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Layperson Version

Getting Started

 

The only thing this blog will be selling is knowledge and hopefully, a better understanding of how our immune system works, “for better and for worse” (sound like a marriage!). The system is “our best friend and worst enemy.” Such contradictory statements begin to explain the title of the book, The Paradox of the Immune System. My goal was to translate the extensive research I had done on the inconsistencies, paradoxes if you will, of the immune system and identify them and “try to explain” them in the context of their biomedical relevance. Of course, I hoped to reach the broadest audience possible with the information, knowing however that the material may be at too high a level for some readers with limited or no medical or science background.    

 

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Blog #1: Introduction

As I wrote the book, I wrestled constantly with the fact and frustration that my hope of reaching that broader audience with such complex material was likely unattainable. So I decided to do an abridged version of the book as a “user friendly” blog for the less technically oriented, but no less interested reader. Among my career literary successes and flops, producing this “user friendly” companion blog to Paradox proved to be right near the bottom. The first person I asked to review the blog was a physician (who had also reviewed the book) and he felt the blog did a good job of capturing the essence and key information in the book. I then asked a second person (with limited biomedical background) to read the blog and the response was a bemused ”dear in the headlights” look. My goal of a Plan B had tanked.

 

One of my most trusted mentors in immunology, Dr. Howard Young of NIH (who had already mentioned my blog content as being too technical for a lay audience) suggested that he ask one of his Ph.D. students to review the blog and make any constructive suggestions he might feel worthwhile. Not surprising, a student, Adam Fairris, came back with the assessment, “good technical content, but hopelessly out of reach for anybody less than Ph.D. level (student of postdoc) immunologist. Adam kindly volunteered to do a rewrite of one of the early blogs (#2) which he proceeded to do brilliantly. Using his writing style as my model, I attempted a rewrite of a couple of blogs and asked for his opinion. When he commended them as “…so much easier to read”, it was my Hallelujah moment! I was off and running and am now humbled and honored, on behalf of Dr. Young and Adam, to present what I’m calling the “Layperson Version" of www.ImmuneParadox.com blog.

 

And so, depending on your background and interest, I present to you 3 choices:

  1. The “Layperson Version” of www.ImmuneParadox.com blog, a discussion on immunology at a lay level with minimal technical jargon and terminology;

  2. An abridged “Science Version“ of the blog” with key scientific information from the book, ; and

  3. The full, unabridged, 300-page book,

 

The blog contains 45 segments (Posts) which parallel the 7 chapters of the book, divided into 2 sections: Section 1, “Our friendly immune system” covering the basic science of immunology in 3 chapters; and Section 2, “The enemy within us” dealing with the dark side of the immunology in the remaining 4 chapters. The blog Posts cover the most interesting and relevant highlights from each of the seven chapters in the book along with interspersed additional blogs on essential topics when and where appropriate. I have also included a few questions (in the “Science Version” blog)  relating to the respective Post’s information for you to ponder and/or respond to and comment on in the blog’s webpage (Forum), if you would like. If you request or if a response is indicated, I will do so. 

 

Before we start on Chapter 1, I would like to describe three themes that will be developed through all the collective blogs. I had planned to develop only one of the themes (on chronic inflammation) when I wrote the book, but I did not realize that, in taking a “deeper dive” than I had ever done into the science and mechanics of the immune system, the second and third themes pretty much developed surreptitiously and caused me to do a lot more research.

 

I’ll identify and describe the three themes in this first blog (a cliffhanger). Then in three consecutive subsequent blogs I’ll describe each theme in greater detail. Then through the chapter and relevant topic discussions I will interject aspects and considerations of each theme and their impact on our immune system. The three themes are:

  1. The concept of chronic inflammation as the basis of “all” diseases (I’ll give a brief explanation of just what chronic inflammation is in Blog #2 and then expand on it in the subsequent blogs and chapter discussions);

  2. The concept of all forms of stress (physiologic, physical, mental, emotional, environmental, and more) constituting the cause of all immune responses; and finally:

  3. The unique features (“for better and for worse”) regarding the “bias” of the female immune system versus that of the male.

 

The first and second themes are rather new thinking regarding the immune system and will require a fair amount of explanation, logic, and justification for their unique, all-inclusive nature. The third theme regarding female immune “bias” is long recognized as a significant aspect of the human immune system. It is receiving extensive study and research, specifically because of the increasing prevalence of autoimmune diseases, primarily in women. Most of the blogs will address this female bias and its various dimensions including the ongoing science and new developments in this area of sex and gender immunology.

 

So, whether you choose the Layperson Version Blog; the Scientific Version Blog; or the book, The Paradox of the Immune System; I think you will agree that we have an enormous amount of information ahead of us for discussion and for your questions which you’ll be able to submit through the blog’s webpage. We’ll start that journey with our first theme regarding chronic inflammation.

 

One last personal note, if I may. I would like to dedicate this blog to two, heroes of mine, Dr. Anthony Fauci, a man most of you probably know and Dr. Howard Young, an NIH senior investigator, and a very special guy. 

 

Today’s science of immunology and more so, humanity itself, is indebted to Dr. Anthony Fauci for his tireless, unselfish efforts in the development of the National Institute of Health, Laboratory of Immunoregulation in 1980 (along with Dr. Francis Collins, another hero for his work in the Human Genome Project); and Dr. Fauci’s Directorship of National Institute of Allergy and Infectious Diseases from 1984 until 2023. His work in monoclonal antibodies, HIV-AIDs, Ebola research, autoimmune diseases, and certainly, his impassioned efforts during the COVID-19 pandemic, is legendary. He is a 5’7” giant and a hero who stands head and shoulders above all of us who appreciate the science of immunology and his immeasurable contribution.

 

Second, I am disappointed that I got to know Dr. Howard Young so late in my life and career in immunology. He is an immunology researcher, scholar, and teacher and more so, he is an exceptional human being. His generous, unselfish, and kind manner bespeaks a heart and mind filled with caring and love. His impact on the science of immunology and so many who study it and love the science is immeasurable. Albeit brief, I weigh his friendship as a highlight of my years in science. Thank you.

Blog #2: Chronic Inflammation (CI): It's what it's all about

As a general rule, scientists avoid the word “all”. All implies no exceptions, all implies we’re certain, all implies things we couldn’t possibly prove in just one lifetime. I fully expect readers of this blog, both scientists and non-scientists, to object to me using the word all. Yet, I will. I have. Let this show just how confident I am, and how much I believe in this. Chronic Inflammation is the basis of all disease. Of course, I will go into more detail in my book, but this blog can be a good introduction for how I back up my claim.

So, what is Chronic Inflammation? When most of us think of Inflammation, we think of Acute Inflammation: the rapid, i.e. acute, response to outside substances getting inside our bodies. We’ve known about it since forefather of medicine Celsus described it back in Ancient Rome: redness, heat/fever, pain, swelling and loss of tissue/organ function. Or in Latin, rubor, calor, dolor, tumor and functio laesa. We will come back to this in greater detail in Chapter 1 and 2. We will talk about all the cells and signals involved and cover just how acute “Acute Inflammation” really is. For now, though, remember that that is Acute Inflammation, and we want to learn about Chronic Inflammation.

 

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We used to believe that Chronic Inflammation was just extended Acute Inflammation. It turns out, whether we look at the cellular level or the whole-body level, the two processes are completely separate and behave completely differently. One may lead to the other, one may appear without the other, but they are utterly separate. In fact, in my book I suggest the National Institute of Health use a new name for Chronic Inflammation to make the separation clear. I suggested Pathomelitis; patho- meaning disease, -ome meaning the complete set of, and -itis meaning inflammation. Fat chance of them taking me up on it! 

 

There are three main avenues of differences between Acute Inflammation and Chronic Inflammation:

  1. The different ways they affect the body’s cells, tissues, and processes.

  2. The different signals used, the different drugs that can be used against them, and the way those signals and drugs behave in the body

  3. Most importantly, the different ways these processes affect the body clinically, both during the disease and after.  

The clinical basis for my thesis, that Chronic Inflammation is the root cause of all disease, is in how widespread, and how destructive Chronic Inflammation is to the body’s processes. Acute inflammation stays local. If you get a paper cut on your finger, and the skin either side of the cut is red and warm, you won’t feel it in your other hand. Chronic inflammation and its signals can cause damage locally too, like in psoriasis, but more importantly chronic inflammation can affect the entire body, like in rheumatoid arthritis or systemic lupus erythematosus. Chronic Inflammation can even alter your blood vessel walls throughout your body in a disease called, perivasculitis. The ability for Chronic Inflammation to affect the whole body and cause diverse and intense changes to how your body can function, is the first step that allows all future disease states to exist. Without Chronic Inflammation, they could not happen. So when you hear “inflammation” is associated with a disease, remember that it is Chronic Inflammation. 

 

I will get into more depth into how Chronic Inflammation affects your cells and tissues and the bioscience behind Chronic Inflammation in the section “The Enemy Within Us.” But generally, most blogs will work case by case, explaining how Chronic Inflammation is the basis of infectious diseases, cancers, autoimmune diseases and, indeed, all categories of human diseases.  

Blog #3: Stress: The kind we have in us and the kind outside of us

When I did the research for my book, The Paradox of the Immune System, I began to realize that “stress” disrupts the normal state of our body in ways we have never considered. Whether it’s mental, physical or caused by environmental factors like foreign, “antigen” or “non-self” substances (Einstein once said, “The environment is everything that isn’t me”). It has been scientifically proven that stress produces a loss of the normal balance in the functions, cells and fluids that control our health and well-being (this balance is called "homeostaasis"). That being the case, we can conclude that external and internal forms of stress create a “dysregulation” (a loss of homeostasis) or an abnormal state in our body, including our immune system. This imbalance leads to injury and death of cells and tissues within our body, all of which are constantly accumulating as abnormal debri. The immune system interprets this debri as an “autoantigen” that is, a substance produced by the body itself, i.e.,   “auto,” but foreign to it, “antigen.” It treats this “non-self” autoantigen substance as it would any antigen. As such, the immune system is now reacting to both this autoantigenic stimulus along with the originating (stress) factors. This combination produces a cycle sometimes referred to as the ”clinical autoimmune cycle” or the “danger hypothesis” intoning a dangerous situation.

 

Taking this process to its logical conclusion, if we recall from the previous blog on the cause of chronic inflammation being an unrelenting immune response, we can conclude that this stress “cycle” is a potential cause of chronic inflammation. And when considering the driving force of a stress-related immune response being autoantigens, along with its originating external or internal cause(s), we can begin to see the basis for chronic inflammation and stress as the basis for all disease categories. Such categories include autoimmune diseases, cancers and the range of almost all other diseases.   

 

Based on this immunology logic about stress as the basis for chronic inflammation and all diseases, why aren’t all humans in a constant state of clinical or subclinical “disease”? Could it be that we actually are in varying stages of stress-related  dysregulation, but controlled by forces in the body (genetic, immunologic, neurologic and more) yet undetermined? Certainly, more research must be conducted to identify such forces that amplify or mitigate human disease in the presence of stress antigenicity.

Blog #4: "Women are from Venus and men are from Mars"

 

Among the many paradoxes of the human immune system that we will be presenting throughout this blog and in its companion book, The Paradox of the Immune System, the differences between the male and female immune systems may turn out to be the most puzzling to readers. But more important, the differences will also be among the most clinically significant. And, almost  all of our blog discussions, as well as most chapters in the book will directly or indirectly address these dilemmas, “for better and for worse,” an appropriate phrase for a “man and woman” topic.

 

I think we can all agree with relative certainty that everyone reading this knows that there are differences between women and men or females and males. Whether it’s their obvious anatomy or their biological functions, things like pregnancy or hormones, or even evolutionary changes over eons of time. Women are different than men (or as the author John Gray  said in his 1992 book,  “Women are from Venus and men are from Mars”). And medical science has proven that biologically, women are stronger than men, especially when it comes to the immune system. But that strength also carries with it the “sword of Damocles” or more simply, an increase in risks leading to paradoxes in womens’ health. The perfect example of this type of inconsistency would be a woman’s significant increased risk of autoimmune diseases. This will be a big part of our discussions.

 

Sex and gender are actually different. Sex measures differences in the biology of a person like genetics and functions of their body. Gender is more a measure of their cultural and environmental behaviors, like a person’s exposure, transmission and removal of microorganisms from their patterns of life or their access to healthcare. It’s worth understanding that both sex and gender influence the differences in the male and female immune system, but our discussions will focus mostly on the biological factors that produce these differences in the immune systems. These differences are due in large part to the evolution we mentioned above and its Darwinian or natural selection results over time.

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