Table Of ContentMalaria Immunology
Chemical Immunology
Vol.80
Series Editors
Luciano Adorini Milan
Ken-ichi Arai Tokyo
Claudia Berek Berlin
Anne-Marie Schmitt-Verhulst Marseille
Byron H. Waksman New York, N.Y.
Malaria Immunology
2nd,revised and enlarged edition
Volume Editors
Peter Perlmann Stockholm
Marita Troye-Blomberg Stockholm
29 figures and 13 tables, 2002
Basel(cid:1)Freiburg(cid:1)Paris(cid:1)London(cid:1)New York(cid:1)
New Delhi(cid:1)Bangkok(cid:1)Singapore(cid:1)Tokyo(cid:1)Sydney
Chemical Immunology
Formerly published as ‘Progress in Allergy’
Founded in 1939 by Paul Kallòs
Vol. 41 (1st edition)
Malaria Immunology
Editors:Hans Wigzell; Peter Perlmann, Stockholm
X+374 p., 38 fig., 13 tab., hard cover, 1988. ISBN 3–8055–4672–6
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents®and
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Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and
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However, in view of ongoing research, changes in government regulations, and the constant flow of information
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when the recommended agent is a new and/or infrequently employed drug.
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© Copyright 2002 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
www.karger.com
Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel
ISSN 1015–0145
ISBN 3–8055–7376–6
Contents
XV Preface
Malaria Parasites and Disease
3 Structure and Life Cycle
Fujioka, H., Cleveland, Ohio; Aikawa, M.,Kanagawa
3 Introduction
3 Life Cycle
4 Erythrocytic Schizogony Merozoites
4 Host Cell Entry
7 Trophozoites and Schizonts
8 Host Cell Alterations by Malaria Parasites
8 Knob Formation and Cytoadherence
30 Cytoplasmic Clefts
33 Tubovesicular Network
33 Caveola-Vesicle Complexes
33 Sexual Forms
33 Mosquito Stages
33 Fertilization and Zygote Formation
34 Ookinete and Oocyst
36 Sporozoite
37 Preerythrocytic Schizogony
39 Acknowledgements
20 References
27 Malaria Parasites and the Anopheles Mosquito
Dimopoulos,G., London; Kafatos,F.C., Heidelberg; Waters,A.P., Leiden;
Sinden,R.E., London
27 Introduction
28 The Biology of Malaria Development in the Mosquito Bloodmeal
28 Gametocytes
30 Gametogenesis
30 Zygote-Ookinete Differentiation
32 Biology of Malaria Development within and beyond the Midgut Epithelium
32 Biology of Oocyst Differentiation
34 Biology of Sporozoite Development
35 Insect Innate Immunity
36 Mosquito Antimalarial Defence
36 Melanisation and Encapsulation of Malaria Parasites
38 Spatio-Temporal Immune Responses to Malaria Infection
39 Immunity Genes of A. gambiae
39 Pattern Recognition Receptors
39 Serine Proteases and Serpins
40 Transcriptional Control of Immune Responses
43 Antimicrobial Peptides
43 Prophenoloxidases
43 Parasite Development in the Mosquito as a Target for Malaria Control
42 Antibodies and Drugs Delivered from the Host
42 Engineering Parasite Refractory Mosquitoes
43 Acknowledgements
43 References
50 Malaria:Pathogenicity and Disease
English, M.; Newton,C.R.J.C., Kilifi
50 Introduction
50 Epidemiology of Disease
53 Virulence of Falciparum Malaria
53 Mediators of Severe Disease
53 Reactive Oxygen Species
52 Cytokines
54 Nitric Oxide
55 Red Cell Deformability
55 Disease Caused by Malaria
55 Mild Malaria
56 Syndromes of Severe Malaria
56 Severe Malarial Anaemia
58 Respiratory Distress
59 Neurological Manifestations of Malaria
59 Disturbances of Consciousness and CM
60 CM in African Children
Contents VI
60 Pathogenesis of CM
60 Brain Swelling
63 Neurological Sequelae
63 Seizures and Malaria
63 Other Manifestations of Severe Disease
63 Renal Disease
62 Shock, Cardiovascular and Pulmonary Disease
63 Hypoglycaemia
63 Disease in Pregnancy
64 Future Approaches to the Treatment of Clinical Malaria
64 References
Malaria Antigens
70 Sporozoite Antigens:Biology and Immunology of
the Circumsporozoite Protein and Thrombospondin-Related
Anonymous Protein
Sinnis,P.; Nardin,E., New York, N.Y.
70 Introduction
73 Identification of Sporozoite Antigens
73 CS Protein
73 Thrombospondin-Related Anonymous Protein
74 Biological Function of Sporozoite Antigens
74 Sporozoite Development in the Mosquito
75 Sporozoite Invasion of Salivary Glands
76 Development of Infectivity by Sporozoites
77 Sporozoite Inoculation into the Skin of the Vertebrate Host
77 Sporozoite Invasion of Hepatocytes
80 Immunologic Responses to Sporozoites
80 Experimental and Naturally Acquired Immunity to Sporozoites
83 Immune Effector Mechanisms
83 Subunit Vaccines Based on Sporozoite Antigens
83 Targeting the Extracellular Sporozoite
83 T and B Cell Epitopes of CS Proteins
85 Synthetic Peptide Vaccines Based on the CS Protein
89 Targeting the Intracellular Parasite
90 Conclusions
93 References
97 Immune Responses to Liver-Stage Parasites:Implications
for Vaccine Development
Hollingdale,M.R., London; Krzych,U., Silver Spring, Md.
97 Introduction
98 Biology of Liver-Stage Malaria Parasites
Contents VII
99 Antigens Detected in Liver Stages
99 Liver-Stage Antigen-1
300 Liver-Stage Antigen-2
300 Liver-Stage Antigen-3
303 P. falciparumSporozoite and Liver Stage Antigen
303 Sporozoite Threonine- and Asparagine-Rich Protein
303 PfEXP-1/PyHEP17
303 Glutamate-Rich Protein
303 Other Antigens
303 CSP-2
302 Pbl.1
302 Heat Shock Proteins
302 Blood-Stage Antigens
302 Mechanisms of Protective Immunity to Liver-Stage Parasites
307 Evidence that Liver Stage Immunity Is Protective in Humans
307 LSA-1
309 LSA-3 and PfEXP-1
309 SALSA
309 SALSA and STARP
309 GLURP
330 Heat Shock Protein Pfhsp60
330 HLA and Genetic Resistance to Liver-Stage Antigens
333 Experimental Immunization with Liver-Stage Antigens
333 Adjuvants and Delivery Systems
332 CpG
332 Granulocyte-Macrophage Colony-Stimulating Factor
333 Lipopeptides
333 Immunization with Individual Liver-Stage Antigens
333 LSA-1
334 LSA-3/SALSA/STARP
334 GLURP
334 Ty and VLP Articulate Delivery Systems: The Importance
of Prime-Boost Strategies
335 Recombinant Viruses
335 DNA Prime, Vaccinia Virus Boost
335 Ty Particle Prime, Vaccinia Virus Boost
336 Conclusions
336 References
325 Merozoite Antigens Involved in Invasion
Berzins,K., Stockholm
326 Erythrocyte Receptors
328 Merozoite Surface Antigens
328 Integral Membrane Proteins
332 Merozoite Surface-Associated Antigens
334 Antigens Present in the Apical Organelles of Merozoites
334 Antigens of Micronemes
Contents VIII
335 Rhoptry Antigens
336 Antigens of Dense Granules
337 Concluding Remarks
337 Acknowledgements
338 References
344 Asexual Blood Stages of Malaria Antigens:Cytoadherence
Baruch,D.I., Bethesda, Md.; Rogerson,S.J., Parkville; Cooke,B.M., Melbourne
345 Host Adhesion Receptors
347 Adhesion and Pathogenesis
349 Antigenic Diversity and Antigenic Variation
349 VarGenes and the P. falciparumAdhesion Receptor, PfEMP1
353 Adhesion Domains in PfEMP1
352 DBL1-(cid:2): A GAG-Binding Domain that Mediates Rosetting
352 CIDR1-(cid:2): A Multi-Adhesive Domain that Binds to CD36
353 DBL-(cid:3)-C2: An ICAM-1-Binding Domain
353 DBL-(cid:4)an d A d hesion to CSA
354 DBL-(cid:5): Role in PECAM-1/CD31 Binding
354 Other Host Receptors
354 Modulation of Parasite Adhesion
355 Other Parasite-D e rived or Parasite-Induced Adhesion Receptors
355 Adhesio n o f PEs under Flow
357 Acknowledgements
357 References
363 Rosetting and Autoagglutination in Plasmodium falciparum
Fernandez, V.; Wahlgren, M.,Stockholm
363 Rosetting
365 Autoagglutination
365 Giant Rosetting
365 Prevalence of Rosetting and Autoagglutinating Malaria Parasites
369 Association of Rosetting and Autoagglutination with Severe Disease
370 The Molecular Basis of Rosetting: Multiple Host R e c eptors
374 Several Serum Proteins
375 One Parasite Ligand Family
378 Autoagglutination Mechanisms
379 RBC Polymorphisms and Rosetting
379 Rosetting, Autoagglutination, Multiadhesion, and Severe Malaria
383 Closing Remarks
383 References
388 Sexual and Sporogonic Stage Antigens
Sauerwein, R.W.; Eling, W.M.C.,Nijmegen
388 Introduction
389 Antigens Expressed on Surface Membrane of Red Blood Cells with Gametocytes
Contents IX
