Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- CHAPTER 1 Introduction -- REFERENCES -- CHAPTER 2 Application of genetic epidemiology to dissecting host susceptibility/resistance to infection illustrated with the study of common mycobacterial infections -- 1. INTRODUCTION -- 2. LINKAGE ANALYSIS -- 2.1 Model-Based Methods -- 2.2 Model-Free Methods -- 2.3 Conclusions -- 3. ASSOCIATION STUDIES -- 4. MYCOBACTERIAL INFECTIONS -- 5. GENOME SCREENS -- 6. THE MAJOR HISTOCOMPATIBILITY COMPLEX -- 6.1 The NRAMP1 Gene -- 6.2 The VDR Gene -- 6.3 The MBL Gene -- 6.4 The IL-1 Genes -- 7. DISCUSSION -- 8. CONCLUSION -- REFERENCES -- CHAPTER 3 The diverse genetic basis of immunodeficiencies -- 1. INTRODUCTION -- 2. INFECTIONS AND TREATMENT -- 3. IMMUNODEFICIENCY INFORMATION SERVICES -- 4. GENETIC BASIS -- 4.1 Immunological Recognition Molecules -- 5. ANTIBODY DEFICIENCIES -- 6. SEVERE COMBINED IMMUNODEFICIENCIES -- 6.1 T-B+ SCID -- 6.2 T-B+ SCID -- 6.3 Deficiencies in Purine Metabolism -- 6.4 Major Histocompatibility Complex Deficiencies -- 6.5 Hyper IgM Syndrome -- 6.6 Other CIDs -- 7. OTHER WELL-DEFINED PIDs -- 8. PHAGOCYTE DEFECTS -- 8.1 Chronic Granulomatous Disease -- 8.2 Leukocyte Adhesion Defects -- 8.3 Chediak-Higashi Syndrome -- 8.4 Glucose 6-Phosphate Dehydrogenase Deficiency -- 8.5 Myeloperoxidase Deficiency -- 9. DNA BREAKAGE-ASSOCIATED SYNDROMES -- 10. COMPLEMENT DEFECTS -- 11. IMMUNODEFICIENCY MUTATION DATABASES (IDBASES) -- REFERENCES -- CHAPTER 4 Genetic diversity in the major histocompatibility complex and the immune response to infectious diseases -- 1. INTRODUCTION: THE NATURAL HISTORY OF INFECTIOUS DISEASES -- 2. GENETIC CONTRIBUTIONS TO IMMUNE RESPONSES AGAINST INFECTIOUS AGENTS -- 3. THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX -- 4. LINKAGE DISEQUILIBRIUM AND HLA HAPLOTYPES.

5. THE DESIGN OF STUDIES OF HLA AND DISEASE OUTCOME -- 6. STATISTICAL ISSUES IN MHC ASSOCIATIONS -- 7. THE MHC, IMMUNE RESPONSE, AND THE NATURAL HISTORY OF INFECTIOUS DISEASES -- 8. DISEASE ASSOCIATION STUDIES -- 9. MECHANISM OF MHC ASSOCIATIONS -- 10. HOST-PARASITE INTERACTIONS -- 11. EVOLUTIONARY ORIGINS OF THE HLA COMPLEX -- 12. CLINICAL USE OF MHC DISEASE ASSOCIATION STUDIES -- 12.1 Prognostic Information -- 13. RESPONSES TO THERAPY AND VACCINATION -- 14. VACCINE DEVELOPMENT -- 15. CONCLUSIONS -- ACKNOWLEDGMENTS -- REFERENCES -- CHAPTER 5 The cystic fibrosis transmembrane conductance regulator -- 1. INTRODUCTION -- 2. WHAT IS CF? -- 3. APICAL MEMBRANE LOCATION OF CFTR -- 4. THE ROLE OF CFTR IN EPITHELIAL TRANSPORT PROCESSES -- 5. IS AIRWAY INFECTION IN CF DUE TO LACK OF CFTR? -- 5.1 Effects on Airway Surface Liquid (ASL) -- 5.2 Protein Processing, Bacterial Adherence, and CF -- 5.3 Other Regulatory Functions of CFTR and Bacterial Infection -- 6. CFTR AND THE MALARIAL PARASITE -- 7. HETEROZYGOTE ADVANTAGE AGAINST INFECTIOUS DISEASE -- 8. SUMMARY -- REFERENCES -- CHAPTER 6 The influence of inherited traits on malaria infection -- 1. INTRODUCTION -- 2. THE CONTRIBUTION OF GENETIC TRAITS TO RESISTANCE TO MALARIA -- 3. THE SEARCH FOR INHERITED TRAITS CONFERRING RESISTANCE TO MALARIA -- 3.1 Association Studies -- 3.2 Studies Comparing Ethnic Groups -- 3.3 Linkage Studies -- 4. PROTECTIVE TRAITS -- 4.1 Haemoglobinopathies -- 4.1.1 Sickle Cell Trait -- 4.1.2 The Thalassaemia Syndromes -- 4.1.2.1 Population Genetics of the Thalassaemias -- 4.1.2.2 Epidemiological Studies -- 4.1.3 Other Haemoglobinopathies -- 4.2 Red Cell Enzymes -- 4.3 Mechanisms of Protection in the Haemoglobinopathies and G6PDH Deficiency -- 4.3.1 Reduced Invasion and Growth -- 4.3.2 Cytoadherence of P. falciparum-Infected Variant Red Blood Cells -- 4.3.3 Phagocytosis.

4.3.4 Immune-Mediated Mechanisms -- 4.3.5 Conclusion -- 4.4 Membrane Proteins -- 4.4.1 Duffy Blood Group System -- 4.4.2 Other Red Blood Cell Surface Antigens -- 4.5 Red Blood Cell Cytoskeletal Proteins -- 4.5.1 Southeast Asian Ovalocytosis -- 4.5.2 Other Red Cell Cytoskeletal Proteins -- 4.6 Immune Response Genes -- 4.6.1 HLA Class I and Class II -- 4.6.2 Tumour Necrosis Factor and Other Cytokines -- 4.6.3 Nitric Oxide Synthase -- 4.6.4 Other Immune Response Genes -- 4.7 Host Receptors for Infected Erythrocytes on Endothelium and Uninfected Erythrocytes -- 5. NEGATIVE ASSOCIATION STUDIES -- 6. CONCLUSION -- ACKNOWLEDGMENTS -- REFERENCES -- CHAPTER 7 Polymorphic chemokine receptor and ligand genes in HIV infection -- 1. CLASSIFICATION, EVOLUTION, AND FUNCTION OF CHEMOKINE RECEPTORS AND THEIR LIGANDS -- 2. CHEMOKINE SYSTEM AND HIV-1 INFECTION -- 3. CHEMOKINE RECEPTOR AND LIGAND POLYMORPHISMS: REGIONAL AND GLOBAL DISTRIBUTION AND DELINEATION OF GENOTYPE-PHENOTYPE RELATIONSHIPS -- 4. POLYMORPHISMS OF CHEMOKINE RECEPTOR AND LIGAND GENES IN RELATION TO HIV-1 INFECTION, HOST-VIRUS EQUILIBRATION, AND DISEASE PROGRESSION -- 5. APPLICATIONS OF IMMUNOGENETIC FINDINGS -- 6. SUMMARY -- ACKNOWLEDGMENTS -- REFERENCES -- CHAPTER 8 NRAMP1 and resistance to intracellular pathogens -- 1. INTRODUCTION -- 2. STUDIES IN MICE -- 2.1 Discovery of the Ity/Lsh/Bcg Locus -- 2.2 Positional Cloning of the Mouse Nramp1 Gene -- 2.3 Expression of Nramp1 in Professional Phagocytes -- 2.4 Divalent Cation Transport by Nramp Proteins -- 2.5 Nramp1 Transport at the Phagosomal Membrane -- 2.6 Consequences of Nramp1-Dependent Divalent Cation Transport on Microbial Virulence -- 2.7 Conclusions and Perspectives from Studies in Mice -- 3. STUDIES IN SPECIES OTHER THAN MICE -- 3.1 Livestock Species -- 3.2 Human NRAMP1 -- 3.3 Genetic Studies Employing NRAMP1 as Candidate Gene.

4. NRAMP1 AND TUBERCULOSIS -- 5. NRAMP1 AND LEPROSY -- 6. NRAMP1 AND INFECTIONS OTHER THAN TUBERCULOSIS AND LEPROSY -- 7. NRAMP1 AND AUTOIMMUNE DISORDERS -- 8. CONCLUSIONS FROM STUDIES IN HUMAN POPULATIONS -- REFERENCES -- CHAPTER 9 The interleukin-12/interferon-gamma loop is required for protective immunity to experimental and natural infections by Mycobacterium -- 1. INTRODUCTION -- 2. MOLECULAR BASIS OF THE HUMAN SYNDROME OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL INFECTION -- 2.1 IFNGR1 Mutations -- 2.1.1 Complete IFNgammaR1 Deficiency -- 2.1.2 Partial IFNgammaR1 Deficiency -- 2.2 IFNGR2 Mutations -- 2.2.1 Complete IFNgammaR2 Deficiency -- 2.2.2 Partial IFNgammaR2 Deficiency -- 2.3 STAT1 Mutations -- 2.4 IL-12B Mutations -- 2.5 IL-12RB1 Mutations -- 3. SUSCEPTIBILITY TO EXPERIMENTAL MYCOBACTERIAL INFECTION IN MICE WITH IMPAIRED IL-12/IFNgamma LOOP -- 3.1 IFNgamma o/o Mice and IFNgamma R o/o Mice -- 3.2 IL12p40 o/o, IL12p35 o/o, and IL12p35 o/o p40 o/o Mice -- 3.3 IL-18 and IL-1alpha/beta and IL-1R1 o/o Mice: Parallel IFNgamma Inducing Pathways -- 3.4 TNFgamma, TNFR1 o/o Mice: IFNγ-Inducible Genes -- 4. IRF-1 AND NOS2: OTHER IFNγ-INDUCIBLE GENES -- 5. CONCLUSIONS -- REFERENCES -- CHAPTER 10 Mannose-binding lectin deficiency and susceptibility to infectious disease -- 1. INNATE IMMUNITY -- 2. THE COMMON OPSONIC DEFECT -- 3. MANNOSE-BINDING LECTIN -- 4. MBL DEFICIENCY AND GENETICS -- 5. MBL IN INFECTIOUS DISEASE -- 6. MBL DISEASE ASSOCIATIONS -- 6.1 Meningococcal Disease -- 6.2 HIV Infection -- 6.3 Neutropenia -- 7. THE ROLE OF MBL DEFICIENCY -- 8. CLINICAL PRESENTATION OF MBL DEFICIENCY -- 9. CONCLUSIONS -- ACKNOWLEDGMENTS -- REFERENCES -- CHAPTER 11 Blood group phenotypes and infectious diseases -- 1. INTRODUCTION -- 2. HYPOTHESES -- 3. BLOOD GROUP ANTIGENS AS RECEPTORS FOR MICROORGANISMS OR THEIR TOXINS.

3.1 Binding of Microorganisms to Host Cells -- 3.2 Studies on Inhibition of Binding of Microorganisms -- 3.3 Binding of Synthetic Blood Group Antigens -- 3.4 Isolation of Adhesins By Affinity Adsorption with Synthetic Antigens -- 3.5 Blood Group Antigens as Receptors or Inhibitors for Bacterial Toxins -- 4. FREQUENCY AND DENSITY OF COLONISATION OF EPITHELIAL SURFACES -- 4.1 Frequency of Colonisation -- 4.2 Density of Colonisation -- 4.3 Secretor Status and Density of Colonisation -- 5. BINDING OF BACTERIA TO BLOOD GROUP ANTIGENS: ASSESSMENT OF EXPERIMENTAL STUDIES IN RELATION TO EPIDEMIOLOGY -- 5.1 Environmental Factors Affect Expression of Blood Group Antigens and Bacterial Binding -- 6. IMMUNE/INFLAMMATORY RESPONSES AND BLOOD GROUPS -- 6.1 Immune Responses -- 6.1.1 Protection -- 6.1.2 Tolerance -- 6.2 Inflammatory Responses -- 7. DISEASES TRIGGERED BY INFECTIOUS AGENTS? -- 7.1 H. pylori and Peptic Ulcers -- 7.2 H. pylori and Gastric Carcinoma -- 7.3 H. pylori and Ischaemic Heart Disease (IHD) -- 8. CONCLUSIONS AND APPLICATIONS -- REFERENCES -- CHAPTER 12 Genetics of human susceptibility to infection and hepatic disease caused by schistosomes -- 1. HUMAN RESISTANCE TO INFECTION BY SCHISTOSOMES IN A BRAZILIAN POPULATION -- 1.1 Evidence that a Major Gene is Involved in the Control of Infection -- 1.2 Localisation of SM1 on Chromosome 5q31-q33 -- 1.3 Search for Additional Loci Controlling the Levels of S. mansoni Infection -- 2. HEPATIC FIBROSIS IN SCHISTOSOME-INFECTED SUBJECTS -- 2.1 The Egg Granuloma -- 2.2 Susceptibility to Periportal Fibrosis Caused by Schistosoma mansoni in a Sudanese Population -- 2.3 Severe Hepatic Fibrosis is Controlled by SM2 Located in the 6q22-q23 Region -- 3. HOW DOES (DO) THE GENE(S) IN 5q31-q33 CONTROL S. MANSONI INFECTION?.

4. ROLE OF INTERFERON-gamma AND TNF-alpha IN SUSCEPTIBILITY TO HEPATIC FIBROSIS CAUSED BY S. MANSONI.