Immune Fitness: Potential Barriers to Optimal Immune Responses

Composition of assorted organic food products. Immune system function is influenced by a range of factors, including diet, microbial makeup, sleep habits, and stress level.
                                                                                                                                                                                            Read time 5 minutes

An immune system with healthy reactivity and resilience is significant for fighting infections, preventing diseases, and achieving overall mental and physical wellness. Health inequities, including affordability, accessibility, and other social determinants of health, sustain barriers to optimal health care for some communities and may present challenges for an individual’s development of robust immune resilience.1-4 Consideration of such factors and understanding the inequities that contribute to health outcome disparities help clinicians develop effective treatment plans that are personalized and promote patient empowerment.

Social & Environmental Factors: The Immune System Response

A 2019 meta-analysis of 35 studies found that compared to higher socioeconomic status (SES), low SES exposure in childhood and adolescence increased levels of inflammation in adulthood (measured by C-reactive protein (CRP), IL-6, and fibrinogen).5 Echoing these results, a 2023 cross-sectional study consisting of 1,359 healthy adults found that lower childhood SES was associated with higher circulating levels of CRP and a greater risk for cardiometabolic disease at midlife measured by adiposity, blood lipids, glucose control, and blood pressure.6 In addition to SES, other environmental and social factors such as healthy food access, exposure to pollutants, and chronic psychosocial stress may also impact immune system responses.

Nutrition & a Healthy gut

Adequate and uninterrupted access to healthy and varied foods is essential for positive health outcomes. Dietary patterns that include anti-inflammatory foods such as fruits and vegetables supply nutrients and natural antioxidants that may contribute to a more robust immune system through reducing inflammation.7 However, for some patients and communities, reliable access to affordable, nutritious foods can be a potential challenge for immune health. Data from 2022 suggested that 12.8% of all US households experienced food insecurity at least some of the time during that year while 36.7% of households with incomes below the federal poverty line experienced food insecurity.8 Further, results from a cross-sectional study of over 10,000 participants suggested that food security status may be associated with dietary inflammatory potential.9 Specifically, those with low or very low food security reported a lower intake of several anti-inflammatory foods and nutrients compared to those with greater food security, including fiber, vitamins A, B6, C, and E, β-carotene, and magnesium.9

Accessibility and consumption of varied and healthy foods also influences gut microbiome function, a key regulator of immune system homeostasis. Communication between the microbiome and the intestinal mucosal immune system impacts immune response,10 and dysbiosis may contribute to blunted immune reactivity.11 In addition to nutrition-based studies, microbioscape research, which combines microbiome science and landscape research,12 suggests microbial input from the environment also influences immunoregulation pathways.13 Accessibility to green spaces, for example, has been shown to benefit health and lower all-cause mortality risk,14 yet studies indicate that access to urban green spaces within under-resourced US neighborhoods is limited.15

Exposure TO POLLutants

Ambient pollutants and toxicants such as heavy metals, pesticides, and other endocrine-disrupting chemicals have been associated with immune system imbalances.2,16,17 Disproportionate exposure levels among different racial populations and socioeconomic classes continues to be documented.18-20 A 2020 assessment by the Environmental Protection Agency indicated that unsafe air quality (with the highest fine particulate matter [PM2.5] concentrations) was most often recorded in low-income communities and among Hispanic and Black populations.21 The American Lung Association has echoed concern for environmental exposure inequities, indicating that people of color are 3.7 times more likely than white people to live in a US county that has failing grades for daily and long-term measures of particle pollution and daily measures of ozone.20

Chronic exposure to pollutants and toxicants may lead to an overloaded body burden, increased systemic inflammation, and clinical manifestations of immune dysfunction.22 A 2020 review reported common themes among cell and animal model studies that investigated the mechanistic effects of air pollutants on different immune cells.17 Ambient pollutants were found to directly activate cellular signaling pathways, triggering inflammatory cytokine release from the epithelium and macrophages. In addition, the pollution particulates enhanced TH lymphocyte 2 and 17 responses.17



Chronic exposure to social, physical, or environmental stressors is a determinant of mental and physical health impacting a patient’s quality of life and wellness. Studies have found that communities of color disproportionately experience chronic stressors,23 and worries such as limited access to health care and food insecurity may compound the elevated risk of chronic stress.24 Experiencing stress can activate inflammatory responses, with acute stressors potentially enhancing immune response and chronic stressors ultimately suppressing immune function.25 A 2019 systematic review and meta-analysis of 75 studies explored this stress-immune relationship further by evaluating the effectiveness of stress-reducing psychological interventions on the activation of immune responses.26 After the specific intervention (i.e., stress management, relaxation, meditation, mindfulness, cognitive-behavior technique, or counseling), immune-related outcomes were measured either through in-vitro, in-vivo, or psychophysiological challenges (i.e., natural killer cell and cytokine responses, wound healing and skin testing, or speech tasks and treadmill exercise test). Overall, a small to medium effect size was suggested for all interventions, with those studies measured through in-vitro stimulations and psychophysiological challenges showing more optimal immune responses.26

Clinical Considerations

Immune system function is influenced by a range of factors, from diet to stress to toxicant exposures, and racial, economic, social, and cultural barriers to optimal health and health care create immune resilience challenges for some patients. These barriers and social determinants of health are antecedents and mediators of physiological dysfunction in the functional medicine matrix model. They are important factors when considering immune health strategies and when determining what lifestyle practices are modifiable for a patient.

Meeting a patient where they are, understanding access barriers, and recognizing social conditions that may be beyond their immediate control are all part of a patient-empowered collaborative relationship. These considerations ultimately help to provide the most effective personalized intervention that supports optimal immune health. Learn more about immune reactivity and boosting resilience from functional medicine experts at IFM’s Immune Advanced Practice Module (APM).

Learn More About Immune Imbalance

Related Articles & Podcasts

Supporting Health in Underserved Populations

Food Insecurity and Chronic Disease

Chronic Stressors, Disease Burden, and Sustainable Lifestyle Interventions

Neighborhood Health: Pollutant Exposures and Chronic Disease Risk


  1. Grant T, Croce E, Matsui EC. Asthma and the social determinants of health. Ann Allergy Asthma Immunol. 2022;128(1):5-11. doi:1016/j.anai.2021.10.002
  2. Nowak K, Jablonska E, Ratajczak-Wrona W. Immunomodulatory effects of synthetic endocrine disrupting chemicals on the development and functions of human immune cells. Environ Int. 2019;125:350-364. doi:1016/j.envint.2019.01.078
  3. Barroso I, Ramos E, Craveiro V, Guimarães JT. White blood cells in a healthy adolescent population according to social and health characteristics. Arch Pediatr. 2023;30(6):361-365. doi:1016/j.arcped.2023.03.008
  4. Leung CW, Zhou MS. Household food insecurity and the association with cumulative biological risk among lower-income adults: results from the National Health and Nutrition Examination Surveys 2007-2010. Nutrients. 2020;12(5):1517. doi:3390/nu12051517
  5. Milaniak I, Jaffee SR. Childhood socioeconomic status and inflammation: a systematic review and meta-analysis. Brain Behav Immun. 2019;78:161-176. doi:1016/j.bbi.2019.01.018
  6. Natale BN, Manuck SB, Shaw DS, et al. Systemic inflammation contributes to the association between childhood socioeconomic disadvantage and midlife cardiometabolic risk. Ann Behav Med. 2023;57(1):26-37. doi:1093/abm/kaac004
  7. Wu PY, Chen KM, Tsai WC. The Mediterranean dietary pattern and inflammation in older adults: a systematic review and meta-analysis. Adv Nutr. 2021;12(2):363-373. doi:1093/advances/nmaa116
  8. USDA Economic Research Service. Food security and nutrition assistance. US Department of Agriculture. Updated October 31, 2023. Accessed November 3, 2023.,2011%20and%20has%20declined%20since
  9. Bergmans RS, Palta M, Robert SA, Berger LM, Ehrenthal DB, Malecki KM. Associations between food security status and dietary inflammatory potential within lower-income adults from the United States National Health and Nutrition Examination Survey, cycles 2007 to 2014. J Acad Nutr Diet. 2018;118(6):994-1005. doi:1016/j.jand.2017.12.003
  10.  Fung TC. The microbiota-immune axis as a central mediator of gut-brain communication. Neurobiol Dis. 2020;136:104714. doi:1016/j.nbd.2019.104714
  11.  Aziz T, Khan AA, Tzora A, Voidarou CC, Skoufos I. Dietary implications of the bidirectional relationship between the gut microflora and inflammatory diseases with special emphasis on irritable bowel disease: current and future perspective. Nutrients. 2023;15(13):2956. doi:3390/nu15132956
  12.  Robinson JM, Jorgensen A. Rekindling old friendships in new landscapes: the environment–microbiome–health axis in the realms of landscape research. People Nat. 2020;2(2):339-349. doi:1002/pan3.10082
  13.  Rook GAW. The old friends hypothesis: evolution, immunoregulation and essential microbial inputs. Front Allergy. 2023;4:1220481. doi:3389/falgy.2023.1220481
  14.  Rojas-Rueda D, Nieuwenhuijsen MJ, Gascon M, Perez-Leon D, Mudu P. Green spaces and mortality: a systematic review and meta-analysis of cohort studies. Lancet Planet Health. 2019;3(11):E469-E477. doi:1016/S2542-5196(19)30215-3
  15.  Klompmaker JO, Hart JE, Bailey CR, et al. Racial, ethnic, and socioeconomic disparities in multiple measures of blue and green spaces in the United States. Environ Health Perspect. 2023;131(1):17007. doi:1289/EHP11164
  16.  Lima C, Falcão MAP, Rosa JGS, Disner GR, Lopes-Ferreira M. Pesticides and their impairing effects on epithelial barrier integrity, dysbiosis, disruption of the AhR signaling pathway and development of immune-mediated inflammatory diseases. Int J Mol Sci. 2022;23(20):12402. doi:3390/ijms232012402
  17.  Glencross DA, Ho T-R, Camiña N, Hawrylowicz CM, Pfeffer PE. Air pollution and its effects on the immune system. Free Radic Biol Med. 2020;151:56-68. doi:1016/j.freeradbiomed.2020.01.179
  18.  Ruiz D, Becerra M, Jagai JS, Ard K, Sargis RM. Disparities in environmental exposures to endocrine-disrupting chemicals and diabetes risk in vulnerable populations. Diabetes Care. 2018;41(1):193-205. doi:2337/dc16-2765
  19.  Nardone A, Casey JA, Morello-Frosch R, Mujahid M, Balmes JR, Thakur N. Associations between historical residential redlining and current age-adjusted rates of emergency department visits due to asthma across eight cities in California: an ecological study. Lancet Planet Health. 2020;4(1):E24-E31. doi:1016/S2542-5196(19)30241-4
  20.  American Lung Association. State of the Air 2023: key findings. American Lung Association. Published 2023. Accessed November 6, 2023.
  21.  US EPA Office of Air Quality Planning and Standards. Policy assessment for the review of the National Ambient Air Quality Standards for Particulate Matter. EPA-452/R-20-002. Environmental Protection Agency. Published January 1, 2020. Accessed November 6, 2022.
  22.  Hahad O, Lelieveld J, Birklein F, Lieb K, Daiber A, Münzel T. Ambient air pollution increases the risk of cerebrovascular and neuropsychiatric disorders through induction of inflammation and oxidative stress. Int J Mol Sci. 2020;21(12):4306. doi:3390/ijms21124306
  23.  Brown LL, Mitchell UA, Ailshire JA. Disentangling the stress process: race/ethnic differences in the exposure and appraisal of chronic stressors among older adults. J Gerontol B Psychol Sci Soc Sci. 2020;75(3):650-660. doi:1093/geronb/gby072
  24.  McKnight-Eily LR, Okoro CA, Strine TW, et al. Racial and ethnic disparities in the prevalence of stress and worry, mental health conditions, and increased substance use among adults during the COVID-19 pandemic – United States, April and May 2020. MMWR Morb Mortal Wkly Rep. 2021;70(5):162-166. doi:15585/mmwr.mm7005a3
  25.  Liu Y-Z, Wang Y-X, Jiang C-L. Inflammation: the common pathway of stress-related diseases. Front Hum Neurosci. 2017;11:316. doi:3389/fnhum.2017.00316
  26.  Schakel L, Veldhuijzen DS, Crompvoets PI, et al. Effectiveness of stress-reducing interventions on the response to challenges to the immune system: a meta-analytic review. Psychother Psychosom. 2019;88(5):274-286. doi:1159/000501645

Related Insights