AI and the Bioscience and Clinical Considerations for Immunology
Louis J. Catania in AI for Immunology, 2021
One other critical element to mention at the beginning of any immunology discussion is the intimate relationship between the science of immunology and genetics, a relationship referred to as immunogenics, immunogenetics, and immunogenomics. The immune system and its activity is effectively dictated and controlled by the human genome. AI is playing an enormous role in our better understanding of this complex relationship both in health and disease. Research and advances in our understanding of the immune system and autoimmune diseases, cancers, infectious diseases, and beyond are indelibly related to immunogenetics. As such, there will be a future volume in this “AI for Everything” series addressing genetics. In this volume on “AI for Immunology,” by necessity, there will be some discussion on genetics as related to immunogenetics.
HLA and autoimmunity
Irun R. Cohen in Perspectives on Autoimmunity, 2020
We will start the second part of this chapter with a question: What has immunogenetics to offer for the prevention or treatment of autoimmune diseases? This question may be answered by using the HLA class I and II Ir genes just described as an example. The aim of the immunogenetic approach to an autoimmune disease is to unravel the following chain of events: polymorphic Ir-genes (1) contain the information for Ir gene products (2) which regulate the immune response and differ among individuals. These differences lead to differences in immune reactivity among individuals (3), which in their turn cause differential susceptibility to or expression of autoimmune diseases (4). Possibilities for intervention at each level (1 through 4) are feasible and may lead to preventive or therapeutic applications. The power of this approach lies particularly in the use of Ir gene differences among healthy individuals as a probe for a mechanism leading to autoimmune disease, in a similar way as the study of immune-deficient individuals led to a better insight into how the immune system prevents disease. The potential usefulness of this approach is illustrated in several animal models discussed in other chapters of this book (Chapters 11 and 12). Here we will discuss the state of the art in humans.
Mite Allergens
Richard F. Lockey, Dennis K. Ledford in Allergens and Allergen Immunotherapy, 2014
Molecular genetic studies about the influence of specific genes and genetic variants on the control of the IgE response began with the discovery of the major histocompatibility complex (MHC). Following the pioneering research developed by McDevitt and Benacerraf in the field of immunogenetics of immune related diseases, specialists worked together in several International Histocompatibility Workshops and individual projects trying to find associations between MHC genes and the IgE response to allergens derived from many different sources, including dust mites. D. Marsh was the first to demonstrate strong associations between class II MHC molecules and the IgE response to allergens, particularly ragweed, and promoted the search for more genes in other chromosomal regions. After a long period of exploration of the entire genome, where many associations were found (not all confirmed) between variants (usually SNPs) and IgE response to allergens, the genetic reasons for the predisposition to overreact against the apparently innocuous natural molecules remains an enigma. One of the important aspects of these investigations is their relation to the question why a molecule is an allergen, since it seems that the IgE response of the genetically predisposed host (and not any particular intrinsic property of the molecules) is the main determinant of whether or not a molecule is an allergen.
Therapeutic blockade of CXCR2 rapidly clears inflammation in arthritis and atopic dermatitis models: demonstration with surrogate and humanized antibodies
Published in mAbs, 2020
Md Jahangir Alam, Liang Xie, Caroline Ang, Farnaz Fahimi, Stephen B. Willingham, Andrew J. Kueh, Marco J. Herold, Charles R. Mackay, Remy Robert
Total cellular RNA was extracted from 5 × 106 hybridoma cells using TRIzol reagent (Invitrogen) and poly-A+ RNA was isolated from total cellular RNA using the Oligotex mRNA mini kit (Qiagen, Vic., Australia). Single-stranded (ss) cDNA was produced by reverse-transcription of RNA using the Omniscript reverse transcriptase kit (Qiagen). Reactions contained 500 ng of poly-A+ RNA and 10 pmol of isotype-specific anti-sense oligonucleotide primer (CH1-γ and CL-κ cDNA). A poly-G tail was appended to the 3ʹ-end of ss-cDNA using terminal transferase (NEB, MA, USA). Double-stranded cDNA was generated by PCR using Vent polymerase (NEB) with the poly-C anchor and CH-γ or CL-κ specific primers. The VH and VL genes were sequenced and analyzed by the IMGT® databases (the international ImMunoGeneTics information system®, http://www.imgt.org).
Polymeric nanostructure vaccines: applications and challenges
Published in Expert Opinion on Drug Delivery, 2020
Rosana Simón-Vázquez, Mercedes Peleteiro, África González-Fernández
Some dextran derivatives have also associated immunogenic properties, such as the case of dextran sulfate (DS). The presence of the sulfate groups, confers a highly negative charge to this polysaccharide, that allows the accommodation and controlled release of positively charged molecules [28]. It has also been attributed to activate cellular and humoral immunity [52,53]. In fact, oral administration in mice induced acute and chronic colitis through the activation of Th1 and Th2 cytokines [54]. Yet, the molecular weight of DS influences cell activation [55]. In skin hypersensitive test, high molecular weight DS was a potent adjuvant to induce suppression of cell-mediated delayed-type hypersensitivity immune responses in mice and guinea pigs when administered s.c. in the same place than the irritant [53,56]. On the other hand, the genetic background on T cell proliferation influences the DS-mediated immune response. While Th1-polarization in C57BL/6 mice confers them sensitivity to DS-induced colitis, a Th2/Th17/Treg-polarized immunity protects the BALB-C mice strain against the challenge [57]. In summary, the DS immunogenicity seems to be dependent on the polymer characteristics, the administration route, and on immunogenetics, among other factors.
The regulatory capacity of B cells directs the aggressiveness of CLL
Published in OncoImmunology, 2019
Audrey Mohr, Marie Cumin, Cristina Bagacean, Pierre Pochard, Christelle Le Dantec, Sophie Hillion, Yves Renaudineau, Christian Berthou, Adrian Tempescul, Hussam Saad, Jacques-Olivier Pers, Anne Bordron, Christophe Jamin
The immunoglobulin variable heavy chain (IgVH) gene mutation status was determined after PCR amplification and sequencing based on the BIOMED-2 consortium guidelines.50100ng of genomic DNA isolated with the BioSprint 15 DNA Blood kit (Qiagen), 0.25µl of Ampli Taq Gold DNA Polymerase (Applied Biosystem), 10pmol of each primer, 0.2mM dNTP Mix, 1.5mM MgCl2, 1x PCR Buffer II, and water adjusted to 50µl were used to perform the multiplex PCR amplifications. PCR products were controlled through 2% agarose gel, purified with ExoSAP-IT PCR product cleanup kit (Affymetrix, High Wycombe, United Kingdom) and sequenced with a Big Dye Terminator v3.1 cycle sequencing kit (Applied Biosystem). Results were analyzed with the database IMGT/HighV-Quest (The international ImMunoGeneTics information system, Montpellier).51 A homology sequence >98% defined an un-mutated status.
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