The Paradox of the Immune System:

Protection, Chronic Inflammation,

Autoimmune Disease, Cancer, and
Pandemics 1st Edition Louis J. Catania
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The Paradox of the Immune
System

Protection, Chronic Inflammation,

Autoimmune Disease, Cancer and
Pandemics

Louis J. Catania
Salus University, College of Health Sciences, PA, United States
University of North Florida, Osher Lifelong Learning Institute, FL, United
States
Table of Contents

Cover image

Title page

Copyright

Dedication

List of Figures

List of Tables

Louis J. Catania, O.D., F.A.A.O., D.Sc. (Hon.)

Preface

Acknowledgements

Three reasons to understand the immune system

First…
 Second…

Third…

Section 1. Our friendly immune system

Section 1 Our friendly immune system

1. Introduction

1. The innate (aka “natural”) immune system and immunity

1. Some simple definitions of the immune system, immunology,

the immune response, and immunity

2. Development (embryology and beyond) of the immune

system [1]

3. The gross and microanatomy of the immune system

4. Innate (aka “natural”) immune response and active immunity

[7]

5. Brief research summaries on the innate immune system

Chapter highlights (key points and paradoxical-related

information)

2. The adaptive (aka “acquired”) immune system: from friend to foe

1. The path to “dysregulation”

2. Acute inflammation
 3. Clinical considerations in acute inflammation

4. Using the adaptive immune response to help and prevent

disease

5. The path to chronic inflammation

6. Brief research summaries on the innate and adaptive immune

system

Chapter highlights (key point and paradoxical-related

information)

3. Genetics and genomics

1. Introduction

2. Basic science of genetics

3. Immunogenetics

4. Immunogenomics

5. Genetics and genomics by the numbers

6. The Human Genome Project [14]

7. Precision (personalized) medicine and prevention [15]

8. XCI (lyonization)

9. The “microbiome”

10. Epigenetics [26]

11. Cytogenetics

12. Big data analytics in genetics and genomics [32]

 13. Brief research summaries on genetics and genomics

Chapter highlights on genetics and genomics

Section 2. The enemy within us

Section 2 The enemy within us

1. Introduction

4. Chronic inflammation: “Enemy #1”

1. Introduction

2. Causes (etiologies) of chronic inflammation [2]

3. Advancing adaptive immunity (from acute to chronic

inflammation)

4. Differences in chronic inflammation from acute inflammation

5. Some (but not all by a long shot) disease categories

associated with chronic inflammation [7]

6. Clinical diagnosis and treatment of chronic inflammation

7. Neural downregulation of the immune system and chronic

inflammation

8. Brief research summaries on chronic inflammation

Chapter highlights (key points and paradoxical-related

information)
5. Autoimmune disease: when self becomes the villain

1. Introduction

2. Female predilection for autoimmune disease

3. Theories on the pathogenesis of autoimmune diseases [7]

4. Classification of autoimmune diseases

5. General clinical considerations with autoimmune diseases

[21]

6. “Top 10” autoimmune diseases (clinical descriptions,

diagnosis, and treatment options) [28,29]

7. General therapeutics considerations with autoimmune

diseases

8. Therapeutic (cellular and genetic) procedures

9. Brief research summaries on autoimmune diseases

Chapter highlights (key points and paradoxical-related

information)

6. Cancer: immunology's cruelest enemy and greatest challenge

1. Introduction

2. “Cancering”

3. The incidence and prevalence of cancer

4. Description and etiologies of cancers

5. Clinical presentations in cancers [26]

 6. Treatment considerations in cancer

7. Brief research summaries on cancers

Chapter highlights (key points and paradoxical-related

information)

7. Immunology: The science of pandemics, infectious disease and

COVID-19

1. Introduction

2. Background considerations

3. Incidence and prevalence of COVID-19

4. Pathogenesis, immunologic, and immunogenic considerations

for SARS-CoV-2

5. Clinical considerations for coronavirus (SARS-CoV-2)

infection

6. Immunoinformatics (computational immunology) [68]

7. Epidemiology and public health considerations in COVID-19

8. Brief research summaries on infectious diseases and COVID-

19

Chapter highlights (key points)

Epilogue

Glossary
Index
Copyright
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Dedication

For those souls lost during the COVID-19 pandemic and to their
families, my deepest sympathy, and to all those in health care and
their families who have sacrificed so much, my sincere appreciation.
List of Figures
Figure 1-1 Organs of the immune system.7
Figure 1-2 White blood cells (WBCs or Leukocytes).8
Figure 1-3 Antigen presenting complex (Dendritic cell)—
diagram #1.12
Figure 1-4 Early innate immune response—diagram #2.14
Figure 1-5 Continuing innate immune response—diagram #3.17
Figure 1-6 The adaptive (acquired) immune response—diagram
#4.19
Figure 2-1 The inflammatory cascade—diagram #5.28
Figure 2-2 Clinical manifestations of acute inflammation—
diagram #6.32
Figure 2-3 Treatment considerations in acute inflammation—
diagram #7.37
Figure 2-4 Leukocyte (neutrophil) extravasation.38
Figure 3-1 Chromosome.47
Figure 3-2 DNA and RNA structure.48
Figure 3-3 Human karyotype.49
Figure 3-4 Cellular biology of the human genome.50
Figure 3-5 Transcription and translation.52
Figure 3-6 Central dogma of molecular biology.53
Figure 4-1 Acute versus chronic inflammation.75
Figure 4-2 Chronic inflammation and disease.77
Figure 5-1 Clinical autoimmune cycle—diagram #8.100
Figure 5-2 Stem cell renewal and differentiation.133
Figure 5-3 Direct and cell-based stem cell therapy.135
Figure 5-4 Chimeric autoantigen receptor T-cells (CAART-T).138
Figure 5-5 CRISPR-Cas9 procedure.139
Figure 6-1 Monoclonal antibody binding to C19 and C3
receptors.164
Figure 6-2 Idiotype-Anti-idiotype Regulatory Circuit (or Loop)
—Diagram #9.166
Figure 6-3 Chimeric antigen receptor T-cells (CART-Ts).167
Figure 7-1 SARS-CoV-2 life cycle.189
Figure 7-2 mRNA (messenger RNA) vaccine.205
List of Tables
Table 4-1 Theories on etiologies and pathogenesis of chronic
inflammation.73
Table 4-2 Proinflammatory mediators.79
Table 4-3 Most common chronic inflammatory orthopedic
(musculoskeletal) conditions (Alphabetical).83
Table 4-4 Ten Most Common Chronic Conditions (ranked by
death rate).85
Table 5-1 Listing of prevalent autoimmune diseases.98
Table 5-2 Theories on etiologies and pathogenesis of
autoimmune disease.98
Table 5-3 Classification of autoimmune diseases by clinical
presentation.106
Table 5-4 Examples of biologic
immunopharmacotherapeutics.112
Table 5-5 Ten (10) most common autoimmune diseases.112
Table 5-6 Immunotherapeutic medication options for chronic
inflammation, autoimmune diseases and cancers (Generic
and brand names/… mab suffix = monoclonal antibody).127
Table 5-7 Monoclonal antibody options (generic and brand
names).128
Table 6-1 Common cancer types.153
Table 6-2 Top 10 (10) cancers in America.154
Table 6-3 Clinical diagnostic tests for cancer.160
Louis J. Catania, O.D., F.A.A.O.,
D.Sc. (Hon.)

(Biographical)
Dr. Louis J. (Lou) Catania is an internationally acclaimed educator,
and a recognized expert in eye care, health care, artificial intelligence
(AI), and immunology. He has authored over 160 journal articles and
12 textbooks, one of which, “Primary Care of the Anterior Segment”
received the Baron's Five Star (highest) rating for a medical textbook.
He is currently a lecturer with the University of North Florida,
Department of Continuing Education, Osher Lifelong Learning
Institute; and a visiting Professor at Salus University, College of
Health Sciences. During his 52-year clinical and academic career he
has taught and lectured extensively worldwide. Dr. Catania's career
in health care started as an optometric physician with an interest in
corneal immunology. That interest grew into postdoctoral pursuits
over the past 35 years with studies in virology, immunology, and
public health (University of Rochester, UPenn, Stanford Continuing
Studies and MIT OpenCourseWare). He has dedicated himself to
research, teaching, and writing with his three most recent books on
AI in health care, AI in immunology, and an inspired new text on the
mercurial nature of the human immune system (“The Paradox of the
Immune System”). Dr. Catania's professional accomplishments in
eye care, health care, and immunology have produced countless
honors and awards including two Honorary Doctor of Science
degrees; Distinguished Faculty Scholar at three academic
institutions; induction into the National Optometry Hall of Fame;
and innumerable domestic and international keynote and
commencement addresses. In his personal time, Dr. Catania is an
active volunteer with the National Park Service; a sea turtle patrol
monitor in his beach community; and involved in multiple
environmental, humanitarian and human welfare agencies.
Preface
Paradox: Something (such as a situation) that is made up of two
opposite things that seems impossible but are actually true or possible

Merriam-Webster's Unabridged Dictionary (2021).

The concepts of “self-versus nonself” and “our best friend and

worst enemy” are of themselves a paradox. Yet these two apparently
contrasting, coupled pairs define the essence of the human immune
system. That being so, understanding this biomedical system of
inconsistencies requires an appreciation of its components and more
so, their relationship to one another. Those intricate and enigmatic
relationships represent the science of immunology. They also
embrace the inherent evolutionary genetics and human biology that
produce and collectively culminate in what this book will attempt to
define as “the paradox of the immune system.”
It is not typical to jump to the Epilogue of a book from its Preface,
but allow me this brief, albeit unorthodox, digression for what I
hope will be a worthwhile departure for you the reader. I start the
Epilogue with the question, “So, just what is ‘the paradox of the
immune system?’” Then I affirm that “the paradox” is actually a
collection of paradoxes, whereupon I proceed to list them (some not
all). I am providing this list for you up front so you can enjoy
watching the “puzzle” unfold, piece-by-piece (or, if you will,
“paradox-by-paradox”) as you read the book. No need to remember
them now as I will be identifying them one-by-one as they surface in
the narrative:

• Self-versus nonself;
 • Innate versus adaptive immunity;
• Adaptive immunity as a friend and foe;
• Our “best friend and worst enemy”;
• Immunity's regulated and dysregulated systems;
• Health protection and health threat;
• Dangerous versus benign nonself and the toll-like receptor
(TLR) “sentry”;
• Acute inflammation healing and ulceration;
• Acute versus chronic inflammation;
• Accumulation of immune (cellular and humoral) substances
in tissue;
• Tumor Necrosis Factor (TNF-α) inflammatory and
antiinflammatory effects;
• Self-versus self (autoimmunity);
• Autoimmunity (“the mother of all immune system
paradoxes”);
• Female versus male predilections to autoimmune diseases
and certain cancers;
• Rogue B-cells attacking self;
• Epitope spreading;
• The role of the X chromosome and miRNA in males versus
females;
• Immunosuppressive agents as therapeutics and as threats;
• The immune system and COVID-19 (the infection's best
friend and worst enemy).
To achieve the ambitious and unique goal of this book, I will
concentrate on a few key objectives. First, I hope to explain in
uncomplicated (make that minimally complicated), understandable
language, the postulate of “self-versus nonself,” our first paradox.
The “self” part is easy, but “nonself” starts getting tricky along the
way as you will see. Second, I must make some sense of, and define
the human immune system in its dual role as our (i.e., humankind's)
“best friend and worst enemy.” As a friend, it protects us 24/7 and
helps us defeat the forces that threaten our wellbeing, until…it
becomes the enemy itself, and endangers our health and even our
lives.
 To define “the paradox of the immune system,” my plan is to first
describe the innate immune system as “our best friend.” Then our
journey will take us to the darker side of immunology, the adaptive
(acquired) immune system. This cryptic, more ominous side includes
chronic inflammation (“Enemy #1”), autoimmune diseases (“Enemy
#2”), cancer (“the cruelest enemy”), and now, COVID-19. But please
understand that the theme of this book and its emphasis on the
“evil” side of our immune system is not meant as a negative,
pessimistic, or fatalistic discussion of immunology. Quite the
contrary. It is an opportunity for us to understand all the dimensions
of our ever-present immune responses and the power and control
they exert on the human body, for better and for worse. Through
such an understanding we are learning how to harness the immune
system's biologic potential, both in vivo (within the body) and
through medical (molecular biology and genetic) manipulations or
“immunotherapies.” This leads us to improvements in the health
and wellness of the human organism and its ability to fight, cure,
and even prevent disease. But notwithstanding the benefits or the
potential benefits of the immune paradox, I will also present the
challenges we have yet to fully understand. Leading those
challenges is autoimmunity, a clinical entity wherein the immune
system uses its enormous potential to turn on itself (us) and create
clinical disorders like autoimmune diseases and cancers which we
have yet to fully understand or conquer.
There is one additional goal I will advance and defend in this
book. It is the hypothesis that chronic inflammation, the
fundamental immunopathophysiology of the adaptive immune
system is in fact, the basis for all disease (emphasis on all). I
emphasize all because I fully realize that one must not use the word
all in science or healthcare irresponsibly. In fact, I use it with due
respect and regard for its unqualified meaning of the boundless,
intrinsic nature of chronic inflammation in the human disease
process. I will use the information in the second section of this book,
particularly Chapter 4, to defend this proposition. I would even
propose a new name, “pathomelitis,” to better distinguish chronic
Another random document with
no related content on Scribd:
Hjalmar Théel, "On a singular Case of Hermaphroditism in
Holothurids," Bih. Svenska Vet. Akad. Hand. xxvii. Af. 4, No. 6,
1901.

[508]

Bronn's Thier-Reich, vol. ii. Abt. 3, Buch i. "Die Seewalzen," 1891,

pp. 327 et seq.

[509]

Genuine suckers appear never to be developed; but the ends of

the ventral podia are sometimes rounded, sometimes slightly
flattened.

[510]

"Mémoire sur l'Elpidia nouveau genre d'Holothuries," K. Sv. Vet.

Akad. xiv. No. 8, 1877.

[511]

Gerould, "The Anatomy and Histology of Caudina armata," Bull.

Mus. Comp. Zool. No. 56, 1895, p. 124.

[512]

"Structure, Physiology, and Development of Antedon rosaceus,"

Phil. Trans. Roy. Soc. 1866, pp. 671-756.

[513]

"On the Nervous System of Antedon rosaceus," Q.J.M.S. xxiv.

1884, p. 507.

[514]

Bather calls the side-plates "adambulacral." The name is

unfortunate, as it suggests that the side-plates correspond to the
adambulacrals of Asteroidea; but when the groove is closed the
position and function of adambulacrals and covering plates is the
same (Lankester's Treatise on Zoology, iii. "Echinodermata,"
1900).

[515]

Challenger Reports (Stalked Crinoids), vol. xi. pt. xxxii. 1884.

[516]

Stammesgeschichte der Pelmatozoen, pt. i. 1899.

[517]

"Die Echinodermenlarven der Plankton Expedition," Ergebn.

Plankton Exp. Bd. ii. J, 1898.

[518]

"Über die Larvenzustande und die Metamorphose der Ophiuren

und Seeigel," Abh. K. Akad. wiss. Berlin, 1846, and other papers in
the same publication in subsequent years.

[519]

This is clearly seen by comparing the larva of Asterina gibbosa

with a young Bipinnaria in which the longitudinal band is as yet
undivided. The shape of the prae-oral lobe is practically the same
in both.

[520]

"The Fate of the Body-cavities in the Metamorphosis of Asterias

pallida," J. Coll. Japan, x. 1898, p. 239.

[521]

Yves Delage, "Elevage des Larves parthénogénétiques d'Asterias

glacialis," Arch. Zool. Exp. (4) ii. 1904, p. 27.

[522]
"The Metamorphosis of Echinoderms," Quart. Journ. Micr. Sc.
xxxviii. 1895, p. 45.

[523]

In the type figured (larva of Synapta digitata) the feelers are

budded off directly from the ring-canal and alternate with the
rudiments of the radial canal.

[524]

Observed in Plymouth, 1905.

[525]

"Die Entwicklung der Synapta digitata," Jen. Zeitschr. xxii. 1888, p.

175.

[526]

"Die Cambrische Stammgruppe der Echinodermen," Jen. Zeitschr.

xxx. 1895.

[527]

Lankester's Treatise on Zoology, "Echinodermata," pt. iii. 1900, p.

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[528]

Brit. Mus. Cat. "British Echinodermata," 1892, p. 14.

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