Table 2.

The immune functions and mechanisms of minerals.

Immune functions and mechanisms	Minerals
	Iron	Zinc	Copper	Selenium	Magnesium
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).	Helps the growth and differentiation of epithelial tissues.	Has a role in maintaining the integrities of mucosal membranes and skin.
2. Effects on immune cells. A. Innate immune cells (differentiation, proliferation, functions, and movement).	Helps in the bacterial killing by neutrophils through the formation of toxic hydroxyl radicals. It is a component of enzymes essential for immune cell function (such as ribonucleotide reductase helps in synthesis of DNA). Regulates the action and production of cytokines. Iron-rich status negatively regulates. M1 pro-inflammatory response and promotes M2-like macrophage phenotype.	Enhances or maintains the cytotoxic activity of NK cells. Has a key function in the differentiation and growth of immune cells. Enhances the phagocytic activity of peritoneal macrophages and monocytes.	Helps the normal functions of neutrophils, monocytes, NK, and macrophages (copper can accumulate in phagolysosomes in macrophages to counteract certain infections).	Selenoproteins are important antioxidants and help the functions of leukocytes and NK cells.	Acts as cofactor for nucleic acids metabolizing enzymes and helps in replication and repair of DNA, has a role in binding of antigen to macrophage, regulates the activity of leukocyte, and regulates the apoptosis process.
B. Antimicrobial activities.	Helps the production of IFN.	Helps complement activation and has a role in the production of IFN.	Has intrinsic antimicrobial property.	Enhances the production of IFN.
C. Importance in inflammation and antioxidant activities.	Helps in the production and function of cytokines. Helps in killing of pathogens by neutrophils through generation of ROS.	Acts as anti-inflammatory substance. Modulates the release of cytokines via dampening the pro-inflammatory Th9 and Th17 cell developments. Helps the IL-2, IL-6, and TNF generation. Acts as antioxidant and enhances the activities of antioxidant proteins against ROS and reactive nitrogen species.	Can accumulate at inflammation sites. Acts as a free radical scavenger and enters in the copper/zinc-superoxide dismutase, which is an important enzyme that counteracts the ROS. Helps the IL-2 production and response. Keeps the antioxidant balance inside the cells and has anti-inflammatory action.	Important for the functions of selenoproteins, which are redox regulators and cellular antioxidants against ROS generated during oxidative stresses.	Protects DNA from oxidative damage and decrease the production of superoxide anion.
D. T cell differentiation, proliferation, and normal functions.	Helps in proliferation and differentiation of T cells and regulates the ratio of T helper to T cytotoxic cells.	Promotes cytotoxic T cell proliferation. Helps the production of Th1 cytokines and supports their response. Important for intracellular binding of tyrosine kinase to T cell receptors. Helps the differentiation activation and development of development of Treg cells thereby maintaining immune tolerance.	Helps in proliferation and differentiation of T cells.	Helps in proliferation and differentiation of T cells and improves the count of Th cells.
3. Antibodies A. Production and development of antibody.		Helps the production of antibodies, mainly IgG.		Has a role in maintaining the levels of antibodies.	Acts as a cofactor in synthesis of antibody helps the antibody-dependent cytolysis and IgM lymphocyte bindings.
B. Response to antigens.		Aids in antibody response and could maintain the immune tolerance (the ability to recognize “self” from “non-self”).			Has an important role in binding of antigens to the RNA of macrophages and helps the antibody-dependent cytolysis.
References	(35, 45, 46)	(1, 35, 45, 47, 65, 66, 68–70)	(46, 47, 54, 70–73)	(45, 47, 54, 74)	(75–77)