The intact skin and mucosal surfaces provide a physical barrier to microorganisms and foreign substances. Tight junctions between the cells and the continuous basement membrane are important components. The keratinised surface of the skin is particularly tough; only a minority of microorganisms can breach intact skin.

The acidity of the gastric and vaginal secretions creates a hostile microenvironment which kills many organisms. Lysozyme, found in tears, has an antibacterial action. Paneth cells in the intestine secrete antibacterial proteins called defensins when stimulated by the presence of bacteria. Activation of the complement cascade by the alternative and mannose-binding lectin (MBL) pathways are also part of innate immunity (see Ch. 5).

The flow of urine regularly flushes away any bacteria that ascend the urethra, helping to keep the bladder sterile. Bronchial mucus is constantly swept towards the pharynx, carrying with it any contaminating bacteria; when it reaches the pharynx it is coughed out or swallowed into the acid environment of the stomach. Tears have an analogous effect. Stasis of the normal flow of secretions or excretions is a potent cause of infection.

Although neutrophils and macrophages participate in adaptive immune reactions and their activity is greatly enhanced when stimulated by specific immune responses, they have phagocytic and antimicrobial properties independent of the adaptive immune system. Thus, neutrophils and macrophages also contribute to innate immunity.

Like neutrophils and macrophages, mast cells and eosinophils participate in adaptive immune responses. However, they can also act independently of adaptive immunity. Mast cells (and the closely related basophils) release histamine, cytokines and other substances from their granules when stimulated, promoting inflammation (see Table 13, Ch. 8). Eosinophils secrete a range of substances that are toxic to microorganisms. The actions of mast cells and eosinophils seem to be particularly involved in defence against parasites, but they have other defensive roles and are also involved in allergic reactions.

Natural killer (NK) cells are lymphocytes that have the ability to lyse host cells, in particular virally infected cells and neoplastic cells. In this respect, they form part of innate immunity. In addition, NK cells take part in adaptive immunity by their ability to lyse cells opsonised with IgG (antibody-dependent cell-mediated cytotoxicity, see Section 7.4).

These receptors are found on many cells of the immune system and recognise a wide range of molecules found on bacteria, viruses and fungi. They represent a type of host defence found not only in animals but also in bacteria and plants. Binding of a pattern-recognition receptor triggers a response in an effector cell. An important group of pattern-recognition receptors comprises the toll-like receptors. For example, toll-like receptor 1 (TLR1) is expressed on macrophages, dendritic cells and B cells, and recognises a kind of lipopeptide found in bacteria.

Central to the adaptive immune response are two types of lymphocyte, called B cells and T cells. Both these cell types possess membrane receptors which can bind to foreign material (antigen). This triggers a series of intracellular events in the lymphocyte which leads to its activation, multiplication and enhanced ability to destroy or neutralise the antigen. By definition, adaptive immunity (as opposed to innate immunity) involves the antigen-specific receptors on B cells and T cells.

Both types of lymphocyte are derived from precursor cells in the bone marrow. B cell maturation occurs in the bone marrow itself, whereas T cells migrate to the thymus for maturation. B and T cells have distinct functions, but they are interdependent and rely on cooperation with each other and other cells of the immune system.

In order to optimise the combined functions of surveillance of the body’s tissues for antigen and production of a coordinated immune response, the cells of the adaptive immune response are organised into structured lymphoid tissues, namely lymph nodes, thymus, mucosa-associated lymphoid tissue and spleen. Lymphocytes are also found in the bone marrow.

The bone marrow and the thymus are sometimes known as primary lymphoid organs, where lymphocytes are produced and mature (B cells in bone marrow, T cells in thymus), whereas the peripheral lymph nodes and other lymphoid sites are called secondary organs, where lymphocytes live and recognise antigens and initiate the immune response. The spleen is primarily involved in clearing the blood of unwanted antigens, while the lymph nodes are responsible for clearing the lymphatic fluid. The mucosal surfaces represent potential portals of entry for microbes, and the mucosa-associated lymphoid tissue forms an important part of the body’s defences. This lymphoid tissue is often concentrated into distinct structures such as the tonsils in the throat, the Peyer patches in the intestine, and the lymphoid tissue of the appendix.

There are similarities in the structure of many of the lymphoid tissues. In general, B cells are found in the discrete nodular structures known as lymphoid follicles. These follicles are surrounded by a sea of T lymphocytes admixed with other cells of the immune response and small blood or lymphatic channels. A lymph node is shown in Figure 17. Lymphocytes can circulate via the lymphatics and bloodstream between the lymphoid organs.

The basic structure of an antibody is shown in Figure 18. In its simplest form, an antibody is composed of two identical light chains and two identical heavy chains. The molecular weight is about 150 000. The light chains are joined to the heavy chains and the heavy chains to each other by covalent disulphide bonds. Overall, the antibody molecule has a ‘Y’ shape, with movement of the arms possible at the hinge. Light chains and heavy chains can be further subdivided into domains, each approximately 110 amino acid residues long. There are four domains per heavy chain and two per light chain. The amino acid sequence in the N-terminal domain of both the light and heavy chains is very variable – the so-called variable region – and it is here that antigen binding occurs. The remaining domains are relatively constant. The different types of immunoglobulin are classified according the Fc region, which is responsible for the actions of the antibody. For example, IgG and IgM opsonise bacteria to which they are bound (because phagocytes have receptors for IgG and IgM Fc regions), and IgE uses its Fc portion to attach to the surface of mast cells and basophils. There are different classes of antibody, which have different functions (Table 9), but they all are based on the simple prototype.