I previously asserted that the ratio of the 5 different types of white blood cells explains our history interacting with pathogens. A colleague used what is called "AI Deep Dive" to see if it validated my original thesis (reproduced below):
My Thesis:
"Therefore, we should be concerned about pathogens as follows:
Bacterial infections: 74%
Viral infections: 21%
Parasitic infections: 5%
YOUR BLOOD DOESN'T LIE!
This is based on white blood cells only and does not consider immunoglobulins and other components of immunity. However, white blood cells are primary."
Here is what Deep Dive AI determines when asked pointed questions. I am providing this as the raw report from AI with my comments and considerations.
Key: Yellow highlights: Important conclusions determined by AI
Blue or grey highlights: Questions I have about AI's conclusion(s) or follow-on questions based on AI's answer(s).
Red text: I don't agree with AI's conclusion(s)
Evolutionary Reasons for White Blood Cell Distribution
Overview of White Blood Cell Types and Proportions in Humans
Human blood contains several types of white blood cells (WBCs), each with specialized immune functions. In healthy adults, neutrophils are typically the most abundant WBC, followed by lymphocytes, with monocytes, eosinophils, and basophils present in much smaller numbers
. A normal differential count is approximately:
Neutrophils: ~40–60% of circulating WBCs (the largest fraction)
.
Lymphocytes: ~20–40% of WBCs
.
Monocytes: ~2–8%
(many of these leave blood to become tissue macrophages).
Eosinophils: ~1–4%
.
Basophils: ~0.5–1%
(usually the rarest).
This distribution is not arbitrary – it reflects an immune system shaped by evolution to prioritize the cell types most needed for survival in our environment. Pathogens have been among the strongest selective pressures on humans
The proportions of WBCs in our blood today bear the imprint of countless generations of adaptation to infectious threats.
Innate Defenders: Neutrophils (and Monocytes) as the Majority
Neutrophils are the frontline soldiers of the immune system – fast-acting phagocytes that rush to sites of infection or injury. Evolutionarily, having a large standing army of these first responders confers a clear survival advantage. Neutrophils can ingest and destroy bacteria and fungi within minutes of detection, limiting the spread of infection. In fact, neutrophils are the dominant leukocyte population in adult humans, with the bone marrow churning out around 100 billion neutrophils daily to patrol the body
Ratio not indicated.
. This high baseline supply is “consistent with their role in serving as first responders to infectious and inflammatory stimuli” which ones specifically and in what ratios - approximately?
. In other words, because acute bacterial infections and wound contaminations were constant threats throughout human evolution, natural selection favored individuals who could rapidly deploy many neutrophils to contain microbes before they cause severe harm. Infectious diseases have likely killed many humans historically, so those with robust innate defenses (like plentiful neutrophils) had higher survival and reproductive success
This strongly suggests that the immune system is developed chiefly around bacterial infections.
.
Monocytes, which circulate in smaller numbers, complement neutrophils in the innate defense. Monocytes (~5% of WBCs) can migrate into tissues and mature into macrophages or dendritic cells, providing longer-term cleanup and alert functions. Evolution keeps monocyte counts lower than neutrophils because many monocytes are not needed in the blood at once – they largely act within tissues.
This complicates the ratio discussion because the monocytes are not exclusive to the blood. This is similarly true with lymphocytes that are recruited into the lymphatic system out of serum.
A few patrol the bloodstream and can be recruited as needed to sites of infection or to replace tissue macrophages. This strategy is efficient: enough monocytes are present to seed tissues and respond to chronic infections, but not so many that they cause unnecessary inflammation (hmm - not sure this is correct). The fact that phagocytic immune cells (granulocytes and macrophages) evolved very early – even simple invertebrates have amebocytes and hemocytes that act as phagocytes
– underscores how fundamental this innate defense is. The prevalence of neutrophils in humans today is an extension of that ancient immune architecture, scaled up to meet the heavy microbial exposure that comes with being a large, injury-prone organism. what about acute/chronic disease - not just injury?
Another reason neutrophils dominate is their generalist nature. They are effective against a broad range of common pathogens without needing prior exposure. This broad utility meant that throughout evolution, increasing neutrophil numbers yielded diminishing returns only at very high levels, whereas too few neutrophils was immediately detrimental (leading to fatal infections). Thus, the optimal strategy was to invest heavily in neutrophils. However, there are trade-offs – neutrophils are powerful but also potentially damaging. Their weapons (reactive oxygen species, enzymes, and NETs) can harm host tissue - is this supported - do they attack self and non-self? what about the herx reaction - no mention here.
, so the body must regulate and turn over neutrophils rapidly. Evolution has struck a balance where we maintain a large reserve of neutrophils ready to fight, but each cell is short-lived and tightly controlled to minimize collateral damage. hmm - but despite the short life, there is a steady state HIGH concentration. Conclusion seems to be in conflict with reality.
Adaptive Specialists: Lymphocytes in Reserve
Lymphocytes (T cells, B cells, and natural killer cells) are the central players in adaptive immunity. They are fewer in number at baseline (~20–40% of WBCs)
, but they provide highly specialized responses and immunological memory. The evolutionary logic here is different from neutrophils: instead of keeping huge numbers of every possible lymphocyte on hand, the body maintains a diverse but relatively small pool of lymphocytes that can proliferate explosively when needed. Each lymphocyte carries receptors for a specific antigen. Upon encountering their target (e.g. a virus or bacterium), they clone themselves into an army of effector cells. This clonal expansion means a small starting population can effectively mount a large response, but only when appropriate. From an evolutionary perspective, this is a resource-efficient strategy – it saves energy and avoids cluttering the bloodstream with massive numbers of cells that might never be needed unless a specific pathogen is present.
I wonder if lowering lymphocyte levels during infection is explained. Also, how lymphocyte levels sometimes go up with neutrophil counts - so lymphocytes can either go up or down in the blood during infection.
The adaptive immune system evolved later in the history of life (it’s found in vertebrates but not in more primitive animals), and it complemented the innate system by granting long-term immunity. Our ancestors who survived infections often did so because they developed lymphocyte-mediated immunity that prevented reinfection or fought persistent viruses.
Specialization and memory allowed by lymphocytes meant that even if their baseline numbers are lower, individuals with effective lymphocyte responses could survive diseases like smallpox or measles and then be immune for life. Over time, selection favored an immune composition that included these adaptable cells. However, maintaining too many lymphocytes at all times isn’t ideal either.
First, many lymphocytes reside in lymphoid organs (lymph nodes, spleen, etc.) rather than blood until needed.
Second, an overabundance of active lymphocytes without infection can increase the risk of autoimmune reactions (attacking the body’s own tissues).Hmmm - not sure this happens - always a more logical/scientific reason. Thus, evolution tuned lymphocyte levels to be sufficient for immune surveillance and rapid expansion, but not so high as to cause unnecessary immune activation.
Interestingly, human infants and children naturally have a lymphocyte-heavy profile – in early life, lymphocytes often outnumber neutrophils
I thought it was just the opposite - innate immunity is higher at birth because the new human has NOT been exposed to create now lymphocyte antibodies. - I could be wrong - needs to be explored.
– reflecting the process of building up immunological memory. As we reach adulthood and accumulate memory cells, neutrophils become predominant again
again - this seems backwards.
. This developmental shift suggests that the immune system allocates resources differently when learning about pathogens (childhood) versus when it already has an experienced repertoire (adulthood).
seems this is the opposite of what happens.
Specialized Minor Players: Eosinophils and Basophils
Eosinophils and basophils are much less numerous under normal conditions, but they are evolutionarily preserved for specific, critical tasks. Eosinophils (only ~1–4% of WBCs) are mainly fighters of multi-cellular parasites (like worms) and modulators of allergic responses
In environments where parasitic infections were common, the ability to ramp up eosinophil production or activation would have been beneficial. However, having too many eosinophils all the time isn’t advantageous; these cells release toxic granules and enzymes that can damage host tissues and cause chronic inflammation if activated inappropriately.
Thus, evolution favored a strategy where eosinophils are kept at low baseline levels, but can be quickly produced in greater numbers when a parasitic infestation or certain infection demands it.
How long do they stay elevated upon exposure - if they return to "low baseline levels?"
In a sense, eosinophils are a reserve force designed for a particular type of threat – they remain few in number until the body “decides” it’s facing a parasite or allergen, at which point cytokine signals (like IL-5) stimulate eosinophil proliferation and release. People whose ancestors lived in regions with high parasite burdens might have slightly higher baseline eosinophil counts or a more vigorous eosinophil response, as that would confer a survival edge against diseases like schistosomiasis or hookworm (I think hookworm can go both ways - including beneficial - if so, what is the threshold concentration? I kind of know what the baseline is for H pylori) . But if parasites aren’t present, those extra eosinophils could cause harmful inflammation (e.g. asthma, allergies), so there is a trade-off. Evolution appears to have settled on keeping eosinophils scarce but ready – a balance that minimizes damage in parasite-free periods yet allows potent responses when needed.
Basophils are the rarest WBC type (often <1%)
and are closely related to tissue mast cells. They are involved in defending against parasites and in mediating allergic reactions (through release of histamine and other inflammatory mediators). Basophils likely didn’t need to be numerous in circulation because their role is more about signaling and orchestrating inflammation rather than directly killing pathogens. A few basophils can release enough histamine to recruit other immune cells and expel parasites, so having many would be overkill and potentially dangerous. Indeed, an excessive basophil/mast cell activation can lead to anaphylaxis or chronic allergic conditions. Evolutionary pressure thus kept basophil counts low to prevent spontaneous hypersensitivity, while ensuring that the capacity for a strong basophil/mast cell response exists when triggered by something significant (like a venomous animal bite or parasite invasion).
In summary, for both eosinophils and basophils, the infrequency of their primary targets (parasitic worms, etc.) in any given moment, and the potential collateral damage these cells can cause, led to their minimal representation in blood under normal conditions. They are the specialized units that mobilize on demand rather than patrol en masse.
Interesting as there is a trend in functional medicine to believe parasites cause all types of disease rather than bacteria and viruses.
Immune Trade-offs and Optimized Balance
The current distribution of WBC types in humans reflects an evolutionary compromise between maximizing protection and minimizing self-damage or waste. Each cell type is costly to produce and maintain, so there is an implicit resource allocation problem that evolution solves: allocate cells in proportion to their expected usefulness.
Pathogen prevalence was a major driver – common threats like bacteria (especially pyogenic bacteria causing wound infections) selected for high neutrophil reserves, whereas rarer threats like large parasites did not justify a permanent large contingent of eosinophils or basophils.
Additionally, the speed vs. specificity trade-off shaped WBC proportions. Fast, nonspecific responses are handled by abundant neutrophils and macrophages, whereas slower, highly specific responses are handled by lymphocytes which can be fewer initially because they will multiply if the trigger is encountered.
The innate immune cells act immediately but lack target specificity, so having them in great numbers ensures a rapid generic defense. Adaptive immune cells are specific and create memory; having a smaller number suffices because upon recognition of their target they swiftly expand and provide long-lasting immunity. where do they go? where to they act?
Another key factor is the avoidance of immunopathology. Too robust an immune presence can be as dangerous as too little. For instance, if all your WBCs were neutrophils, you might fight bacteria well, but you’d be ill-equipped for viruses (where did this statement come from?) and you’d risk tissue damage from an overzealous inflammatory response. Conversely, if lymphocytes were the majority, an initial infection could run rampant before the slower adaptive response kicks in. The evolved solution is a balanced team: neutrophils and monocytes handle immediate firefights, lymphocytes stand ready to tailor the response and remember the enemy, and eosinophils/basophils lie in wait for specific scenarios.
This balance confers a survival advantage by covering all bases – an individual can respond to a cut infected with bacteria within hours (neutrophils), eliminate a virus over days and then be immune to it thereafter (lymphocytes), and still handle an intestinal worm if one appears (eosinophils), all without keeping the less-needed forces at high levels all the time.
The way this above is worked - we only have acute bacterial infections.
Importantly, the “healthy” distribution of WBCs in humans is itself flexible and can shift with context, which is a feature shaped by evolution. Stress or acute infections cause a surge of neutrophils (and a relative drop in lymphocyte percentage) – a response known as the neutrophil/lymphocyte shift – giving a transient boost to innate defense when it’s most needed
Chronic parasitic infections will raise eosinophil counts over time, essentially recalibrating the baseline in those individuals. These dynamic adjustments show that while we have an average WBC makeup, our bodies can deviate from it adaptively. Evolution favored not a fixed ratio, but a responsive system that generally maintains one distribution in health and can alter it in disease.
Comparative Perspectives Across Species
Looking at other species provides a “natural experiment” to understand how different evolutionary pressures shape WBC distributions. Humans are actually somewhat unusual in being so neutrophil-heavy – many other mammals share this trait, but some animals have evolved different balances. For example, laboratory mice (and many small rodents) have far more lymphocytes in their blood than neutrophils. In adult mice, lymphocytes typically comprise about 75–90% of WBCs, with neutrophils being only 10–25%
By contrast, adult humans usually show the reverse (neutrophils ~50–70%, lymphocytes ~20–40%)
This difference likely reflects each species’ life history and immune strategy. Mice are short-lived and often face threats like viral infections or certain intracellular bacteria where rapid adaptive responses (and continual immune surveillance by lymphocytes) are crucial; also, being small, they might deal with wound infections differently or have alternate mechanisms (like a faster metabolic rate aiding innate immunity).
Humans and larger mammals, on the other hand, suffer frequently from tissue injury and pyogenic infections, favoring a strong neutrophil system. The disparity between mice and humans is a reminder that “one size fits all” doesn’t apply to immune systems – each species’ WBC distribution is tuned to its typical pathogen exposure and physiology.
Among vertebrates, we see even broader variation. Birds provide a striking comparison: in many bird species, the circulating leukocyte profile is lymphocyte-dominant rather than neutrophil-dominant. Birds have neutrophil-equivalents called heterophils, but in species like chickens and turkeys, lymphocytes are often the most common WBC, whereas some other birds (e.g. certain parrots) have more heterophils.
Why would birds lean more on lymphocytes? One hypothesis is that their high body temperature and rapid metabolic rate (birds often run hotter than mammals) might naturally impede many bacterial infections, reducing the need for as many neutrophils. Birds also encounter different sets of pathogens (for instance, fewer suppurative wound infections and more viral or protozoal diseases in some cases), and they rely heavily on adaptive immunity and antibody protection (for example, bird antibodies can be transmitted via egg yolk to offspring). Evolution may have thus favored a lymphocyte-heavy strategy for many avian species. Reptiles and fish show varied patterns too – some reptiles have lymphocyte-dominant blood, while others have more granulocytes
, indicating the balance evolved in conjunction with environmental exposures (cold-blooded animals might face slower-spreading infections, altering the optimal immune mix). The emergence of neutrophil-like granulocytes in evolution is tied to specific genetic developments (e.g. the appearance of certain colony-stimulating factors in mammals)
, which gave mammals an enhanced ability to produce neutrophils. As a result, mammals in general tend to have higher neutrophil counts than more primitive vertebrates – an evolutionary innovation that contributed to mammals’ success in surviving infections.
Even within the mammals, lifestyle and ecology drive WBC differences. A vivid example is seen in the cat family (Felidae): large wild cats (like lions or tigers) have significantly higher neutrophil and monocyte counts – and relatively fewer lymphocytes – compared to smaller feline species
. Researchers hypothesize this is due to diet and feeding habits
. Big cats often take down large prey and feed on the carcass for days, exposing themselves to a buildup of bacteria, fungi, and other microbes on the rotting meat. Consequently, a strong innate immune response (lots of neutrophils and monocytes to fight off infections from wound bacteria or food-borne germs) would be highly advantageous, and evolution favored that immune profile in large felids
. Small cats (like domestic cats or ocelots), which tend to kill smaller prey and eat it quickly (limiting microbial growth), don’t face the same degree of pathogen exposure from food; their WBC profile tilts more toward lymphocytes in line with handling the viruses and other pathogens typical of smaller animals
. This felid comparison elegantly illustrates how ecological niches and pathogen exposure shape immune cell distribution: predators, scavengers, herbivores, etc., all evolve immune systems optimized for their likely dangers.
Humans themselves are not monolithic in WBC distribution either – there is evidence of genetic and environmental influence on our immune profiles. For instance, people of certain ancestries have slightly different baseline counts; a well-known example is benign ethnic neutropenia in individuals of African, Middle Eastern, or West Indian descent, who often have lower average neutrophil counts (and total WBC counts) without ill effect
. This trait has been linked to genetic variants (like the Duffy antigen receptor mutation common in African populations, which incidentally confers resistance to malaria). The prevalence of this neutropenia trait in malaria-endemic regions suggests a possible evolutionary trade-off – a mutation giving malaria protection also resulted in fewer neutrophils, but presumably those populations had other compensations or faced fewer bacterial infections that made this trade-off tolerable. Likewise, throughout history, as humans migrated to new environments or changed lifestyles (for example, from nomadic hunting to settled agriculture), their pathogen exposures changed (new diseases from domesticated animals, different parasites, etc.), which could gradually recalibrate immune priorities. While these shifts might not dramatically overturn the basic neutrophil-lymphocyte balance in humans, they likely fine-tuned aspects of our immune responsiveness (e.g. tendency toward higher IgE and eosinophil activity in populations plagued by helminths, or differences in inflammatory set-points). In short, the human immune system shows plasticity and has been continuously molded by the specific selective pressures our ancestors faced.
Conclusion
The distribution of white blood cell types in healthy humans today is the result of long-term evolutionary tuning of the immune system. Neutrophils dominate because our ancestors lived in a world where immediate innate defense against wounds and bacterial invasion was absolutely critical for survival
. Lymphocytes are fewer but invaluable, providing adaptive immunity and memory that allowed humans to survive repeated exposures to pathogens (with the ability to carry immunity forward). Monocytes bridge these systems, available in modest numbers to sustain longer-term innate responses and tissue surveillance. Eosinophils and basophils are kept as a small but ready contingent, evolved to tackle specific threats like parasites and to mediate necessary inflammatory reactions – deployed only when needed to avoid the harm they could cause if overactive. All of these proportions represent evolutionary compromises, balancing the need to defend against diverse enemies with the need to prevent friendly-fire damage and conserve resources.
Moreover, comparing across species and considering our evolutionary history reinforces that there is no one “ideal” WBC distribution for all organisms – the optimal mix depends on what an organism has encountered over millennia. In humans, the heavy skew toward neutrophils and the presence of specialized minorities (lymphocytes, eosinophils, etc.) reflects the spectrum of infectious challenges that Homo sapiens has typically faced and overcome. Evolution by natural selection has essentially calibrated our immune cell lineup to maximize survival: ensuring that the most frequently needed warriors are abundantly at hand, the precision weapons are held in reserve but can multiply rapidly, and the niche defenders are present at low levels ready to surge in their moment of need. This dynamic, evolved balance allows healthy individuals to meet everyday microbial threats effectively while retaining the flexibility to combat a wide array of diseases – a testament to the powerful shaping force of pathogen exposure and immune specialization in our evolutionary past.
Sources: Proper scientific understanding of WBC distribution and its evolutionary basis is supported by immunology research and comparative studies. For instance, standard hematology references document the normal human WBC differential
, and evolutionary immunology findings highlight how infections have been a dominant force in shaping the immune system
. Comparative studies across species (e.g. differences between human and mouse immune profiles
, or between large and small felids
) provide real-world examples of how ecology and evolution influence WBC proportions. Overall, the consensus is that our immune cell distribution is no accident – it’s a product of adaptive evolution, honed to give us the best fighting chance in a world full of pathogens.
Grok:
Key Points
Research suggests white blood cell (WBC) types maintain stable proportions in healthy people due to evolutionary adaptation to common pathogens.
It seems likely that neutrophils are more abundant because they fight frequent bacterial infections, while others like basophils are less common due to specialized, less frequent roles.
The evidence leans toward these proportions being optimized through natural selection, balancing immediate and long-term immune needs.
Why WBC Types Maintain Stable Proportions
White blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils, work together to protect the body. In healthy people, their proportions stay relatively stable because the body has regulatory mechanisms (what are they and why?) that control how many of each type are produced and how long they live. This balance is likely a result of evolution, helping us handle common infections like bacteria and viruses effectively.
Why Some WBC Types Are More Abundant
Neutrophils, making up 50-70% of WBCs, are the most common because they quickly respond to bacterial infections, which are frequent. Basophils, at just 0.5-1%, are rarer because they handle allergies and parasites, which are less common. This difference reflects the body's prioritization based on the threats it faces most often.
Unexpected Detail: Evolutionary Trade-Offs
An interesting aspect is that these proportions might involve trade-offs, like balancing energy use between producing short-lived neutrophils and long-lived lymphocytes, shaped by our ancestors' environments. This helps explain why deviations, like more neutrophils in bacterial infections, signal health issues. (not sure our body would "balance energy" if it's trying to eliminate a deadly pathogen!)
Survey Note: Detailed Analysis of White Blood Cell Proportions
White blood cells (WBCs), also known as leukocytes, are critical components of the immune system, defending the body against infections and foreign invaders. Dr. Tom Lewis's inquiry focuses on two key aspects: why different WBC types (neutrophils, lymphocytes, monocytes, eosinophils, and basophils) maintain relatively stable proportions in healthy individuals, and why some types, particularly neutrophils, are significantly more abundant than others, such as basophils. This analysis explores the biological and evolutionary reasons behind these patterns, considering their relevance to chronic disease management, especially through biomarkers like the neutrophil-to-lymphocyte ratio (NLR).
Background on WBC Types and Proportions
WBCs are produced from hematopoietic stem cells in the bone marrow, and their production is regulated by growth factors and cytokines, such as granulocyte-colony stimulating factor (G-CSF) for neutrophils and granulocyte-macrophage colony-stimulating factor (GM-CSF) for neutrophils and monocytes. In healthy adults, the total WBC count typically ranges from 4,000 to 11,000 per microliter, with the following approximate proportions:
WBC Type | Percentage Range | Primary Function |
Neutrophils | 50-70% | First responders to bacterial infections, phagocytosis |
Lymphocytes | 20-40% | Adaptive immunity, antibody production, viral defense |
Monocytes | 2-8% | Phagocytosis, antigen presentation, cleanup |
Eosinophils | 1-4% | Allergic responses, parasite defense |
Basophils | 0.5-1% | Allergic responses, inflammation, histamine release |
These proportions are maintained through homeostatic mechanisms, ensuring a balance that supports immune function without excessive energy expenditure. Another focus on energy - which in life/death - should not be a consideration.
Why Stable Proportions Are Maintained in Healthy People
The stability of WBC proportions in healthy individuals is likely a result of evolutionary adaptation and regulatory processes. The body's immune system has evolved to allocate resources optimally, balancing immediate, non-specific defenses (innate immunity) with delayed, specific responses (adaptive immunity). This is supported by research on immune response from a resource allocation perspective (Immune response from a resource allocation perspective), which suggests that natural selection has led to an optimal distribution of resources across different immune functions.
Neutrophils, with a short lifespan of 6-8 hours in circulation, require continuous production to maintain their numbers, reflecting their role as the first line of defense against bacterial infections.
Lymphocytes, with lifespans ranging from weeks to years, are produced at a lower rate but maintained for long-term immunity against viruses and other pathogens. This balance is regulated by feedback mechanisms involving cytokines, ensuring steady-state levels that match the body's needs in a healthy state.
Evolutionary pressures likely shaped these proportions to match the pathogen environment our ancestors faced. (has this changed - according to Paul Ewald - plaque time - NO - ie our environment of pathogens has not changed) For instance, bacterial infections, historically common, would favor higher neutrophil counts, while viral infections, also prevalent, would support significant lymphocyte populations. This is consistent with findings on the evolutionary history of blood cells, tracing back to phagocytic origins in unicellular ancestors (Tracing the evolutionary history of blood cells to the unicellular ancestor of animals).
Why Neutrophils Are More Abundant Than Others
Neutrophils are the most populous WBC type, comprising 50-70% of the total, due to their critical role in fighting bacterial infections, which have been a major selective pressure in human evolution. Their short lifespan necessitates high production rates, and their immediate, non-specific action requires large numbers to swarm infection sites quickly. This is supported by data showing neutrophils are produced at a rate of about 100 billion daily in a normal adult, with a circulation time of hours before migrating to tissues (Blood - Leukocytes, Immunity, Defense | Britannica).
In contrast, basophils, at 0.5-1%, are the least abundant, reflecting their specialized role in allergic responses and inflammation, which are less frequent and less critical for survival compared to bacterial defense. (Important point - less of a % = less frequent insult = less critical for survival)
Eosinophils, at 1-4%, handle parasites and allergies, functions less commonly needed in many environments, especially in modern settings with reduced parasite exposure. (Doubt we really have less parasite exposure. Indeed, we seldom are bare foot - which can be a source of parasites - but where have they gone if we are being exposed to less - what are the sources and roots of entry - I agree to some small degree with this statement only - that is, exposure is barely reduced)
Lymphocytes and monocytes, at 20-40% and 2-8% respectively, bridge innate and adaptive immunity, with lymphocytes crucial for viral defense (mixed messages about the actual target)(s) of lymphocytes - they clearly "fight" bacteria too based on IgG ) and monocytes for cleanup and antigen presentation, justifying their intermediate abundance.
This hierarchy suggests a prioritization based on the frequency and urgency of immune challenges, with neutrophils at the forefront due to their role in immediate, life-threatening infections. The resource allocation perspective (Optimal immune responses: immunocompetence revisited) further supports this, indicating trade-offs between energy costs and immune efficacy, where maintaining high neutrophil counts is energetically costly but essential for survival. (OK - maybe this is true - Have to think about this whole energy thing some more)
**Evolutionary and Functional Considerations (simple rationale)
The proportions are likely a result of evolutionary adaptation to the pathogen landscape, with natural selection favoring individuals whose immune systems were best equipped to handle common threats. For example, in environments with high bacterial infection rates, higher neutrophil counts would confer a survival advantage, while in areas with more parasitic infections, higher eosinophil counts might be favored. This is indirectly supported by studies showing genetic variations in WBC counts across populations, though specific proportion data across diverse groups is less documented (Multi-ethnic genome-wide association analyses of white blood cell and platelet traits).
Additionally, the lifespans of WBCs influence their proportions. Neutrophils' short lifespan (hours) versus lymphocytes' long lifespan (weeks to years) means the body must produce more neutrophils continuously, maintaining their high numbers. This dynamic is part of the homeostatic regulation, ensuring the immune system is prepared for both immediate and long-term threats without overextending resources. (plausible)
Relevance to Chronic Disease Management
Dr. Lewis's interest in these proportions, particularly the NLR, is crucial for chronic disease management, as deviations can signal pathological processes. For instance, bacterial infections typically increase neutrophils, while viral infections may decrease lymphocytes (not always! why the exceptions? I have not been able to answer this question with confidence), altering these ratios and indicating disease states. Understanding the baseline proportions helps interpret these changes, aiding in diagnosis and treatment strategies.
Mathematical and Ecological Analogies
While mathematical models of WBC population dynamics exist, they primarily focus on changes during disease or treatment, not the baseline proportions in healthy states (Mathematical Modeling of White Blood Cell Population Dynamics for Diagnosis and Prognosis). However, ecological concepts like trade-offs in resource allocation provide a useful analogy, suggesting that WBC proportions reflect an optimal strategy for maximizing fitness, balancing energy costs with immune efficacy.
Conclusion
In summary, the stable proportions of WBC types in healthy people are maintained by regulatory mechanisms and reflect evolutionary adaptation to common pathogens, with neutrophils being most abundant due to their role in frequent bacterial defense, and basophils least abundant due to their specialized, less frequent functions. These patterns are shaped by natural selection, balancing immediate and long-term immune needs, and are critical for understanding deviations in disease states.
Key Citations
I like the summary as it supports my overarching thesis - but leaves many questions (in blue) unanswered
In a recent blog, I explained what each type of white blood cell does. That blog is provided below (yellow highlight).
Based on that evaluation, one could conclude that parasites play a small role in overall health because our immune system produces very few white blood cells that target parasites.
However, white blood cells do not explain total immunity. Immunoglobulins play a role too!
LOOK FOR AN ANNOUNCEMENT FOR AN OFFER TO GET IMMUNOGLOBULIN TESTING AS PART OF 1 (OR MORE) OF OUR LAB PANELS.
AI gives us a starting point to determine the difference between these 2 types of immune components.
"Immunoglobulins (antibodies) and white blood cells are both crucial for the immune system, but they play distinct roles. While white blood cells are the "soldiers" that patrol and attack invaders, immunoglobulins are the "specialized weapons" that target and neutralize specific threats."
Translation: White blood cells change (in blood) upon sensing any pathogen. Immunoglobulins may or may not change depending upon the specific nature of the "insult."
Immunoglobulin G (IgG)
An immunoglobulin G (IgG) test measures the levels of IgG antibodies in your blood, which are crucial for fighting infections from bacteria and viruses, and can help determine immunity to certain infections or diagnose conditions like immunodeficiencies.
Here's a more detailed explanation:
What it tests for:
The primary purpose of an IgG test is to assess the amount of IgG antibodies present in your blood. IgG is the most common type of antibody in the body and plays a vital role in the immune system's defense against various pathogens.
Why it's ordered:
Doctors may order an IgG test for several reasons:
To check for infections: High IgG levels can indicate a past or current infection, while low levels might suggest an increased risk of infections.
To determine immunity: IgG levels can show if you've been previously exposed to a specific pathogen and developed immunity to it.
To diagnose immunodeficiencies: Low IgG levels can be a sign of an underlying immune system disorder.
To evaluate autoimmune conditions: In some autoimmune diseases, the immune system mistakenly attacks the body's own tissues, and IgG levels can be elevated in these cases.
Note, many doctors will tell you that IgG is elevated only from a past infection. This is seldom - if ever - true. If IgG of any type is elevated, you most likely have a chronic infection and the manifestation of a chronic condition! PERIOD!
Here is a statement from
"IgG only provides temporary protection, typically for 1-4 weeks. Most antibodies, whether produced by the individual’s immune system or given in the form of Ig replacement, are used up by the body and must be constantly replenished. Repeat doses of Ig are required at regular intervals to provide those with antibody deficiencies with high enough Ig levels to ward off infection."
Here is how long antibodies against influenza last.
"Antibodies against influenza, induced by either natural infection or vaccination, are long-lived, potentially lasting for decades, but can wane over time, especially against different strains of the virus."
Notice, they did NOT say that they last a lifetime. For example, if you test positive (IgG) for EBV and you are 60 years old, there is a VERY GOOD CHANCE this reflects a CURRENT chronic EBV infection.
"Waning Immunity:
While the immunity can be long-lasting, antibody titers (levels of antibodies) can decrease over time, especially against influenza strains that differ significantly from those previously encountered."
"Another major challenge to studying immunological memory is the potential of a host’s pathogen-specific memory response to wane over time. This plasticity allows the immune system to modify its memory response as it encounters various pathogens—each with a unique antigenic fingerprint—enabling effective protection against known and emerging pathogens. However, such flexibility also makes it difficult to predict how long protective immunity established by memory cells will last.
You can enhance your body's IgG with a product distributed by Microbiome Labs named Mega Igg 2000.
Immunoglobulin E (IgE)
Immunoglobulin E (IgE) is a type of antibody that plays a crucial role in the body's immune response, particularly in allergic reactions, parasitic infections, AND VENOMS by triggering the release of histamine and other inflammatory mediators.
Here's a more detailed explanation of what IgE does:
Allergic Reactions:
IgE is produced in response to allergens, substances that the immune system mistakenly identifies as harmful.
When IgE binds to allergens, it triggers the release of histamine and other inflammatory mediators from mast cells and basophils, leading to symptoms like itching, hives, sneezing, and difficulty breathing.
IgE is involved in various allergic conditions, including allergic rhinitis (hay fever), asthma, atopic dermatitis (eczema), and food allergies.
Parasitic Infections:
IgE also plays a role in the body's defense against parasitic infections.
It helps to activate immune cells to eliminate parasites, particularly worms.
Mechanism of Action:
IgE antibodies bind to mast cells and basophils through high-affinity receptors (FcεRI).
When an allergen binds to the IgE antibody, it causes the mast cells and basophils to release inflammatory mediators, such as histamine, leading to allergic symptoms.
Testing:
IgE levels can be measured in the blood to help diagnose allergies and other conditions.
Allergy blood tests measure the amount of IgE antibodies in the blood, which can help identify specific allergens that trigger allergic reactions.
Some key statements from this article:
Host defense against parasites has long been considered the only beneficial function that might be conferred by IgE and mast cells. No immune cell has absolute specificity but IgE is an excellent marker for parasitic infections.
Host responses to intestinal nematode infections are typically characterized by Th2 immunity [18–23], with elevated levels of parasite antigen-specific and nonspecific IgE, tissue and blood eosinophilia (and sometimes increased numbers of basophils), and intestinal pathology, including crypt hyperplasia, goblet cell hyperplasia, and mucosal MC (MMC) hyperplasia [18, 19, 23]. Data from epidemiological studies suggest a protective role of IgE antibodies in infections with certain parasites in humans, as the levels of parasite-specific IgE and resistance to infection correlate positively [24–26].
Intrinsically toxic molecules, such as components of animal venoms, represent an obvious danger for the host, and IgE-associated allergic reactions against a variety of venoms have been reported [135–140]. Some of them, for instance those against components of the venoms of hymenoptera like the honeybee or the yellow jacket, have a high prevalence [141], whereas fewer cases of allergic reactions to components of snake or jellyfish venoms, have been reported [136, 142], perhaps because of lower rates of exposure to such toxins.
IgA and IgM will be covered in a subsequent blog post.
PREVIOUS BLOG ON WHITE BLOOD CELLS
Have you ever wondered why our blood's 5 types of white blood cells are at such different concentrations?
Let's look at the standard levels in healthy people:
Neutrophils: 53%
Lymphocytes: 40%
Monocytes: 4%
Eosinophils: 2%
Basophils: 1%
The above values yield an NLR = 1.3 for those who understand the neutrophil-to-lymphocyte ratio. When white blood cell counts are evaluated based on early mortality, markers at this level are optimal. Research data indicates that people with these levels live the longest, all other things being approximately equal.
HERE IS MY CONSIDERATIONS.
Be aware that I cannot find any literature that studies explicitly how white blood cells react to types of pathogens. That is, to what percentage are they specific to given types of pathogens? Therefore, my conclusion is based on the following:
Neutrophils are specific to bacterial infections.
Lymphocytes respond to bacterial and viral species at approximately equal ratios.
Monocytes capture and neutralize larger "things" like the spike protein and parasites.
Basophils and Eosinophils split their activity between allergens and parasites.
Assuming their concentrations in blood reflect that level of the type of pathogen they combat, this is where our immune system places emphasis:
Bacteria: 53% (from neutrophils) and 20% (half of the lymphocyte level) = 73%
Viruses: (half of the lymphocyte level) = 20%
Parasites: 4% from monocytes and 1.5% from the sum of Eosinophils and Basophils.
HERE ARE MY CONCLUSIONS.
Our primary immunity—white blood cells—allocates 3/4th of their effort to fighting bacterial infections. Therefore, bacterial infections are the primary type of pathogen impacting our health. Why else would our immune system act in that way?
Viruses constitute ~20% of the harm that impacts human health.
Parasites have a low impact on human health at ~2% compared to viruses and bacteria.
Therefore, we should be concerned about pathogens as follows:
Bacterial infections: 74%
Viral infections: 21%
Parasitic infections: 5%
YOUR BLOOD DOESN'T LIE!
This is based on white blood cells only and does not consider immunoglobulins and other components of immunity. However, white blood cells are primary.
Now, let's explore some interesting historical/evolutionary facts.
Question 1: What do the various white blood cells do?
Neutrophils: The main job is to fight bacterial infections.
According to the NIH, neutrophils are a type of white blood cell (leukocyte) that are a critical part of the immune system, specifically acting as the first responders to infections by ingesting and destroying microorganisms through phagocytosis and releasing enzymes. The main type of pathogen they fight is bacteria. Many sites, including many governmental sites, indicate that this type of white blood cell also fights fungal infections. That may be the case. However, antibiotic therapy that targets bacteria mainly often improves (lower) neutrophil blood levels in the direction of the above mentioned optimal level.
Here is a comprehensive reference of neutrophils.
Excerpt from the article: Neutrophils, also known as polymorphonuclear (PMN) leukocytes, are the most abundant cell type in human blood. They are produced in the bone marrow in large numbers, ~1011 cells per day. Under homeostatic conditions, neutrophils enter the circulation, migrate to tissues, where they complete their functions, and finally are eliminated by macrophages, all in the lapse of a day. Neutrophils are important effector cells in the innate arm of the immune system (Mayadas et al., 2014). They constantly patrol the organism for signs of microbial infections, and when found, these cells quickly respond to trap and kill the invading pathogens. Three main antimicrobial functions are recognized for neutrophils: phagocytosis, degranulation, and the release of nuclear material in the form of neutrophil extracellular traps (NETs)
Lymphocytes: The main job is to support neutrophils by fighting viral and bacterial infections.
Lymphocytes, a type of white blood cell, play a crucial role in the immune system, fighting bacteria and viruses, with B cells producing antibodies and T cells directly targeting and destroying infected cells. There are two main types of lymphocytes:
B cells (B lymphocytes): These cells produce antibodies, which are proteins that target and neutralize specific pathogens, including bacteria and viruses.
T cells (T lymphocytes): These cells directly attack and destroy infected cells, including those infected with viruses or bacteria.
Even though antibodies are not probably the chief control process in parasitic infections with intracellular phases, they increase in response to all protozoal infections such as Leishmania, Trypanosoma cruzi, Toxoplasma gondii, and Plasmodium.
Monocytes: The main job is to fight fungal and protozoal infections.
Monocytes originate from progenitors in the bone marrow and traffic via the bloodstream to peripheral tissues. During homeostasis and inflammation, circulating monocytes leave the bloodstream and migrate into tissues where, following conditioning by local growth factors, pro-inflammatory cytokines, and microbial products, they differentiate into macrophage or dendritic cell populations. Recruitment of monocytes is essential for effectively controlling and clearing viral, bacterial, fungal, and protozoal infections.
Studies of these different diseases have revealed the remarkable multipotency of monocytes in different inflammatory environments. The ability of monocytes to mobilize and traffic to where they are needed is central to their functions in promoting immune defense during infection and driving inflammatory diseases. This review focuses on the mechanisms that allow monocytes to traffic from their site of origin — the bone marrow — to distinct tissue sites.
Monocytes were often elevated during COVID-19 due to the SARS and/or the spike protein.
Basophils: The main job is to fight fungal and protozoal infections.
Basophils are a type of white blood cell that plays a crucial role in the immune system. Basophils are essential for regulating allergic reactions, supporting immune responses, defending against parasites, and maintaining blood clotting.
Their primary functions include:
1. Allergic Reactions:
Basophils contain granules filled with histamine, heparin, and other chemicals.
When exposed to allergens, basophils release these granules, leading to symptoms such as swelling, redness, itching, and mucus production.
2. Immune Regulation:
Basophils help regulate the immune response by releasing cytokines, which are signaling molecules that influence the activity of other immune cells.
They promote the development of Th2 (helper T cell 2) cells, which are involved in allergic reactions and anti-parasitic immunity.
3. Anti-parasitic Defense:
Basophils play a role in defending the body against parasites.
They release chemicals that attract and activate other immune cells to fight parasites.
4. Blood Clotting:
Heparin, contained in basophil granules, acts as an anticoagulant, preventing excessive blood clotting.
5. Wound Healing:
Basophils release factors that promote wound healing by attracting fibroblasts, which produce collagen.
Eosinophils: The main job is to fight fungal and protozoal infections.
Eosinophils are a type of white blood cell that play a crucial role in the body's response to parasites and allergic reactions, contributing to inflammation and potentially damaging tissue.
Eosinophils and Parasites:
Eosinophils are known for targeting and killing parasitic worms (helminths). They do this by binding to the parasites, releasing toxic substances, and contributing to inflammation at the site of infection.
Eosinophils and Allergies:
During allergic reactions, eosinophils are also recruited to the affected tissues, contributing to the inflammatory response. They release substances that can cause tissue damage and contribute to the symptoms of allergies.
While primarily known for their roles in parasitic infections and allergies, eosinophils also play a role in other immune responses, including fighting bacteria, viruses, and fungi.
Immunoglobulins:
Immunoglobulins are included in this discussion because of their action against parasitic infections.
A hallmark of the immune response to parasite infection is immunoglobulin (Ig) E binding to Fc receptors on the surface of mast cells and basophils, leading to degranulation and secretion of inflammatory mediators [58,124,125]. This interaction, which bridges antigen-specific and innate immunity, is primarily mediated by the high-affinity IgE receptor (FcεRI) constitutively expressed on mast cells and basophils [58,111,124–126].
Question 2: What came first, white blood cells or organisms that these cells manage?
Bacteria, as the earliest form of life on Earth, came before humans, with evidence suggesting their existence around 3.5 billion years ago. In contrast, humans evolved much later, with modern humans originating in Africa within the past 200,000 years.
Viruses likely predated humans, possibly existing as self-replicating entities in the pre-cellular world, with some scientists proposing they could even be older than the first cells.
Ancient Origins:
Scientists believe viruses are at least as old as the first cells, which emerged around 4 billion years ago. Some theories suggest viruses could have existed even earlier, in a pre-cellular world, as self-replicating entities that later evolved into forms that parasitize cells.
Viral Evolution:
Over time, these early replicative entities may have evolved into more complex structures and gained the ability to infect cells, eventually leading to the viruses we know today.
Human Evolution:
Humans, as a species, evolved much later, with the oldest evidence of early humans dating back millions of years, but not billions.
Viral Genetic Material in Human DNA:
It's also worth noting that viral genetic material is embedded in our own DNA, constituting close to 10% of the human genome.
Protozoa evolved and existed long before humans, with protozoa appearing in the Precambrian era and humans evolving much later.
Protozoa:
These are single-celled eukaryotic organisms, a group that includes organisms like amoebas and paramecia. They are considered a subkingdom of the kingdom Protista, though, in the classical system, they were placed in the kingdom Animalia.
Fungi:
Fungi existed before humans, with evidence suggesting their emergence around 1 billion years ago, while the earliest evidence for humans dates back to 6-2 million years ago.
Here's a more detailed breakdown:
Fungi:
Fossil and DNA evidence indicate that fungi emerged at least a billion years ago.
Humans:
The earliest evidence of humans, including fossils of early humans, dates back to 6-2 million years ago, with modern humans originating in Africa within the past 200,000 years.
The key difference between protozoa and fungi is that protozoa are unicellular eukaryotic organisms, while fungi are primarily multicellular eukaryotic organisms.
Mold, as a type of fungus, predates humans, having existed on Earth for millions of years, while humans evolved relatively recently.
Here's a more detailed explanation:
Mold's Origins:
Molds are a type of fungus and have been around for millions of years, playing a vital role in decomposition and nutrient cycling in ecosystems.
Human Evolution:
Humans, as a species, are relatively recent evolutionary developments. Our closest living relatives, the great apes (chimpanzees and bonobos), share a common ancestor with us that lived about 5-7 million years ago.
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