Role of zinc in immunity

Overview

• Zinc is an essential trace element (micromineral) required by the body in small quantities (less than 100 mg/day or <0.01% of body weight) for the maintenance of health, growth, and normal physiological processes.
• It is the second most abundant trace element in the human body after iron.
• It is ubiquitous in nature and is required for the normal functioning of almost all organ systems, including the immune, gastrointestinal, central nervous, skeletal, epidermal, and reproductive systems.
• Zinc status is regulated both at the absorptive step in the intestine and by intestinal re-excretion.

Enzymatic and Catalytic Functions

Zinc acts as a cofactor or integral component for more than 200 enzymatic reactions, making it critical for metabolic homeostasis.

• Nucleic Acid Metabolism: Zinc is essential for the synthesis of DNA and RNA. It is a component of DNA polymerase and RNA polymerase, enzymes critical for cell division and replication.
• Protein Synthesis: It plays a vital role in protein synthesis and amino acid metabolism.
• Carbonic Anhydrase: Zinc is a cofactor for carbonic anhydrase, which is essential for acid-base balance and respiration.
• Alkaline Phosphatase: It is a component of alkaline phosphatase, an enzyme involved in bone mineralization and liver function.
• Thymidine Kinase: This zinc-dependent enzyme is involved in DNA synthesis.

Genetic and Genomic Functions

• Zinc Finger Proteins: Zinc is a constituent of "zinc finger proteins".
• Gene Transcription: Through these proteins, zinc regulates gene transcription.
• Cellular Growth: By regulating gene expression and nucleic acid metabolism, zinc is fundamental to cellular growth and differentiation.

Physiological Role in Immunity

Zinc is often referred to as a "nutrient of immunity" due to its central role in host defense mechanisms. It affects both non-specific (innate) and specific (adaptive) immunity.

1. T-Cell Lymphopoiesis and Thymic Function

• Thymic Development: Zinc is essential for the development and maintenance of the thymus gland. Zinc deficiency leads to thymic atrophy.
• Thymulin Activity: Zinc is required for the biological activity of the thymic hormone thymulin. Serum thymulin levels can be used as a marker to detect early zinc deficiency.
• T-Lymphocyte Function: It is essential for the development, differentiation, and function of T-lymphocytes.
• Cell-Mediated Immunity (CMI): Zinc deficiency impairs cell-mediated immunity, leading to lymphopenia and a reduced T-helper to suppressor cell ratio. This creates a state comparable to a nutritionally acquired immunodeficiency syndrome.

2. Mucosal Immunity and Barrier Function

• Epithelial Integrity: Zinc maintains the integrity of the skin and mucous membranes.
• Mucosal Repair: It improves epithelial repair and regeneration of the intestinal mucosa.
• Barrier Function: By restoring mucosal barrier integrity, zinc prevents the translocation of bacteria and toxins from the gut into the circulation.
• Gut-Associated Lymphoid Tissue (GALT): Nutritional composition, including zinc, supports gut microflora and enhances immunity via GALT.

3. Cytokine Regulation and Inflammation

• Inflammatory Response: Zinc plays a role in coordinating the inflammatory response to various stimuli.
• SIRS/CARS Balance: An uncontrolled inflammatory response often results from an imbalance between pro-inflammatory mediators (like free radicals) and anti-inflammatory mediators (free radical scavengers like zinc). Nutritional modulation with zinc helps balance the Systemic Inflammatory Response Syndrome (SIRS) and the Compensatory Anti-inflammatory Response Syndrome (CARS).

4. Clinical Implications of Immune Function

• Infection Resistance: Zinc deficiency significantly increases susceptibility to infections, particularly diarrhea, pneumonia, and possibly malaria.
• Diarrhea Management:
  • Zinc supplementation reduces the duration, severity, and recurrence of diarrhea.
  • It improves brush border enzyme function and T-cell immunity in the gut.
  • It aids in the regulation of water and electrolytes, decreasing stool output.
  • Administration of zinc for 14 days during an acute episode prevents subsequent episodes for the next 2-3 months.

Antioxidant Functions

• Superoxide Dismutase (SOD): Zinc is a key component of the enzyme Copper-Zinc Superoxide Dismutase (Cu-Zn SOD).
• Free Radical Scavenging: As part of SOD, zinc acts as an antioxidant by scavenging superoxide free radicals, protecting cells from oxidative stress and lipid peroxidation.
• Cell Membrane Stability: By preventing oxidative damage, zinc helps maintain the stability of biological membranes.

Growth and Development

• Linear Growth: Zinc is necessary for linear growth. Deficiency is strongly associated with growth retardation and stunting.
• Catch-up Growth: Zinc supplementation has been shown to result in better catch-up height in children with low birth weight (LBW) and malnutrition.
• Neurodevelopment: It plays a role in brain development and function. Deficiency may be associated with an impaired ability to learn.

Reproductive Physiology

• Sexual Maturation: Zinc is essential for normal sexual maturation.
• Gonadal Function: Deficiency in adolescents causes delayed sexual maturation and hypogonadism (gonadal atrophy).

Sensory Functions

• Taste Perception: Zinc is required for the synthesis of Gustin, a protein involved in taste perception. Deficiency leads to hypogeusia (decreased taste sensation) or ageusia.
• Vision:
  • Zinc is essential for night vision.
  • It is required for the synthesis of retinol-binding protein (RBP), which transports Vitamin A. Thus, zinc deficiency can lead to secondary Vitamin A deficiency and night blindness.

Dermatological Function

• Skin Health: Zinc is vital for skin integrity and wound healing.
• Acrodermatitis Enteropathica: This is a genetic disorder of zinc absorption (defect in ZIP4 transporter) characterized by severe zinc deficiency. Physiological failure here leads to the classic triad of periorificial dermatitis, alopecia, and diarrhea.
• Wound Healing: Deficiency is associated with delayed wound healing and skin ulcers.

Interaction with Other Minerals

• Copper: Excess zinc intake can interfere with copper absorption, potentially leading to copper deficiency. This property is therapeutically used in Wilson's disease to block copper absorption.
• Iron: Zinc and iron can compete for absorption; high doses of one can inhibit the uptake of the other.