Exploring Immunology

The immune system is the body organ that protects all higher organisms against infections and parasites. The immune system of vertebrates is particularly complex and is one of only two immune systems which allows - in the form of antibodies - for almost unlimited variability through genetic rearrangements. Almost any disruption in the immune system results in a more or less severe disease and/or will render the carrier susceptible to a variety of infectious agents. In addition, it has become clear that the immune system often plays a critical role during cancer development and an inappropriate immune response is responsible for the development of autoimmune diseases and allergies. Understanding the immune system is thus not only critical for the treatment of many infectious diseases but also for the treatment of autoimmune diseases, allergies and increasingly cancer. This concise introductory textbook uses carefully chosen examples from clinical and experimental observations to provide an insight into the principles underlying the immune system. As a result, it encourages readers to ask critical questions in order to further advance our understanding of this unique organ. Both authors are experienced lecturers and highly regarded researchers. Gordon MacPherson is Reader in Experimental Pathology at the Sir William Dunn School of Pathology, University of Oxford and Tutor in Medicine, Oriel College Oxford. He has taught immunology to medical students for over 30 years in lectures, practical classes and tutorials at both introductory and Honours levels. He teaches all aspects of immunology, and in tutorials also covers microbiology and general pathology. His research interests are in immune regulation, particularly mucosal immunity, and the properties and roles of dendritic cells. He has published many papers (experimental and reviews) and has been an invited speaker at many international conferences. Jon Austyn is Professor of Immunobiology in the Nuffield Department of Surgery at the University of Oxford. He has taught extensively in all areas of fundamental immunology over many years, and designed the MSc course in Integrated Immunology at the University of Oxford, which he now co-directs. Jon Austyn has over 25 years research experience of dendritic cell immunobiology, particularly as applied to transplantation, infectious diseases and more recently cancer. He was recently awarded with distinction the Diploma in Learning and Teaching in Higher Education by the University of Oxford. CONTENTS Preface XVII A Note to the Reader XIX Introduction 1 1 Introduction 1 2 Immune Responses 1 3 Infection and Immunity 1 4 Immunopathology and Immunotherapy 2 5 Exploring Immunology 3 1 The Immune System 5 1.1 Introduction 5 1.2 Host Defence Against Infection 5 1.3 Anatomical Basis of Immunity 9 1.4 Cellular Basis of Immunity 12 1.5 Molecular Basis of Immunity 24 1.6 Immune Responses and Disease 37 2 Infection and Immunity 49 2.1 Introduction 49 2.2 Pathogens and Infectious Disease 49 2.3 Host Defence Against Infection 57 2.4 Infection and Immunity in Action 69 2.5 Immunity and Vaccines 94 3 Functional Anatomy of the Immune System 99 3.1 Introduction 99 3.2 Natural Barriers 99 3.3 Functional Anatomy of Innate Immunity 103 3.4 Functional Anatomy of Adaptive Immunity 111 3.5 Development of Blood Cells and Organs of Immunity 126 3.6 Stem Cell and Gene Therapy 130 4 Innate Immunity 133 4.1 Introduction 133 4.2 Induction of Innate Immunity 133 4.3 Tissue-Resident Cells of Innate Immunity 145 4.4 Recruited Effectors of Innate Immunity 153 4.5 Haematopoiesis and Myeloid Cells 169 4.6 Vaccines and Adjuvants 171 5 T Cell-Mediated Immunity 175 5.1 Introduction 175 5.2 Major Histocompatibility Complex (MHC) and Antigen Presentation 179 5.3 T Lymphocyte Activation 191 5.4 Effector and Memory Functions of T Cells in Infection 196 5.5 T Cell Development and Selection 209 5.6 Adoptive Cell Therapy 215 6 Antibody-Mediated Immunity 217 6.1 Introduction 217 6.2 Antibody Structure and Function 218 6.3 B Cell Responses 236 6.4 B Cell Memory, Antibodies and Long-Term Resistance to Re-Infection 250 6.5 B Cell Differentiation and Selection 252 6.6 Therapeutic Antibodies 254 7 Immunity, Disease and Therapy 259 7.1 Introduction 259 7.2 What are the Mechanisms of Tissue Damage Caused by the Immune System? 262 7.3 Why Do We Make Harmful Immune Responses to Harmless Antigens? 268 7.4 Immunopathology and Therapy in Action 278 7.5 Transplantation Immunology 300 7.6 Tumour Immunity 306 7.7 Conclusions 310 Answers to the Questions 313 Further Study Questions 333 Index 337