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Systemic lupus erythematosus (SLE) is an autoimmune disease associated with hyperactive innate and adaptive immune systems that cause dermatological, cardiovascular, renal, and neuropsychiatric problems in patients. SLE's multifactorial nature and complex pathogenesis present significant challenges in its clinical classification. In addition, unpredictable treatment responses in patients emphasize the need for highly specific and sensitive SLE biomarkers that can assist in understanding the exact pathogenesis and, thereby, lead to the identification of novel therapeutic targets. Recent studies on microRNA (miRNA), a non-coding region involved in the regulation of gene expression, indicate its importance in the development of the immune system and thus in the pathogenesis of various autoimmune disorders such as SLE. miRNAs are fascinating biomarker prospects for SLE categorization and disease monitoring owing to their small size and high stability. In this paper, we have discussed the involvement of a wide range of miRNAs in the regulation of SLE inflammation and how their modulation can be a potential therapeutic approach. [ABSTRACT FROM AUTHOR]

Simple Summary: This article addresses the topic of primary immunodeficiencies, with particular emphasis on antibody deficiencies with near-normal immunoglobulin levels or hyperimmunoglobulinemia. This paper goes beyond genetics and emphasizes the importance of the immune system and particularly immune checkpoints and Epstein–Barr virus (EBV) reactivation in the context of these disorders. The article delves into the immune dysregulations occurring in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical picture of patients and, in the future, may contribute to the development of cancer, especially those related to hematological malignancies. Disturbances observed in the immunopathogenesis of the presented diseases go beyond the accepted scheme, with the development of PID largely associated only with genetic disorders, and the article emphasizes that the regulation of immunity and virus reactivation also contributes to the progression of PID. This study delves into the intricate landscape of primary immunodeficiencies, with a particular focus on antibody deficiencies characterized by near-normal immunoglobulin levels or hyperimmunoglobulinemia. Contrary to the conventional focus on genetic dysregulation, these studies investigate the key roles of immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, on selected subpopulations of T and B lymphocytes and their serum concentrations of soluble forms in patients recruited for the studies in healthy volunteers. In addition, the studies also show the role of Epstein–Barr virus (EBV) reactivation and interactions with tested pathways of immune checkpoints involved in the immunopathogenesis of this disease. By examining the context of antibody deficiencies, this study sheds light on the nuanced interplay of factors beyond genetics, particularly the immune dysregulations that occur in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical presentation of patients and may contribute to the development of cancer in the future, especially related to hematological malignancies. [ABSTRACT FROM AUTHOR]

Immunological memory can be regarded as the key aspect of adaptive immunity, i.e. a specific response to first contact with an antigen, which in mammals is determined by the properties of T, B and NK cells. Re-exposure to the same antigen results in a more rapid response of the activated specific cells, which have a unique property that is the immunological memory acquired upon first contact with the antigen. Such a state of immune activity is also to be understood as related to "altered behavior of the immune system" due to genetic alterations, presumably maintained independently of the antigen. It also indicates a possible alternative mechanism of maintaining the immune state at a low level of the immune response, "directed" by an antigen or dependent on an antigen, associated with repeated exposure to the same antigen from time to time, as well as the concept of innate immune memory, associated with epigenetic reprogramming of myeloid cells, i.e. macrophages and NK cells. Studies on Teleostei have provided evidence for the presence of immunological memory determined by T and B cells and a secondary response stronger than the primary response. Research has also demonstrated that in these animals macrophages and NK-like cells (similar to mammalian NK cells) are able to respond when re-exposed to the same antigen. Regardless of previous reports on immunological memory in teleost fish, many reactions and mechanisms related to this ability require further investigation. The very nature of immunological memory and the activity of cells involved in this process, in particular macrophages and NK-like cells, need to be explained. This paper presents problems associated with adaptive and innate immune memory in teleost fish and characteristics of cells associated with this ability. • The presence of adaptive and innate immune memory has been confirmed in fish. • Adaptive immune memory in fish develops with the participation of T and B lymphocytes. • Innate immune memory is related to the properties of macrophages and NK-like cells. • There is a need to further verify the biological basis of this property. [ABSTRACT FROM AUTHOR]

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease that is common in elderly people. Its classification in the spectrum of autoinflammatory and autoimmune diseases is difficult because of its only partially understood immune-mediated mechanisms. The literature concerning the innate and adaptive immune system activation in PMR was systematically reviewed highlighting the relative weight of autoinflammation and autoimmunity in its pathogenesis and disease progression. A literature search on PubMed Central and Embase scientific databases was performed by two independent reviewers. To be eligible, the studies needed to fully satisfy our initial PICO framework: a primary diagnosis of PMR as a population, the search for immune/inflammatory cells, cytokines and autoantibodies as an intervention, a control group consisting in healthy controls, patients with other inflammatory rheumatic diseases or PMR patients in remission after treatment and as outcomes the results of the investigations in the analyzed tissue samples. The most relevant data of the included papers were extracted by using a standardized template. Of the 933 screened abstracts, 52 papers were included in the systematic review and categorized depending on their primary research objectives. The hyper-activity of neutrophils and monocytes, expressing toll-like receptor 7 in active disease, an impaired phagocytosis and endothelial dysfunction, as well as an increased count of innate T cells in patients with remission emerged among the major derangements of the innate immune response in PMR. Among the cytokines profile, interleukin-6 plays a key role but other pro-inflammatory mediators and angiogenesis markers such as chemokines, B-cell activating factor, vascular endothelial growth factor and angiopoietins seem to be involved in refractory or glucocorticoid-resistant PMR. The aberrant adaptive immune response was documented by tissue and serum findings of polarized T cells towards T helper 1 and 17 phenotypes, an increased expression of immunosenescent surface markers and a downregulated immunoregulatory response. The altered distribution of peripheral B cells, detected during active disease, suggested their peripheral migration towards unidentified sites. The interaction between innate and adaptive immune response was documented by a synovial infiltrate of macrophages and T cells. Despite multiple autoantibodies have been detected in PMR patients, none proved to correlate with disease activity seeming to be reactive to the marked inflammation or antigenic determinants provided by environmental triggers or tissue/cell damage. The complex network between innate and adaptive immune system in PMR is supported by findings at molecular and cellular levels. By considering both the ends of the pathophysiological spectrum of immune-mediated rheumatic diseases, PMR may be regarded as an inflammatory immune-mediated disease with mixed mechanisms in a background of genetic and epigenetic factors together with immunological and endocrine senescence. • High concentrations of serum pro-inflammatory cytokines and cell growth factors identify active PMR patients • Innate immune cells might play a role both in PMR disease activity and sub-clinical ongoing inflammation. • T cells are dysregulated in PMR for a hyper-expression of immunosenescent markers and deficient immunoregulatory pathways. • B cells peripheral distribution is altered during active disease suggesting an inflammatory-driven compartmentalization. • Autoantibodies do not seem pathogenetic in PMR but may be reactive to external triggers or damaged tissues self-antigens. [ABSTRACT FROM AUTHOR]

It is currently postulated that steroid-sensitive idiopathic nephrotic syndrome (SSNS) and steroid-resistant idiopathic nephrotic syndrome (SRNS), which are not related to the mutation of a gene coding for podocyte structures or for glomerular basement membrane proteins, result from a circulating factor affecting podocyte shape and function. T lymphocytes have for a long time been suspected to be involved in the pathophysiology of these diseases. The successful treatment of steroid-dependant nephrotic syndrome with rituximab suggests a potential role for B lymphocytes. Clinical and experimental data indicate roles for cytokines IL-13, TNFα, circulating cardiotrophin-like cytokine factor 1 (member of the IL-6 family), circulating hemopexin, radical oxygen species, and the soluble urokinase-type plasminogen activator receptor (suPAR) in the development of nephrotic syndrome. Podocyte metabolism modifications-leading to the overexpression of the podocyte B7-1antigen (CD 80), hypoactivity of the podocyte enzyme sphingomyelin phosphodiesterase acid-like 3 b (SMPDL3b), and to the podocyte production of a hyposialylated form of the angiopoietin-like 4 (Angptl4)-are mechanisms possibly involved in the changes in the podocyte cytoskeleton leading to SSNS and or SRNS. Different multifactorial pathophysiological mechanisms can be advocated for SSNS and SRNS. The present paper reviews the experimental and clinical data upon which the different hypotheses are based and reports their possible clinical applications. [ABSTRACT FROM AUTHOR]

In this paper a detailed mathematical and physical model is presented in order to simulate the immune system using neural networks and non-linear circuits. This model allows us to understand the interaction between T-cells and B-cells which are produced in bone marrow and mature in thymus. The alterations of the biompedance of the immune system and the changes in the interaction between cells create immune diseases. [ABSTRACT FROM AUTHOR]

This paper deals with the interaction between dispersed cancer cells and the major populations of the immune system, namely, the T helper cells, T Cytotoxic cells, B cells, and antibodies produced. The system is described by a set of five ordinary differential equations. Both local and global stability of the system has been investigated. It has been observed that under appropriate conditions this interaction is capable of controlling the growth of these cancer cells. The analytical findings are supported by numerical and computational analytical methods. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is represents the most common chronic inflammatory joint disease and is still a major medical challenge because of unsolved issues related to the etiologic and pathogenetic questions. Intensive research has been conducted over the last years that focused on the inappropriate activation of the immune system: although T cells have long been deemed to play a central role in the origin and propagation of joint inflammation, data accumulated so far have widened this perspective recognizing the contribution of other cells, as well as the major histocompatibility complex class II proteins and a composite set of costimulatory signals responsible for the production of proinflammatory cytokines and other soluble mediators implicated in tissue destruction typical of the disease. This paper will provide an insight into the immune system in RA, dissecting cellular and humoral aspects both in serum and in synovium of patients. [ABSTRACT FROM AUTHOR]

Decisions by uncommitted cells to differentiate down one lineage pathway or another is fundamental to developmental biology. In the immune system, lymphocyte precursors commit to T- or B-cell lineages and T-cell precursors to CD4 or CD8 independently of foreign antigen. T and B cells must also decide whether or not to respond to antigen and when a response is initiated, what sort of response to make such as the type of antibody, CD4 or CD8, and CD4 Th1 or Th2. The two basic mechanisms for these decision-making processes are selection and instruction. Selection depends on prior stochastic production of precommitted cells, which are then selected to respond by an appropriate signal; for example, CD8 and CD4 responses selected by peptide presented in association with major histocompatibility complex class I or II. In contrast, instruction occurs when an uncommitted precursor embarks upon a differentiation pathway in response to a particular set of signals; for example, Th1 and Th2 lineage commitment. In this paper, the signals that determine Th1 and Th2 differentiation are examined with a mathematical model and shown to act as a bistable switch permitting either Tbet or Gata3 to be expressed in an individual cell but not both. The model is used to show how the Tbet Gata3 network within an individual cell interacts with cytokine signals between cells and suggests how Th1 and Th2 lineage commitment can become irreversible. These considerations provide an example of how mathematical models can be used to gain a better understanding of lymphocyte differentiation in an immune response.Immunology and Cell Biology (2007) 85, 300–305; doi:10.1038/sj.icb.7100060; published online 1 May 2007 [ABSTRACT FROM AUTHOR]