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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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.
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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.
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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.
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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.
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Bacterial pathogenesis
Lynn G. Dover
This chapter focuses on bacterial pathogenesis. Most of the bacteria that colonize our bodies do so without causing us any harm. However, some bacteria are inherently more damaging than others. Their degree of pathogenicity is described in the term ‘virulence’, which can be quantified by establishing experimental metrics such as median lethal dose and median time to death. Virulence and pathogenicity are dependent upon the composition of the bacterial genome; pathogen genomes encode many virulence factors which operate in a concerted fashion to express pathogenicity. The chapter then describes the characteristics of pathogenic bacteria that allow them to adhere to epithelial surfaces (adhesins), evade the immune system (evasins and impedins), invade tissues (invasins), and damage underlying tissues (toxins). It looks at toxinogenesis and considers pan-genomes, mobile genetic elements, and the acquisition virulence factors.
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Blood cultures
Derek Law
This chapter focuses on blood cultures, which are extremely important clinical samples that are requested by clinicians when the signs and symptoms suggest the possibility of bacteraemia or septicaemia. Because of the importance of obtaining rapid results with blood cultures, this is one area of microbiology where automation is commonplace. The chapter then explores the different blood culture methods, outlining the procedures for sample taking, transport, and processing. A blood culture involves taking a sample of blood from a patient and inoculating the blood into a blood culture bottle; the bottle is then transported to the laboratory for incubation. The chapter explains the different procedures for dealing with negative and positive bottles. It also looks at bacterial pathogens, false-positive results, and specialized testing for endocarditis.
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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.
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Clinical mycology
Derek Law
This chapter evaluates clinical mycology, which is the study of human infections caused by fungi. Mycology is a small but growing part of clinical microbiology, and the laboratory practitioner must be aware of fungal diseases commonly encountered in the laboratory. Fungi are being more commonly isolated, often as a result of more patients with underlying conditions such as diabetes, as these facilitate proliferation of yeasts in particular. In addition, more patients are immunocompromised, and in this patient group fungal infections are more common and more life threatening. The chapter begins by differentiating between bacteria and fungi. Bacteria are simple prokaryotic cells; fungi are more complex and are classed as eukaryotic, like human cells. The chapter then considers the infections of the skin, nails, and hair; Candida infections of the mucosa; and invasive fungal infections. It also looks at antifungal susceptibility testing and the role of the reference laboratory.
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Clinical parasitology
Tony Worthington
This chapter focuses on clinical parasitology, which is an important sub-discipline of pure parasitology and may be defined as the study of human infections caused by ecto- and endoparasites. During the twenty-first century, parasites have come to contribute to an ever-increasing number of human blood, tissue, and gastrointestinal infections that are often associated with important risk factors. The chapter begins by differentiating between protozoa, nematodes, cestodes, and trematodes. It looks at the diagnosis of gastrointestinal parasitic infections acquired through the gastrointestinal tract, before describing the examination of faeces for ova, cysts, and parasites (OCP). The chapter then examines immunological and molecular techniques, and discusses the treatment of parasitic infections acquired through the gastrointestinal tract.
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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.
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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.
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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
Culture media
John Perry
This chapter discusses the basic ingredients of culture media and the different types of media available. A bacterial culture medium must provide all of the nutritional requirements for the bacterial species it is expected to recover. In practice, culture media used by diagnostic laboratories are not defined as they contain extracts of complex biological materials of which the exact composition is unknown. The reasons for this are convenience and the fact that bacteria generally grow better on complex, undefined media. Some common constituents of complex culture media include water, protein derivatives, yeast extract, gelling agents, buffers, blood and serum, charcoal, and other additives for fastidious bacteria and anaerobes. The chapter then explores selective, differential, and enrichment media and what they are used for. It also explains chromogenic media, antimicrobial susceptibility testing, and the principles and pitfalls of culture media preparation.
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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.
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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.
