Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- Preface to the first edition -- Preface to the second edition -- 1 Molecular and cell biology -- Key points -- Molecular biology -- The human genome and gene structure -- Gene transcription -- Transcription factors -- Zinc fingers -- Leucine zippers -- Helix-turn-helix motifs -- Activation domains -- Repression -- Control of transcription: tissue specificity -- mRNA and protein synthesis -- Protein synthesis: mRNA translation -- Ribosomes -- tRNA -- Translation -- Protein secretion -- Post-translational processing -- Cellular signalling and growth regulation -- Membrane receptors -- G protein-linked receptors -- G protein-independent receptors -- Nuclear receptors -- G proteins -- Second messengers: the cAMP/protein kinase A system -- Cyclic AMP -- Protein kinase A -- Second messengers: the phospholipid/calcium signalling system -- Inositol lipid signalling -- Protein kinase C and DAG -- IP3, intracellular calcium and calmodulin -- Effects of signalling pathways on gene transcription -- Cyclic AMP and CREB -- Protein kinase C and activator protein-1 -- Alterations of signalling pathways in human disease -- Membrane receptors -- G proteins -- Kinases -- Nuclear receptors and transcription factors -- Summary: signalling, proto-oncogenes, and oncogenes -- Cell cycle and growth regulation -- Tumour suppressor genes -- p53 -- Apoptosis -- Molecular biology: methods of investigation -- Enzymes -- Endonucleases (restriction endonucleases) -- Ligases -- Polymerases -- Reverse transcriptase -- cDNA synthesis -- Cloning -- Vectors -- Libraries -- Library screening -- Subtractive hybridisation -- Nucleic acid analysis -- Gel electrophoresis -- Blotting techniques -- Labelling nucleic acids -- Identification -- Sequencing -- Polymerase chain reaction.

Application of molecular techniques -- Analysis of gene transcription -- mRNA analysis -- Mechanisms of regulation: gene promoter analysis -- Transgenic animals -- Gene targeting by homologous recombination -- Targeted dominant negative receptor mutants -- Analysis of abnormal DNA -- Southern blotting: gene deletions -- Southern blotting: restriction fragment length polymorphisms -- Disease genes: mutation analysis -- Gene therapy -- Example: homozygous familial hypercholesterolaemia -- Antisense gene therapy -- Cell biology: methods of investigation -- Cell culture -- Primary culture -- Clonal cell lines -- Immortalisation of cells -- Protein detection -- Antibody production: monoclonal antibodies -- Immunocytochemistry -- Flow cytometry and fluorescence activated cell sorting -- Immunoassay techniques -- Immunoassay -- Immunometric assays -- Future perspectives -- Summary -- FURTHER READING -- 2 Gaucher's disease: a model disorder for therapeutic exploration of the lysosome -- Lysosomes -- Lysosomal storage diseases -- Access to the lysosomal space -- Lysosomal complementation and biogenesis -- Inherited defects in the lysosomal targetting mechanism -- Relevance to therapeutic lysosomal complementation -- Gaucher's disease: a special lysosomal disorder -- Definition -- Pathology of Gaucher's disease -- Biochemical genetics of Gaucher's disease -- Diagnosis -- Family screening -- Clinical manifestations -- Other rare manifestations of Gaucher's disease -- Parkinsonian manifestations -- Metabolic abnormalities in Gaucher's disease -- Secondary release of lysosomal enzymes -- B-cell proliferative responses -- Course of Gaucher's disease -- Treatment of Gaucher's disease -- Supportive therapy -- Bone marrow transplantation -- Development of enzyme replacement therapy -- Other stratagems for treating Gaucher's disease -- Substrate reduction therapy.

Iminosugars as substrate-reducing agents -- Clinical trials of substrate-reduction therapy -- Development of pharmacological chaperone therapy -- Pathophysiology -- Summary -- Multiple-choice questions -- Answers -- FURTHER READING -- 3 Obesity -- Epidemiology -- Definition and classification -- Body mass index (BMI) -- Topography of fat -- Waist-to-hip ratio (WHR) -- Waist circumference (WCR) -- Imaging -- Skinfold thickness -- Total body water (TBW) -- Aetiology of obesity -- Genetic factors -- Thrifty-genotype and thrifty-phenotype hypotheses -- Environmental factors -- Physiological mechanisms for the regulation of body weight -- Gastrointestinal signals -- Central regulation of appetite -- Anorexigenic signals -- Pro-opiomelanocortin (POMC) -- Leptin -- Regulation of energy expenditure -- Cellular mechanisms of thermogenesis -- Consequences of obesity -- Mortality -- Hypertension -- Dyslipidaemia -- Coronary heart disease (CHD)/ cerebrovascular disease -- Sleep apnoea/Pickwickian syndrome -- Psychological -- Economic -- Insulin resistance (IR) and diabetes mellitus -- Resistin -- Adiponectin -- Tumour necrosis factor α (TNF-α) -- Interleukins -- Treatment of obesity -- Assessment of the obese patient -- Dietary therapy -- Behaviour modification -- Exercise -- Drug therapy -- Centrally active drugs -- Surgery -- Clinical scenarios -- Multiple-choice questions (true or false) -- Answers -- FURTHER READING -- 4 Autoimmune mechanisms -- Key points -- The normal immune response -- Antigen presentation -- T-cell stimulation -- B cells and antibody production -- Discrimination between self and non-self -- Clonal deletion of T cells -- Anergy and T cells -- T-cell suppression -- B-cell tolerance -- Initiation of autoimmune disease -- Immunogenetics and autoimmunity -- The role of MHC class I and II genes -- Other MHC genes -- Non-MHC genes.

Non-genetic factors in autoimmunity -- Effector mechanisms -- Treatment of autoimmune disease -- The spectrum of autoimmune disease -- Autoimmune thyroid disease -- Autoimmune hypothyroidism -- Lessons from experimental autoimmune thyroiditis -- Immunogenetics of autoimmune hypothyroidism -- Non-genetic factors -- Autoimmune responses to thyroid autoantigens -- Graves' disease -- Precipitating factors -- TSH receptor antibodies -- Thyroid-associated ophthalmopathy -- Summary -- Clinical scenarios -- Thyroid-associated ophthalmopathy -- Postpartum thyroiditis -- Graves' disease and other autoimmune disorders -- Multiple-choice questions (true or false) -- Answers -- FURTHER READING -- General -- Specific topics -- 5 Mechanisms of disease - allergy and anaphylaxis -- Mechanisms of acute hypersensitivity reactions -- Introduction -- Behaviour mimicking hypersensitivity -- Behavioural aspects of allergic reactions -- Target organs -- Tissues affected by IgE-mediated allergic responses -- Secondary effects of allergic reactions on tissues -- Release of mediators -- Immune responses leading to IgE antibodies -- Atopy and the timing of exposure -- The nature of allergens -- Evolution of allergic responses -- Anaphylaxis -- Non-allergic anaphylaxis and non-IgE-mediated anaphylaxis -- Anaphylactic sensitisation -- Fatal anaphylaxis -- Milder reactions -- Local type I responses -- Investigating allergic reactions -- Management of acute hypersensitivity reactions -- Allergen avoidance -- Reduction of risk of a severe response -- Hyposensitisation -- Good daily control of asthma -- Rescue from the effects of reactions -- Clinical scenarios -- Scenario 1 -- Scenario 2 -- Scenario 3 -- Scenario 4 -- Scenario 5 -- FURTHER READING -- 6 Infection - bacterial -- Introduction -- Innate immune responses -- Inflammatory mediators -- Lipid inflammatory mediators.

Complement system -- Kinin, clotting and fibrinolytic systems -- Chemokines -- Proinflammatory cytokines -- Triggers of acute inflammation -- The inflammatory process -- Local response -- Systemic acute-phase response -- Immunopathology of innate immune responses -- Specific acquired immune responses -- Antigen presentation -- TCR-CD3 complex -- Co-receptors and co-stimulatory signaling -- Cytokines and inflammation -- TH1 and TH2 cytokines -- TNF-α, IFN-γ and chronic inflammation -- Immunopathology of acquired immune responses -- Type I reactions -- Type II reactions -- Type III reactions -- Type IV reactions -- Host response and the pathogenesis of tuberculosis -- Host response to M. tuberculosis (MTB) -- The immunopathology of tuberculosis -- Immunomodulating drugs and tuberculosis -- Host immune response and HIV-1 pathogenesis -- HIV-1 life cycle -- HIV-1 cellular entry -- Reverse transcription -- Proviral transcription -- Cytokines and HIV-1 transcription -- HIV-1 replication during antigen presentation -- Immune activation and HIV-1 pathogenesis -- Copathogenesis of tuberculosis and HIV-1 infection -- Impact of HIV-1 on tuberculosis -- Histological effects -- Clinical effects -- Epidemiological effects -- Impact of tuberculosis on HIV-1 infection -- Conclusions -- Summary -- Acknowledgements -- Clinical scenarios -- Glandular fever -- Jarisch-Herxheimer reaction -- Erythema nodosum leprosum -- Pulmonary tuberculosis -- HAART and immune reconstitution TB -- Multiple-choice questions (true or false) -- Answers -- FURTHER READING -- 7 Infection - parasitic -- Malaria -- The febrile illness -- Severe malaria -- Pathogenesis of complicated disease -- Cytoadherence and sequestration -- Cytokine responses -- Severe anaemia -- Coma and convulsions -- Hypoglycaemia -- Acidosis -- Acute renal failure -- Disseminated intravascular coagulation.

Pulmonary oedema and acute respiratory distress syndrome (ARDS).