5 Surprising truths about your immune system
Internal medicine physician Dr. Sharon Bergquist explains how metabolism, beneficial stress, and circadian biology shape your body's defenses—and why understanding the connections matters more than individual lab values.
The immune system operates as both a defense network and a surveillance system, constantly distinguishing between threats and benign substances while maintaining enough flexibility to respond to novel challenges. White blood cells serve as the primary actors in this system, divided into two main branches: the innate immune system provides immediate, non-specific responses to any perceived threat. In contrast, the adaptive immune system learns from experience to mount targeted attacks against specific pathogens.
Understanding this system matters because inflammation---the immune system's primary tool for responding to damage or infection---can become chronic when dysregulated. While acute inflammation helps heal injuries and fight infections, persistent low-grade inflammation contributes to metabolic disease, cognitive decline, and accelerated aging. Internal medicine physician Dr. Sharon Bergquist explains how the connections between metabolism, stress, and immune function reveal surprising opportunities for intervention.
Dr. Sharon Bergquist is an internal medicine physician, the author of The Stress Paradox, the Medical Director of Emory University's Executive Health program, and the leader of the research program at the Paul W. Seavey Comprehensive Internal Medicine Clinic. She conducts NIH-funded research on early disease markers, biological aging clocks, and epigenetics.
1. Metabolic dysfunction drives more inflammation than gut health
While gut microbiome optimization dominates wellness conversations, Dr. Bergquist argues that metabolic dysfunction is actually the bigger contributor to chronic low-grade inflammation. "When you have impaired mitochondria, you cannot have an immune system that's functioning with precision," she explains. This creates a vicious cycle in which metabolic dysfunction weakens immune responses, allowing more inflammation to persist.
The immune system requires substantial glucose and energy to activate properly. When cells become insulin resistant or mitochondria struggle to produce ATP efficiently, immune cells literally lack the fuel to do their job. Rather than viewing inflammation solely as a gut problem or an isolated immune issue, chronic inflammation often signals that the body's fundamental energy production system is compromised. Addressing metabolic health through improved insulin sensitivity and mitochondrial function may be the most effective way to reduce systemic inflammation.
2. Your white blood cell ratio matters more than the total count
Most people focus on whether their total white blood cell count falls within the normal range, but Dr. Bergquist emphasizes that the differential---the breakdown of different white blood cell types---provides far more useful information. The key is understanding the balance between neutrophils and lymphocytes, the two main categories that make up the majority of white blood cells.
Neutrophils are part of the innate immune system, the body's first-line defense that responds quickly but non-specifically to threats. Lymphocytes represent the adaptive immune system, which creates targeted, learned responses to specific pathogens. In healthy individuals, neutrophils typically outnumber lymphocytes by a ratio of about 2:1 or 3:1.
When this ratio shifts, it can reveal important patterns. A high neutrophil-to-lymphocyte ratio often indicates chronic stress or inflammation---the body is constantly mobilizing its immediate defenses. Conversely, when lymphocytes dominate, it might suggest the body is fighting a viral infection or recovering from acute stress. "The ratio between neutrophils and lymphocytes can give you a sense of whether you're in more of a stressed state or whether you're mounting a more adaptive immune response," Dr. Bergquist notes.
Context matters enormously here. Someone who exercises intensely will temporarily show elevated neutrophils as part of the normal inflammatory response to training. The key is distinguishing between acute, beneficial stress responses and chronic patterns that signal dysfunction.
3. "Normal" lab ranges weren't designed for optimal health
Standard laboratory reference ranges for immune markers are typically based on population averages, rather than on optimal health. This creates a significant problem: if the general population is metabolically unhealthy, then "normal" becomes a mediocre benchmark rather than a target for wellness.
Dr. Bergquist sees this disconnect regularly in her clinical practice. A patient's white blood cell count might fall within the normal range, yet they're experiencing symptoms of immune dysfunction---frequent infections, slow healing, persistent fatigue. The lab says everything is fine because the numbers compare favorably with those of other people in the database, but that database includes many people with suboptimal health.
This is why Dr. Bergquist emphasizes personalized baselines. "What's optimal for you might be different than what's optimal for another person," she explains. Someone whose white blood cell count sits at the high end of normal might actually be experiencing chronic inflammation, even though the number doesn't trigger any red flags. Similarly, someone at the low end might have perfectly healthy immune function if that represents their stable baseline.
The solution is longitudinal tracking. By measuring markers over time and correlating them with how you actually feel and function, you can establish your personal optimal range. This approach transforms lab testing from a binary normal-versus-abnormal assessment into a dynamic tool for optimizing health.
4. Beneficial stress strengthens your immune system through hormesis
Not all stress is harmful---in fact, the right kinds of stress in the proper doses can make the immune system more resilient. This concept, called hormesis, describes how mild stressors trigger adaptive responses that leave the body stronger than before. Dr. Bergquist considers this principle crucial for immune health but notes it's rarely discussed in clinical settings.
Exercise provides the clearest example. When you work out, you create temporary inflammation and stress on tissues. This acute stress activates cellular pathways that reduce chronic inflammation and strengthen immune defenses. The same principle applies to temperature exposure: cold plunges and sauna sessions trigger the body's endogenous anti-inflammatory mechanisms by challenging it to maintain homeostasis under demanding conditions.
Even certain dietary compounds work through hormesis. Phytochemicals in plant foods---the bitter, pungent, or astringent compounds in vegetables, herbs, and spices---are mild toxins that plants produce as defense mechanisms. When humans consume them in small amounts, these compounds activate stress-response pathways that enhance antioxidant defenses and reduce oxidative stress. "The phytochemicals mount a stress response that is anti-inflammatory," Dr. Bergquist explains.
The key distinction is between acute, intermittent stress and chronic, unrelenting stress. Brief challenges followed by recovery periods strengthen the system. Constant stress without adequate recovery depletes it. This is why exercise builds resilience while overtraining causes immune suppression, or why intermittent fasting can be beneficial while chronic caloric restriction becomes harmful.
5. Circadian alignment is the most underappreciated immune intervention
Of all the interventions that support immune function, Dr. Bergquist believes aligning with circadian biology is the most overlooked. "I think the role of our circadian biology is still not something that we talk about enough, certainly not in a clinical setting," she notes. Yet this synchronization between internal biology and external environment profoundly affects immune system performance.
The body operates on predictable rhythms that optimize different functions at different times. Digestion, cognitive function, and exercise performance peak during daylight hours. Healing, repair, and immune surveillance intensify at night. When lifestyle patterns conflict with these rhythms---eating late at night when the body expects to be repairing tissues, or exposing yourself to bright lights when melatonin should be rising---you're working against your biology.
A single night of partial sleep deprivation is enough to raise C-reactive protein, a key inflammation marker. Chronic circadian disruption weakens immune defenses, impairs the ability to clear damaged cells, and increases susceptibility to both acute infections and chronic inflammation.
Implementing circadian alignment involves managing three variables: light exposure (bright during the day, minimal at night), meal timing (stopping food intake at least 2-3 hours before bed and waiting at least an hour after waking), and sleep consistency (maintaining regular bedtimes and wake times). While individual variation exists---some people naturally skew toward morning or evening---the fundamental principles remain consistent across populations because they reflect millions of years of human adaptation to living outdoors under natural light-dark cycles.
The Path Forward
Understanding immune health requires moving beyond simplistic interpretations of lab values toward a more nuanced view of how metabolism, stress, and circadian biology interact. The immune system doesn't operate in isolation---it's deeply connected to how well your cells produce energy, how you respond to different types of stress, and whether your lifestyle aligns with your body's natural rhythms.
The most encouraging insight from Dr. Bergquist's work is that the capacity for resilience already exists within us. Start with metabolic health as the foundation, then build on that with strategic stress exposure through exercise and temperature challenges, attention to meal and sleep timing, and personalized interpretation of lab values based on your own baseline patterns. As she puts it: "It's so profound that you and I have it in our genome to become stronger, fight disease, and we have these innate defenses." The challenge isn't acquiring new capabilities---it's learning to activate what's already there.
This article is based on insights from Dr. Sharon Bergquist, an internal medicine physician with a research focus on biological aging, epigenetics, and early disease detection.
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