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An Introduction to the Immune System and Vaccines
Published in Patricia G. Melloy, Viruses and Society, 2023
The use of sequencing techniques (ways to read the genetic code) and genome-wide analysis has greatly aided the process of finding an antibody that would work to block a pathogen, as well as candidate antigens that might work well in a vaccine. The approach of starting with a candidate structure or sequence first and then testing for the ability to induce an immune response is known as “reverse vaccinology” (Ahmed, Ellis, and Rappuoli 2017). One can examine all the potential antigens of the pathogen first, in a large-scale study, and select which antigens to test for vaccine development. Researchers emphasize that you may not even need to culture the pathogen in the lab with this approach, starting with computational analysis instead and then moving to working with recombinant pathogen proteins for testing in animal models (Del Tordello, Rappuoli, and Delany 2017). In addition, high throughput approaches have been used to identify all the antibodies produced in an immune response, “the antibody repertoire” (Ahmed, Ellis, and Rappuoli 2017). Not only has antibody repertoire analysis been used in vaccine development, but this approach has also been useful in studies of autoimmune diseases. One can identify potential “autoantigens,” which are proteins from one’s own body that are recognized abnormally by the immune system, and also the “autoantibodies” created by the immune system to treat and screen for autoimmune diseases (Robinson 2015).
Systemic Lupus Erythematosus
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Vaneet K. Sandhu, Neha V. Chiruvolu, Daniel J. Wallace
Despite the 2019 EULAR/ACR criteria heavily emphasizing ANA as the entry criterion for the diagnosis of SLE, a positive ANA can be found in up to 30% of the general population and in other autoimmune conditions such as scleroderma, rheumatoid arthritis, Sjögren’s syndrome, and mixed connective tissue disease. ANA has been heavily criticized for its poor specificity,10 and there is emerging investigation into autoantigen arrays. Proteome microarray-based technology has been utilized for years to identify biomarkers in many diseases. Autoantigen arrays are used to screen and identify interactions between antigens and antibodies on a large scale.11 One of the benefits of this technology is that antibodies can be detected at a level of less than 1 ng/ml. Small samples, close to 1–2 microliters, can be obtained from serum, body fluids, or cell culture supernatant. Antibodies that bind to corresponding antigens on the array are detected using a fluorophore conjugate of second antibodies against different isotypes of autoantibodies (IgG, IgM, IGA, IgE). One of the marvels of autoantibody arrays is their capacity to detect hundreds of thousands of autoantibodies quantitatively and even prior to clinical onset of disease, thereby serving as an early diagnostic tool. Furthermore, quantification of antibodies may be helpful in monitoring disease activity and response to treatment. Data obtained from these arrays have demonstrated greater sensitivity in comparison to enzyme-linked immunosorbent assay (ELISA).12
The Inducible System: Antigens
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
While it is generally the case that immunocompetent individuals do not respond to their own molecular structures, it is, unfortunately, not always true. Complex systems can be expected to fail on occasion. A pathological response to self-antigens is called autoimmunity, and the self-materials to which the response occurs are called autoantigens. The danger of autoimmune disease clearly led to the evolution of self-tolerance, in the very early 1900s, Ehrlich and Morgenroth proposed the existence of a “regulating contrivance” for the development of self-tolerance, an avoidance of self-reaction they called horror autotoxicus. Chapter 10 is specifically concerned with autoimmunity.
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).
IgG4-related disease: advances in pathophysiology and treatment
Published in Expert Review of Clinical Immunology, 2023
Francesco Peyronel, Paride Fenaroli, Federica Maritati, Nicolas Schleinitz, Augusto Vaglio
Many researchers have directed their efforts toward the identification of autoantigens that could trigger an autoimmune response, eventually leading to the development of IgG4-RD. In patients with an organ-limited IgG4-related autoimmune pancreatitis, several molecules have been identified as possible autoantigens (i.e. carbonic anhydrase [36,37], lactoferrin [37], pancreatic secretory trypsin inhibitor [38], plasminogen binding protein [39], amylase alpha-2A [40], annexin A11 [41], and laminin-511-E8 [42]). Only two studies examined self-reactive autoantibodies in patients with multi-organ IgG4-RD, identifying two more molecules, namely prohibitin [43] and galectin-3 [44]. However, these findings could not be generalized, since differences between the examined populations were detected: for example, autoantibodies against laminin-511-E8 were found in about half of the individuals of a Japanese cohort of patients affected by autoimmune pancreatitis [42], whereas the same self-reactive response was detected in only a minority of individuals belonging to a cohort from the United States [45]. The wide variety of molecules capable of enhancing a self-reactive immune response in IgG4-RD probably reflects the wide clinical heterogeneity hallmarking this disorder, particularly as regards the diversity of organs involved.
Plasma exchange as an adjunctive therapy in anti-neutrophil cytoplasm antibody-associated vasculitis
Published in Expert Review of Clinical Immunology, 2023
Kavita Gulati, Charles D Pusey
The underlying etiology of AAV is poorly understood; however, both genetic and environmental factors have been implicated. Genome-wide association studies have linked the presence of circulating PR3-ANCA with polymorphisms in HLA-DP, PRTN3 (which encodes proteinase 3) and SERPINA1 (which encodes α1-antitrypsin, a circulating inhibitor of PR3); similarly, the presence of MPO-ANCA has been associated with variations in HLA-DQ [48,49]. With respect to environmental precipitants, infection has been reported to trigger induction of AAV, and precipitate relapse [6,50,51]. Infectious agents may promote loss of tolerance by inducing autoantigen exposure through formation of NETs, or inducing autoimmunity through molecular mimicry. In addition, they can directly prime neutrophils for ANCA-induced activation [52,53]. Certain drugs, such as propylthiouracil, and exposure to silica have also been implicated in development of AAV [54–58].