On the origin of immunopathology

Vaz, Nelson M.; Carvalho, Celso Morato de

doi:10.1016/j.jtbi.2014.06.006

Cited by 13 publications

(7 citation statements)

References 70 publications

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“…The italicized text of Figure 1 shows a hypothetical explanation of the events behind ME/CFS. A known function of microbes in the gut is to train, from within, the immune system to recognize and react correctly to microbes (including bacteria and viruses), which come from the outside ( 25 – 29 ). The correct reaction includes, among other things, anergy and unresponsiveness to microbial antigens that cross-react with self-antigens.…”

Section: Trying To Place It All Under One Umbrella: a Hypothesis For mentioning

confidence: 99%

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

Gottfries²,

et al. 2018

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Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.

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Section: Trying To Place It All Under One Umbrella: a Hypothesis For mentioning

confidence: 99%

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

Gottfries²,

et al. 2018

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“…The necessity of developing an appropriate conceptual immunological framework has been stated by various groups [ 31 , 38 ], but has been accompanied by significant challenges. Genome-wide transcription profiling in human sepsis has indicated that both pro- and anti-inflammatory mechanisms occur at various times over the course of sepsis [ 39 , 40 ], that a patient may cycle through each phase multiple times [ 41 ] and that the transition from infection with pathogen clearance over sepsis with organ failure to septic shock with death [ 42 ] calls for a unifying integrated hypothesis linking inflammation, energy metabolism, coagulopathy and organ dysfunction by studying the interaction between leukocytes, endothelial cells and platelets in a phenotype- and time-dependent design.…”

Section: Discussionmentioning

confidence: 99%

Integrative model of leukocyte genomics and organ dysfunction in heart failure patients requiring mechanical circulatory support: a prospective observational study

et al. 2017

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BackgroundThe implantation of mechanical circulatory support devices in heart failure patients is associated with a systemic inflammatory response, potentially leading to death from multiple organ dysfunction syndrome. Previous studies point to the involvement of many mechanisms, but an integrative hypothesis does not yet exist. Using time-dependent whole-genome mRNA expression in circulating leukocytes, we constructed a systems-model to improve mechanistic understanding and prediction of adverse outcomes.MethodsWe sampled peripheral blood mononuclear cells from 22 consecutive patients undergoing mechanical circulatory support device (MCS) surgery, at 5 timepoints: day −1 preoperative, and postoperative days 1, 3, 5, and 8. Clinical phenotyping was performed using 12 clinical parameters, 2 organ dysfunction scoring systems, and survival outcomes. We constructed a strictly phenotype-driven time-dependent non-supervised systems-representation using weighted gene co-expression network analysis, and annotated eigengenes using gene ontology, pathway, and transcription factor binding site enrichment analyses. Genes and eigengenes were mapped to the clinical phenotype using a linear mixed-effect model, with Cox models also fit at each timepoint to survival outcomes.ResultsWe inferred a 19-module network, in which most module eigengenes correlated with at least one aspect of the clinical phenotype. We observed a response of advanced heart failure patients to surgery orchestrated into stages: first, activation of the innate immune response, followed by anti-inflammation, and finally reparative processes such as mitosis, coagulation, and apoptosis. Eigengenes related to red blood cell production and extracellular matrix degradation became predictors of survival late in the timecourse corresponding to multiorgan dysfunction and disseminated intravascular coagulation.ConclusionsOur model provides an integrative representation of leukocyte biology during the systemic inflammatory response following MCS device implantation. It demonstrates consistency with previous hypotheses, identifying a number of known mechanisms. At the same time, it suggests novel hypotheses about time-specific targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-017-0288-8) contains supplementary material, which is available to authorized users.

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“…Various theories were proposed and largely debated among immunologists, mathematicians, and philosophers about the immune system organization and cognitive systems properties (Maturana 2002;Maturana and Varela 1980) (Perelson and Weisbuch 1997), (Vaz 2011) (Vaz and Carvalho 2015). From a defense machine war historically perceived since vaccination developed, a critical approach of the classical view of the immune system, was given by (Coutinho et al 1984) and Nelson Vaz (Vaz et al 2006).…”

Section: • Immunoception and Individuation Through The Dynamic Adaptimentioning

confidence: 99%

Individuation and the Organization in Complex Living Ecosystem: Recursive Integration and Self-assertion by Holon-Lymphocytes

Thomas‐Vaslin

2019

Acta Biotheor

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Individuation and organization in complex living multi-level ecosystem occurs as dynamical processes from early ontogeny. The notion of living "holon" displaying dynamic self-assertion and integration is used here to explain the ecosystems dynamic processes. The update of the living holon state according to the continuous change of the dynamic system allows for its viability. This is interpreted as adaptation, selection and organization by the human that observes the system at posteriori from its level. Our model concerns the complex dynamics of the adaptive immune system, integrating holon-lymphocytes that collectively preserve the identity and integrity of the organism. Each lymphocyte individualizes as a dynamic holon-lymphocyte, with somatic gene individuation leading to an individual, singular antigen immunoreceptor type, promoting the self-assertion. In turn, the "Immunoception" allows for perception of the environmental antigenic context, thus integration of the holon in its environment. The self-assertion/integration of holon-lymphocyte starts from fetal stages and is influenced by mother Lamarckian acquired historicity transmissions, a requisite for the integrity of the holobiont-organism. We propose a dynamic model of the perception by holon-lymphocyte, and at the supra-clonal level of the immune system functions that sustain the identity and integrity of the holon-holobiont organism.

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On the origin of immunopathology

Cited by 13 publications

References 70 publications

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

Integrative model of leukocyte genomics and organ dysfunction in heart failure patients requiring mechanical circulatory support: a prospective observational study

Individuation and the Organization in Complex Living Ecosystem: Recursive Integration and Self-assertion by Holon-Lymphocytes

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