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How Your Immune System Works & How to Improve It | Dr. Max Krummel
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Key Moments
Your body's immune system changes dramatically with age, becoming a 'mosaic' of mutations that challenges its ability to distinguish self from non-self, potentially explaining why cancer and autoimmune conditions are more prevalent later in life.
Key Insights
Immunology was considered an undeveloped field 30 years ago, but cancer immunotherapy (pioneered by Dr. Krummel's advisor, a Nobel laureate) changed this by showing the immune system's reactivity can be 'tuned' to fight tumors, leading to cures previously unattainable.
During childhood (up to age 10), the immune system is actively learning, facing numerous pathogens for the first time, leading to frequent illness but also robust immunity; conversely, in later life, immune efficacy tapers, and cells become less functional, contributing to increased sickness.
The thymus, named for its role in T-cell development ('thymus cells'), is crucial for educating T-cells to distinguish self from non-self; it is very large in children but involutes (shrinks) in adults, raising interest in revitalizing it for therapeutic benefits, especially in cancer.
Research suggests a strong connection between the brain's insular cortex, emotions, and immune states; studies (e.g., inducing inflammatory bowel disease in mice) indicate that merely recalling a memory associated with a past immune state can reactivate that immune response in specific tissues.
Vaccine hesitancy, particularly regarding timing and combinations, is a nuanced issue; while the overall efficacy and safety of vaccines are well-established, there's a lack of public research on optimal scheduling, leading to concerns that are not always addressed by the scientific community.
Biological systems are inherently resilient, allowing humans to withstand extreme conditions and various stressors; this resilience implies that diseases often require multi-faceted interventions rather than single 'one-and-done' drugs, which can be easily exploited or circumvented by complex biological processes.
The immune system constantly redefines 'self' as we age, influencing disease
Initially, the immune system distinguishes 'self' from 'non-self,' like submarines identifying friendly versus enemy vessels by engine sounds. However, as humans age, our bodies accumulate an estimated 10,000 to 30,000 DNA mutations per skin cell per day, turning us into a "mosaic" of genetically diverse cells. This cellular mosaicism means that 'self' becomes increasingly varied, making it harder for the immune system to identify genuinely foreign threats or cancerous cells that are only slightly different from their mutated neighbors. This phenomenon contributes to the higher prevalence of cancer in later life, as the immune system's detection threshold for abnormal cells becomes muddied by the sheer diversity of 'self.' This dynamic redefinition of self highlights the immune system's continuous adaptation and the profound challenge aging poses to its finely tuned surveillance mechanisms.
Childhood and old age present unique immune challenges
Newborns possess a relatively undeveloped immune system for their first six months, presumed to prevent self-attack during rapid development. Children, up to age 10, frequently get sick as they encounter new pathogens, building a strong, diverse immune memory. Conversely, in the last quarter of life, immune cells become less functional and are produced in smaller quantities, increasing susceptibility to illness. This decline might be due to a lack of evolutionary pressure to maintain peak immune function post-reproduction. This dual perspective on age illustrates the immune system's developmental trajectory, from rapid learning and robust response in youth to a gradual decline in efficacy later in life.
The thymus: A critical organ for immune education and a target for revitalization
The thymus, a key organ in T-cell development, was historically misunderstood; doctors in the 1970s often removed it in children during heart surgeries, leading to severe opportunistic infections. Research by Jo Miller, now 97, demonstrated in mice that removing the thymus caused susceptibility to bacterial infections and even tumors, revealing its crucial role in immune function. The thymus is where stem cells from bone marrow mature into T-cells, learning to distinguish healthy 'self' cells from potential threats. In children, the thymus is large and highly active, churning out vast numbers of T-cells to build a foundational immune repertoire. However, it significantly shrinks (involutes) with age, reducing the production of new T-cells. This involution is a major reason for the increased susceptibility to infections and cancer in older adults. Revitalizing the thymus, perhaps through peptides or other interventions, is a promising area of research to bolster the immune system, particularly in cancer therapy, by generating new T-cells specifically tuned to target tumors that older T-cells might no longer recognize as foreign. This potential therapeutic avenue underscores the profound impact of this often-overlooked organ on lifelong immunity.
Mindset and memories can directly influence immune states
Emerging research indicates that brain states and even memories can directly impact immune function. Studies using functional MRI show that recalling memories can trigger physiological responses similar to those experienced when the memory was formed, including changes in immune status. For example, experiments with mice where inflammatory bowel disease was induced showed that by reactivating specific neuronal circuits in the insular cortex (a brain region involved in interoception and emotion), the gut's immune system could be reset to an inflammatory state, even after recovery. This suggests that thoughts and emotions, particularly those mediated by the insular cortex, can directly program immune responses in various organs via neural pathways like the vagus nerve. This fascinating discovery bridges the gap between psychology and immunology, offering a potential mechanistic basis for how practices like meditation might influence health by modulating immune states.
Vaccine timing and nuance in public health discussions
The discussion around vaccines often polarizes, but many individuals express valid concerns about the timing and combinations of immunizations, rather than outright opposition. While the scientific community generally agrees on vaccine efficacy and safety, the optimal scheduling of multiple childhood vaccines and their long-term combined effects have not been as thoroughly studied or publicly communicated. The current protocols are often based on initial studies and convenience, but alternative schedules might offer similar protection with less perceived disruption. The lack of transparent, accessible data and nuanced dialogue contributes to public distrust, particularly when individuals experience adverse events after vaccination, leading to a profound sense of anger and betrayal. Addressing these questions through open research and clear communication is essential to build public confidence and foster more informed decision-making.
The scientific process: A long road of failures leading to breakthroughs
Scientific discovery is a lengthy process characterized by numerous failures, dead ends, and incremental advancements. For every breakthrough like CRISPR or cancer immunotherapy, there are hundreds of experiments that yield no clear results. This 'orthogonal discovery' often comes from unexpected areas; for instance, CRISPR originated from studying how bacteria defend themselves, not from an initial goal to edit human genes. This highlights the importance of basic research driven by curiosity, as significant advancements often arise from exploring fundamental biological questions without an immediate application in mind. The journey of science is less about a direct path and more about navigating a complex landscape, where persistence through countless disappointments eventually leads to profound insights that reshape our understanding and capabilities.
Autoimmune conditions: Misplaced immune responses with genetic and environmental roots
Autoimmune conditions arise when the immune system mistakenly targets the body's own tissues, viewing them as foreign. These conditions, such as lupus or inflammatory bowel disease, often have genetic predispositions; for example, a familial mutation in a B-cell receptor can lead to lupus by causing overactive antibody production. However, autoimmune diseases are complex and often represent a misfiring of immune 'playbooks' that are genetically and historically wired to deal with external threats. For instance, asthma is not a single disease but rather a syndrome with multiple "immune flavors," each triggered by different factors (e.g., chlorine, cold) and involving distinct immune cell types (eosinophils vs. neutrophils). This complexity means that treatments effective for one form of autoimmunity may not work for another, and patients can develop resistance over time. Understanding these nuanced immune archetypes is crucial for developing more targeted and effective therapies, moving beyond a one-size-fits-all approach. Interestingly, some mild autoimmune conditions, like psoriasis, might even confer a degree of resistance to viral or bacterial infections, suggesting a trade-off in immune system design where heightened reactivity against self in one context might offer protection in another.
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Common Questions
Initially, the immune system was viewed as a simple defense mechanism against foreign invaders. However, it's now understood as a highly complex and tunable system that measures and regulates various bodily functions, including in the brain, gut, liver, and heart, adapting to changes within the body itself.
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Mentioned in this video
Host of the Huberman Lab podcast and Professor of Neurobiology and Ophthalmology at Stanford School of Medicine.
Guest on the podcast, Professor and leading expert in immunology and cancer biology at the University of California, San Francisco. He also runs a Substack called 'The Immune Beyond'.
A 97-year-old scientist in Australia who conducted foundational experiments demonstrating the thymus's role in the immune system by removing it from newborn mice.
Another scientist mentioned to whom Huberman previously spoke about engineering cells.
A developmental biologist from UC Santa Cruz and a mutual friend and longtime collaborator of Andrew Huberman, known for a memorable quote about having 'successfully reproduced'.
Nobel Prize-winning scientist in whose lab David Felheim trained.
Max Krummel's mentor, who won the Nobel Prize for his work on cancer immunotherapy involving an antibody against T-cells.
Mentioned as a previous guest on the podcast who raised questions about vaccine timing and combinations.
Institution where Dr. Max Krummel is a Professor of Immunology and Cancer Biology.
An organ critical for the education and production of T-cells in early life, which involutes (shrinks) in adults. Its potential revitalization is a subject of therapeutic interest.
Discussed as an institution focused on stem cell research and therapies, with noted challenges in rapid translation to clinical use.
Immune cells, named for the thymus, that act as sensors for biomolecules and can be activated or suppressed. They are crucial for fighting infections and cancer.
Immune cells responsible for making antibodies. Their overactivity is linked to autoimmune conditions like lupus.
Refers to a set of transcription factors used to reprogram differentiated cells into induced pluripotent stem cells.
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