**3. The impact of ascorbic acid in immunological system**

Ascorbic acid is an important vitamin for health, with numerous benefits associated to its potency as antioxidant and immune-modulator. It is a powerful antioxidant and a co-factor for a family of biosynthetic and gene modulatory enzymes, supporting various cellular functions that contribute to immune defense of both the innate and adaptive immune system [14, 15].

The epithelial defense function against pathogens is improved by ascorbic acid, promoting the oxidant scavenging ability of the skin. Ascorbic acid has the potential to protect against oxidative stress resulting from environmental exposure, through increased collagen formation and stabilization, induction of keratinocyte differentiation and lipid production, increased proliferation and migration of fibroblasts, and accelerated wound healing. The chemotaxis, phagocytosis, and the formation of free radical are elevated in phagocytic cells (like PMN leukocytes and macrophages), which accumulate ascorbic acid, which in turn increases the ability of cells to kill microbes. Apoptosis and elimination of the PMN leukocytes from areas of inflammation by macrophages are also need ascorbic acid, in order to reduce necrosis/ NETosis and potential tissue destruction, but unfortunately its role in lymphocytes is insufficient of understanding. Ascorbic acid has been exhibited to increase differentiation and proliferation of B- and T-cells (and increases antibody levels), it's possible because of its gene modulating impacts. Ascorbic acid also regulates cytokine and interferon formation and also reduces histamine levels [14].

Infection and inflammation mostly related to ascorbic acid level in tissues, that the insufficiency of ascorbic acid involves in disturbance of immune function and the risk of infections. Infections enhanced inflammation and metabolic requirements, so may

significantly impact on ascorbic acid levels. However, its supplementation can prevent and medicate respiratory and systemic infections. Intake of ascorbic acid supplementation that provides at least adequate is needed for prophylactic prevention of infection. The saturating plasma concentrations (i.e., 0.1–0.2 g/day) may enhance cellular concentrations, but in the treatment of underlying infections need much greater doses of ascorbic acid to neutralize the inflammatory response and metabolic demand [14, 15].
