This document discusses the concept of natural autoimmunity and its role in human health and disease from a pathophysiological perspective. It proposes that the immune system's main function is to regulate molecular homeodynamics in the body, rather than to defend against foreign pathogens. The hypothesis of "Immunculus" and principle of "Immunacea" are presented as ways to understand physiological autoimmunity and the predictive roles of natural autoantibodies. Clinical examples are provided to correlate immunopathological data with these concepts. The potential for "autoimmunomics" to enable early disease diagnosis through autoantibody profiling is also described.
Maternal immunity plays an important role in pregnancy and a child's health. The document discusses how pregnancy can be viewed not as a conflict between mother and fetus, but as a mutually beneficial relationship where they function as a temporary superorganism. A healthy maternal immune system recognizes the fetus and supports development, while immune suppression can increase risks of miscarriage due to incomplete fetal recognition. The role of maternal immunity in pregnancy is complex and not fully understood.
This document discusses adaptive maternal immune deviations as a potential ground for autism spectrum disorders (ASD) development in children. It proposes that one of the most likely mechanisms inducing ASD may be maternal immune imprinting, where maternal antibodies cross the placenta and epigenetically 'tune' the fetus's immune system. While this mechanism provides early infection resistance, it can also cause inborn pathologies like ASD in some cases. The document examines how different maternal autoantibody repertoires, influenced by microbes or environmental toxins, may impact fetal development and argues that immune changes are generally adaptive for the mother but potentially pathogenic for the fetus in some situations.
Immunophysiology and practical medicine (octt 13-short)Александр Полетаев
This document discusses natural autoantibodies and their role in disease prediction and diagnosis. It proposes that autoantibody profiles can serve as immune markers for pre-disease states and early disease detection. The presence of certain autoantibodies is correlated with organ pathology and future health issues. Monitoring autoantibody levels over time through tests like ELI-Tests may help reveal pre-disease changes, diagnose unclear cases, and track health changes during treatment. Autoimmunity plays both pathological and physiological roles, with natural autoimmunity serving important clearance and repair functions.
The document discusses various treatments for spinal cord injuries, including stem cell research and regenerative medicine. Stem cell treatments show promise but also risks, as demonstrated in an experiment where stem cells overgrew in rats and caused hypersensitivity. Another study found that combining stem cell injections with a gene to stop overgrowth could prevent side effects. Additional research examines using medications and scaffolding to guide neuronal regrowth after injury. While treatments provide hope, more work is still needed to fully address spinal cord damage without risks.
Maternal immunity plays an important role in pregnancy and a child's health. The document discusses how pregnancy can be viewed not as a conflict between mother and fetus, but as a mutually beneficial relationship where they function as a temporary superorganism. A healthy maternal immune system recognizes the fetus and supports development, while immune suppression can increase risks of miscarriage due to incomplete fetal recognition. The role of maternal immunity in pregnancy is complex and not fully understood.
This document discusses adaptive maternal immune deviations as a potential ground for autism spectrum disorders (ASD) development in children. It proposes that one of the most likely mechanisms inducing ASD may be maternal immune imprinting, where maternal antibodies cross the placenta and epigenetically 'tune' the fetus's immune system. While this mechanism provides early infection resistance, it can also cause inborn pathologies like ASD in some cases. The document examines how different maternal autoantibody repertoires, influenced by microbes or environmental toxins, may impact fetal development and argues that immune changes are generally adaptive for the mother but potentially pathogenic for the fetus in some situations.
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This document discusses natural autoantibodies and their role in disease prediction and diagnosis. It proposes that autoantibody profiles can serve as immune markers for pre-disease states and early disease detection. The presence of certain autoantibodies is correlated with organ pathology and future health issues. Monitoring autoantibody levels over time through tests like ELI-Tests may help reveal pre-disease changes, diagnose unclear cases, and track health changes during treatment. Autoimmunity plays both pathological and physiological roles, with natural autoimmunity serving important clearance and repair functions.
The document discusses various treatments for spinal cord injuries, including stem cell research and regenerative medicine. Stem cell treatments show promise but also risks, as demonstrated in an experiment where stem cells overgrew in rats and caused hypersensitivity. Another study found that combining stem cell injections with a gene to stop overgrowth could prevent side effects. Additional research examines using medications and scaffolding to guide neuronal regrowth after injury. While treatments provide hope, more work is still needed to fully address spinal cord damage without risks.
Introduction to Immunity Antibody Function & Diversity 2006 L1&2-overview & AbLionel Wolberger
This document provides an overview of a lecture on antibody function and diversity. It introduces antibody gene rearrangement and discusses how antibodies recognize an almost infinite number of antigens through genetic diversity mechanisms like variable gene segments and junctional diversity during lymphocyte development. Key textbooks on immunology are also referenced.
This monograph details the history and results of a 10-year study conducted by O.I. Epstein exploring the biological effects of ultralow doses, which led to the development of a new class of medical products derived from ultralow doses of antibodies. The study integrated immunology, pharmacology, and homeopathy, progressing from examining homeopathic remedies to demonstrating various physiological effects of ultralow doses and creating new drugs based on a phenomenon of "pro-antigenic" effects of antibodies at ultralow concentrations. Extensive preclinical and clinical research demonstrated the safety, effectiveness, and mechanisms of action of these novel ultralow dose antibody
Behavioral Science and Social Sciences_280316013607.pdfSumni Uchiha
This document is a chapter from a textbook on behavioral science and social sciences for the USMLE Step 1 exam. It covers key epidemiological measures including incidence rate, prevalence rate, and attack rate.
The incidence rate is defined as the number of new cases of a disease or event that occur in a population over a specific time period, divided by the total number at risk during that period. Prevalence rate refers to all cases, both new and existing, in a population at a particular point in time or over a specified time period, divided by the total population at risk. Attack rate refers specifically to the cumulative incidence of infection during an outbreak or epidemic.
Graduate Research - Review of LiteratureDaniel Martin
This document discusses bacteria and food safety. It provides background information on bacteria, including their ability to adapt and become resistant to stressors like heat. Bacteria can survive cooking temperatures thought to be safe if they have adapted. The document then examines various factors that influence thermal inactivation of bacteria, such as water activity, temperature, and the parts of the bacterial cell affected by heat. Higher water activity increases the effectiveness of heat in destroying bacteria, while lower water activity allows bacteria to survive cooking. The document suggests that recognizing how bacteria can adapt will help develop more effective food safety strategies beyond relying solely on heat treatment.
Source SummaryYou should be very careful to avoid plagiarism when .docxrafbolet0
Source Summary
You should be very careful to avoid plagiarism when summarizing your sources. All source content in your summaries should be in your own words (preferred) or in quotation marks with page numbers provided (try to avoid quotes). Keeping plagiarism out of your summaries is an important step in keeping it out of your literature review. DO NOT JUST READ AND SUMMARIZE THE ABSTRACT! READ THE ENTIRE ARTICLE UNLESS OTHERWISE SPECIFIED.
1. Identify the main research hypothesis or thesis.
2. Describe how the researchers tested their hypothesis/hypotheses. In other words, describe their methodology (what they did, including what behaviors they recorded, how often they observed the primates, how they recorded the data, etc), the participants (who were they, how many were used/observed, where were they housed, where were they from), and a brief overview of the procedure.
3. Describe what the researchers found (focus on their main findings from the results section, discussion, and conclusions). Make sure that you understand their overall results, including the statistics and charts/graphs/figures they reported.
Source Evaluation (Excerpted from Galvan, 2006, p. 8)
In addition to summarizing the relevant information from a source, you should also evaluate the information in the source. Critique/analysis of the literature is an important part of a good article summary.
· Are there any obvious problems with the way the authors are discussing the background literature, their methods, or misconstruing their findings? Explain.
· Are there any obvious biases from the authors trying to downplay abnormal behaviors or justify what they are doing for human good? Explain.
· Did you notice any other flaws? Explain.
· Overall, do you think the research makes an important contribution to advancing knowledge?
Critical Reading (Excerpted from Lawson, 1999)
You should find the following questions useful as you evaluate the strengths and weaknesses of each of your sources.
· What is the quality of the evidence used to support the claim?
· Is there a control or comparison group against which to assess the performance of the experimental group?
· Is the person concluding there is a causal relationship on the basis of correlational data?
· Are there confounding variables that might account for the findings, or are there confounding variables that they are not considering (e.g. exposure to humans on a daily basis, invasive experimental procedures, single housing)?
· Has the person made it impossible to falsify his or her theory or hypothesis? Does he or she consider positive evidence as support for the theory but negative evidence as not being relevant?
· Is the person acknowledging that complex behaviors or phenomena have multiple causes?
Neuroscience and Biobehavioral Reviews 30 (2006) 1246–1259
Review
Psychopathology in great apes: Concepts, treatment options and
possible homologies to human psychiatric disorders
Martin Brüne.
The document discusses how systems biology approaches can help improve vaccine design and testing. Researchers are able to measure immune system responses to potential vaccines at the genetic, protein, and cellular levels. By analyzing these complex data sets, they can identify signature profiles of protective immunity and use them to guide vaccine development. This allows them to quickly evaluate many candidates and focus on improving the most promising ones. The approach has provided insights into why some vaccines like yellow fever are highly effective. Researchers are now applying these methods to develop an HIV vaccine by studying immune responses in monkeys infected with simian immunodeficiency virus.
Investigation of IgA Antinuclear Antibody responses in AutoimmunityCiarán Frewen
This document provides background information on autoimmunity and antinuclear antibodies (ANAs). It discusses the immune system, including the innate and adaptive responses. Autoimmunity occurs when the immune system attacks the body's own tissues, leading to autoimmune diseases. ANAs are autoantibodies that bind to components in the cell nucleus. The presence of certain ANAs is associated with connective tissue diseases like lupus and Sjögren's syndrome. The document aims to establish an immunofluorescent assay to detect IgG and IgA ANAs in serum samples from patients with connective tissue diseases. It will optimize the assay and compare ANA patterns between IgG, IgA and anti-light chain responses
The immune system responds to pathogens through both innate and adaptive immunity; B lymphocytes produce antibodies that help destroy pathogens, and memory B cells trigger a rapid response upon secondary exposure. Vaccines expose the immune system to antigens to stimulate antibody production and memory cell formation without causing disease. Monoclonal antibodies produced from hybridoma cells provide a pure form of antibodies useful for diagnostic tests and targeted therapies.
Auto Immune Disorders and Its Homoeopathic Approachijtsrd
Each and Every human being living on this earth possesses a power to protect self from the external harmful environmental agents. This power is called Immunity. It is the ability of the body to resist the entry of different types of foreign bodies like bacteria, viruses, toxic substances etc. Initially the word Immunity was used to indicate a state of insusceptibility or complete resistance to infection. But in the light of modern concept immunity depends on various factors like host resistance, dosage and virulence of organism. The primary function of the Immune system is to protect an individual The Host against invasion of infectious agents. Normally the immune system is able to distinguish friend from foe ignoring the body's own components and attacking foreign invaders. But in certain conditions this weapon turns against the self and causing severe illness and even death also such disorders are called as Auto Immune Disorders. In Autoimmune Diseases the Immune system reacts against self antigens and destroys host tissues. Antibodies against self antigens are termed as auto antibodies. Prof. (Dr.) Jatin Dhagat | Prof. (Dr.) Dhwanika Dhagat "Auto Immune Disorders and Its Homoeopathic Approach" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-7 | Issue-4, August 2023, URL: https://www.ijtsrd.com/papers/ijtsrd59811.pdf Paper Url:https://www.ijtsrd.com/medicine/other/59811/auto-immune-disorders-and-its-homoeopathic-approach/prof-dr-jatin-dhagat
This document is an assignment on psychoneuroimmunology submitted by a group of students. It includes an introduction defining psychoneuroimmunology as the study of the interaction between psychological processes, the nervous system, and immune system. It then covers topics such as the effects of stress on the immune system, the role of the brain and HPA axis in mediating stress responses, and how psychoneuroimmunology relates to diseases like cancer and mental health conditions. References from several sources are provided at the end.
Alligator serum and the battle against HIVPKaragiannis
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Microbiota, vitamin D receptor VDR and autoimmuityfathi neana
The big question is what is behind sickness during our life ?. How the pathogens can prevail and what happen to our immune system and microbiota. How the pathogens in a clever way shut down the innate immunity causing persistent chronic illness, chronic inflammation, maladaptive autoimmunity and other chronic diseases. What is the rule of vitamin D and its receptor VDR . What about the current debate regarding the best choice for managing vitamin D deficient function. Hope we can find the answer in this presentation.
The study in immunology provides the fundamental understanding of how the human body defend itself against foreign organisms, materials or particles that have the ability to cause harm to host tissues.
Vaccines And Its Effects On The DiseaseGina Alfaro
Multiple sclerosis is thought to be caused by an autoimmune reaction where the immune system mistakenly attacks the myelin sheath and oligodendrocytes in the central nervous system, leading to demyelination. Both cellular and humoral immune responses are involved, with T cells and macrophages first damaging the myelin sheath and B cells later secreting antibodies that further attack myelin. While the exact cause is unknown, genetic and environmental factors such as low vitamin D levels and Epstein-Barr virus infection are thought to increase the risk of developing multiple sclerosis.
This document provides a summary of a student's research project on using personalised learning strategies to overcome difficulties in understanding biology topics related to pathogens and antibiotic resistance. The research project involved examining educational placement, background, aims and objectives. Effectiveness of strategies was assessed through references and an appendix providing details on case studies and educational introduction, biological introduction on pathogens and antibiotic resistance, as well as further learning sections on HIV and Ebola.
Expository Essay: Examples and Tips of a Proper Writing That Will Be .... Expository Essay Sample: Academic Guide. Expository Essay - 6+ Examples, Format, Pdf | Examples. Expository Essay | Essays | Cognition. Descriptive Essay: Expository essay definition and examples.
EVIDENCE FOR EFFECTS ON THE IMMUNE SYSTEM - EMF Sensitivity Not Relevant
The document discusses the immune system and its response to electromagnetic fields. It provides background on the basic components and functions of the immune system. It then discusses how the immune system can have hypersensitivity reactions to environmental substances, including electromagnetic fields. It notes several types of hypersensitivity reactions and cells involved. Finally, it discusses natural and human-made sources of electromagnetic fields and how different frequencies interact with the body.
Cell Culture Techniques (Michael Aschner, Lucio Costa) (Z-Library).pdfsymbssglmr
This document provides prefaces and contributor information for the book "Cell Culture Techniques, Second Edition". The prefaces discuss the Neuromethods series focusing on tools and techniques for investigating the nervous system. The book aims to provide technical protocols as well as theoretical background to help readers understand the origins and potential developments of the techniques. The contributors section lists researchers who contributed chapters applying specific neuroscience methods and models.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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You should be very careful to avoid plagiarism when summarizing your sources. All source content in your summaries should be in your own words (preferred) or in quotation marks with page numbers provided (try to avoid quotes). Keeping plagiarism out of your summaries is an important step in keeping it out of your literature review. DO NOT JUST READ AND SUMMARIZE THE ABSTRACT! READ THE ENTIRE ARTICLE UNLESS OTHERWISE SPECIFIED.
1. Identify the main research hypothesis or thesis.
2. Describe how the researchers tested their hypothesis/hypotheses. In other words, describe their methodology (what they did, including what behaviors they recorded, how often they observed the primates, how they recorded the data, etc), the participants (who were they, how many were used/observed, where were they housed, where were they from), and a brief overview of the procedure.
3. Describe what the researchers found (focus on their main findings from the results section, discussion, and conclusions). Make sure that you understand their overall results, including the statistics and charts/graphs/figures they reported.
Source Evaluation (Excerpted from Galvan, 2006, p. 8)
In addition to summarizing the relevant information from a source, you should also evaluate the information in the source. Critique/analysis of the literature is an important part of a good article summary.
· Are there any obvious problems with the way the authors are discussing the background literature, their methods, or misconstruing their findings? Explain.
· Are there any obvious biases from the authors trying to downplay abnormal behaviors or justify what they are doing for human good? Explain.
· Did you notice any other flaws? Explain.
· Overall, do you think the research makes an important contribution to advancing knowledge?
Critical Reading (Excerpted from Lawson, 1999)
You should find the following questions useful as you evaluate the strengths and weaknesses of each of your sources.
· What is the quality of the evidence used to support the claim?
· Is there a control or comparison group against which to assess the performance of the experimental group?
· Is the person concluding there is a causal relationship on the basis of correlational data?
· Are there confounding variables that might account for the findings, or are there confounding variables that they are not considering (e.g. exposure to humans on a daily basis, invasive experimental procedures, single housing)?
· Has the person made it impossible to falsify his or her theory or hypothesis? Does he or she consider positive evidence as support for the theory but negative evidence as not being relevant?
· Is the person acknowledging that complex behaviors or phenomena have multiple causes?
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2. Please cite this article in press as: A.B. Poletaev, et al., Immunophysiology versus immunopathology: Natural autoimmunity in human
health and disease, Pathophysiology (2012), http://dx.doi.org/10.1016/j.pathophys.2012.07.003
ARTICLE IN PRESSPATPHY-755; No.of Pages11
2 A.B. Poletaev et al. / Pathophysiology xxx (2012) xxx–xxx
Fig. 1. Founder of physiological autoimmunity concept Ilya I. Metch-
nikoff (1845–1916) and supporter of preventive medicine ideas L.N. Tolstoy
(1828–1910) during conversation. 30th May 1909. “Yasnaya Polyana”
estate, photo by S.A. Tolstaya (Bers).
of the whole body, and the terms: “sense of antigenic-
ity”, “immune analyzer”, “immunological image”, “immune
reflex” (instead of “secondary immune response”) etc., could
have become quite customary from the very beginning, in the
same way as “immunological memory” or “immunosynapse”
in modern texts. In this case the term “immunity” has been
associated not with the metaphor of “alerted guard” involved
in permanent war against microbes (which is until now a rou-
tine view) but rather a housekeeper of factors challenging for
homeodynamics, mostly endogenous in their origin.
Almost 120 years ago Ilya Ilyich Metchnikoff (who put
Darwinian logics into the very foundation of his Immunol-
ogy) (Fig. 1) suggested that the main predestination of the
immune system is not “struggle” against non-self, but rather
“harmonization of self”, or even ontogenetic creation of
multi-cellular organism, in spite of interior contradictions of
its elements [3]. Participation of immune cells in permanent
host struggle against aliens is just one of the facets of a much
wider biological predestination of the immune system which
is responsible for the control of dynamic self-maintenance,
self-reparation, self-construction and self-optimization of
an organism, and perpetual self-harmonization of the
primarily imperfect and contradictory body under the con-
ditions of permanent pressure of the environment [4,5].
Metchnikoff prophesied the existence and role of “physiolog-
ical inflammation” or natural autoimmunity. Unfortunately,
his lone voice was not heard at that time, and it was only
much later that similar ideas were expressed. For exam-
ple, Matzinger‘s [6] “danger hypothesis” implies that the
immune system is not concerned with discrimination and
killing of the alien, but it is aimed to identify and block the
potentially dangerous. It may serve as grounds for expla-
nation of many previously unexplained phenomena such
as: constant presence of abundant “normal” microbial flora
(“aliens”!) in each healthy organism and physiological preg-
nancy, in which any healthy woman is capable to let the
development of a semi-allogenic fetus without destroying
it, etc. As it was stated by Iwasaki and Medzhitov in their
review of relations between innate and adaptive immunity
[7], “. . .there are still many fundamental questions that
remain poorly understood,. . ., including the mechanisms by
which pathogen-specific innate immune recognition activates
antigen-specific adaptive immune responses”. In this connec-
tion we shall mention a concept recently coined by Marshall
and colleagues [8]. According this concept, a great number
of microorganisms are able to persist within human cells of a
“clinically healthy” individual (their genes forming so called
“interactome” with human genome). It is possible because
they possess with antagonists of vitamin-D-dependent recep-
tor (VDR), which controls the start of human innate immunity
mechanisms. Hence, our cells cannot kill these intracellular
germs by means of innate bactericidal effectors and develop
adaptive immune responses toward their antigens. The latter
areinvolvedinmimicrywithselfepitopes,whichsupportsthe
autoantibody production. Disorders of vitamin D metabolism
and VDR-depending innate immunity are reported in many
autoimmune diseases, as well as in chronic infections. Re-
activators of VDR in combination with antibiotics were
successfully applied in some chronic autoimmune diseases,
such as rheumatoid arthritis and Hashimoto’s autoimmune
thyroiditis (AIT) [8–10].
In pathophysiological approach, the systems supervising
the growth, development and aging of the whole organism
and all its components are supposed to coordinate primarily
the sequence and intensity of reading of the genetic infor-
mation in various cells. This task can be achieved neither
by neural mechanisms, nor via hormonal agents, which are
involved in accelerating or slowing down the metabolic pro-
cesses. The neurotransmitters, hormones and their receptors
lack ontogenetic and event-driven variability needed for this
purpose, while the cells producing them lack the necessary
mobility and all-embracing dispersal – the qualities inher-
ent to the immune system [11]. Transfer of the emphasis
in the main purpose of the immune system from defense
to homeodynamic regulation will necessarily lead to re-
evaluation of some conventional views, for example, such as
the phenomena of physiological autoimmunity and the gen-
eral role of natural autoantibodies (auto-Abs). In our opinion,
it is physiological autoimmunity that provides for bringing-
together and co-tuning of genetic information processing in
3. Please cite this article in press as: A.B. Poletaev, et al., Immunophysiology versus immunopathology: Natural autoimmunity in human
health and disease, Pathophysiology (2012), http://dx.doi.org/10.1016/j.pathophys.2012.07.003
ARTICLE IN PRESSPATPHY-755; No.of Pages11
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Fig. 2. Immunculus and neurological “Homunculus”: analogy of concepts. Two main regulatory systems operate with 2 principles of body image reflection.
Neurological homunculus reflects body structure via activities of neurons in somato-sensoric cortical zones and represents for CNS operations an image of
the body [12]. Immunculus (Immune Homunculus) of the body consists of clonal mosaics, represented by auto-antiidiotypic antibodies. They form internal
immunological images of all autoantigens. Immunculus is used by immune system for physiological self-control of homeodynamics [13–15].
different cells of the holistic “Body” through the complete
ontogeny.
2. Regulatory autoantibodies, Immunculus and
Immunacea effect
Auto-Ab(s) can be regarded as recognizing molecules,
bearing in mind that all regulatory processes in the
organism are based upon complementary intermolecular
recognition. The system of autoimmunity serves as a mir-
ror in dynamic maintenance of individual self-identity,
because it is capable of universal inducible reproduction
of complementary molecules. This is known, by analogy
with Penfield’s somatosensory homunculus, as principle of
immune homunculus (Immunculus) [12–15] and illustrated
in Fig. 2.
Moreover, the network of idiotype–anti-idiotypic reg-
ulation includes receptors of hormones, autacoids and
neurotransmitters, as well as auto-anti-idiotypic Abs to
bioregulators, which in turn, are mirror “internal immuno-
logical images” of their ligands. By means of production of
auto-Abs to any regulatory molecules and their receptors the
immune system may exert influence upon cellular prolifera-
tion,differentiationanddying,aswellasanyothergenetically
determined events at molecular and cellular levels. For
example, specific antibodies against chromatin receptors of
endocrine cells penetrate cell nuclei in vitro and in vivo,
and influence specific mRNA transcription, DNA replica-
tion and production/secretion of hormones [11,13,16–18].
Idiotype–antiidiotypic mechanisms may cause the appear-
ance of auto-antiidiotypic antibodies. Their CDR regions
can be stereochemically similar to receptor-binding parts
of primary antigens (including hormones, neurotransmitters,
autacoids, drugs, etc.). Such auto-antiidiotypes could repro-
duce or antagonize, at least partially, the biologic activity
of original bioregulators. Many experimental and clinical
data directly witness that phenomena of this kind are real.
Antibodies with biological activity similar to hormones,
autacoids, enzymes and drugs of different classes have
been obtained or registered in patients or healthy donors
[11,17–20]. Hypothetically by such anti-idiotypic mecha-
nism the immune system may reproduce functionally active
copies of ANY (!) biologically active molecule. Is this not
something like a realization of an ancient myth about Panacea
( ␣´␣␣, Panakeia) – all-healing? The term “effect of
4. Please cite this article in press as: A.B. Poletaev, et al., Immunophysiology versus immunopathology: Natural autoimmunity in human
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Immunacea” may be proposed as applicable to this potency
of immune system [18].
Polyclonal natural human immunoglobulins taken from
many donors and admixed can contain a lot of these
immunological images, as a kind of collective impact of
their individual immunological experiences. Could unique
wideness and effectiveness of intravenous immunoglobulin
(IVIG) therapy be partially related to the phenomenon of
“Immunacea”? In our opinion, the effect of Immunacea is
still underestimated in its application in the treatment of non-
infectioussomaticdiseases.Recently,thepossibilitytomodel
some autoimmune disorders by means of immunization with
antibodies toward absent antigen has been shown by Shoen-
feldetal.inanimalsnotexpressingcertaintargetautoantigens
[17]. We predict that the introduction of antibodies against a
protein missing in a genetically deficient organism will allow
for the immune system to produce its immune analog, which
may be a promising approach to treatment of some hereditary
diseases [18].
3. Clearance function of the immune system
Probably, one of the most important (evolutionary
archetypical) homeodynamic functions of the immune sys-
tem is its involvement in clearance [15,19], a prototype of the
immune system eliminating such erratic objects as viruses,
bacteria and fungi. It includes the elimination of immune
complexes. But, first of all, this function is directed to utiliza-
tion of permanently emerging debris products from lastingly
dying self cells of the body. Many activities of the immune
system can be derived from this ancient function.
Starting from classical Metchnikoff’s works it has been
assumed that clearance of both endogenous and exogenous
products is carried out by macrophages, which express Toll-
like receptors (for conservative microbial by-products) and
scavenger receptors (for some modified alien or self proteins)
[21]. However, this does not explain the whole spectrum of
phagocytic clearance. Macrophages do not “sense” via these
receptors the vast majority of intact alien and self molecules;
neither can they “sense” waste products of self cell apo-
ptosis which must also be utilized. Here we encounter an
evident obstacle in the comprehension of clearance mech-
anisms, because macrophages cannot “notice” most of the
targets. Any macrophage per se cannot discriminate a nor-
mal serum albumin from a defective one, or a senescent
erythrocyte from a young one. Nonetheless, the question as
to what the macrophage must gobble and what it should not
touch has an effective solution. Phagocytes use specialized
signatures (“tags”) attached to items that are to be utilized
– namely auto-antibodies [22]. These attach themselves to
any product which is to be “gulped down” by macrophages,
and, first of all, to waste products of apoptosis or eryptosis
[23]. By means of superficial Fc-receptors macrophages are
boundtoAb-antigencomplexes(solubleaswellasparticulate
ones) and take them up efficiently by receptor endocytosis.
Figuratively speaking, antibodies (opsonins) play the part of
scent marks for “blind dogs” (phagocytes) and help them
recognize effectively the objects intended for utilization.
4. Autoantibodies, cell death, physiological and
pathological autoimmunity
Nota bene: Production of antibodies is regulated (accord-
ing to feedback principle) by the quantity of complementary
antigens(processedandavailableforrecognitionbyimmuno-
competent cells) [24]. That is why any increase of garbage
product concentrations is a signal for appropriate raise in
the synthesis of specific antibodies, used as signatures for
withdrawal of this discharge. Individual rates of apopto-
sis/replacement of different specialized cells are roughly the
same in any healthy adult. Nearly constant level of antigenic
waste production under normal conditions is probably the
main reason for nearly the same serum levels of various (in
terms of specificity) auto-antibodies in each healthy adult
individual, practically regardless of sex and age [13,14,19].
On the contrary, pathological changes in heart or lungs,
kidneys or liver, and any other organs lead to abnormal
increase of “cardiotropic”, “pulmotropic”, “renotropic” or
other “organotropic” auto-antibodies [19], because virtually
all diseases from the earliest latent onset are accompanied
by notable augmentation in the apoptosis rate among cer-
tain populations of cells, with more or less massive splash
of their specific antigens (Figs. 3 and 4). In Fig. 3 we have
superimposed the distribution of the auto-Ab toward several
separated by isoelectric focusing cardiac proteins, obtained
in 10 healthy donors (thin lines) and in 1 our patient with
cardiomyopathy (thick dashed line), thus demonstrating the
change of “normal” pattern of autoimmunity to unusual one
– in disease. Fig. 4 results from our study of anti-thyroid
auto-Ab and thyroid function in 95 Russian families, where
at least one of parents has diagnosis AIT, proven clinically
and paraclinically according Japanese thyroidological asso-
ciation (JTA) criteria of 2002 [24]. The seemingly healthy
children of these parents, still having no established AIT
diagnosis and full set of JTA criteria, were compared to
their ill parents and to 100 healthy children of nearly the
same age, but without AIT in families. It has been shown that
both anti-thyroglobulin (anti-TG) and anti-thyroperoxidase
(anti-TPO) autoantibodies, considered to be typical for AIT
[24] presented in sera of all 3 groups. But, not only par-
ents with overt AIT manifested significantly higher levels of
anti-thyroid autoimmunity, than healthy children. Seemingly
healthy children of sick parents had elevation of anti-TPO
and anti-TG long before the establishment of overt AIT, and
with still normal thyroid function.
The potential triggering roles for anti-thyroid autoim-
munity may be attributed to certain infections with
cross-specificity of germ and self antigens, or to alternative
splicing of thyroglobulin under the influence of differ-
ent iodine supply in various periods of life [20,22,25].
5. Please cite this article in press as: A.B. Poletaev, et al., Immunophysiology versus immunopathology: Natural autoimmunity in human
health and disease, Pathophysiology (2012), http://dx.doi.org/10.1016/j.pathophys.2012.07.003
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Fig. 3. Cumulated data of cardiotropic autoimmunity in healthy donors (thin lines) and in one case of cardiomyopathy (thick dashed line). Along horizontal
axis – isoelectric focusing replica for human myocardial proteins, along vertical axis – levels of autoantibodies toward these antigens, measured by ELI ELISA
test. The pattern of sick person differs from typical health pattern of autoimmunity.
In view of Metchnikoff’s concept of autoimmune harmo-
nization for phylogeny and ontogeny, among these triggers
of autoimmunity one should not forget the phenomenon
of spontaneous microchimerism in humans, especially in
multiparous women. This has been long ago suggested as
principally important reason of AIT, although Lee Nel-
son appreciated the significance of such microchimerism
as a potentially defensive mechanism of normal pregnancy
[26,27]. An interesting question, arisen in this connection,
is: “Why women live longer than men?” Is gender-connected
longevity related not only to freedom from bad habits of men,
but also to women’s ability to give a new life? Possibly, it
depends partly from persistence of fetal cells in maternal
tissues (microchimerism) [28]. But, at the same time preva-
lence of almost all autoimmune diseases (like AIT) among
females is much greater, than in males [29]. In our opin-
ion, anti-idiotypic mechanism may signalize to mother about
proper or improper status of fetus via autoimmune images of
fetal antigens. Recently we have demonstrated that allogeneic
stem cells, at least in parabiotic models, may penetrate into
organism of rodents and differentiate into thyrocytes, thus
contributing into thyroid regeneration [30]. It is a question, if
similar phenomenon takes place in human pregnancy? This
has been supposed for cases of perinatal autoimmune thyroid
disease [31]. Perhaps, in such mosaics it is autoimmunity
which acts in order to harmonize chimerical organism, in full
Fig. 4. Anti-thyroid autoimmunity and thyroid function in families with AIT and their so far healthy children and in controls. Asterisks mark statistically
significant difference with controls.
6. Please cite this article in press as: A.B. Poletaev, et al., Immunophysiology versus immunopathology: Natural autoimmunity in human
health and disease, Pathophysiology (2012), http://dx.doi.org/10.1016/j.pathophys.2012.07.003
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6 A.B. Poletaev et al. / Pathophysiology xxx (2012) xxx–xxx
accordance to statement of Metchnikoff. For full consistency
of such mechanism, however, we should hypothesize the
possibility of bidirectional Fc-receptor depending IgG trans-
portation across placental barrier, as it was already proven for
similar transfer via intestinal and urogenital barriers [32,33].
Maybe, spontaneous human chimerism is much more
common phenomenon than it was supposed earlier. Retro-
spective analysis of our database of 3717 proven AIT patients
has revealed among them – 8 cases of anamnaestic blood
group change (or Rh-factor change) – all of them medically
documented with double check. Seven of the patients were
multiparous ladies and one male, who experienced blood
transfusions [34]. Blood group has been changed from AB for
B (2 cases), 0 for B (1) or A for B (1), and Rh was changed
from positive to negative (3 cases), or vice versa (1). We
believe that this could result from chimerism or cell mosaics,
which probably was key link of AIT pathogenesis in these
patients. Interestingly, blood group 0 is predominating among
AIT patients of our cohort much more obviously than in local
population of St. Petersburg. We suggest that it is related to
greater reaction of “nullers” toward microbial polysaccharide
antigens and possible provocative role of germs for AIT [34].
Not only phenomena related to pregnancy, but also
excessive emission of apoptotic garbage (including usually
“hidden” intracellular tissue-specific antigens, e.g. TG and
TPO from perishing thyrocytes) triggers off a rise in pro-
duction of auto-antibodies of appropriate specificity [19]. In
systemic autoimmune connective tissue diseases with pres-
ence of non-organ specific autoantibodies (systemic lupus
eruthematosus – SLE, scleroderma, rheumatoid arthritis
etc.) one can observe high titers of autoantibodies against
chromatin-associated and caryolemma-associated antigens
(e.g. dsDNA, nucleohistones, or cardiolipin). But these par-
ticular antigens are most plentiful in apoptotic bodies, which
contain chromatin and membrane material. Normally they
are rapidly eliminated by tangible bodies’ macrophages, with
minor fraction of debris only taken up by antigen-presenting
dendritic cells. This supports minimal physiological level
of natural autoimmunity. There are some evidences that
the rate of withdrawal of apoptotic debris is decreased in
SLE and related diseases; and appropriate function of CD68-
positive tangible bodies’ macrophages in lymph nodes of
these patients is weakened [35,36]. As a result, there is much
greater uptake of apoptotic material by antigen-presenting
elements, with survival signaling for appropriate autore-
active lymphocytes and much more intensive autoimmune
response, exceeding the normal level. To a certain degree,
this kind of an easily detected secondary autoimmune reac-
tion should be considered as essentially adaptive, because
these events tend to restore the disturbed homeodynamics,
intensifying clearance in the organ involved and activating
reparative processes. The latter can be proven by the fact that
many auto-antibodies stimulate DNA synthesis, mitotic rates
and cell proliferation [11,16–20,22]. Presumably, if the con-
tent of “cardiotropic”, “thyrotropic” or other “organotropic”
auto-antibodies, as well as antinuclear ones, in blood sera of
Fig. 5. Autoantibody level in patient B.C., investigated for anti-2-
glycoproteinIantibodies(b2-GP)bymono-kits“Orgentec”,Germany(black
column) was shown below of population norm (average normal level from
3000 healthy donors accepted here and in all other diagrams as zero line).
Autoantibodies of the same specificity and other serologic markers of anti-
phospholipid syndrome were revealed in the same sample by using of
multiparametric kits (ELI-P-Complex Method), gray columns. All abbre-
viations decoded in the text.
investigated persons stay within the normal range – this result
may indicate that apoptotic rates in heart, thyroid or other
organs do not exceed physiological intensity and witness for
the normal rate of clearance of apoptotic debris. On the other
hand, in case of long-term increase of some organotropic
auto-antibody production (for example, “pulmotropic”) one
may suggest the presence of some pathological process in
that organ (e.g., in lungs), even if there are still no evident
clinical symptoms at the time of investigation. This process
need not be of obligate immunopathological origin, like AIT.
It can be any process, killing this organ’s cells. In our clinical
diagnostic practice we have regularly observed that specific
increase in serum level of “organotropic” auto-antibodies
appears months or even years before the first clinical signs
of different somatic diseases, formally not included into the
group of autoimmune pathology [37]. It is the same for “non-
organ specific”, or better to say “universal anti-apoptotic”
autoantibodies: for example, in SLE and rheumatoid arthritis
they are proven to appear years before overt clinical disease
[38].
Here follow several clinical examples from our practice
with brief case histories and appropriate spectra of autoan-
tibodies, shown in Figs. 5–7. Because mono-tests for single
particular kind of auto-Ab may not be always informative,
we have elaborated and produced in our medical center mul-
tiparametric non-competitive solid phase ELISA assay kits
for simultaneous determination of different auto-Ab(s) with
the panels of autoantigens attached (ELI-test (Immunculus,
Russia)) [19,39]. Level of certain auto-Ab(s) in an individual
is evaluated in % compared to average one for population,
last is taken for 100%. Algebraic total of deviations for
7. Please cite this article in press as: A.B. Poletaev, et al., Immunophysiology versus immunopathology: Natural autoimmunity in human
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Fig. 6. (a) ELI-Viscero-Test data in patient M.N. before treatment, all abbreviations decoded in the text. (b) ELI-Viscero-Test data of the same person, M.N. 6
months after successful treatment of pyelonephritis and secondary arterial hypertension. All abbreviations decoded in the text.
all auto-Ab(s) controlled is referred to as index of Average
Individual Immune Reactivity (AIIR, which average level in
population considered to be 0).
5. Clinical examples
Example 1. Case History IMC-08-134, Patient B.C.
(29 y.o., female) (Fig. 5). Pregnancy 9–10 weeks, symptoms
of threatening of miscarriage, elevated blood coagulation,
echographic signs of placental blood flow disorder (by
dopplerography). Leucopenia. Serum level of auto-Abs
against beta2-Glycoprotein I (b2-GP) was below of popula-
tion norm (data obtained by means of commercially available
mono-kits “Orgentec”, Germany, shown with black column).
Serological markers of anti-phospholipid syndrome were not
revealed.
Results of multiparametric diagnostic investigation by
non-competitive solid phase ELISA assay with ELI-P-
Complex Kit (“Immunculus”, Russia) are shown with gray
columns: auto-Abs against chorionic gonadotropin (Ch-GT):
−51% from population norm; auto-Abs against double strand
DNA (dsDNA): −31%; auto-Abs against b2-GP: −4%; auto-
Abs against collagen: −45%; auto-Abs against Fc-fragment
of IgG (Rheumofactor): −26%; auto-Abs against insulin:
−49%; auto-Abs against thyroglobulin (Thyroglob., TG):
−42%; auto-Abs against S100 protein (S100): −35%; auto-
Abs against spermal antigen (SPR06): −46%; auto-Abs
againstsmallbloodvesselantigen(ANCA):−63%;auto-Abs
against platelet antigen (TrM03): −58%; auto-Abs against
kidney antigen (Kim05): −64%.
AIIR = −45% (that is referred to as sign of prominent
immune suppression); level of reactivity related to auto-Abs
against beta2-Glycoprotein I is +76% compared to AIIR.
8. Please cite this article in press as: A.B. Poletaev, et al., Immunophysiology versus immunopathology: Natural autoimmunity in human
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Fig. 7. ELI-Viscero-Test data of patient B.R. Ds.: prostate cancer in situ. All
abbreviations decoded in the text.
Conclusion: prominent serological markers of anti-
phospholipid syndrome were revealed with multiparametric
kits Eli-test for analysis of individual profile of immune reac-
tivity, but not with monoparametric kits (Fig. 5).
Catamnestic clinical observations: Miscarriage had hap-
pened at 12–13th weeks of pregnancy, most probably in
relation to anti-phospholipid syndrome and placental blood
flow disturbances.
Example 2. Case History IMC-09-13, Patient M.N. (48
y.o., male); complaints of unexplained weakness and indis-
position; 4 episodes of abnormal elevation of blood pressure
(up to 160/100) during the last 4–5 months.
Results of multiparametric diagnostic investigation by
ELI-Viscero-Test-24Kit(“Immunculus”,Russia)(Fig.6aand
b): auto-Abs against dsDNA: +1% to population norm; auto-
Abs against b2-GP: +12%; auto-Abs against Fc-fragment of
IgG (Fc-igG): +5%; auto-Abs against heart antigen beta2-
adrenoreceptor (b-AR): −9%; auto-Abs against heart antigen
Com: −3%; auto-Abs against platelets antigen TrM: −3%;
auto-Abs against small blood vessel antigen ANCA: −5%;
auto-Abs against kidney antigen Kim: +38%; auto-Abs
against kidney antigen Kis: +25%; auto-Abs against lung
antigen Lus: −8%; auto-Abs against lung antigen Lum:
−8%; auto-Abs against stomach wall antigen Gam: −14%;
auto-Abs against intestinal wall antigen Itm: +7%; auto-
Abs against liver antigen HMMP: −3%; auto-Abs against
liver antigen Hes: −8%; auto-Abs against insulin (Ins): −11;
auto-Abs against insulin receptors (Ins-RC): −9%; auto-Abs
against TSH receptor (TSH-R): −8%; auto-Abs against TG:
−14%; auto-Abs against adrenal antigen Adr-QC: −12%;
auto-Abs against prostate/spermal antigen SPR: +18%; auto-
Abs against S100: −6%; Abs against astrocyte’s protein
GFAP: −11%; Abs against myelin basic protein MBP: +3%.
Index AIIR = −1% (which is normal); prominently ele-
vated immune reactivity against kidney antigens, and against
prostate antigen was found (Fig. 6a). Additional investiga-
tion of urine revealed a moderate bacteriuria and plenty
of white blood cells. Antibacterial treatment course with
antibiotics and uroantiseptics in accordance with germ sensi-
tivity was effective and bacteriuria/leucocyturia disappeared.
Arterial blood pressure also normalized during 18 months
regular observation did not reveal any episodes of arterial
hypertension. After treatment Eli-test demonstrated tendency
to normalization of autoantibodies spectrum with levels of
anti-kidney and anti-prostate immunoreactivity decreased
(Fig. 6b).
Conclusion: Early stage of secondary renal arterial hyper-
tension was revealed; treatment of kidney infection was
effective and resulted also in successful stopping at early
stage of disease.
Example 3. Case History IMC-08-201, Patient B.R. (64
y.o., male); considered himself as healthy person, having no
complaints.
Results of multiparametric diagnostic investigation by
ELI-Viscero-Test-24 Kit (“Immunculus”, Russia) (Fig. 7):
auto-Abs against dsDNA: +46%; auto-Abs against b2-GP:
+1%; auto-Abs againstFc-igG: +15%; auto-Abs againstheart
antigen b-AR: −11%; auto-Abs against heart antigen Com:
−8%; auto-Abs against platelet antigen TrM: −7%; auto-Abs
against small blood vessel antigen ANCA: −5%; auto-Abs
against kidney antigen Kim: −8%; auto-Abs against kid-
ney antigen Kis: −13%; auto-Abs against lung antigen Lus:
−16%; auto-Abs against lung antigen Lum: −12%; auto-
Abs against stomach wall antigen Gam: −14%; auto-Abs
against intestinal wall antigen Itm: −11%; auto-Abs against
liver antigen HMMP: −6%; auto-Abs against liver antigen
Hes: −12%; auto-Abs against Ins: −11%; auto-Abs against
Ins-RC: −10%; auto-Abs against TSH-R: −3%; auto-Abs
against TG: −1%; auto-Abs against adrenal antigen Adr-
QC: −2%; auto-Abs against prostate/spermal antigen: SPR
+28%; auto-Abs against S100: +36%; Abs against astrocyte’s
protein GFAP: −6%; Abs against MBP: −8%.
Index AIIR = −2% (which is normal); prominently ele-
vated immune reactivity against kidney cells, and against
prostate antigen was found (Fig. 7). Additional investigation
of prostate gland with positron emission tomography (PET)
revealed abnormally intensive accumulation of glucose in
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prostate; concentration of prostate-specific antigen in cir-
culating blood was at high-normal level; later diagnosed
prostate cancer in situ (confirmed by pathomorphological
investigation of biopsy samples). Patient was successfully
treated. Three years later any signs of malignancy were
absent.
Conclusion: Early stage of prostate cancer was revealed;
surgical treatment was effective.
6. Autoimmunomics in early diagnosis
Thus, elevation of the titers of autoAb(s) seems to be the
earliestsignofincipientdevelopmentofalatentdisease,com-
ing long before the overt insufficiency of appropriate organ.
But, why is it so? Probably it may be related to an enor-
mous excess of specialized cells in an organ (one of ways
to achieve functional reliability) [22,23]. As a result, any
chronic pathological process of almost every etiology will
reach the stage of organ insufficiency only after a prolonged
silent period, that is, not until the potential of regenera-
tion is exceeded by long-lasting degenerative events with
cell loss. Signs of functional insufficiency (such as peculiar
biochemical changes and clinical manifestations) will only
appear at an overt stage. Good example of that is progressive
nephrosclerosis, which gives first functional and laboratory
clinical manifestations of chronic renal failure after many
years of unapparent course only, when more than half of
nephrons has been already perished [22]. So, biochemical
and pathophysiological deviations reflect perceptible func-
tional failure of an organ relatively late. On the contrary,
changes in auto-Ab level appear long before that, because
they are related not to an organ’s functional decline, but to
abnormal activation of cell death events. For example, in large
prospective study of the thyroid health in migrants from Cher-
nobyl area [40] as well as in cohort study of adolescents and
adults with marfanoid phenotype and Simpson-Page’ syn-
drome [41] we have revealed elevated levels of anti-thyroid
autoimmunity long before subsequent overt manifestation
of AIT, hypothyroidism and metabolic syndrome. Poten-
tially early pre-nosologic changes in any organ also may be
early revealed by pathomorphological investigation of biopsy
materials or cytological analysis of smears. However, unlike
auto-antibody determination, this approach can hardly be
applied for broad population screening (with little exclusion –
like Pap smears in oncogynecology) and in some cases biopsy
is not applicable physically (brain) or counterindicated clin-
ically (AIT).
On the basis of our own clinical experience [19,37,39–41]
and literature data [38,42] we believe that in the overwhelm-
ing majority of cases an abnormal rise of serum auto-Ab
level with different antigen specificity is a secondary event
(reflection), induced by some primary damage of an organ
or a tissue. This kind of autoimmune reactions should be
considered as sanogenic or beneficial in essence. How-
ever, autoimmune diseases, related to primary abnormal
elevation of auto-Ab production and/or excessive activation
of autoreactive lymphoid clones are also highly spread. How
can sanogenic (beneficial) autoimmune reactions be differ-
entiated from the pathogenic (harmful) ones? It seems that
primary autoimmune reactions (the ones not justified by real
needs of an organism) in most cases are poorly regulated.
Immune response may sometimes be inadequate in inten-
sity, or incorrectly targeted, or badly driven, and in each
case the result may be rather detrimental for an organism.
All these situations, when immune response brings more
harm than defense, are referred in Pathophysiology by the
collection term “allergy” [22]. From a didactical point of
view, we propose to use the term “autoimmunity” prefer-
ably in relation to physiological autoimmune processes.
Adaptive secondary autoreactive responses (autoimmune)
should be distinguished from “autoallergic” (mostly, pri-
mary) pathogenic immune reactions. We recommend using
the term “autoallergy” for abnormal rise in production
of auto-Ab(s) and autoreactive lymphocytes (provoked by
viruses, bacteria, chemicals or other harmful factors, or
related to disorders in the regulation of natural autoimmunity
and non-conditioned by real needs of an organism).
7. Concluding remarks
1. Primary pathological processes in any organ usually lead
to activation of cell death in populations and are reflected
by secondary (adaptive, compensatory) rise of production
and blood serum level of auto-Ab(s) with appropri-
ate specificity. This reaction of the immune system is
sanogenic and represents autoimmunity.
2. Much more rarely physicians can observe primary rise of
auto-Ab production, mostly induced by different exter-
nal stimuli or related to defects in autoimmunity control
and not associated with to pre-existing disease of organ
or tissue. Such situations are pathogenic in essence and
may lead to autoallergy (autoallergic diseases). In our own
practice correlation of occurrence of adaptive (secondary)
autoimmune reactions and that of pathogenic (primary)
autoallergic reactions is about 95/5.
3. Secondary quantitative changes in auto-Ab production
may be detected months or years before the appearance of
early clinical signs of a disease, and should be considered
as a universal marker for virtually all chronic diseases,
including those not entered today in the registry of autoal-
lergic disorders. The analysis of quantitative changes in
the content of natural auto-Ab may become an effective
instrument for early pre-clinical and even pre-nosologic
detection of pathological processes with different organic
location and cellular targeting. In future, success in this
area may result in revision of the main paradigm of
medicine (DISEASE–TREATMENT), and transition to
the new one (PROGNOSIS–PREVENTION), see also
[38].
10. Please cite this article in press as: A.B. Poletaev, et al., Immunophysiology versus immunopathology: Natural autoimmunity in human
health and disease, Pathophysiology (2012), http://dx.doi.org/10.1016/j.pathophys.2012.07.003
ARTICLE IN PRESSPATPHY-755; No.of Pages11
10 A.B. Poletaev et al. / Pathophysiology xxx (2012) xxx–xxx
Of course, for this forecast to come true, we need not
only diagnostic methods of autoimmunomics, but also effec-
tive and realizable algorithms of individualized prophylaxis
adopted by health care practice. The problem of earliest pre-
nosological diagnosis also has some bioethical aspects.
Reviewing the history of ideas in Immunology, we may
notice that Metchnikoff shifted the accents in understanding
the functions of immunity and emphasized its key role in
peace, unlike other scientists, who stressed on its role in war
[43]. It is quite symbolical that on May 30th 1909 he visited
author of “War and Peace” and spent that day in conversations
with L.N. Tolstoy.
Out of two thinkers, photographed together (Fig. 1), Tol-
stoy [44] wrote bitterly: “each human being has his own
peculiarities, and has his peculiar, his own, new, complex
disease; unknown to medicine . . . The field of medicine . . .
still remains a wilderness. In comparison with the deeds of
the organism itself, all that known medications can achieve
is like one per mille”. Another, Metchnikoff [45] was a little
bit more optimistic: “There is nothing unconceivable in the
world, but a lot of it is not understood so far”.
Acknowledgements
Authors are grateful to Prof. Osmo P. Hanninen, Editor-in
Chief for valuable advices during preparation of this article
and to Ms. Irina Nicolaevna Konashonok, senior lecturer of
St. Petersburg State University, Faculty of Philology – for
excellent help in preparation of this text.
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