Exploring Immunology

Concepts and Evidence

Gordon MacPherson, Jon Austyn

• Publisher: Wiley-Blackwell
• Year: 2013
• ISBN:
  9783527673131
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Cell Biology
• Index: Biological Sciences

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.
The book is professionally illustrated in four color throughout with beautiful artwork which by itself distinguish the title from any comparable title.
Website: www.wiley-vch.de/home/immunology

1

The Immune System

1.1 Introduction

All living things – animals, plants and even bacteria – can act as hosts for infectious organisms and thus have evolved mechanisms to defend themselves against infection. Infection can be by other living things, non-living things (viruses) and possibly even molecules (prions). Since it is so crucial to our own survival, much of our understanding of immunity has come from studies in humans – particularly in relation to the causes and prevention of disease – but deep insights have also come from experimental studies in animals such as mice. For these reasons, in this book we concentrate on the immune systems of humans and mice. These, along with other more recently evolved organisms (e.g. birds and amphibians), have the most complex and sophisticated immune systems, but the origins of these can in many instances be traced back to the most distant and ancient species in evolutionary history.

In this chapter we provide an overview of immunology in which we introduce the key players in immunity, largely focussing on the immune systems of humans and mice. We start by briefly considering how infection can be sensed by the host organism and how it is possible for a host to recognize many very different infectious agents (Section 1.2). We then introduce the tissues and specialized organs where immune responses occur (Section 1.3). To eliminate different infections effectively, immune responses need to be tailored to particular types of infection. This requires a variety of cells and molecules that can interact coherently to generate the mechanisms that are needed to eliminate each type of infection. As these mechanisms help to bring about or “effect” the elimination of infectious agents they are termed effector mechanisms.

Defence against infection is divided into two main forms termed innate immunity and adaptive immunity. Innate defence mechanisms are present in different forms in all multi-cellular organisms, including plants. Adaptive defence mechanisms have evolved more recently in vertebrates. In vertebrates, the interaction of innate and adaptive immune mechanisms is essential for the generation of effective immunity to infection.

To introduce the mechanisms of immunity we start by describing the different types of immune cells and their function in innate and adaptive immunity to infection (Section 1.4). We then introduce the major classes of molecule involved in functions such as the detection of infection, the recruitment of cells to infected sites, communication between cells and tissues, signalling within cells, and, usually, elimination of the infectious agent (Section 1.5).

The immune system that humans have evolved is, however, not perfect and we discuss some of these imperfections at the end of this chapter (Section 1.6). The immune system is a very effective killing machine, and if it goes wrong it can cause severe disease and even death of its host. To cover these latter areas we first consider how the immune system is able to discriminate between what needs to be eliminated and what does not – particularly in the case of adaptive immunity, which has evolved to recognize molecular structures largely at random. We then introduce the different ways in which the immune system can cause damage if it becomes directed not to infectious agents, but to otherwise harmless targets, including many inert substances around us and within the tissues of the host itself. We discuss the problems of transplants (some of which can even attack their hosts) and why the immune system fails to reject malignant tumours (cancer). Finally, we turn from problems to solutions and introduce two areas in which either the intact immune system and components of immunity can be harnessed for our own benefit and from which tools can be derived to treat disease.

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By the end of this chapter you should have insight into of the basic properties and functions of the immune system, and will understand the principles of its roles in defence against infectious disease. You will start to have an appreciation of why it is pivotal to life, disease and death, and how it is important not only in prevention of disease but in its causation. This chapter will lead you on to the following chapters where different areas of immunity are discussed in greater depth.

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1.2 Host Defence Against Infection

We need immune responses to defend ourselves against infection. Many different kinds of organism have the potential to infect us and, if they do so, can cause us harm in many different ways. To deal with all these potential threats we, as hosts for infectious agents, need a variety of different kinds of host defence mechanisms. Indeed this applies for any living organism.

1.2.1 Infectious Agents

To understand how the immune system works in infection we need to know who the aggressors are. Potentially infectious agents include the following:

• Viruses, which are non-living entities. Common examples are influenza virus, human immunodeficiency virus (HIV) and herpes simplex virus (HSV, which can cause cold sores or genital ulcers).
• Bacteria, are single-celled prokaryotic organisms. Examples include Staphylococcus and Streptococcus that cause acute infections such as abscesses and sore throats, and Mycobacteria that cause chronic infections such as tuberculosis and leprosy.
• Fungi, which are unicellular, such as Candida that causes thrush, or multicellular.
• Parasites, which are eukaryotic organisms. Some are single-celled protozoa that cause diseases such as malaria, others are large, multicellular organisms (metazoa) such as tapeworms.

In this book, for convenience, we will sometimes refer to smaller infectious agents, including viruses, as microbes because they are microscopic in size. However, many parasites, the metazoa, are often far from microscopic in size.

1.2.2 Host Defence

All organisms possess mechanisms to defend themselves against infection, and immunity is a specialized form of host defence. In mammals, defence mechanisms can be passive or active. Passive defence comes in the form of natural barriers that hinder infection. Examples are skin, which prevents access of microbes to the underlying tissue, and gastric acid in the stomach which, not surprisingly, can kill many microbes that might be ingested with food. Their existence is quite independent of the presence of infection. Active defence is brought about by immune responses that involve a diversity of different effector mechanisms that are induced by the presence of infection and which may eliminate the microbe. Thus, all forms of active immunity depend on specific recognition of molecules present in the infecting agent. This is turn leads to a response, involving the interaction of cells and molecules to produce different effector mechanisms that can often eliminate the infection.

Immunity is itself divided into two different forms – innate and adaptive. Innate responses occur rapidly and can generate effector mechanisms that are effective within minutes or hours of infection. In contrast, adaptive immunity takes much longer to become effective, usually over a few days. In immunity to most forms of infection, however, both innate and adaptive immunity are essential. A major advantage of adaptive immune responses, not seen with innate immunity, is that they generate memory – a second infection with the same microbe elicits a stronger, faster and usually more effective response. See Figure 1.1.

Fig. 1.1 Mechanisms of defence against infection. Natural barriers. These stop infectious agents entering the host or provide a hostile environment. Physical barriers to infection include the epithelia of the skin, lung and airways, and the gastro-intestinal and urogenital tracts. Cells in these barriers may also secrete agents that kill infectious agents. Innate immunity. This is the first form of immunity induced by infectious agents. Cells and molecules such as phagocytes and complement can make rapid responses that may eradicate the infection. Adaptive immunity. Later adaptive responses may be generated if the infectious agent is not killed by innate immunity. Cells and molecules such as lymphocytes and antibodies take longer to become effective, but adaptive immunity can also lead to a state of long-lasting resistance to re-infection termed immunological memory (not shown).

1.2.3 Immune Recognition

Different types of cells and molecules are involved in the initiation of innate and adaptive immune responses although, as mentioned above, their interaction is essential in defence against most infectious agents. So what do the innate and adaptive arms of immunity do in general terms? Broadly speaking we can view some components of the innate immune system as being involved in the detection of “harmful” things that represent “danger” to the organism, such as general classes of microbes that may have infected the host. Other components then endeavour to eliminate the microbe. In contrast, the adaptive immune system can discriminate very precisely between individual microbes, even of the same type, but can generally only make a response if it has been informed by the innate system that what is being recognized is “dangerous”. If so, adaptive responses may then help to eliminate the microbe, if it has not already been eradicated during the earlier innate response. Recognition of infectious agents is essential for any form of immunity and thus for host defence against them. Generally speaking, the types of receptors used for recognition differ in innate and adaptive responses. See Figure 1.2.

Fig. 1.2 Immune recognition. Innate immunity. PRRs directly or indirectly recognize conserved features of infectious agents called PAMPs. PRRs are widely expressed throughout the innate immune system. Adaptive immunity. The two main types of lymphocytes, B cells and T cells, have highly discriminatory receptors for microbial components or antigens, BCRs and TCRs respectively. These recognize antigens in totally different ways. BCRs can be secreted as soluble antibodies and bind to different types of antigen, such as carbohydrates on glycoproteins in their unfolded, native form. In contrast, TCRs generally recognize small peptides, generated by degradation of microbial proteins, in association with specialized presenting molecules (MHC molecules) on the surface of other cells (i.e. as peptide–MHC complexes).

1.2.3.1 Recognition in Innate Immunity: Pattern Recognition Receptors

The key components of the innate immune system include cells such as phagocytes and soluble molecules such as complement. These work together to sense the presence of infection. The recognition of potentially dangerous microbes usually leads to the generation of inflammation, familiar to us all. One way of viewing this is that the innate immune systems of multi-cellular organisms can generate “alarm” signals in response to danger, and that some of these signals cause inflammation. Alarm is not a conventionally used term, but is one that we find helpful and therefore will use it from time to time in this book. Inflammation enables effector cells and molecules to be targeted to the site of infection. As noted above, other signals generated during innate responses can also determine whether, and in what way, the lymphocytes of adaptive immunity will respond.

The recognition of infectious agents in innate immunity is mediated by germline-encoded receptors called pattern recognition receptors (PRRs). These receptors generally recognize conserved features of infectious agents that are often shared by different classes of microbes, these microbial features are called pathogen-associated molecular patterns (PAMPs). PAMPs directly or indirectly stimulate innate immune responses by acting as agonists for PRRs. An agonist is anything that stimulates a response through a receptor, as opposed to an antagonist that inhibits it. PAMPs may bind directly the PRRs, therefore acting directly as ligands for these receptors, but some PAMPs can trigger responses by binding to a different molecule that then associates with a PRR, so it is useful to use the general term agonist. This also allows us to discriminate clearly between components of microbes that trigger innate responses, and molecular structures which are recognized in adaptive immunity that are termed antigens (below).

The cells re...

Table of contents

• Cover
• Related Titles
• Title Page
• Copyright
• Dedication
• Preface
• A Note to the Reader
• Introduction
• Chapter 1: The Immune System
• Chapter 2: Infection and Immunity
• Chapter 3: Functional Anatomy of the Immune System
• Chapter 4: Innate Immunity
• Chapter 5: T Cell-Mediated Immunity
• Chapter 6: Antibody-Mediated Immunity
• Chapter 7: Immunity, Disease and Therapy
• Answers to the Questions
• Further Study Questions
• Index