Background

Our body is constantly insulted by a variety of pathogens such as bacteria, viruses, fungi and parasites from the environment. These pathogens are different in shape and size (e.g. from 20 nm [viruses] up to 7 m [tapeworm]) and can cause infectious disease and cancer in different ways. Our body has evolved three kinds of defence strategy against these foreign invaders and other antigens: (1) physical (e.g. intact skin and mucosa) and chemical (e.g. acid in stomach) barriers; (2) natural (also called innate or non-specific) immune responses (e.g. phagocytosis); and (3) adaptive (also called acquired or specific) immune responses. in most cases, the penetration of pathogens into our body and their consequent destruction may be achieved successfully by the first two lines of body defences. If not, the pathogens can multiply and disease ensues and the body recovers as a result of activation of the adaptive response against the invading pathogens (Figure 7.1). The adaptive immune response against pathogens is mediated by a special group of immune cells called lymphocytes. The activation, proliferation and differentiation of different types of lymphocytes can result in the elimination of such pathogens by the antibody-mediated immune (AMI) response or cell-mediated immune (CMI) response. More importantly, once the infection is cleared, most of the expanded population of antigen-specific lymphocytes undergo programmed cell death, whereas a small number of these lymphocytes differentiate into long-lived memory lymphocytes, which remain in the circulation for decades after the first exposure to that particular pathogen. As a result, when the body encounters the same pathogen a second time, these pathogens are destroyed very rapidly (within hours) and more efficiently by activation of the memory cells. In such situations, the individual is said to have developed immunity or specific resistance against that particular pathogen. Obviously, the pathogens have also developed

(1) Physiochemical barriers, e.g. intac skin, acidity of stomach, sebum, mucus, cilia, commensal organisms in the body, perspiration, coughing

(1) Physiochemical barriers, e.g. intac skin, acidity of stomach, sebum, mucus, cilia, commensal organisms in the body, perspiration, coughing

No disease

Disease

Recovery

Immunity

Figure 7.1 Three different strategies used by the body against foreign pathogens. The first two lines of defence are usually sufficient to eliminate infectious agents. If not, the body recovers as a result of activation of the adaptive immune responses, which generate specific populations of lymphocytes against the invading pathogens. Some of these lymphocytes remain in circulation as memory cells and provide immunity against re-infection by the original antigen. The principle of immunization is to alter the antigen in a way that prevents it causing disease but stimulates production of memory B or T lymphocytes against such antigens. NK, natural killer.

No disease

Disease

Recovery

Immunity

Figure 7.1 Three different strategies used by the body against foreign pathogens. The first two lines of defence are usually sufficient to eliminate infectious agents. If not, the body recovers as a result of activation of the adaptive immune responses, which generate specific populations of lymphocytes against the invading pathogens. Some of these lymphocytes remain in circulation as memory cells and provide immunity against re-infection by the original antigen. The principle of immunization is to alter the antigen in a way that prevents it causing disease but stimulates production of memory B or T lymphocytes against such antigens. NK, natural killer.

various strategies (e.g. by mutation, downregulation of immunogenic antigens) to overcome the body's defences. So it is a constant battle between the invader and the host.

In addition to their prime role in fighting infectious agents, it is clear that the immune system plays an important role in a number of pathological conditions, e.g. abnormal immune responses against a harmless substance (e.g. food, pollen) or self-antigens have been associated with allergies and autoimmune diseases. In contrast, normal immune responses against a tissue or organ transplantation from an incompatible individual are associated with transplant rejection (Buckley, 2003). The immune cells in transplanted organs and tissues may also attack and destroy the tissues of the host causing graft-versus-host disease (Gulbahce et al., 2003).

There are convincing lines of evidence that suggest that a fully functional immune system can prevent the incidence of cancer, e.g. cancer incidence together with infectious diseases increase rapidly in old age (see Chapter 1) as the ability of the immune system to recognize and provoke a strong immune response against pathogens declines (Franceschi et al., 2000; Effros, 2003). In addition, the incidence of cancer has been shown to be increased in immunosup-pressed patients such as those treated with cytotoxic drugs and those with AIDS (acquired immune deficiency syndrome) (Appay and Rowland-Jones, 2002; Vial and Descotes, 2003).

In general, as cancer cells are almost identical to other healthy body cells, the immune system is less efficient at dealing with tumours than with infectious agents. Indeed, most human antigens are tumour-associated antigens and are expressed in lower amounts in normal cells. In recent years, as a result of our better understanding of the cells and molecules of the immune system, the identification and characterization of tumour antigens of biological and clinical significance, and the development of novel adjuvants, we have been able to manipulate the immune system and provoke immune responses against human tumour antigens that are not normally immunogenic in cancer patients. Several clinical trials are currently under way in cancer patients using tumour cells that have been transfected with genes for cytokines and other co-stimulatory molecules, tumour antigens or antigen fragments in combination with new adjuvants as the source of cancer vaccines (Moingeon, 2001; Romero et al., 2002). Monoclonal antibodies have been developed against human tumour antigens and some of these antibodies are currently used for the management of human cancers (see Chapter 9).

In this chapter, a detailed account of the cells and molecules of the normal immune system is presented together with their functions. The relationship between the immune system and cancer, novel immunotherapeutic strategies (e.g. cancer vaccines) for human cancers, together with the effects of cytotoxic drugs on the immune system, are then discussed.

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