The HHVI takes a different approach 454

25.3.10 Developments through the last century and the future 455

References for further reading 456

25.4 Current Approaches to the Development of a Vaccine Against Filarial Nematodes 459
Sara Lustigman

25.4.1 Introduction to anti-filarial nematode vaccines 459

25.4.2 Anti-O. volvulus and anti-LF vaccines are a valid approach to advance control measures against onchocerciasis and lymphatic filariasis 461

25.4.3 Future directions for vaccine development 466

25.4.4 Discovery of new vaccine candidates 467

References for further reading 468

Abbreviations 471

Glossary 479

Index 493