CHAPTER 1
Basic Components: Structure and Function

Key topics

• 1.1 Introduction
• 1.2 Key molecules
  • 1.2.1 Molecules recognized by immune systems
  • 1.2.2 Recognition molecules
  • 1.2.3 Accessory molecules
  • 1.2.4 Effector molecules for immunity
  • 1.2.5 Receptors for effector functions
  • 1.2.6 Adhesion molecules
• 1.3 Functional basis of innate responses
  • 1.3.1 Endothelial cells
  • 1.3.2 Neutrophil polymorphonuclear leucocytes
  • 1.3.3 Macrophages
  • 1.3.4 Dendritic cells
  • 1.3.5 Complement
  • 1.3.6 Antibody‐dependent cell‐mediated cytotoxicity
  • 1.3.7 Natural killer cells
  • 1.3.8 Innate lymphoid cells
• 1.4 Functional basis of the adaptive immune responses
  • 1.4.1 Antigen processing
  • 1.4.2 T‐cell‐mediated responses
  • 1.4.3 Antibody production
• 1.5 Physiological outcomes of immune responses
  • 1.5.1 Killing of target cells (virally infected/tumour cells)
  • 1.5.2 Direct functions of antibody
  • 1.5.3 Indirect functions of antibody
  • 1.5.4 Regulation
• 1.6 Tissue damage caused by the immune system
  • 1.6.1 Inflammation: a brief overview30
• 1.7 Organization of the immune system: an overview
• 1.8 Conclusions

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1.1 Introduction

The immune system evolved as a defence against infectious diseases. Individuals with markedly deficient immune responses, if untreated, succumb to infections in early life. There is, therefore, a selective evolutionary pressure for a really efficient immune system. Although innate systems are fast in response to pathogens, the evolution to adaptive responses provided greater efficiency. However, a parallel evolution in pathogens means that all species, plants, insects, fish, birds and mammals have continued to improve their defence mechanisms over millions of years, giving rise to some redundancies as well as resulting in apparent complexity. The aim of this chapter is to provide an initial description of the molecules involved, moving on to the role of each in the immune processes rather than the more traditional sequence of anatomical structure, cellular composition and then molecular components. It is hoped that this gives a sense of their relationship in terms of immediacy and dependency as well as the parallel evolution of the two immune systems. An immune response consists of five parts:

• Recognition of material as foreign and dangerous.
• An early innate (non‐specific) response to this recognition.
• A slower specific response to a particular antigen, known as an adaptive response.
• Non‐specific augmentation of this response.
• A memory of specific immune responses, providing a quicker and larger response when that particular antigen is encountered the second time.

Innate immunity, though phylogenetically older and important in terms of speed of response, is less efficient. Humoral components (soluble molecules in the plasma) and cells in blood and tissues are involved. Such responses are normally accompanied by inflammation and occur within a few hours of stimulation (Table 1.1).

Adaptive immune responses are also divided into humoral and cellular responses. Adaptive humoral responses result in the generation of antibodies reactive with a particular antigen. Antibodies are proteins with similar structures, known collectively as immunoglobulins (Ig). They can be transferred passively to another individual by injection of serum. In contrast, only cells can transfer cellular immunity. Good examples of cellular immune responses are the rejection of a graft by lymphoid cells as well as graft‐versus‐host disease, where viable transferred cells attack an immunologically compromised recipient that is unable to fight back.

Antibody‐producing lymphocytes, which are dependent on the bone marrow, are known as B cells. In response to antigen stimulation, B cells will mature to antibody‐secreting plasma cells. Cellular immune responses are dependent on an intact thymus, so the lymphocytes responsible are known as thymus‐dependent (T) cells. The developmental pathways of both cell types are fairly well established (Fig. 1.1).

The recognition phase is common to both adaptive and innate immunity. It involves professional cells, known as classical dendritic cells (DCs), that recognize general pathogen features or specific antigenic molecules, process the antigens and present antigen fragments to the other cells of the immune system, as well as initiating non‐specific inflammation to the pathogen. In the effector phase, neutrophils and macrophages (innate immunity) and antibodies and effector T lymphocytes (adaptive immunity) eliminate the antigen.

In terms of disease, like other organs, the immune system may fail (immunodeficiency), may become malignant (lymphoid malignancies) or may produce aberrant responses (such as in autoimmunity or allergy). This chapter describes the normal immune system in order to lay the basis for discussing these ways in which it can go wrong and so cause disease.

1.2 Key molecules

Many types of molecules play vital roles in both phases of immune responses; some are shared by both the innate and the adaptive systems. Antigens are substances that are recognized by immune components. Detection molecules on innate cells recognize general patterns of ‘foreignness’ on non‐mammalian cells, whereas those on adaptive cells are specific for a wide range of very particular molecules or fragments of molecules. Antibodies are not only the surface receptors of B cells (BCRs) that recognize specific antigens, but, once the appropriate B cells are activated and differentiate into plasma cells, antibodies are also secreted into blood and body fluids in large quantities to prevent that antigen from causing damage. T cells have structurally similar receptors for recognizing antigens, known as T‐cell receptors (TCRs). Major histocompatibility complex (MHC) molecules provide a means of self‐recognition and also play a fundamental role in T lymphocyte effector functions.

Effector mechanisms are often dependent on messages from initiating or regulating cells; soluble mediators, which carry messages between cells, are known as interleukins, cytokines and chemokines.

Table 1.1 Components of innate and adaptive immunity

NK, natural killer; PAMPs, pathogen‐associated molecular patterns; pattern‐recognition receptors (PRRs); Tregs, regulatory T cells.

Fig. 1.1 Development of different types of blood cells from a pluripotential stem cell in the bone marrow. The developmental pathway for natural killer (NK) cells is shown separately because it is thought that NK cells may develop in both the thymus and the bone marrow.

1.2.1 Molecules recognized by immune systems

Foreign substances are recognized by both the innate and adaptive systems, but in different ways, using different receptors (see section 1.2.2). The innate system is activated by ‘danger signals’, due to pattern‐recognition receptors on DCs recognizing conserved microbial structures directly, often repeated polysaccharide molecules, known as pathogen‐associated molecular patterns. Toll‐like receptors (receptors that serve a similar function to toll receptors in drosophila) make up a large family of non‐antigen‐specific receptors for a variety of individual bacterial, viral and fungal components such as DNA, lipoproteins and lipopolysaccharides. Activation of DCs by binding to either of these detection receptors leads to inflammation and subsequently activation of the adaptive system.

Phagocytic cells also recognize particular patterns associated with potentially...