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The nature of immunity

Key objectives

This chapter will enable you to:

Outline the general purpose and properties of the immune system

Distinguish the features of innate and adaptive immunity and the components of the immune system involved in each

Give an overview of the processes that generate an immune response appropriate for defence of the body against the pathogen that instigated the response

Immunology is a relatively new science. It is a branch of biomedical science that covers the study of all aspects of immunity and the immune system in organisms. Immunity is a state of resistance to infection, and the immune system is composed of those constituents of the body (i.e. molecules, cells, tissues and organs) that contribute to generating this resistance. Immunology deals with the physiological functioning of the immune system in states of both health and disease. It incorporates malfunctions of the immune system, as well as the physical, chemical and physiological characteristics of the components of the immune system. These components can be studies individually (in isolation), in terms of their mutual interactions, and within the body as a whole. Its origin is usually attributed to events in the eighteenth century - firstly, to Lady Mary Wortley Montagu, the wife of the British ambassador in Constantinople (now known as Istanbul), who observed the positive effects of variolation on the native population in 1712. Variolation is the deliberate infection with smallpox, where dried smallpox scabs were blown into the nose of an individual who then contracted a mild form of the disease. She introduced it into England with royal patronage following initial experiments on condemned criminals and orphaned children. However, this procedure was not without risk of causing smallpox (variola) itself and the high morbidity and mortality associated with it made others look for less dangerous and more effective ways of controlling the disease.

Subsequently, Edward Jenner, a Gloucestershire family doctor, made the important observation that dairymaids, who frequently contracted cowpox (an infection of the hands acquired during milking), were remarkably resistant to smallpox and did not develop the disfigured pock-marked faces of those who had had smallpox infection.

Edward Jenner had suffered painfully from variolation performed when he was 8?years old. The increasing spread of smallpox throughout the population led him to develop the alternative technique of vaccination. This was first performed in 1796 when he inoculated material obtained from cowpox pustules into the arm of a healthy boy. Jenner was subsequently able to inoculate the boy with smallpox more than 20 times without any untoward effect. This courageous experiment aroused much criticism, but Jenner offered his new preventive treatment to all who sought it and performed many of his vaccinations in a thatched hut - which became known as the Temple of Vaccinia - in the grounds of his house at Berkeley. These are restored and now contain the Jenner Museum and a Conference Centre.1

Although this vaccination was successful, it took almost two centuries (1796-1980) before the World Health Organization (WHO) was able to announce that smallpox was eradicated in 1980.

Interestingly, Jenner knew nothing of infectious agents that cause disease. Numerous scientific breakthroughs occurred, but it was not until Robert Koch first demonstrated, in 1876, that bacterial infectious agents (pathogens) cause disease. Any organism with the potential to cause disease is called a pathogen. There are five broad categories of pathogens, namely, viruses, bacteria, fungi, other relatively large and eukaryotic organisms (termed parasites) and prions (Table 1.1).

Table 1.1 Examples of types of pathogens and the diseases they cause.

Type of pathogen Example pathogens Diseases Virus Variola Smallpox Human immunodeficiency virus Acquired immune deficiency syndrome Bacteria Staphylococcus aureus or Streptococcus pneumoniae Community-acquired pneumonia Fungi Candida albicans Thrush Parasite Plasmodium malariae Malaria Prion Creutzfeldt-Jakob disease (CJD) prion CJD

Recognition and defence components

Before considering the complexity of the immune system as it exists, it is useful to consider some of the general design requirements of an immune system in order for it to protect the host organism. Clearly, the two important biological events are recognition of the target pathogen and effective defence against it. A major consideration is how many recognition specificities are required and how many kinds of defence, that is, methods of pathogen destruction, are necessary.

There exists an enormous variety of infectious pathogens, including many types of bacteria, viruses, fungi, parasites and prions, each with its own mechanisms of transmission, infection and reproduction. This means that no single recognition or defensive strategy is effective against all pathogens and therefore a wide variety of cellular and secreted components are present within the body that collectively constitute the immune system. Examples of the main cells and molecules of the immune system are given in Tables 1.2 and 1.3, respectively. These components vary in terms of whether their main role is recognition or defence, although most possess a combination of these properties.

Table 1.2 Cells of the immune system.

Cell type Developmental lineage Morphological definition Type of immunity Neutrophils Myeloid PMN leucocytes or granulocytes Innate Eosinophils Myeloid PMN leucocytes or granulocytes Innate Basophils Myeloid PMN leucocytes or granulocytes Innate Mast cells Myeloid PMN leucocytes or granulocytes Innate Monocytes/macrophages Myeloid Mononuclear leucocytes Innate Dendritic cells Myeloid Mononuclear leucocytes Innate Natural killer cells Lymphoid Mononuclear leucocytes Innate Cytotoxic T lymphocytes Lymphoid Mononuclear leucocytes Adaptive Helper T lymphocytes Lymphoid Mononuclear leucocytes Adaptive B lymphocytes Lymphoid Mononuclear leucocytes Adaptive

PMN, polymorphonuclear.

Table 1.3 Secreted mediators of immunity.

Antimicrobial Antibodies/immunoglobulins (IgM, IgG, IgA, IgE, IgD) Pentraxins (e.g. C-reactive protein) Collectins (e.g. mannan-binding lectin) Complement proteins Defensins Lytic enzymes Interferons Cytotoxins (perforins, granzymes) Regulatory/inflammatory Cytokines (e.g. interleukins, interferons, tumour necrosis factors) Chemokines (and other chemoattractants) Eicosanoids (e.g. prostaglandins, leukotrienes) Histamine

Innate and adaptive immunity

The cellular components that mediate recognition and defence can be categorized by various criteria, including their developmental lineage from stem cells in the bone marrow (myeloid or lymphoid) and their morphology as mature blood leucocytes (Table 1.2). Polymorphonuclear leucocytes (PMNs) are distinguished from mononuclear cells by their lobulated nuclei, and they largely coincide with the granulocytes defined by distinctive cytoplasmic granules. The immune system's cellular components can also be considered as mediators of either innate or adaptive immunity (Table 1.2).

The recognition properties associated with innate immunity may have evolved to recognize chemical structures that are characteristic of infectious pathogens and differ from constituents of host organisms. These include various microbial lipids, carbohydrates, proteins and even nucleic acids that are collectively termed pathogen-associated molecular patterns (PAMPs). They are bound by secreted proteins (e.g. mannose-binding lectin and C-reactive protein) and by cell surface and cytoplasmic proteins (e.g. macrophage mannose receptor and Toll-like receptors) called pattern recognition molecules that are inflexible in their specificities and identical between cells; these are considered in detail in Chapter 2. Innate immunity is rapidly activated in the early stages of an infection,...