Immune Paradigm Research Articles

Disease tolerance: concept and mechanisms.

Two distinct defense strategies provide a host with survival to infectious diseases: resistance and tolerance. Resistance is dependent on the ability of the host to kill pathogens. Tolerance promotes host health while having a neutral to positive impact of pathogen fitness. Immune responses are almost inevitably defined in terms of pathogen resistance. Recent evidence has shown, however, that several effects attributed to activation of innate and adaptive immune mechanisms, cannot be readily explained with the paradigm of immunity as effectors of microbial destruction. This review focuses on integrating the concept of disease tolerance into recent studies of immune system function related to the regulation and resolution of tissue damage, T cell exhaustion, and tolerance to innocuous antigen.

Leprosy As a Complex Infection: Breakdown of the Th1 and Th2 Immune Paradigm in the Immunopathogenesis of the Disease.

Leprosy is a chronic infectious disease whose evolution involves complex immune mechanisms of the host that influence the clinical presentation of the disease. For many years, the main interpretation of the host defense response was based on characterization of the established immune paradigm between T helper (Th) 1 and Th2 lymphocytes. However, with advances in the knowledge of immunology, new approaches have emerged along with the development of new immunological pathways that have changed the interpretation of the long-established paradigm of the polar forms of the disease, especially with the identification of new subtypes of T lymphocytes such as Th9, Th17, Th22, and Tregs. Thus, this review discusses the role of these new subtypes of T helper lymphocytes and how the development of the immune response of these cells modifies the pattern of the Th1/Th2 response in the immunopathogenesis of leprosy.

Development of an Artificial Immune System for Power Plant Abnormal Condition Detection, Identification, and Evaluation

In this paper, the artificial immune system paradigm is used to develop a computational scheme for the detection, identification, and evaluation of abnormal operation of advanced power plants. The self/non-self generation relies on a novel approach consisting of partitioning the Universe and representing clusters as integer strings that can be produced and used with reduced computational effort. The design of the proposed scheme utilizes a positive-selection-type approach combined with a dendritic cell mechanism. The methodology is demonstrated using a high performance model of the acid gas removal unit implemented in Dynsim® that is part of the power plant simulation environment available at West Virginia University AVESTAR Center. Fourteen different abnormal conditions have been considered including solid deposits and leakages occurring at typical locations throughout the system. The proposed monitoring scheme provides excellent performance in terms of false alarm and detection, identification, and evaluation rates.

Immunity-based accommodation of aircraft subsystem failures

PurposeThis paper aims to describe the design, development and flight-simulation testing of an artificial immune-system-based approach for accommodation of different aircraft sub-system failures/damages.Design/methodology/approachThe approach is based on building an artificial memory, which represents self- (nominal conditions) and non-self (abnormal conditions) within the artificial immune system paradigm. Self- and non-self are structured as a set of memory cells consisting of measurement strings, over pre-defined time windows. Each string is a set of features values at each sample time of the flight. The accommodation algorithm is based on the cell in the memory that is the most similar to the in-coming measurement. Once the best match is found, control commands corresponding to this match are extracted from the memory and used for control purposes.FindingsThe results demonstrate the possibility of extracting pilot compensatory commands from the self/non-self structure and capability of the artificial-immune-system-based scheme to accommodate an actuator malfunction, maintain control and complete the task.Research limitations/implicationsThis paper concentrates on investigation of the possibility of extracting compensatory pilot commands. This is a preliminary step toward a more comprehensive solution to the aircraft abnormal condition accommodation problem.Practical implicationsThe results demonstrate the effectiveness of the proposed approach using a motion-based flight simulator for actuator and sensor failures.Originality/valueThis research effort is focused on investigating the use of the artificial immune system paradigm for control purposes based on a novel methodology.

Is Immunity a Historical Concept?: Medical and Juridical Immunity in the European Enlightenment

The inoculation of smallpox was the major topic that connected the late eighteenth-century Italian proponents of the Enlightenment and the new Romantic movement. From Parini to Manzoni, from Giovanni Bicetti to Carlo Porta, both the Illuministi and the Romantics were active proponents of vaccination and wrote poems to celebrate it. Despite their intellectual and medical engagement with immunization, however, neither group attempted to transform vaccination into a political trope. In the context of the rise of Italian nationalism, despite the abundance of biopolitical metaphors, there is a surprising, notable lack of an immunity paradigm. My paper looks at the history of the rise of the Italian Intellectuals' interest in vaccination and analyzes the creation of Italian nationalist tropes in Manzoni and in the Romantic movement, and it tries to discuss the reasons behind their lack of interest of immunization as a political trope.

Cellular immune responses in red blood cell alloimmunization.

In excess of 340 blood group antigens have now been described that vary between individuals. Thus, any unit of blood that is nonautologous represents a significant dose of alloantigen. Most blood group antigens are proteins, which differ by a single amino acid between donors and recipients. Approximately 1 out of every 70 individuals are transfused each year (in the United States alone), which leads to antibody responses to red blood cell (RBC) alloantigens in some transfusion recipients. When alloantibodies are formed, in many cases, RBCs expressing the antigen in question can no longer be safely transfused. However, despite chronic transfusion, only 3% to 10% of recipients (in general) mount an alloantibody response. In some disease states, rates of alloimmunization are much higher (eg, sickle cell disease). For patients who become alloimmunized to multiple antigens, ongoing transfusion therapy becomes increasingly difficult or, in some cases, impossible. While alloantibodies are the ultimate immune effector of humoral alloimmunization, the cellular underpinnings of the immune system that lead to ultimate alloantibody production are complex, including antigen consumption, antigen processing, antigen presentation, T-cell biology, and B-cell biology. Moreover, these cellular processes differ to some extent with regard to transfused RBCs as compared with other better-studied immune barriers (eg, infectious disease, vaccines, and solid organ transplantation). The current work focuses on illustrating the current paradigm of humoral immunity, with a specific focus on particulars of RBC alloimmunization and recent advances in the understanding thereof.

Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient.

Vertebrates are endowed with a closed circulatory system, the evolution of which required novel structural and regulatory changes. Furthermore, immune cell trafficking paradigms adapted to the barriers imposed by the closed circulatory system. How did such changes occur mechanistically? We propose that spatial compartmentalization of the lipid mediator sphingosine 1-phosphate (S1P) may be one such mechanism. In vertebrates, S1P is spatially compartmentalized in the blood and lymphatic circulation, thus comprising a sharp S1P gradient across the endothelial barrier. Circulatory S1P has critical roles in maturation and homeostasis of the vascular system as well as in immune cell trafficking. Physiological functions of S1P are tightly linked to shear stress, the key biophysical stimulus from blood flow. Thus, circulatory S1P confinement could be a primordial strategy of vertebrates in the development of a closed circulatory system. This review discusses the cellular and molecular basis of the S1P gradients and aims to interpret its physiological significance as a key feature of the closed circulatory system.

Artificial Dendritic Cell Algorithm for Advanced Power System Monitoring

The functionality of dendritic cells, as part of the biological immune system, exhibits significant capabilities for class discrimination, pattern recognition, data processing, and information structuring and storage. These properties provide the basis for developing biomimetic techniques for monitoring and control of complex dynamic systems and processes. In this paper, a novel artificial dendritic cell algorithm in conjunction with the hierarchical multi-self strategy is developed within the artificial immune system paradigm to support advanced power plant health management. The proposed algorithm is addressing the specific characteristics of modern power plants, which include complexity, multidimensionality, and high coupling. The self/non-self representing the power plant is defined as a set of lower dimensional projections corresponding to the constituent sub-systems and capturing their inter-connections. The artificial dendritic cell is defined as a computational unit that collects the outcomes of the self/non-self discrimination process produced by all projections, structures and stores information, and presents it to the system health monitoring logic for abnormal condition detection and identification. The functionality of the proposed algorithm is illustrated using the self for an acid gas removal unit by detecting the occurrence of several abnormal conditions and identifying the affected sub-systems. Excellent detection and identification performance is obtained in terms of detection time, false alarms, detection rate, and identification rate for all cases considered. It is concluded that the proposed approach can potentially represent an effective and efficient tool for complex system health monitoring.

Comparison of immunity-based schemes for aircraft failure detection and identification

In this paper, two approaches are proposed and compared for the detection and identification of aircraft subsystem failures based on the artificial immune system paradigm combined with the hierarchical multiself strategy. The first approach relies on the heuristic ranking of lower order self/non-self projections and the generation of selective immunity identifiers through structuring of the non-self. The second approach is based on an information processing algorithm inspired by the functionality of the dendritic cells. The artificial dendritic cell is defined as a computational unit that centralizes, fuses, and interprets information from the multiple selves to produce a unique detection and identification outcome. A hierarchical multi-self strategy is used with both approaches considering 2-dimensional self/non-self projections or subselves. A mathematical formulation of the concepts and detailed implementation algorithms are presented. The proposed methodologies are demonstrated and compared using simulation data for a supersonic fighter from a motion-based flight simulator at nominal conditions, under failures of actuators, malfunction of sensors, and wing damage. In all cases considered, both detection and identification schemes achieve excellent detection and identification rates with practically no false alarms.

Abstract A01: Innate lymphoid cells (ILCs) in murine melanoma: A new paradigm in cancer immunity

Abstract Introduction: Innate lymphoid cells (ILCs), have emerged as novel important immune effector cells, playing a critical role also in tumor immune-surveillance. Recently, it was shown that the number of ILCs in patients with different types of cancer is significantly reduced after chemotherapy/radiotherapy as compared to healthy donors. However, so far, no data on ILC frequency, subset distribution and function in patients with melanoma are available. Therefore, we analyzed the frequency, subset distribution and function of ILCs in a murine model of melanoma with/without treatment, a parameter that is of paramount importance to understand the role of ILCs during melanoma and to assess the impact of current treatments on this type of cancer. Methods: C57/BL6 mice were injected with B16F10 murine melanoma cell line (1 x 106 cells/mouse, subcutaneous). Tumor growth monitored. Once tumors reached 12mm in size, the mice were sacrificed and tumor cells subjected to flow-cytometry and cell culture to identify the ILC subclasses in the tumor. Results: Our findings establish, for the first time in melanoma at diagnosis, base-line reference values for ILC frequency and function, as well as the ILC subtype distribution. Conclusion: Our studies extend previously published work on changes in innate lymphoid cells. Our findings will help better understanding of tumor microenvironment and its interaction with immune system. These values indicate the potential of ILCs as crucial players in the treatment of cancer, specifically melanoma. Citation Format: Blake Christianson, James Walker, Marsha Kocherla, Xu Qin, Jack C. Yu, Babak Baban. Innate lymphoid cells (ILCs) in murine melanoma: A new paradigm in cancer immunity. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A01.

Tissue-Resident T Cells as the Central Paradigm of Chlamydia Immunity.

For almost 2 decades, results from Chlamydia pathogenesis investigations have been conceptualized using a cytokine polarization narrative. Recent viral immunity studies identifying protective tissue-resident memory T cells (Trm) suggest an alternative paradigm based on localized immune networks. As Chlamydia vaccines enter the preclinical pipeline and, in the case of an attenuated trachoma vaccine, are given to human subjects, it may be useful to ask whether cytokine polarization is the appropriate framework for understanding and evaluating vaccine efficacy. In this review, we revisit C. trachomatis pathogenesis data from mice and humans using a Trm narrative and note a comfortable concordance with the Chlamydia pathogenesis literature.

Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine.

Viruses that infect the intestine include major human pathogens (retroviruses, noroviruses, rotaviruses, astroviruses, picornaviruses, adenoviruses, herpesviruses) that constitute a serious public health problem worldwide. These viral pathogens are members of a large, complex viral community inhabiting the intestine termed "the enteric virome." Enteric viruses have intimate functional and genetic relationships with both the host and other microbial constituents that inhabit the intestine, such as the bacterial microbiota, their associated phages, helminthes, and fungi, which together constitute the microbiome. Emerging data indicate that enteric viruses regulate, and are in turn regulated by, these other microbes through a series of processes termed "transkingdom interactions." This represents a changing paradigm in intestinal immunity to viral infection. Here we review recent advances in the field and propose new ways in which to conceptualize this important area.

Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines.

Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV.

Smallpox and Dracunculiasis: The Scientific Value of Infectious Diseases That Have Been Eradicated or Targeted for Eradication. Is Schistosomiasis Next?

Smallpox and Dracunculiasis: The Scientific Value of Infectious Diseases That Have Been Eradicated or Targeted for Eradication. Is Schistosomiasis Next?

Natural Killer T cell subsets in eutopic and ectopic endometrium: a fresh look to a busy corner.

Invariant Natural Killer T cells (iNKT) are a specialized subset of T cells that use their T cell receptor to recognize self and foreign lipids presented by CD1d as cognate antigens. iNKT have been shown to have either protective or harmful roles in many pathological states, including microbial infection, autoimmune disease, allergic disease and cancer. Accumulating evidence seems to suggest that this unique T cell subset combines both classically innate and adaptive immunologic characteristic. Considering these recent data, the aim of work was to review the current knowledge about iNKT in eutopic and ectopic endometrium. Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Currently, the immune paradigm of reproduction is gradually changing shape: recent data confirmed that cytokine milieu influences the development and plasticity of different subtype of mononuclear cells, and in turn it can be influenced by the cytokine production of the latter. Among the different NKT cell populations, the recently characterized iNKT seems to share actions typical both of innate and adaptive immunity, being capable of secreting Th1 as well as Th2 cytokine pattern. Moreover, several subtypes of iNKT were identified, who partially express the same master transcription factors of the corresponding T cells counterpart. Although the data about iNKT's actions in eutopic and ectopic endometrium are still scarce, it is possible to hypothesize that future investigation can shed light on this point, thus allowing a better knowledge about the regulation of these two microenvironments.

A hybrid swarm intelligence of artificial immune system tuned with Taguchi–genetic algorithm and its field-programmable gate array realization to optimal inverse kinematics for an articulated industrial robotic manipulator

This article presents a hybrid swarm intelligence of artificial immune system tuned with Taguchi–genetic algorithm and its field-programmable gate array realization to optimal inverse kinematics for a 5-degree-of-freedom industrial robotic manipulator using system-on-a-programmable-chip technology. This hybridization strategy with a Taguchi–genetic algorithm parameter tuner improves the performance in conventional artificial immune system paradigms. The field-programmable gate array realization of the proposed artificial immune system tuned with Taguchi–genetic algorithm is more effective in practice for real-world embedded applications. This system-on-a-programmable-chip–based artificial immune system tuned with Taguchi–genetic algorithm is then applied to the optimal inverse kinematics redundancy solver of a 5-degree-of-freedom robotic manipulator. The optimal joint configuration is obtained by minimizing the pre-defined affinity function in artificial immune system tuned with Taguchi–genetic algorithm for real-world embedded robotics application. The experimental results and comparative works are presented to show the effectiveness and merit of the proposed system-on-a-programmable-chip–based artificial immune system tuned with Taguchi–genetic algorithm intelligent inverse kinematics redundancy solver for a 5-degree-of-freedom industrial robotic manipulator. This system-on-a-programmable-chip–based artificial immune system tuned with Taguchi–genetic algorithm solver outperforms the conventional solvers, such as geometric solvers, Jacobian-based solvers, hybrid genetic algorithm solvers, and particle swarm optimization solvers.

Simplified Estimation Algorithms for Aircraft Structural Damage Effects Using an Artificial Immune System

The development of simplified models for the estimation of flight envelope reduction under damages to aircraft structural components, within the artificial immune system paradigm, is presented in this paper. The proposed methodology is part of a comprehensive and integrated framework for aircraft abnormal condition detection, identification, evaluation, and accommodation aimed at ensuring aircraft high survivability rates and operation safety. An artificial immune system built through simulation for a fighter aircraft is used in conjunction with a hierarchical multi-self strategy for estimating ranges of flight envelope relevant variables under structural damages affecting the wing, the horizontal tail, and the vertical tail. Flight envelope ranges are predicted when the lift-generating capabilities of the main aerodynamic surfaces are reduced, based on algorithms that are tailored to the nature and characteristics of the failure and 2-dimensional self projections. The performance of the proposed approach is evaluated using ad-hoc metrics and demonstrated successfully through simulation tests in a motion-based flight simulator.

Allogenic benefit in stem cell therapy: cardiac repair and regeneration.

Stem cell (SC)-based therapies are a developing mean to repair, restore, maintain, or enhance organ functioning through life span. They are in particular a fast track to restore function in failing heart. Various types of SCs have been used in experimental and clinical studies showing the potential of these cells to revolutionize the treatment of heart diseases. Autologous cells have been privileged to overpass immunological barriers. The field has progressed tremendously and the hurdles, which have been largely overlooked in the excitement over the expected benefit the immunogenicity, have been revealed. Also, manufacturing of patient-specific clinical grade SC product, whether adult stem or reprogrammed induced pluripotent SCs, and the availability of these cells in sufficient amounts and status when needed is questionable. In contrast, adult SCs derived from healthy donors, thus allogeneic, have the advantage to be immediately available as an 'off-the-shelf' therapeutic product. The challenge is to overcome the immunological barriers to their transplantation. Recent research provided new insights into the mode of action and immune behavior of SCs in autologous as well as allogeneic settings. Lessons are learned and immune paradigms are changing: allogenicity, if balanced could be part of the dynamic and durable mechanisms that are critical to sustain cardiac regeneration and repair. We discuss the hurdles, lessons, and advances accomplished in the field through the progressive journey of cardiac-derived stem/progenitor cells toward allogeneic cardiac regenerative/reparative therapy.

Immunotherapy Approaches in Cancer Treatment.

Tumor immune surveillance paradigm presumes that most pre-malignant cells or early malignant lesions can be eliminated (or at least controlled) by cells of the immune system. A critical feature that distinguishes advanced tumors from early neoplastic lesions is their capability to evade immune control. As a consequence, vast majority of clinically evident (advanced) tumors are poorly immunogenic. The principle goal of immunotherapy is thus a resurrection of the patient's inefficient or suppressed immune system so that it would once again become capable of launching sustained cytolytic attacks against tumor cells, which would ideally result in total and permanent eradication of cancer. Such activation of patient's anticancer immunity, however, can be achieved by strikingly different ways. This current review discusses diverse innovative immunotherapy approaches, which in the last 20 years achieved miraculous successes in the ever-lasting battle against cancer, including cytokine-based immunotherapy approaches, therapeutic monoclonal antibodies and their derivatives, cancer vaccines, and cell-based immunotherapy approaches.

Evaluation of Aircraft Sensor Failures Effects Using the Artificial Immune System Paradigm

This paper presents the development of simple models for the assessment of flight envelope reduction under aircraft sensor failures within the artificial immune system paradigm. The proposed methodology is expected to facilitate the design of on-board augmentation systems increasing aircraft survivability and improving operation safety. It demonstrates and exploits the capability of the artificial immune system to not only detect and identify aircraft subsystem abnormal conditions but also evaluate their impact and consequences. An artificial immune system built through simulation for a fighter aircraft is used in conjunction with a hierarchical multi-self strategy for estimating ranges of flight envelope relevant variables at post-failure conditions affecting angular rate sensors that are needed within the control augmentation system. Failure-specific algorithms correlated with the characteristics and dimensionality of self projections are developed for roll, pitch, and yaw rate sensors affected by bias. Metrics for the performance evaluation of the proposed approach are defined and used for successful demonstration in a motion-based flight simulator.