The Lymphatic/Immune System and Its Disorders
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss in Understanding Medical Terms, 2020
The objective of the immune system is to identify and remove foreign invasion. The body, however, is capable of developing antibodies and sensitized lymphocytes directed against components normally present in the individual. Autoimmunity (immunity to one's self) leads to a number of conditions, depending on the tissues to which the immune system reacts. For example, systemic lupus erythematosus (SLE) is a connective tissue disorder that presents with skin eruptions, arthralgia, leukopenia, and other symptoms. Autoimmunity is generally implicated by the presence of hypergammaglobulinemia (excess of gamma globulins). Other diseases with an autoimmune component include rheumatoid arthritis and autoimmune thyroiditis.
Hematopoietic Stem Cell Biology
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
Animal models have been helpful in better understanding the biology of both hematopoietic stem cells (HSC) and autoimmunity. Autoimmunity is caused by a complex interplay of genetic and environmental factors. Spontaneous animal models of autoimmunity result from germ-line mutations; these include the lpr/lpr mouse as a model for arthritis and vasculitis,1 the NOD (nonobese diabetic) mouse for diabetes, and the NZB/W mouse for systemic lupus erythematosus.2 Although studies of murine susceptibility genes are likely to provide insights into the genetic mechanisms involved in the human predisposition to autoimmunity, these models differ significantly from most cases of human autoimmune disease. Spontaneous animal models with germ-line mutations virtually always develop autoimmunity, while only a fraction of individuals who harbor susceptibility genes develop autoimmunity; there are rare exceptions to this, such as patients with the autoimmune lymphoproliferative syndrome (ALPS), who, like lpr/lpr mice, inherit loss-of-function mutations of the Fas gene (refer to Chapter 17).3,4 Induced animal models of autoimmunity focus on the role of environmental factors in the development of autoimmunity.2 These animal models more closely approximate most cases of human autoimmunity, and have the advantage over spontaneous models in that the onset and progression of the disease can be controlled (refer to Chapters 29 and 30).
Immunopathology
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Cross-reactivity of antigens borne by infectious agents with self antigens has been documented in many instances. For example, antibodies against the M protein in the cell walls of certain strains of β-hemolytic group A streptococci cross-react with antigens in the myocardium and in the glomerular basement membrane. This cross-reactivity may form the basis of rheumatic heart disease and post-streptococcal glomerulonephritis. A similar cross-reactivity between topoisomerase and the UL70 protein of cytomegalovirus has recently been observed. Antibodies against topoisomerase are found in the majority of patients with scleroderma. The association of an immune response to CMV and scleroderma has yet to be established. Antibodies reacting with DNA, IgG, and cardiolipin have been found in patients with tuberculosis and Klebsiella infections. Idiotypes associated with autoantibodies may also be found in large amounts in the sera of patients with certain infections. The relationship between these findings and autoimmunity in general remain to be determined. It is possible that cross-reacting foreign antigen “mimics” a self-antigen and may be capable of stimulating autoreactive clones and breaking tolerance.
Beyond the amyloid hypothesis: how current research implicates autoimmunity in Alzheimer’s disease pathogenesis
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Miyo K. Chatanaka, Dorsa Sohaei, Eleftherios P. Diamandis, Ioannis Prassas
The immune system is a sophisticated organ that orchestrates the fight against foreign pathogens. The B cells of the humoral response of the adaptive immune system, showcase an almost infinite number of different receptors that can bind to pathogenic molecules, leading to their eventual destruction [1]. As explained in detail previously [2], B cells undergo a selection process in the thymus that filters out any cells that cannot distinguish “self” from “non-self” antigens. The T cells of the cell-mediated arm of adaptive immunity undergo a similar process in the thymus that establishes a central tolerance by eliminating naive T cells with T cell receptors (TCRs) that recognize “self” antigens [3,4]. In addition, any autoreactive T cells that escape thymic selection are further subjected to clonal anergy, deletion, and ignorance, and regulatory T cells (Tregs) assist in the tight regulation of these dangerous B and T cells [3]. Through various processes and physiological aging, however, this intricate system frequently deteriorates and the regenerative capacity of the organs that create immune cells progressively reduces their functional capabilities (see [5,6]). This allows for autoantibodies (antibodies directed against self-antigens) to initiate a chain reaction that leads to misdirected and harmful immune responses [7]. Therefore, autoimmunity is a biological process whereby the organism loses its immune tolerance and mounts attacks against self-antigens (autoantigens).
Prospects for CAR T cell immunotherapy in autoimmune diseases: clues from Lupus
Published in Expert Opinion on Biological Therapy, 2022
Marko Radic, Indira Neeli, Tony Marion
Approximately one in 14 people will, sometime during their lifetime, experience one of the known autoimmune disorders [1]. Autoimmunity arises in myriad ways and results in strikingly different pathologies. Dozens of clinical diagnoses for autoimmune disorders are possible and include familiar ones, such as rheumatoid arthritis, multiple sclerosis, type I diabetes, psoriasis, and immune vasculitis, as well as dozens of less frequent autoimmune diseases or syndromes [2]. The defining signs of many autoimmune diseases give clues to the targets of autoimmunity. Autoimmune reactivity thus defines many of the most characteristic features of autoimmune disorders. Destruction of islet cells in the pancreas leads to the insulin insufficiency of diabetes [3], the attack on myelin sheaths of neurons results in the neuropathology of multiple sclerosis [4], and the destruction of cartilage and bone contorts articular joints in rheumatoid arthritis [5]. Mechanisms of autoimmunity may involve the sudden appearance of autoantibodies, the activation of self-reactive cytotoxic T cells, the induction of self-sustaining, chronic inflammation, or a combination of contributing factors that overlap at different stages of pathogenesis in these disorders [6]. Manifestations of each autoimmune disease may be further modified by intrinsic factors or environmental contributions [2].
Evaluation of Expression of LRBA and CTLA-4 Proteins in Common Variable Immunodeficiency Patients
Published in Immunological Investigations, 2022
Fereshte Salami, Saba Fekrvand, Reza Yazdani, Sepideh Shahkarami, Gholamreza Azizi, Yasser Bagheri, Samaneh Delavari, Sahar Shariati, Seyed Alireza Mahdaviani, Mohammamd Nabavi, Afshin Shirkani, Hassan Abolhassani, Morteza Samadi, Asghar Aghamohammadi
In the present case-control study, all newly diagnosed patients (during 2018–2019) with CVID who were under clinical follow up based on the national consensus management for PID (Abolhassani et al. 2019b, 2018) at Children’s Medical Center (Pediatrics Center of Excellence) were enrolled. The diagnosis of CVID was made according to the newest criteria proposed by the European Society for Immunodeficiencies (ESID) (Seidel et al. 2019). At least one of the following should be manifested in the patient; increased susceptibility to infection, autoimmunity, granulomatous disease, unexplained polyclonal lymphoproliferation, or an affected family member with antibody deficiency, together with a marked decrease of IgG and IgA with or without low IgM, and poor antibody response to vaccines or low switched memory B cells in individuals more than four years old. Also, secondary causes of hypogammaglobulinemia should be excluded, and there should be no evidence of profound T-cell deficiency. CVID patients with infection, only phenotype were not recruited for further steps (Tak Manesh et al. 2017). The autoimmunity diagnosis was made by an immunologist and a subspecialist related to the affected organ based on the previously published clinical and laboratory diagnostic criteria (Azizi et al. 2017b). Age and sex-matched healthy individuals were included as the control group. This study was confirmed by the Ethics Committee of the Tehran University of Medical Sciences, and written informed consent was obtained from all the cases and/or children’s parent(s).
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