Immune Subsystem Research Articles

Single-cell Spatial Phenotyping of Immune and Metabolic Landscapes in Systemic Lupus Erythematosus

Abstract Autoimmune diseases like systemic lupus erythematosus (SLE) affect the health of multiple organ systems including the central nervous system, skin, joints, and kidneys. The heterogeneity of clinical profiles observed with SLE reflects a complex dysregulation of cellular processes, including metabolism, apoptotic clearance, and inflammation. Diagnosis and treatment of SLE is thus challenging, and few new treatments have been approved over the past 60 years. In this study, we aimed to characterize the spatial immune and metabolic profiles of SLE at single cell resolution. To do so, we profiled a cohort of human FFPE SLE tissues with an ultrahigh-plex panel of >50 oligo-conjugated antibodies representing immune, apoptotic, metabolic and stress markers. Whole-slide, spatial phenotyping was performed using the PhenoCycler ®-Fusion system, followed by deep bioinformatic analyses to determine the cellular phenotypes, spatial neighborhoods, and metabolic determinants of SLE. By combining immune cell lineage information with expression of key proteins involved in glycolysis, amino acid metabolism, lipid metabolism, hypoxia, oxidative stress, and apoptosis, we elucidated the functional dysregulation in key immune subsystems that may contribute to development of autoimmunity and inflammation associated with SLE. Spatial phenotyping also revealed a high degree of inter- and intra-sample heterogeneity, confirming the complexity of the SLE clinical profile. Collectively, our data amount to new insights into metabolic reprogramming of immune cells in autoimmune diseases and may aid in the identification of novel therapeutic biomarkers within the tissue microenvironment of SLE patients.

Immunologic Roles of Hyaluronan in Dermal Wound Healing.

Hyaluronic acid (HA), a glycosaminoglycan ubiquitous in the skin, has come into the limelight in recent years for its role in facilitating dermal wound healing. Specifically, HA’s length of linearly repeating disaccharides—in other words, its molecular weight (MW)—determines its effects. High molecular weight (HMW)-HA serves an immunosuppressive and anti-inflammatory role, whereas low molecular weight (LMW)-HA contributes to immunostimulation and thus inflammation. During the inflammatory stage of tissue repair, direct and indirect interactions between HA and the innate and adaptive immune systems are of particular interest for their long-lasting impact on wound repair. This review seeks to synthesize the literature on wound healing with a focus on HA’s involvement in the immune subsystems.

Features of the condition of the neuroendocrine-immune complex in different constellations of entropies of morpho-functional immune subsystems in rats

Background. We have previously shown that the Entropy (E) of the Thymocytogram (T), Splenocytogram (S) as well as Leukocytogram (L) and Immunocytogram (I) of the blood in rats are virtually independent of each other. The purpose of this study was to clarify the characteristics of the condition of the neuroendocrine-immune complex in different constellations of E(s) of these four morpho-functional immune subsystems. Materials and methods. Experiment was performed on 108 healthy Wistar rats (48 male and 60 female) weighing 240-290 g divided into 8 groups. Animals of the first group remained intact. Instead, the other rats received various balneofactors for 6 days. The day after the completion of the drinking/application course the parameters of neuroendocrine-immune complex were registered. Results. The method of cluster analysis created four homogeneous groups of rats, significantly different from each other in the constellation of E of four morpho-functional immune subsystems. The members of the first cluster (n=31) are characterized by elevated levels of E (Z±SE) of I (1,12±0,16), T (1,00±0,14) and L (0,88±0,12) at the normal E level of S (0,14±0,16). The members of the second cluster (n=21) are characterized by reduced E level of L (-1,59±0,16) in combination with increased levels of I (0,80±0,17) and T (0,81±0,15) at the normal E level of S (0,13±0,16). A characteristic feature of the members of the third cluster (n=28) is reduced E of T (-1,01±0,17) at normal E levels of S (-0,33±0,23), I (-0,19± 0,14 ) and L (0,35±0,20). The last cluster (n=28) is characterized by reduced E of I (-1,36± 0,14), while the E of other immune subsystems are at the borderline levels: L (-0,52±0,16), S (0,49±0,15), T (0,60±0,15). The method of discriminant analysis revealed 15 parameters of the neuroendocrine-immune complex, the set of which four clusters of Entropies differ from each other with an accuracy of 95%. Conclusion. Each constellation of independent Entropies of the thymocytogram, splenocytogram, immunocytogram and leukocytogram is accompanied by a specific constellation of parameters of the neuroendocrine-immune complex which indicates their natural functional relationships.

Entropies of thymocytogram, splenocytogram, immunocytogram and leukocytogram in rats are regulated by sex and the neuroendocrine parameters while regulates immune parameters

Background. We have previously shown that the Entropy (E) of the relative spectral power density (SPD) of the EEG rhythms is its quite relevant parameter. We also found significant relationships between the SPD E of individual EEG loci and the E of the Leukocytogram (LCG) and Immunocytogram (ICG) of the blood, as well as with their individual components. The purpose of this study was to clarify the relationships between E(s) of these four morpho-functional immune subsystem and sex as well as parameters of the neuroendocrine-immune complex in rats. Materials and methods. Experiment was performed on 108 healthy Wistar rats (48 male and 60 female) weighing 205-300 g (M±SD=260±26 g) divided into 8 groups. Animals of the first group remained intact, using tap water from drinking ad libitum. Instead, the other rats received various balneofactors for 6 days. The day after the completion of the drinking/application course in all rats the parameters of neuroendocrine-immune complex were registered. Results. The drinking/application course did not affect the E level of any morpho-functional immune subsystem, the relationships between which are insignificant. Females have less E TCG than males, whereas sexual dimorphism is insignificant for E SCG and ICG and absent for E LCG. The canonical correlation of mediocre force (R=0,675) between sex index (M=1;F=2) and neuro-endocrine parameters (HRV, calcitonin, parathyroid and mineralocorticoid activities, corticosterone plasma, 17-KS urine) was revealed. Factors linked to female sex upregulates nine immune parameters (R=0,630), while downregulates nine others (R=0,678). The neuroendocrine constellation (testosterone plasma, HRV, calcitonin, parathyroid and mineralocorticoid activities) is associated with the constellation of entropies (R=0,533). Entropy of a single morpho-functional immune subsystem is associated with a certain constellation of immune parameters. In particular, E SCG with 12 (R=0,721), E TCG with 9 (R=0,615), E ICG with 8 (R=0,586), E LCG with 12 (R=0,631). Conclusion. Entropies of thymocytogram, splenocytogram, immunocytogram and leukocytogram in rats are regulated by sex and the neuroendocrine factors while regulates immune parameters.

Autoimmunity in acute ischemic stroke and the role of blood-brain barrier: the dark side or the light one?

This article presents a synopsis of the current data on the mechanisms of blood-brain barrier (BBB) alteration and autoimmune response in acute ischemic stroke. Most researchers confirm the relationship between the severity of immunobiochemical changes and clinical outcome of acute ischemic stroke. Ischemic stroke is accompanied by aseptic inflammation, which alters the brain tissue and exposes the co-stimulatory molecules of the immune system and the neuronal antigens. To date, BBB is not considered the border between the immune system and central nervous system, and the local immune subsystems are found within and behind the BBB. BBB disruption contributes to the leakage of brain autoantigens and induction of secondary autoimmune response to neuronal antigens and long-term inflammation. Glymphatic system function is altered and jeopardized both in hemorrhagic and ischemic stroke types. The receptors of innate immunity (toll-like receptor-2 and toll-like receptor-4) are also involved in acute ischemia-reperfusion injury. Immune response is related to the key processes of blood clotting and fibrinolysis. At the same time, the stroke-induced immune activation may promote reparation phenomena in the brain. Subsequent research on the reduction of the acute ischemic brain injury through the target regulation of the immune response is promising.

Host-based intrusion detection systems adapted from agent-based artificial immune systems

Agent-based artificial immune system (ABAIS) is adopted to intrusion detection system (IDS). An agent-based IDS (ABIDS) inspired by the danger theory of human immune system is proposed. Multiple agents are embedded to ABIDS, where agents coordinate one another to calculate mature context antigen value (MCAV) and update activation threshold for security responses. The intelligence behind ABIDS is based on the danger theory and the functionalities of dendritic cells in human immune systems, while dendritic cells agents (DC agent) are emulated for innate immune subsystem and artificial T-cell agents (TC agent) are for adaptive immune subsystem. Antigens are profiles of system calls while corresponding behaviors are regarded as signals. This ABIDS is based on the dual detections of DC agents for signals and TC agents for antigens. ABAIS is an intelligent system with learning and memory capabilities. According to MCAVs, immune response to malicious behaviors is activated by either computer host or Security Operating Center. Accordingly, computer hosts met with malicious intrusions can be effectively detected by input signals and temporary output signals such as PAMP, danger and safe signals.

The Evolution and Regulation of the Mucosal Immune Complexity in the Basal Chordate Amphioxus

Both amphioxus and the sea urchin encode a complex innate immune gene repertoire in their genomes, but the composition and mechanisms of their innate immune systems, as well as the fundamental differences between two systems, remain largely unexplored. In this study, we dissect the mucosal immune complexity of amphioxus into different evolutionary-functional modes and regulatory patterns by integrating information from phylogenetic inferences, genome-wide digital expression profiles, time course expression dynamics, and functional analyses. With these rich data, we reconstruct several major immune subsystems in amphioxus and analyze their regulation during mucosal infection. These include the TNF/IL-1R network, TLR and NLR networks, complement system, apoptosis network, oxidative pathways, and other effector genes (e.g., peptidoglycan recognition proteins, Gram-negative binding proteins, and chitin-binding proteins). We show that beneath the superficial similarity to that of the sea urchin, the amphioxus innate system, despite preserving critical invertebrate components, is more similar to that of the vertebrates in terms of composition, expression regulation, and functional strategies. For example, major effectors in amphioxus gut mucous tissue are the well-developed complement and oxidative-burst systems, and the signaling network in amphioxus seems to emphasize signal transduction/modulation more than initiation. In conclusion, we suggest that the innate immune systems of amphioxus and the sea urchin are strategically different, possibly representing two successful cases among many expanded immune systems that arose at the age of the Cambrian explosion. We further suggest that the vertebrate innate immune system should be derived from one of these expanded systems, most likely from the same one that was shared by amphioxus.

Fundamentals of vaccine immunology

From a literature review of the current literature, this article provides an introduction to vaccine immunology including a primer on the components of the immune system, passive vs. active immunization, the mechanism(s) by which immunizations stimulate(s) immunity, and the types of vaccines available. Both the innate and adaptive immune subsystems are necessary to provide an effective immune response to an immunization. Further, effective immunizations must induce long-term stimulation of both the humoral and cell-mediated arms of the adaptive system by the production of effector cells and memory cells. At least seven different types of vaccines are currently in use or in development that produce this effective immunity and have contributed greatly to the prevention of infectious disease around the world.

A Computational Model of Oncogenesis using the Systemic Approach

A new theoretical model of oncogenesis that incorporates a systemic view of biodynamics was developed and analyzed. According to our model, the emergent behavior at the cell population level is the result of nonlinear interactions between the neoplastic and immune subsystems. Our approach allows subsequent extensions of the model to span multiple levels of biological organization. The model opens the possibility of a flexible connection between the molecular and tissue level descriptions of oncogenesis.

Functional and phenotypic analysis of lymphocytes isolated from human intestinal mucosa.

It is now well established that immunocytes in mucosal organs, including the gastrointestinal tract, form a relatively autonomous immune subsystem, with specialized adaptations appropriate for the particular microenviron-ment (1,2). The main regulatory cells of the immune system are T lymphocytes; however, little is known about T cell regulation at the gut mucosa. Previous studies on immunoglobulin (Ig) production of lamina propria lymphocytes (LPL) have shown IgA to be the dominant Ig isotype (3–5).