Immunity to Parasitic Infection

Parasitic infections remain a significant cause of morbidity and mortality in the world today. Often endemic in developing countries many parasitic diseases are neglected in terms of research funding and much remains to be understood about parasites and the interactions they have with the immune system. This book examines current knowledge about immune responses to parasitic infections affecting humans, including interactions that occur during co-infections, and how immune responses may be manipulated to develop therapeutic interventions against parasitic infection. For easy reference, the most commonly studied parasites are examined in individual chapters written by investigators at the forefront of their field. An overview of the immune system, as well as introductions to protozoan and helminth parasites, is included to guide background reading. A historical perspective of the field of immunoparasitology acknowledges the contributions of investigators who have been instrumental in developing this field of research. CONTENTS List of Contributors xiii 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 C´esar A. Terrazas,Miriam Rodr´ýguez-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