There are numerous links between free radical reactions and immune cell functions. White blood cell membranes are composed of lipids containing saturated and unsaturated fatty acids. Unsaturated bonds in fatty acids are highly susceptible to free radical attack, one consequence of which is to adversely affect the integrity of the cell membranes. For instance, oxygen-containing radicals and the products of their reactions have been shown to decrease the fluidity of white blood cell membranes and synovial fluids, consequently reducing their function.
The most abundant circulating white blood cell, the neutrophil, utilizes reactive oxygen species to kill invading organisms. When stimulated, neutrophils have the capacity to take up molecular oxygen and generate oxygen-containing free radicals and other reactive molecules. This is often called the oxidative burst. Free radicals and singlet oxygen, along with other reactive molecules, can kill pathogens. Neutrophils can also generate highly toxic halogenated molecules (e.g. hypochlorous acid) when the myeloperoxidase halide enzyme system is activated during the oxidative burst. The halogenated species can also lyse the phagocytosed pathogen. Recently, another reactive oxygen species, peroxynitrite, has been identified as an important component in immune cell killing of pathogens.
Under normal circumstances, the reactive oxygen species generated by neutrophils and other immune cells are used for control of infection; however, in circumstances of chronic activation the reactive oxygen products can result in destruction of normal tissue, as seen in rheumatoid arthritis.
One of the most obvious factors that could reduce anti-oxidant status is an induced dietary deficiency of, for instance, vitamin C. The effects of marginal vitamin C deficiency on immune and other parameters have been determined under highly controlled conditions in healthy males. Serum, white blood cell and sperm vitamin C levels were significantly reduced when the diet contained 5-20 mg of vitamin C for 2 months. Delayed-type hypersensitivity (DTH) responses were significantly depressed during the period of low vitamin C intake.
In addition to DTH responses, an index of oxidative damage to sperm DNA was also measured; these levels were significantly increased when vitamin C intakes were low. This carefully controlled study clearly demonstrated the importance of the balance between anti-oxidant status, oxidant levels and immune response. The study is especially noteworthy since all other dietary anti-oxidants, such as vitamin E and /3-carotene, were provided throughout the study at recommended daily allowance (RDA) levels.
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