Components of the immune system and their functional assessment

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It is well established that diet has an important influence on immunity. Energy malnutrition and deficiencies in specific nutrients result in increased susceptibility to infection and increased mortality, especially in children.

Lipids may be involved in immunity in several ways. The role of some glycosphingolipids in cell-surface antigens is discussed later in Section 4.4.2. The following deals only with the contributions of dietary lipids. Because of their importance as a source of dietary energy, triacylglycerols may contribute to the enhancement of immune function in malnourished individuals. Individual lipids, including some fat-soluble vitamins and different types of fatty acids, play more specific roles through their contribution to membrane structure and integrity (Section 6.5), their metabolism to eicosanoids (Section 2.4), their participation in processes of lipid peroxidation (Box 4.3), or their influence on gene expression (Section 5.3).

The immune system has evolved to protect the body from constant attack by infectious organisms and other non-self molecules that could have detrimental effects on the host. It involves complex interactions between different types of cells, which produce substances that are toxic to invading pathogens. Lymphocytes are key players in the immune system. B-lymphocytes produce antibodies against specific antigens located on the surface of invading organisms (humoral immunity). T-lymphocytes do not produce antibodies. They recognize peptide antigens attached to major histocompatibility complex proteins on the surfaces of so-called antigen-presenting cells. In response to antigenic stimulation, they secrete cytokines (e.g. interleukins, interferon, transforming growth factor, etc.), whose function is to promote the proliferation and differentiation of T-lymphocytes as well as other cells of the immune system. These include B-lymphocytes, monocytes, neutrophils, natural killer cells and macrophages. Whereas life would hardly be possible without this well-integrated system, failure adequately to regulate these processes can lead to damage to the body's own tissues as seen in severe inflammation and in autoimmune diseases.

In the 1970s it was discovered that diets rich in PUFA could prolong the survival of skin allografts in mice and such diets were subsequently employed as adjuncts to conventional immunosuppressive therapy to reduce rejection of human kidney grafts. Such diets also appeared beneficial in treating patients with multiple sclerosis, an autoimmune disease in which an inappropriate immune response to one of the body's own proteins causes damage to the myelin membrane. These findings, and others over the intervening years, strongly suggested that PUFA were acting to suppress the immune system. Recent research has been directed to better understanding the mechanisms of the action of PUFA at the cellular and molecular levels.

Much of the research into the effects of dietary fatty acids on aspects of immune function has been done with lymphocytes 'ex vivo'. The cells are isolated from the blood of animals (including human subjects) given diets differing in fatty acid composition. Commonly used tests are (a) rates of cell division (measured by incorporation of tritiated thymidine into DNA) of lymphocytes stimulated with specific antigens or non-specific mitogens; (b) macrophage migration in an electric field; (c) cyto-kine production by different cell types; (d) expression of lymphocyte cell-surface molecules; (e) lymphocyte-mediated cytolysis; (f) cytotoxic T-lymphocyte activity; (g) natural killer cell activity. Such ex vivo tests have been supplemented by assessment of immune function in vivo by measuring (a) delayed-type hypersensitivity reactions; (b) graft versus host responses; (c) organ transplantation and (d) antibody production. It is not possible to describe these methods here and interested students should consult the reference lists in appropriate publications listed under Further Reading at the end of this chapter.

Interpretation of the results of all these studies is difficult for several reasons. Each of the aforementioned tests measures a different aspect of immune function and dietary lipids may not affect all functions in the same way. Results of tests invol ving lymphocytes in culture are often critically dependent on the type of serum used in the culture medium. When animal models are used, results may differ between species and may not always be relevant to man. Very importantly, dietary experiments have normally used natural fats and oils to represent different classes of fatty acids. For example beef tallow, olive oil, sunflower oil and fish oils have been given to provide dietary fats dominated by saturated, monounsaturated, n-6 polyunsaturated and n-3 PUFA, respectively. Of course all these fats contain mixtures of fatty acids, as well as many minor components, such as fat-soluble vitamins and sterols. Consequently, it can never be certain that the effects observed were due to the fatty acid of interest, even though it may be the major component of the mixture. Some authors have tried to overcome this problem by giving synthetic diets containing the ethyl esters of specific fatty acids. However, with this approach, potential problems of nutrient balance need to be addressed.

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