Immunology 101.1

Vaccines target a small portion of the entire human immune system and often lag behind mutations of microbes. Yet vaccines have dazzled humans for centuries.

© Colleen Huber, NMD

Let’s consider the vastness of the human immune system, the resource that the body utilizes in encounters with any virus or other invading microbe.  This essay gets a bit into the weeds of human immune function and will seem as esoteric on first encounter as it does to first year medical students.  I summarize below the complex and synchronized activities of the vast majority of immune players that are at work and what they accomplish together, before the small remainder, the object of vaccine activity, namely B-cells and the antibodies, which are a kind of protein made by them, even show up.

There are two branches of the immune system in humans.  These are the innate and the adaptive immune systems.  Vaccines target about five percent of immune system cells, namely B-cells, and although some would argue T-cells also, the evidence for that is much weaker.  The innate immune system, which does not make any demonstrated beneficial use of vaccines, is the older of the two, the more widespread in the animal kingdom, and the one that has been active in our bodies since birth. 

Considering first the innate immune system, the larger and far more versatile of the two major branches, it is so ubiquitous throughout the body that cells of the innate immune system are no farther from any other cell than the thickness of a fingernail.  This short distance represents the maximum distance of any living cell to the nearest capillary blood vessel that nourishes it.  When you get a “complete blood count” from your lab, and you see neutrophils, monocytes, etc., you are looking at counts of cells per milliliter (or microliter, as indicated) of liquid blood that move through every blood vessel.  The innate immune system has the larger share of cells in the blood, many more than the adaptive immune system.

Although cells are basic units of the immune system, the epithelial barriers of the skin and mucous membranes are the first defenses involved in innate immunity.  These function best when they are intact barriers.  When those barriers are not abraded, lacerated or punctured, they are better able to exclude invading pathogens, which are microscopic infectious agents, from the far more vulnerable internal tissues and organs.   The skin is more visible than the mucous membranes, but there’s not as much of it - 2 square meters versus 400 square meters for the latter, or the size of two tennis courts.  How is the latter so large?  Think of all the folds and turns of the intestinal villi and the respiratory epithelia.   

The skin is our ultimate shield against the abundant microbial world just outside it.  (Vaccines are Trojan horse mechanisms that, among other effects, breach and defeat the strongest purpose of our very advanced and formidable yet supple armor.)

Our innate immune system continues beneath the surface.  It is the tapestry of the paths of first responding cells that are ready everywhere to attack invading pathogens (from a splinter, insect sting, just inhaled microbes, etc.)  In fact, this level of vigilance is so comprehensive throughout the body, that very often new pathogens are completely defeated and dispatched, even weeks before the antibodies of the adaptive immune system would begin to ramp up to do the job.  The various types of cells in the innate immune system are the tools that the body calls on to destroy the invaders.

Macrophages (literally big eaters) have been just under the skin everywhere throughout the body our whole lives, mainly cleaning up the debris of cellular processes, such as disposing of naturally dying cells.  Normally they just perform these tidying-up tasks, until they are summoned to confront new invading microbes.  Macrophages arrive first to the scene of many pathogenic assaults.  They crawl toward and engulf arriving microbes.  These were relatively dormant monocytes in the blood, about two billion circulating at any one time, until vitamin D helps them to mature to be devastating eating machines, when the need arises.  At that point, macrophages in turn alert the helper T cells of the adaptive immune system, but we haven’t gotten there quite yet.

There are additional chemical signals that alert macrophages to the presence of dangerous infection, taking them to a hyperactive state, enlarging them, increasing their chemical power to devour pathogens, and chemicals called cytokines, particularly a cytokine known as interferon gamma that is produced by another innate immune cell, the natural killer cells. Then macrophages produce another cytokine, tumor necrosis factor, which directly kills cancerous cells and virus-infected cells, and can activate other immune players.

Macrophages need back-up when the body is invaded, and then dog-whistle their allies the neutrophils by means of interleukin-1, which is a type of cytokine, or chemical signaling system.   A half-hour later, neutrophils are at the site of infection, ready for murderous assault.  Neutrophils are so deadly to the pathogens they engulf that they liquefy their prey.  There are 20 billion of these vicious killers circulating throughout the body at any time. 

In response to the alarm from macrophages, neutrophils that have been speeding along their path in the bloodstream, then – by means of multiple chemical signals - begin to stick to the interior walls of blood vessels, gradually roll to a stop, then pry apart cells of the blood vessel walls, exit the bloodstream, and then go into the infected tissues, where they actively eat pathogens.  The feast ensues, where macrophages and neutrophils swallow and destroy invading pathogens.

(Vaccines are not yet relevant to this detailed and intensely synergistic immune activity.)

Natural killer (NK) cells similarly circulate in the blood until needed at a site of viral infection, and then migrate there, where they kill human cells that have been infected by viruses, bacteria or other pathogens.  NK cells also can signal macrophages to hyper-activate and to step up the attack.  Through positive feedback, the numbers and potency of each is increased.

Complement is another feature of the innate immune system.  These are proteins produced by the liver and abundant in the blood and throughout bodily tissues that are especially lethal to bacteria and other microbes.  They are quite poisonous and directly punch holes in or otherwise destroy invaders, but our own cells have so many defenses against complement that we remain unharmed by these naturally produced poisons.  Chemical differences between our own cells and invader cells help guide the work of complement to harm the invaders but not to harm us.

Complement can attract and strengthen macrophages, to make their work more potent.  Complement places obvious signs on viruses, by attaching signaling molecules to viruses, which notify macrophages and neutrophils to attack them.  Complement can also directly destroy viruses.

Interferon is the cytokine mentioned before that human cells produce when viruses are nearby.  This chemical interferes with viral entry and replication, and serves as a warning signal to nearby cells to produce it also.  The blood cells best equipped to make Type 1 interferon, which is our strongest type of interferon are dendritic cells.  These ingest the pieces and debris of foreign pathogens and carry them to the lymph, where T cells will be developed.

The above may seem to be state-of-the-art high tech design, but the innate immune system has worked this way for millions of years.

(Incidentally, nothing involved with a vaccine has shown up yet, except if a prior vaccine happens to significantly match the current attacking pathogen.  This has been especially problematic with respiratory viruses, which mutate so quickly that every vaccine used against them has been partially obsolete by the time of mass distribution, such as flu shots with 14% effectivity, and the COVID vaccines, which do not match the Delta strain, etc.  But that’s okay, because most infectious assaults on the body are dealt with by the innate immune system within just a few days, especially with adequate vitamin D available.  More on that later.)

There are 5 billion red blood cells per milliliter of blood.  There are 5 million white blood cells per milliliter of blood.  Some would argue that red blood cells are also an important component of the innate immune system, because they can produce cytokines and can increase the numbers of and influence activity of other immune cells, such as neutrophils, macrophages and monocytes, and because they carry oxygen to tissues.  We have 20 to 25 trillion red blood cells in the body.  This is roughly 1000 times the number of neutrophils and 2,000 or 3,000 times the number of lymphocytes, and it is about 10,000 to 20,000 times the number of B-cells, which are the target cell of vaccine activity.

The adaptive immune system is the smaller part of the human immune system.  I say this because lymphocytes are less than 30% (with wide variation in individuals) of the white blood cells in a complete blood count, and less than two tenths of one percent of all blood cells.  B-cells are anywhere from one to twenty percent of all lymphocytes at any given time.  This means that probably less than 0.004 % (or 4 in 100,000) of all cells in the blood are targeted by vaccines.  In the generous scenario that all T-cells are stimulated and boosted by vaccines, that would raise the count to 0.1% (or one in one thousand) of all cells in the blood that would be stimulated by vaccines.

In a brazenly deceptive article published in Nature, it is asserted that “functional virus-specific memory CD8 T-cells can be detected in humans for several decades following acute viral infections or immunization with live attenuated vaccines,” while the two studies cited in support of this claim did not show anything at all about this occurring following immunization. [i]  There is not any convincing evidence that T-cells are reliably and permanently influenced by vaccination.  There have been reported brief dead-cat-bounce effects on T-cells in vitro following vaccines while using heavy laboratory manipulation.  Although there have been long-anticipated long-term effects of vaccines on T-cells, it seems the only reliable immune-provoking effect of any vaccines, both the older attenuated and live vaccines up through the mRNA vaccines, is to stimulate B-cell activity, to make antibodies to more quickly attack the exact same invader in the future.  But will you ever meet that exact same invader again?  SARS-CoV-2 is a RNA virus, and those are notorious for fast change, [ii] which is one reason why they have evaded successful vaccine development over the years.

The purpose of a vaccine is to accomplish a task that the innate immune system already does.  That is to indicate to the adaptive immune system which pathogens are dangerous and which are not.  In the event of a threatening pathogen, whether bacteria, viruses, fungi or parasites, it is the innate immune system that stirs the adaptive immune system to activity, and it is the innate immune system that determines which components – of T cells and/or B cells – will be activated, as challenged and honed by ages of real world training in our ancestors.

The immune system cannot be expected to be self-sufficient, however.  Every cell mentioned above in both the innate and adaptive immune systems is stimulated and developed by vitamin D, and cannot function well without it.  This then is the most true, broad-spectrum and valuable vaccine, along with moderate amounts of its synergistic partners, the other basic nutrients: vitamins, minerals and amino acids.  My book The Defeat of COVID cites 130 studies about the immune functions of vitamin D, its effects in strengthening and developing every single type of cell mentioned above and specifically regarding the spectrum of immune effects on SARS-CoV-2 and COVID disease. 

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[i] R Akonda, M Fitch, et al.  Origin and differentiation of human memory CD8 T cells after vaccination.  Nature.  552 (7685).  Dec 2017.  https://pid.emory.edu/ark:/25593/t3gvx

[ii] S Duffy.  Why are RNA virus mutation rates so damn high?  PLoS Biology.  Aug 2018.  https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000003

[iii] Blood.  Miltenyi Biotec.  https://www.miltenyibiotec.com/US-en/resources/macs-handbook/human-cells-and-organs/human-cell-sources/blood-human.html