Variation in the human immune system is largely driven by non-heritable influences

Area of Science:

• Immunology
• Genetics
• Systems Biology

Background:

• Individual differences in immunological parameters are significant but poorly understood.
• Distinguishing between genetic and environmental influences on immunity is crucial for understanding immune system variability.

Purpose of the Study:

• To investigate the relative contributions of heritable versus non-heritable factors to immunological heterogeneity.
• To analyze the impact of age and infections on immune system variability.

Main Methods:

• Systems-level analysis of 210 healthy twins (aged 8-82).
• Measurement of 204 immunological parameters (cell populations, cytokines, serum proteins).
• Analysis of immune responses to influenza vaccination and cytomegalovirus infection.

Main Results:

• 77% of immunological parameters are predominantly influenced by non-heritable factors.
• 58% of parameters are almost completely determined by non-heritable influences.
• Immune variability increases with age and is affected by infections like cytomegalovirus.

Conclusions:

• The immune system is largely reactive and adaptive, shaped more by environmental factors than genetics.
• Non-heritable influences, including infections and cumulative exposures, play a dominant role in immune system diversity.
• Immune responses to vaccination are also largely non-heritable, possibly due to strain variation.