This chapter begins with the description of adaptive immunity. It notes that the term uses the word adaptive because of the way this type of immunity allows both species and individuals to tailor-make their own set of recognition molecules, adapted to the microbes they actually encounter. In immunological language, the system displays high specificity and memory. The chapter then explores the other properties which distinguish lymphocytes from other immunological cells. It brings out the essential differences between lymphocytes and phagocytic cells. The chapter also outlines the lymphoid system, the total mass of lymphocytes in the body, then explains the fundamental part of lymphocyte function. It then considers the antigen, antigen-recognition molecules, clonal selection, and memory. The chapter concludes by discussing the regulation of adaptive immunity.
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Chapter
Adaptive immunity: introduction
Chapter
The antibody response
This chapter examines how B-cells and T-cells, acting together, give rise to the production of antibody molecules: the antibody response. It begins with discussing the activation of B-cells, which occurs mainly in the lymphoid organs (the site depending on the route by which antigen arrives). The chapter then looks at the different sorts of antigen to activate B-cells in different ways, emphasizing the T-independent (Ti antigens) and T-dependent (TD). It then shifts to investigate how an immunoglobulin molecule on the surface of the B-cell switches on the intracellular mechanisms that lead to antibody formation. Next, the chapter outlines the consequences of the activation through the B-cell antigenreceptor complex. It also looks at the signals of T-cell activation, then reviews the B-cell memory and the antibody responses at mucosal surfaces.
Chapter
B cells and antibody
This chapter stresses the function of B lymphocytes (or B-cells), essentially little antibody factories, able to switch on high-rate synthesis and secretion of antibody molecules when stimulated by recognition of the right antigen. It tracks the coordinated recognition and response in B-cells, then explains the diversity of the antibody repertoire. The chapter then describes the antibody molecule and its classes and subclasses. All antibody molecules using a particular heavy-chain constant-region gene are defined as belonging to the same class. The differences between different classes are fairly major, but there are smaller differences within classes, which are referred to as subclasses. The chapter also investigates what exactly do antibodies recognize, then studies the antigenic determinant or epitope. Finally, the chapter elaborates on the affinity of the antibody-antigen bond, then emphasizes the functions of the antibody. It also considers another useful role of antibodies in the monitoring and treatment of disease.
Chapter
Bacteria
This chapter focuses on a discussion about bacteria. It begins by looking at one part of the bacterium with a special significance for both disease and immunity: the cell wall. By providing information on bacterial classification, the chapter illustrates three types of bacterial cell wall which vary greatly in their structure: the gram-positive, mycobacterium, and the gram-negative. The chapter then moves to describe parasitic bacteria and makes a distinction between aerobic and anaerobic bacteria in certain infections. It also examines bacteria which do not fit neatly into classification. Next, the chapter examines bacterial replication, emphasizing the special features of gene expression and the method for bringing about rapid changes in genes: phase variation. The chapter also talks about the control of bacterial disease by antibiotics and the remarkable number of ways in which bacteria, far from being pathogenic, are useful and even essential to humans and animals.
Chapter
Bacterial disease and immunity
This chapter recalls the key properties of bacteria and the all-important distinction between extracellular and intracellular habitat. It reviews the immunological and therapeutic features of the most important pathogenic bacteria. The chapter begins with a discussion on staphylococcal infection, streptococcal infection, and clostridial infection. It then examines a disease of farm animals and farmers, anthrax, and other bacterial skin infections. The chapter also explicates the most important mycobacterial infection and one of the world's major health problems: tuberculosis. It then looks at respiratory infections, whooping cough, and the causes of meningitis. Next, the chapter considers some venereal diseases such as gonorrhoea and syphilis. It also considers plague, tularemia, and brucellosis, then discusses three infections: chlamydial infection, rickettsial infection, and mycoplasma infection.
Chapter
Cell-mediated responses
This chapter considers T-cell responses that do not involve B-cells and antibodies. It begins with examining the points of resemblance of the activation of macrophages by CD4 (helper) T-cells to the activation of B-cells, then explores the CD8 (cytotoxic) T-cell response. The chapter argues that both involve the selection and expansion of clones of effector cells from a tiny number of precursors and both result in the long-term survival of a population of memory cells that ensure a more vigorous secondary response to the same pathogen. The chapter analyzes how T-cells become activated for these responses. Next, the chapter highlights a more drastic approach to kill both the virus and its host-cell with the help of cytotoxic T lymphocytes (CTLs). It also elaborates on the t-cell memory and t-cell responses at mucosal surfaces.
Chapter
Control of infectious disease: chemotherapy
This chapter examines the idea of using chemicals safely to attack microbes. It presents chemical substances which are used at four levels to kill pathogens: disinfectants, antiseptics, chemotherapy, and antibiotics. The chapter then shows that chemotherapy has been extremely successful against many bacteria, because their procaryotic structure offers several targets absent from eucaryotic cells. The chapter also elaborates on some antibacterial agents, highlighting the modern antibacterials such as the synthetic azo-dye sulphanilamide, the true antibiotics penicillin, and streptomycin. The chapter then shifts to investigate how antibiotic resistance can develop at several levels. It looks at the standard susceptibility test, biofilm, and bacterial interference. Next, the chapter analyzes the other problem with antibiotics, as with all drugs: toxicity. It then displays some of the effective drugs against eucaryotic infections.
Chapter
Control of infectious disease: public health measures
This chapter points out the importance of public health measures in controlling disease and its spread. It argues that the control of infectious disease was a matter of both scientific understanding and political will. The chapter also assesses the impact of the general improvement in health, accompanied by better nutrition and food handling, better housing, and housing regulations to the public. It then recounts some success stories that have nothing to do with vaccines or drugs. Next, the chapter presents some examples that highlight the public health approach. About half of the public health measures listed in the chapter are directed at insect or larger animal vectors. The chapter emphasizes that with vector-borne diseases, control or elimination of the vector may sometimes be the most practical approach.
Chapter
Control of infectious disease: vaccination
This chapter uncovers how immunization makes use of the ability of the adaptive immune system to learn and improve. It argues that immunization may be active, inducing the immune system itself to acquire a permanently enhanced resistance to a particular pathogen, or passive, where a preformed antibody is introduced into the individual to be protected. Active immunization directed at a specific organism is known as vaccination. The chapter then explores the function and aim of a vaccine. It begins by explicating the four requirements of a vaccine: effective, safe, stable, and affordable. The chapter also demonstrates some established and some still experimental vaccines. For practical purposes, the essential distinction is between living and non-living vaccines. Finally, the chapter tracks other vaccine strategies and the development of a new vaccine. It also considers the passive ('immediate') immunization and therapeutic vaccines.
Chapter
Defence, immunity, the immune system
This chapter outlines the development of a whole new understanding of the causes and effects of infectious disease and how to treat such diseases. It elucidates the two new disciplinesmicrobiology and immunologytogether with the gradual identification of a body wide repertoire of organs, cells, and molecules devoted to controlling infection: the immune system. The chapter also discusses the problem of defence against a pathogen, then demonstrates the three levels of defence: external defences, the innate immune system, and the adaptive immune system. The chapter then highlights that an immune system requires three sets of components to work properly: recognition molecules, disposal mechanisms, and a communication system. Finally, the chapter presents the distinction of the two parts of the immune system: the innate and the adaptive immune systems.
Chapter
Disease due to adaptive immunity I: hypersensitivity
This chapter uncovers the unwelcome side effects of 'normal' responses against perfectly ordinary non-self antigens. It classifies these effects and displays the causes of hypersensitivity. The chapter begins with describing the most common type of immunopathology, since about one person in six suffers from some kind of allergy: type I (allergic) hypersensitivity. It then examines the ability of IgG antibody to destroy cells by causing them to be either phagocytosed or lysed by complement (IgM will do the latter too), causing the type II (cytotoxic) hypersensitivity. Next, the chapter explicates the cause of type III (immune complex-mediated) hypersensitivity. Here, too, IgG antibody is involved, but the damage is actually initiated by soluble complexes of antigen and antibody. It also considers the harmful aspects of cell-mediated immune responses, the principal one being excessive granuloma formation.
Chapter
Disease due to adaptive immunity II: autoimmunity
This chapter discusses the underlying causes of autoimmunity, focusing on infection and genetic predisposition. It seeks to understand how autoimmunity is normally avoided, and why do some B and T lymphocytes do not recognize and respond to 'self' antigens, considering that their receptors are produced by a random recombination of genes and should be able to recognize virtually everything, instead of being unresponsive, or tolerant, to self. The chapter begins by analyzing the polyclonal activation of anti-self B or T lymphocytes. It then looks into the activation of T lymphocytes by antigens closely similar to self: molecular mimicry. The chapter then shifts to detail the release of sequestered antigens, and displays one of the striking findings in organs affected by autoimmunity, the appearance of MHC class II antigens on cells where they are normally absent. Finally, the chapter reviews the anomalous cytokine production, autoimmune disease, and genetics.
Chapter
Disease due to innate immunity
This chapter examines the ways in which innate immune mechanisms can lead to pathology. It describes a group of microbial molecules which can cause havoc in the immune system. The chapter then distinguishes three related terms: septicaemia, sepsis, and septic shock. Focusing on a discussion about endotoxin and cytokines, the chapter then explores the number of systems affected by lipopolysaccharide (LPS), an innocuous-looking molecule, and other cytokine-mediated diseases. There is evidence that several inflammatory bowel diseases, notably ulcerative colitis and Crohn's disease, may be due to excessive local cytokine secretion. Finally, the chapter investigates how the activation of complement may lead to tissue damage in extreme cases. It then considers the destructive power of phagocytes, particularly polymorphs.
Chapter
Disease: virulence and susceptibility
This chapter addresses elements in the pathogen that predispose to disease. These are collectively known as virulence factors. The chapter begins by displaying the two main categories of virulence factors: pathogen mechanisms directly or indirectly causing host damage, and pathogen mechanisms aimed at escaping host protective mechanisms, including immunity. The chapter also studies the host gene expression, genome sequencing, and deep sequencing. It then shifts to examine how genetic differences on the host side contribute to the occurrence and severity of the disease. Next, the chapter looks at the two situations in which disease is caused directly by the pathogen: pathogens that destroy cells (cytopathic), predominantly viruses, and pathogens that release toxins, predominantly bacteria. It then reviews some common complications of intestinal infection such as diarrhoea and vomiting.
Chapter
Ectoparasites
This chapter highlights the importance of ectoparasites as vectors for many major diseases. It first defines ectoparasites as the arthropods that live on or in the skin, often feeding on blood. The chapter then shifts to describe the mites, which parasitize a wide range of animals and plants. It then investigates the ticks, which live on the skin surface and feed on blood. The chapter assesses their complex life cycle, and how they are vectors for a number of serious diseases. The chapter also describes lice and the three species of human lice. Lice are wingless insects, parasitic on a variety of animals. Next, the chapter examines bacterial and rickettsial diseases in animals such as fleas. It then considers other insect vectors.
Chapter
Ectoparasites and immunity
This chapter explores how skin parasites can be vectors for many major pathogens. It follows how vector-derived substances, largely in saliva, can influence the subsequent host response to the pathogen once transmitted, an interesting example of synergy between three different species which may contribute to the stability of their relationship. The chapter begins with a discussion on leishmaniasis and the sandfly. It then examines ticks, the vectors for several viral, bacterial, and Rickettsial diseases. The chapter also examines the intense reactions of mosquitoes and malaria, then explains the nature of tsetse flies and simulium (blackfly). Finally, the chapter discusses peeks at the effect of vector bites and saliva on the disease. It also studies mites, allergy, and resistance.
Chapter
Emerging and future infectious diseases
This chapter assesses major changes in infectious immunology that have occurred within living memory. It begins with elaborating the newly identified pathogens and newly acquired zoonoses. The chapter also outlines the reasons why the number of immunocompromised individuals in the population during the last 50 years has increased tremendously. It also illustrates the changes in virulence, highlighting influenza as the classic example. The chapter also discusses the artificial creation of new pathogens and attenuated vaccines. It then shifts to examine the widespread use of antibiotics and its enormous effect on the world of pathogens. Finally, the chapter looks at the importance of vaccine uptake and public health. It also investigates the implications of travel and immigration and climate change.
Chapter
Epidemiology
This chapter considers the balance between human populations and their pathogens with two crucial aims: to understand the 'real world' situation, and where necessary, to try and control it. It delves into some of the factors that determine the incidence and distribution of infectious diseases; that is, their epidemiology. The chapter begins by describing the diagnosis, which can be clinical, microbiological, or immunological. It explains the theoretical epidemiology and practical epidemiology, then highlights four main factors, all of which need to be understood by those working in the 'real world': the host and its variables; the pathogen and its variables; the degree of contact between the two; and the effect, if any, of treatment or preventive measures. The chapter illustrates these points in relation to three diseases, one viral (AIDS), one bacterial (tuberculosis), and one protozoal (malaria). Ultimately, the chapter considers infantile diarrhoea, then reviews the value of epidemiology.
Chapter
External defences: entry and exit
This chapter concentrates on the effective barrier against invasion by most pathogens. It begins with discussing the skin and the secretions of its various glands. The chapter then proceeds to track the terminal parts of the respiratory tract and its importance. It also explains the first difficulty encountered by microbes on their way to the intestine. Like the air we breathe, food and water are inevitably contaminated with microbes, although proper cooking and water filtering can substantially reduce this contamination. The chapter then details some episodes of bacterial infection in the bladder (cystitis), specifically in the urogenital tract. Next, the chapter analyzes a number of diseases which can be caught by a baby from the mother. It also elaborates on the main escape routes used by pathogens and the importance of vectors to both the entry and exit of pathogens.
Chapter
Fungal disease and immunity
This chapter illustrates the three main patterns of fungal diseases: (1) filamentous moulds infecting the superficial and subcutaneous tissues, (2) a dimorphic group causing systemic infections; and (3) secondary infections caused by a number of important opportunists which have come to the fore with the increase in immunocompromised patients. It opens with a discussion on primary superficial and subcutaneous infections, focusing on tinea (ringworm) which is more common in children. The chapter also elaborates on the dimorphic fungi Histoplasma, Blastomyces, and Coccidioides. It then examines the evidence for protective immunity and predominant opportunistic fungal infection. Ultimately, the chapter considers the antifungal vaccine and treatment.
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