How does age affect immunity?

How Age Affects Immunity

Aging causes a progressive decline in T cell-mediated immunity while simultaneously triggering chronic low-grade inflammation ("inflammaging"), making older adults more susceptible to infections, less responsive to vaccines, and more prone to chronic diseases. 1

Key Age-Related Immune Changes

Decline in Adaptive Immunity

• T cell function deteriorates significantly with age, particularly affecting naïve CD4+ T cells, which show reduced ability to divide and produce IL-2 (a critical immune signaling molecule) 1
• Lymphocyte proliferation decreases after stimulation in older adults, compromising the body's ability to mount effective immune responses to new pathogens 1
• Vaccine responses decline with age, with older adults showing reduced antibody production to tetanus, influenza, and other vaccines compared to younger individuals 1
• Natural killer (NK) cell activity decreases, reducing the body's ability to eliminate virus-infected and tumor cells 1
• Coordinated immune responses become disrupted in individuals ≥65 years old, with poor synchronization between CD4+ T cells, CD8+ T cells, and antibody responses 2

Rise in Chronic Inflammation

• Prostaglandin E2 (PGE2) production increases with age, acting as a T cell suppressor factor that further impairs immune function 1
• Pro-inflammatory cytokines (TNF-α, IL-6) become chronically elevated, contributing to increased risk of cardiovascular disease, cancer, diabetes, and Alzheimer disease 1
• This "inflammaging" state represents an overactive, prolonged inflammatory response that paradoxically coexists with weakened pathogen defense 1

Clinical Consequences by Age Group

Older Adults (≥65 years)

• Increased susceptibility to respiratory infections, including Streptococcus pneumoniae and influenza 1
• Higher mortality from lower respiratory infections compared to younger adults 1
• Reduced delayed-type hypersensitivity (DTH) responses, indicating impaired cell-mediated immunity 1
• Waning vaccine immunity occurs more rapidly, particularly for influenza A(H3N2) viruses 1

Middle-Aged Adults (50-64 years)

• 24-32% have ≥1 high-risk medical condition that increases vulnerability to infections 1
• Diphtheria immunity declines significantly, with 62% of persons aged 18-39 years lacking adequate protection in some populations 1
• Tetanus immunity varies inversely with time since last vaccination, with 28% lacking immunity 6-10 years after vaccination 1

Adolescents and Young Adults

• Immunity from childhood vaccinations wanes, particularly for pertussis, with the greatest increase in cases occurring in 10-19 year-olds 1
• Approximately 20% of adolescents aged 11-12 years remain susceptible to varicella 1
• Tetanus immunity drops at ages 9-13 years, with 15-36% of these persons unprotected 1

Mechanisms of Age-Related Immune Decline

Cellular Level Changes

• Membrane integrity deteriorates in immune cells due to increased lipid peroxidation, affecting signal transduction 1
• Scarcity of naïve T cells develops with aging, limiting the ability to respond to new pathogens 2
• Key signaling molecules become dysregulated, including ZAP70, LAT, phospholipase-Cγ, and Vav proteins in T cells 1

Systemic Factors

• Redox status becomes dysregulated, with increased oxidative stress damaging cellular components 1
• Cell membrane composition changes, particularly affecting immune cells with high PUFA content 1

Vaccination Implications

Timing Considerations

• Immunity after influenza vaccination wanes over time in adults, though evidence is less clear in children 1
• Very early vaccination (July-August) may result in suboptimal immunity before the end of influenza season in adults 1
• Waning protection varies by age group, with older adults and younger children showing more evident decay in vaccine effectiveness 1

Age-Specific Recommendations

• Adults aged ≥65 years require pneumococcal vaccination with both PCV13 and PPSV23 due to increased infection risk 1
• Zoster vaccination is recommended starting at age 60 years (or 50 years per FDA approval) due to declining cell-mediated immunity 1
• Td/Tdap boosters at ages 11-12 years are essential as immunity from childhood vaccination series declines 1, 3

Common Pitfalls to Avoid

• Do not assume adults born before 1957 are immune to measles/mumps/rubella—healthcare personnel require documented evidence regardless of birth year 1
• Do not delay vaccination in older adults due to concerns about reduced efficacy—some protection is vastly better than none 1
• Do not overlook pertussis in adolescents and adults with chronic cough—immunity wanes and the disease is highly contagious 1
• Do not assume complete childhood vaccination provides lifelong immunity—most vaccines require boosters as immunity wanes with age 1, 3