Table 1.

The immune functions and mechanisms of vitamins.

Immune functions and Vitamins mechanisms	Vitamins
	Vitamin A	Vitamins B6, B12, and folate	Vitamin C	Vitamin D	Vitamin E
1. Effects on physical and biochemical barriers (Role in maintaining the functional and structural integrities of mucosal cells in innate barriers e.g., gut, skin and respiratory tract).	Important for epithelial tissue to be normally differentiated. Retinoic acid helps in the imprinting of B and T cells and IgA into gut and intestinal tissue, thereby enhancing their immune response. Carotenoids act as immunoregulator via reduction of ROS toxic impacts and regulation of fluidity, and gap junction communications of cell membrane.	Regulate the intestinal immunity and support the gut barriers. B6 mediates the migration of lymphocytes into intestinal tissues. Folate helps the regulatory T cells to survive in the intestinal tract. B12 could be used by gut microbes as a cofactor in metabolic pathways.	Supports the epithelial barriers integrity as it could promote the synthesis of collagen and protect cellular membrane against free radicals. It could enhance the differentiation of keratinocytes, synthesis of lipids, and the migration and proliferation of fibroblasts.	Calcitriol supports gut barriers and regulates defensin and cathelicidin (antimicrobial proteins that could modify the gut microorganisms into healthier compositions). It could protect lungs from infection, upregulate the expressions of tight junction proteins connexion 43 and E-cadherin in the gut, maintain the normal function of renal epithelial barriers, and improve the functions of corneal epithelial barriers function.	Supports the epithelial barriers integrity and protects cellular membranes against free radicals
2. Effects on immune cells. A. Innate immune cells (differentiation, proliferation, functions, and movement).	Regulates the function and numbers of natural killer (NK) cells and the phagocytic activity of macrophage cells.	Maintain or enhance the cytotoxic activity of NK and T cells.	Maintains or enhances the cytotoxic activity of NK and chemotaxis. Helps the movement, function and proliferation of monocytes, neutrophils, and phagocytic cells. Enhances the killing of microbes by enhancing ROS generation and phagocytosis and clear the site of infection from spent neutrophils by macrophages. Decrease tissue damage by attenuating the formation of extracellular trap (NET).	The receptor of vitamin present in monocytes, macrophages, and dendritic cells (DCs). It enhances the monocyte differentiation into macrophages. Calcitriol improves the phagocytic activity of macrophages and promotes their movement.	Maintains or enhances the cytotoxic activity of NK cells. It could provide indirect protection of T cell functions via inhibiting the production of PGE2 from macrophages.
B. Antimicrobial activities.	Inhibits the production of IFN.		Has a role in the production of IFN. Can increase the complement proteins level in serum. High level can possess antimicrobial activity.	Calcitriol can regulate the expression of the antimicrobial proteins defensin and cathelicidin responsible for direct killing of pathogenic bacteria. Inhibits the production of IFN.
C. Importance in inflammation and antioxidant activities.	Regulates the IL-2 and TNF-α production that are involved in activation of macrophage phagocytic microbial, and oxidative burst activities during inflammatory reactions.	Vitamin B6 help in amino acids synthesis and metabolism and consequently cytokines. Aid in regulation of inflammation process.	Decreases histamine and modulates the production of cytokines. Keeps the cells' redox homeostasis and protects them from ROS. Helps in regeneration of valuable antioxidants like vitamin E and glutathione.	Calcitriol improves the macrophage potential burst activities. Enhances the synthesis of superoxide, decreases the proinflammatory cytokine production from macrophages, and increases the production of anti-inflammatory cytokines.	Acts as antioxidant, protects cells against free radicals. Enhances production IL-2. It could provide indirect protection of T cell functions via inhibiting the production of PGE2 from macrophages.
D. T cell differentiation, proliferation, and normal functions.	Helps the differentiation and development of T helper cells (Th1 and Th2). Aids in the acquisition of mucosal-homing properties by B and T cells.	Vitamin B6 helps the differentiation, maturation, and activities of lymphocytes. Can maintain the immune response of Th1 cells. Vitamin B12 facilitates the T cells' production and regulates the T helper-to-cytotoxic T cell ratio. Folate enhances the immune response mediated by Th1 cells.	Helps the production, differentiation, and proliferation of T cells (especially cytotoxic T cell).	Calcitriol stimulates the innate immunity and inhibits the adaptive immunity via decreasing the proliferation and functions of T cells and antigen-presenting DCs. Help the homing of T cell into the skin.	Helps the proliferation of lymphocytes and enhances the functions and responses of T cells.
3. Antibodies A. Production and development of antibody.	Helps the differentiation and development of T helper cells (Th1 and Th2). Suppresses the production of TNF-α, IL-12, IFN-γ, and Th1 cells and maintains the normal antibody-mediated Th2 responses.	Vitamin B6 helps in amino acids synthesis and metabolism and consequently cytokines and inhibits the Th2 cytokine-mediated activities. Vitamin B12 and folate are involved in production and metabolism of antibodies through folate mechanisms and is important for optimal clonal expansion.	Enhances lymphocyte proliferation, thereby increasing antibody generation.	Calcitriol suppresses the production of antibodies by B cells.	Suppresses the response of Th2.
B. Response to antigens.	Important for normal functions of B cells and helps in the generation of antibody responses to antigens.			Promotes the processing of antigen. Helps in the downregulation of major histocompatibility complex (MHC-II).	Increases the proportions of antigen-experienced memory T cells.
References	(35, 45–51)	(46, 47, 52–56)	(46, 47, 52, 57, 58)	(47, 48, 59–64)	(35, 45–51, 65, 66)