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Journal articles on the topic 'Immune diversification'

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Author: Grafiati

Published: 10 December 2022

Last updated: 28 January 2023

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1

Sercarz, Eli E. "Immune focusing vs diversification and their connection to immune regulation." Immunological Reviews 164, no. 1 (August 1998): 5–10. http://dx.doi.org/10.1111/j.1600-065x.1998.tb01202.x.

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2

Radic, Marko Z., and Moncef Zouali. "Receptor Editing, Immune Diversification, and Self-Tolerance." Immunity 5, no. 6 (December 1996): 505–11. http://dx.doi.org/10.1016/s1074-7613(00)80266-6.

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3

de Villartay, Jean-Pierre, Alain Fischer, and Anne Durandy. "The mechanisms of immune diversification and their disorders." Nature Reviews Immunology 3, no. 12 (December 2003): 962–72. http://dx.doi.org/10.1038/nri1247.

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4

Borkowsky, William, Elizabeth J. McFarland, Ram Yogev, Yonghua Li, and Paul Harding. "Correlation of HIV-Specific Immunity, Viral Control, and Diversification following Planned Multiple Exposures to Autologous HIV in a Pediatric Population." Clinical and Vaccine Immunology 18, no. 10 (August 3, 2011): 1628–31. http://dx.doi.org/10.1128/cvi.05176-11.

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ABSTRACTRepeated controlled exposure to autologous virus was previously shown to result in increased CD8 T lymphocyte response to HIV antigens and accompanying reduction in viremia. We attempted to see if this immunity contributed to virologic control by correlating the immune response with quasispecies envelope diversification, an indicator of immune selection. The greatest diversification was seen in those with the greatest reduction in viremia but was unrelated to the frequency of Env-specific gamma interferon-producing cells. There was a trend toward correlation between the response to multiple HIV antigens and diversification.

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5

Milstein, C. "From antibody structure to immunological diversification of immune response." Science 231, no. 4743 (March 14, 1986): 1261–68. http://dx.doi.org/10.1126/science.3080810.

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6

Mamula, Mark J., and Charles A. Janeway. "Do B cells drive the diversification of immune responses?" Immunology Today 14, no. 4 (April 1993): 151–52. http://dx.doi.org/10.1016/0167-5699(93)90274-o.

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7

Hughes, Austin L. "Natural selection and the diversification of vertebrate immune effectors." Immunological Reviews 190, no. 1 (December 2002): 161–68. http://dx.doi.org/10.1034/j.1600-065x.2002.19012.x.

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8

Veillette, André. "Introduction: Signaling and signal diversification in antigen‐specific immune cells." Immunological Reviews 291, no. 1 (August 12, 2019): 5–7. http://dx.doi.org/10.1111/imr.12795.

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9

Pasquier, Louis Du. "Germline and somatic diversification of immune recognition elements in Metazoa." Immunology Letters 104, no. 1-2 (April 2006): 2–17. http://dx.doi.org/10.1016/j.imlet.2005.11.022.

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10

Wang, C., M. A. Bogue, D. B. Roth, and K. Meek. "Normal junctional diversification of immune receptors in p53-deficient mice." Journal of Immunology 159, no. 2 (July 15, 1997): 757–62. http://dx.doi.org/10.4049/jimmunol.159.2.757.

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Abstract One of the strategies that the immune system utilizes to generate Ab and TCR diversity is programmed imprecision of coding joint formation. This is accomplished by both nucleotide loss and random nucleotide addition (N segments) to the termini of immune receptor coding segments before resolution. Although it has been known for more than a decade that terminal deoxynucleotidyl transferase is the enzyme responsible for N segment addition, the enzymes responsible for nucleotide loss have not been identified. Recently, the p53 tumor suppressor protein was shown to have an intrinsic exonuclease activity; we reasoned that p53 as an exonuclease might be responsible for coding end processing during V(D)J recombination. Thus, we examined nucleotide loss from Ig and TCR-beta coding joints in mice lacking p53. We find no significant difference in the degree of nucleotide loss in coding joints isolated from these animals as compared with littermate controls. Thus, we conclude that p53 does not play a role in removal of nucleotides from coding termini during V(D)J recombination. Additionally, recent evidence has surfaced suggesting that p53 may play an important checkpoint role in early thymocyte differentiation. More specifically, it has been suggested that p53 is required to prevent thymocytes from maturing to the double-positive stage in the absence of a functionally rearranged TCR-beta allele. Our data suggest that TCR-beta selection is not affected in p53-deficient, V(D)J rearrangement-proficient mice.

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11

Teale, J. M. "B cell immune repertoire diversifies in a predictable temporal order in vitro." Journal of Immunology 135, no. 2 (August 1, 1985): 954–58. http://dx.doi.org/10.4049/jimmunol.135.2.954.

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Abstract The appearance of functional, antigen-specific B cells was studied in an in vitro fetal organ culture system in the absence of environmental influences associated with circulation and cell migration. In this way the B cell diversification process could be analyzed when genetic influences were dominating. By using this system in combination with the splenic focus assay, the frequency of developing B cells responsive to a number of hapten probes was measured. The results indicate that B cell diversification in vitro, in the apparent absence of many environmental influences, results in the appearance of antigen-responsive B cells in a predictable, temporal order. The results suggest that the acquisition of the expressed repertoire to a large extent is genetically controlled.

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12

Smith, L. C. "Diversification of innate immune genes: lessons from the purple sea urchin." Disease Models & Mechanisms 3, no. 5-6 (March 30, 2010): 274–79. http://dx.doi.org/10.1242/dmm.004697.

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13

Essajee, Shaffiq M., Ram Yogev, Henry Pollack, Bryan Greenhouse, Keith Krasinski, and William Borkowsky. "Recombinant Glycoprotein Vaccines for Human Immunodeficiency Virus-Infected Children and Their Effects on Viral Quasispecies." Clinical and Vaccine Immunology 9, no. 1 (January 2002): 79–82. http://dx.doi.org/10.1128/cdli.9.1.79-82.2002.

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ABSTRACT In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversification of the viral envelope in 12 HIV-infected children who received placebo or RGP vaccines. At baseline, 11 of 12 patients had multiple viral variants. On follow-up 6 months later, children who had a strong vaccine-associated lymphoproliferative immune response showed less viral diversification than those in whom the immune response was weak or absent. These results suggest that the immune response elicited by RGP vaccines does not exert a significant selection pressure on the viral quasispecies and therefore may not be helpful in changing the course of the disease.

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14

Milstein, Cesar. "From the structure of antibodies to the diversification of the immune response." Bioscience Reports 5, no. 4 (April 1, 1985): 275–97. http://dx.doi.org/10.1007/bf01116899.

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15

Milstein, Cesar. "From the Structure of Antibodies to the Diversification of the Immune Response." Bioscience Reports 24, no. 4-5 (August 10, 2004): 280–301. http://dx.doi.org/10.1007/s10540-005-2735-6.

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16

Pilosof, Shai, Sergio A. Alcalá-Corona, Tong Wang, Ted Kim, Sergei Maslov, Rachel Whitaker, and Mercedes Pascual. "The network structure and eco-evolutionary dynamics of CRISPR-induced immune diversification." Nature Ecology & Evolution 4, no. 12 (October 19, 2020): 1650–60. http://dx.doi.org/10.1038/s41559-020-01312-z.

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17

MILSTEIN, CEESAR. "From the Structure of Antibodies to the Diversification of the Immune Response." Scandinavian Journal of Immunology 37, no. 4 (April 1993): 386–98. http://dx.doi.org/10.1111/j.1365-3083.1993.tb03309.x.

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18

Milstein, C. "From the structure of antibodies to the diversification of the immune response." EMBO Journal 4, no. 5 (May 1985): 1083–92. http://dx.doi.org/10.1002/j.1460-2075.1985.tb03744.x.

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19

Nunez, Natalia, Louis Réot, and Elisabeth Menu. "Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?" Vaccines 9, no. 6 (June 1, 2021): 584. http://dx.doi.org/10.3390/vaccines9060584.

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Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant’s microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother–fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant’s microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant’s health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.

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20

Chien, N. C., R. R. Pollock, C. Desaymard, and M. D. Scharff. "Point mutations cause the somatic diversification of IgM and IgG2a antiphosphorylcholine antibodies." Journal of Experimental Medicine 167, no. 3 (March 1, 1988): 954–73. http://dx.doi.org/10.1084/jem.167.3.954.

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The genetic mechanism responsible for the somatic diversification of two mAbs was determined. The two PC-binding hybridomas were representative of events early and late in the immune response. The P28 cell line that produces an IgM antibody and thus represents events early in the immune response, was found to have 3 bp changes in its heavy chain variable (VH) region, with some changes in antibody affinity or specificity. The RP93 cell line that produces an IgG2a antibody and thus represents later events in the immune response, was found to have 9 bp changes in its VH region resulting in decreased affinity for PC and altered specificity. Oligonucleotides specific for linked base changes in the second hypervariable regions of both of these antibodies were used to look for previously undescribed V regions or other donor sequences that could have been responsible for these base changes. Since no donor sequences were found, we have concluded that somatic point mutation rather than gene conversion, V region replacement or the expression of an unidentified germline VH region gene is truly responsible for at least some of the somatic diversification of these antibodies.

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21

Winstead, Candace R., Shi-Kang Zhai, Periannan Sethupathi, and Katherine L. Knight. "Antigen-Induced Somatic Diversification of Rabbit IgH Genes: Gene Conversion and Point Mutation." Journal of Immunology 162, no. 11 (June 1, 1999): 6602–12. http://dx.doi.org/10.4049/jimmunol.162.11.6602.

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Abstract During T cell-dependent immune responses in mouse and human, Ig genes diversify by somatic hypermutation within germinal centers. Rabbits, in addition to using somatic hypermutation to diversify their IgH genes, use a somatic gene conversion-like mechanism, which involves homologous recombination between upstream VH gene segments and the rearranged VDJ genes. Somatic gene conversion and somatic hypermutation occur in young rabbit gut-associated lymphoid tissue and are thought to diversify a primary Ab repertoire that is otherwise limited by preferential VH gene segment utilization. Because somatic gene conversion is rarely found within Ig genes during immune responses in mouse and human, we investigated whether gene conversion in rabbit also occurs during specific immune responses, in a location other than gut-associated lymphoid tissue. We analyzed clonally related VDJ genes from popliteal lymph node B cells responding to primary, secondary, and tertiary immunization with the hapten FITC coupled to a protein carrier. Clonally related VDJ gene sequences were derived from FITC-specific hybridomas, as well as from Ag-induced germinal centers of the popliteal lymph node. By analyzing the nature of mutations within these clonally related VDJ gene sequences, we found evidence not only of ongoing somatic hypermutation, but also of ongoing somatic gene conversion. Thus in rabbit, both somatic gene conversion and somatic hypermutation occur during the course of an immune response.

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22

Schick, Alana, and Rees Kassen. "Rapid diversification of Pseudomonas aeruginosa in cystic fibrosis lung-like conditions." Proceedings of the National Academy of Sciences 115, no. 42 (October 1, 2018): 10714–19. http://dx.doi.org/10.1073/pnas.1721270115.

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Chronic infection of the cystic fibrosis (CF) airway by the opportunistic pathogen Pseudomonas aeruginosa is the leading cause of morbidity and mortality for adult CF patients. Prolonged infections are accompanied by adaptation of P. aeruginosa to the unique conditions of the CF lung environment, as well as marked diversification of the pathogen into phenotypically and genetically distinct strains that can coexist for years within a patient. Little is known, however, about the causes of this diversification and its impact on patient health. Here, we show experimentally that, consistent with ecological theory of diversification, the nutritional conditions of the CF airway can cause rapid and extensive diversification of P. aeruginosa. Mucin, the substance responsible for the increased viscosity associated with the thick mucus layer in the CF airway, had little impact on within-population diversification but did promote divergence among populations. Furthermore, in vitro evolution recapitulated traits thought to be hallmarks of chronic infection, including reduced motility and increased biofilm formation, and the range of phenotypes observed in a collection of clinical isolates. Our results suggest that nutritional complexity and reduced dispersal can drive evolutionary diversification of P. aeruginosa independent of other features of the CF lung such as an active immune system or the presence of competing microbial species. We suggest that diversification, by generating extensive phenotypic and genetic variation on which selection can act, may be a key first step in the development of chronic infections.

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23

Willmann, Katharina L., Sara Milosevic, Siim Pauklin, Kerstin-Maike Schmitz, Gopinath Rangam, Maria T. Simon, Sarah Maslen, et al. "A role for the RNA pol II–associated PAF complex in AID-induced immune diversification." Journal of Experimental Medicine 209, no. 11 (September 24, 2012): 2099–111. http://dx.doi.org/10.1084/jem.20112145.

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Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions.

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24

Strout, Matthew P., Naomi Philip, and David G. Schatz. "Regulation of the Mutation Threshold During Immune Diversification by Activation Induced Cytidine Deaminase,." Blood 118, no. 21 (November 18, 2011): 3244. http://dx.doi.org/10.1182/blood.v118.21.3244.3244.

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Abstract Abstract 3244 Activation-induced cytidine deaminase (AID) is expressed in germinal center B cells and is required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes. AID converts cytosine to uracil and resulting U-G mismatches are subsequently processed by low-fidelity base excision and mismatch repair pathways to yield point mutations (for SHM) and DNA strand breaks (for CSR). Under normal conditions, genotoxic stressors activate DNA damage response pathways that result in DNA repair or cell cycle arrest and apoptosis. However, in normal germinal center B cells, key DNA damage checkpoint factors such as ATR, p53 and p21 are repressed by the germinal center transcriptional repressor BCL6. BCL6 thus creates a permissive environment to allow the accumulation of mutations within the Ig loci. However, in addition to this fundamental role in immune diversification, aberrant targeting of AID contributes to point mutations and translocations of proto-oncogenes associated with B cell malignancy. Indeed, the combined effect of BCL6 and AID poses a direct threat to genomic integrity but the mechanism responsible for regulating the mutation threshold in germinal center B cells is not understood. To determine if B cells have a mechanism for down-regulating AID activity in response to genotoxic stress, we subjected the Ramos-A23 cell line to continuous low-dose exposure to several genotoxic agents. Ramos-A23 is a Burkitt lymphoma line that constitutively expresses AID and mutates the Ig heavy chain variable region with high frequency. Mutation frequency can be monitored by flow cytometry through loss of surface expression of IgM (due to AID-dependent nonsense and missense mutations) and by direct sequencing of the variable region. IgM+ Ramos-A23 cells were maintained in continuous culture in the presence or absence of etoposide (100 nM), cytarabine (5 nM), 5-azacytidine (10 nM), or trichostatin A (15 nM). Drug concentrations were titrated to the highest dose that would minimally affect proliferation or survival when compared with untreated cells. After 4 weeks in culture, untreated clones were 20–22% IgM-, consistent with ongoing SHM. In contrast, clones treated with the DNA damaging agents etoposide or cytarabine were only 4–6% IgM- (p<0.0001). Cells treated with the epigenetic modifiers 5-azacytidine or trichostatin A were 15–19% IgM-. Sequence analysis of the Ig variable region (3 clones from each group) demonstrated 6.2 and 3.8-fold reductions in mutation frequency in cells treated with etoposide and cytarabine, respectively, when compared with untreated cells. The mutation frequency in the cells treated with epigenetic modifiers did not differ significantly from untreated controls. This suggests that while epigenetic stress has little effect on SHM, genotoxic stress leads to a significant reduction in AID activity. It has previously been demonstrated that genotoxic stress leads to an ATM-dependent down-regulation of BCL6, a finding that we also observed in our model. In addition, we found that genotoxic stress causes a dose and time-dependent decrease in AID protein and transcript levels, thus explaining the decrease in SHM in our system. Like BCL6, repression of AID by genotoxic stress was inhibited by pre-treating the cells with the ATM inhibitor KU-55933. Further analysis of markers of B cell differentiation revealed up-regulation of IRF4 and Blimp1 with complete down-regulation of PAX5 (a transcriptional regulator of AID) in response to genotoxic stress. Lentiviral expression of BCL6 shRNA in Ramos cells also lead to down-regulation of AID and SHM, consistent with the observation that BCL6-deficient B cells do not undergo SHM. It has also recently been demonstrated that DNA damage in germinal center B cells leads to ATM-dependent inactivation of the CREB transcriptional co-activator CRTC2 with subsequent down-regulation of CRTC2 target genes, including AID. Altogether, these data suggest that, during the germinal center response, a mutation threshold recognized by ATM leads to repression of the SHM machinery and reprogramming to facilitate B cell maturation. Additional investigation is needed to further define the critical steps in this regulatory pathway and how it might breakdown during the pathogenesis of B cell malignancy. Disclosures: No relevant conflicts of interest to declare.

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25

Dubreuil, Géraldine, Emeline Deleury, Didier Crochard, Jean-Christophe Simon, and Christine Coustau. "Diversification of MIF immune regulators in aphids: link with agonistic and antagonistic interactions." BMC Genomics 15, no. 1 (2014): 762. http://dx.doi.org/10.1186/1471-2164-15-762.

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26

Flores-Kossack, C., R. Montero, B. Köllner, and K. Maisey. "Chilean aquaculture and the new challenges: Pathogens, immune response, vaccination and fish diversification." Fish & Shellfish Immunology 98 (March 2020): 52–67. http://dx.doi.org/10.1016/j.fsi.2019.12.093.

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27

George, Julia, Kevin M. Sheehan, Peter H. Brodeur, and J. Latham Claflin. "Junctional diversification in the generation of the precursor of a discrete immune response." Molecular Immunology 30, no. 4 (March 1993): 395–402. http://dx.doi.org/10.1016/0161-5890(93)90069-n.

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28

Weller, Sandra, Maria Mamani-Matsuda, Capucine Picard, Corinne Cordier, Damiana Lecoeuche, Frédéric Gauthier, Jean-Claude Weill, and Claude-Agnès Reynaud. "Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants." Journal of Experimental Medicine 205, no. 6 (June 2, 2008): 1331–42. http://dx.doi.org/10.1084/jem.20071555.

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T cell–dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell–independent responses. We used this dissociation to analyze the repertoire diversification of IgM+IgD+CD27+ B cells (also known as “IgM memory” B cells), comparing these cells with switched B cells in children <2 yr of age, with the aim of determining whether these two subsets are developmentally related. We show that the repertoire of IgM+IgD+CD27+ B cells in the spleen and blood displays no sign of antigen-driven activation and expansion on H-CDR3 spectratyping, despite the many antigenic challenges provided by childhood vaccinations. This repertoire differed markedly from those of switched B cells and splenic germinal center B cells, even at the early stage of differentiation associated with μ heavy chain expression. These data provide evidence for the developmental diversification of IgM+IgD+CD27+ B cells, at least in very young children, outside of T cell–dependent and –independent immune responses.

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Antonia, Alejandro L., Alyson B. Barnes, Amelia T. Martin, Liuyang Wang, and Dennis C. Ko. "Variation in Leishmania chemokine suppression driven by diversification of the GP63 virulence factor." PLOS Neglected Tropical Diseases 15, no. 10 (October 28, 2021): e0009224. http://dx.doi.org/10.1371/journal.pntd.0009224.

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Leishmaniasis is a neglected tropical disease with diverse outcomes ranging from self-healing lesions, to progressive non-healing lesions, to metastatic spread and destruction of mucous membranes. Although resolution of cutaneous leishmaniasis is a classic example of type-1 immunity leading to self-healing lesions, an excess of type-1 related inflammation can contribute to immunopathology and metastatic spread. Leishmania genetic diversity can contribute to variation in polarization and robustness of the immune response through differences in both pathogen sensing by the host and immune evasion by the parasite. In this study, we observed a difference in parasite chemokine suppression between the Leishmania (L.) subgenus and the Viannia (V.) subgenus, which is associated with severe immune-mediated pathology such as mucocutaneous leishmaniasis. While Leishmania (L.) subgenus parasites utilize the virulence factor and metalloprotease glycoprotein-63 (gp63) to suppress the type-1 associated host chemokine CXCL10, L. (V.) panamensis did not suppress CXCL10. To understand the molecular basis for the inter-species variation in chemokine suppression, we used in silico modeling to identify a putative CXCL10-binding site on GP63. The putative CXCL10 binding site is in a region of gp63 under significant positive selection, and it varies from the L. major wild-type sequence in all gp63 alleles identified in the L. (V.) panamensis reference genome. Mutating wild-type L. (L.) major gp63 to the L. (V.) panamensis sequence at the putative binding site impaired cleavage of CXCL10 but not a non-specific protease substrate. Notably, Viannia clinical isolates confirmed that L. (V.) panamensis primarily encodes non-CXCL10-cleaving gp63 alleles. In contrast, L. (V.) braziliensis has an intermediate level of activity, consistent with this species having more equal proportions of both alleles. Our results demonstrate how parasite genetic diversity can contribute to variation in immune responses to Leishmania spp. infection that may play critical roles in the outcome of infection.

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Yin, Xiangyun, Shuting Chen, and Stephanie C. Eisenbarth. "Dendritic Cell Regulation of T Helper Cells." Annual Review of Immunology 39, no. 1 (April 26, 2021): 759–90. http://dx.doi.org/10.1146/annurev-immunol-101819-025146.

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As the professional antigen-presenting cells of the immune system, dendritic cells (DCs) sense the microenvironment and shape the ensuing adaptive immune response. DCs can induce both immune activation and immune tolerance according to the peripheral cues. Recent work has established that DCs comprise several phenotypically and functionally heterogeneous subsets that differentially regulate T lymphocyte differentiation. This review summarizes both mouse and human DC subset phenotypes, development, diversification, and function. We focus on advances in our understanding of how different DC subsets regulate distinct CD4+ T helper (Th) cell differentiation outcomes, including Th1, Th2, Th17, T follicular helper, and T regulatory cells. We review DC subset intrinsic properties, local tissue microenvironments, and other immune cells that together determine Th cell differentiation during homeostasis and inflammation.

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de la Casa-Esperón, Elena. "From mammals to viruses: the Schlafen genes in developmental, proliferative and immune processes." BioMolecular Concepts 2, no. 3 (June 1, 2011): 159–69. http://dx.doi.org/10.1515/bmc.2011.018.

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AbstractThe Schlafen genes have been associated with proliferation control and with several differentiation processes, as well as with disparate phenotypes such as immune response, embryonic lethality and meiotic drive. They constitute a gene family with widespread distribution in mammals, where they are expressed in several tissues, predominantly those of the immune system. Moreover, horizontal transfer of these genes to orthopoxviruses suggests a role of the viral Schlafens in evasion to the host immune response. The expression and functional studies of this gene family will be reviewed under the prism of their evolution and diversification, the challenges they pose and the future avenues of research.

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32

Lauterbach, Henning, Phi Truong, and Dorian B. McGavern. "Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification." Virology Journal 4, no. 1 (2007): 53. http://dx.doi.org/10.1186/1743-422x-4-53.

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33

Milstein, Cesar. "From the Structure of Antibodies to the Diversification of the Immune Responce (Noble Lecture)." Angewandte Chemie International Edition in English 24, no. 10 (October 1985): 816–26. http://dx.doi.org/10.1002/anie.198508161.

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34

Kaetzel, Charlotte S. "Coevolution of Mucosal Immunoglobulins and the Polymeric Immunoglobulin Receptor: Evidence That the Commensal Microbiota Provided the Driving Force." ISRN Immunology 2014 (March 4, 2014): 1–20. http://dx.doi.org/10.1155/2014/541537.

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Immunoglobulins (Igs) in mucosal secretions contribute to immune homeostasis by limiting access of microbial and environmental antigens to the body proper, maintaining the integrity of the epithelial barrier and shaping the composition of the commensal microbiota. The emergence of IgM in cartilaginous fish represented the primordial mucosal Ig, which is expressed in all higher vertebrates. Expansion and diversification of the mucosal Ig repertoire led to the emergence of IgT in bony fishes, IgX in amphibians, and IgA in reptiles, birds, and mammals. Parallel evolution of cellular receptors for the constant (Fc) regions of Igs provided mechanisms for their transport and immune effector functions. The most ancient of these Fc receptors is the polymeric Ig receptor (pIgR), which first appeared in an ancestor of bony fishes. The pIgR transports polymeric IgM, IgT, IgX, and IgA across epithelial cells into external secretions. Diversification and refinement of the structure of mucosal Igs during tetrapod evolution were paralleled by structural changes in pIgR, culminating in the multifunctional secretory IgA complex in mammals. In this paper, evidence is presented that the mutualistic relationship between the commensal microbiota and the vertebrate host provided the driving force for coevolution of mucosal Igs and pIgR.

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Kovács, E., B. Dömötör, and H. Naffa. "Investment decisions in crises — A study of private pension fund investments." Acta Oeconomica 61, no. 4 (December 1, 2011): 389–412. http://dx.doi.org/10.1556/aoecon.61.2011.4.1.

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Private pension funds were thought to be an important pillar of old-age provision when they were introduced throughout (Emerging) Europe. As different as these funds are in different countries with regards to their regulation, their ownership structure and operation, none were immune to the sub-prime led financial crisis. The Hungarian private pension funds are unique amongst the defined contribution (DC) funds. With their decade old recent history, they are maturing to the payout period in a few years’ time; however, their demise appears ever more realistic by means of political decision. This makes uncovering their investment policy during the crises very timely. Examining such a period is of importance in shedding light on the behaviour of traditional financial concepts in periods of stress. In this paper, we assess the optimality of diversification, hedging and short sales decision possibilities of the Hungarian pension funds in the equity investments environment. Was the net asset value (NAV) erosion suffered by the Hungarian private pension funds a result of their investment decision? We examine this question of diversification through a hypothetical simulation of model investment portfolios. Our results show that international diversification yields better risk-adjusted returns only in case of perfect hindsight of future market movements. The high correlation of the stock indices globally in times of crises limits the benefits of diversification.

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Tan, Joshua, Luca Piccoli, and Antonio Lanzavecchia. "The Antibody Response to Plasmodium falciparum: Cues for Vaccine Design and the Discovery of Receptor-Based Antibodies." Annual Review of Immunology 37, no. 1 (April 26, 2019): 225–46. http://dx.doi.org/10.1146/annurev-immunol-042617-053301.

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Plasmodium falciparum remains a serious public health problem and a continuous challenge for the immune system due to the complexity and diversity of the pathogen. Recent advances from several laboratories in the characterization of the antibody response to the parasite have led to the identification of critical targets for protection and revealed a new mechanism of diversification based on the insertion of host receptors into immunoglobulin genes, leading to the production of receptor-based antibodies. These advances have opened new possibilities for vaccine design and passive antibody therapies to provide sterilizing immunity and control blood-stage parasites.

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Boehm, Thomas, Masayuki Hirano, Stephen J. Holland, Sabyasachi Das, Michael Schorpp, and Max D. Cooper. "Evolution of Alternative Adaptive Immune Systems in Vertebrates." Annual Review of Immunology 36, no. 1 (April 26, 2018): 19–42. http://dx.doi.org/10.1146/annurev-immunol-042617-053028.

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Adaptive immunity in jawless fishes is based on antigen recognition by three types of variable lymphocyte receptors (VLRs) composed of variable leucine-rich repeats, which are differentially expressed by two T-like lymphocyte lineages and one B-like lymphocyte lineage. The T-like cells express either VLRAs or VLRCs of yet undefined antigen specificity, whereas the VLRB antibodies secreted by B-like cells bind proteinaceous and carbohydrate antigens. The incomplete VLR germline genes are assembled into functional units by a gene conversion–like mechanism that employs flanking variable leucine-rich repeat sequences as templates in association with lineage-specific expression of cytidine deaminases. B-like cells develop in the hematopoietic typhlosole and kidneys, whereas T-like cells develop in the thymoid, a thymus-equivalent region at the gill fold tips. Thus, the dichotomy between T-like and B-like cells and the presence of dedicated lymphopoietic tissues emerge as ancestral vertebrate features, whereas the somatic diversification of structurally distinct antigen receptor genes evolved independently in jawless and jawed vertebrates.

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Chen, Junfeng, John Huddleston, Reuben M. Buckley, Maika Malig, Sara D. Lawhon, Loren C. Skow, Mi Ok Lee, Evan E. Eichler, Leif Andersson, and James E. Womack. "Bovine NK-lysin: Copy number variation and functional diversification." Proceedings of the National Academy of Sciences 112, no. 52 (December 14, 2015): E7223—E7229. http://dx.doi.org/10.1073/pnas.1519374113.

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NK-lysin is an antimicrobial peptide and effector protein in the host innate immune system. It is coded by a single gene in humans and most other mammalian species. In this study, we provide evidence for the existence of four NK-lysin genes in a repetitive region on cattle chromosome 11. The NK2A, NK2B, and NK2C genes are tandemly arrayed as three copies in ∼30–35-kb segments, located 41.8 kb upstream of NK1. All four genes are functional, albeit with differential tissue expression. NK1, NK2A, and NK2B exhibited the highest expression in intestine Peyer’s patch, whereas NK2C was expressed almost exclusively in lung. The four peptide products were synthesized ex vivo, and their antimicrobial effects against both Gram-positive and Gram-negative bacteria were confirmed with a bacteria-killing assay. Transmission electron microcopy indicated that bovine NK-lysins exhibited their antimicrobial activities by lytic action in the cell membranes. In summary, the single NK-lysin gene in other mammals has expanded to a four-member gene family by tandem duplications in cattle; all four genes are transcribed, and the synthetic peptides corresponding to the core regions are biologically active and likely contribute to innate immunity in ruminants.

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Kang, Byunghyun, Luigi J. Alvarado, Teayong Kim, Michael L. Lehmann, Hyeseon Cho, Jianping He, Peng Li, Bong-Hyun Kim, Andre Larochelle, and Brian L. Kelsall. "Commensal microbiota drive the functional diversification of colon macrophages." Mucosal Immunology 13, no. 2 (November 26, 2019): 216–29. http://dx.doi.org/10.1038/s41385-019-0228-3.

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AbstractMononuclear phagocytes are a heterogeneous population of leukocytes essential for immune homeostasis that develop tissue-specific functions due to unique transcriptional programs driven by local microenvironmental cues. Single cell RNA sequencing (scRNA-seq) of colonic myeloid cells from specific pathogen free (SPF) and germ-free (GF) C57BL/6 mice revealed extensive heterogeneity of both colon macrophages (MPs) and dendritic cells (DCs). Modeling of developmental pathways combined with inference of gene regulatory networks indicate two major trajectories from common CCR2+ precursors resulting in colon MP populations with unique transcription factors and downstream target genes. Compared to SPF mice, GF mice had decreased numbers of total colon MPs, as well as selective proportional decreases of two major CD11c+CD206intCD121b+ and CD11c−CD206hiCD121b− colon MP populations, whereas DC numbers and proportions were not different. Importantly, these two major colon MP populations were clearly distinct from other colon MP populations regarding their gene expression profile, localization within the lamina propria (LP) and ability to phagocytose macromolecules from the blood. These data uncover the diversity of intestinal myeloid cell populations at the molecular level and highlight the importance of microbiota on the unique developmental as well as anatomical and functional fates of colon MPs.

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Willmann, Katharina L., Sara Milosevic, Siim Pauklin, Kerstin-Maike Schmitz, Gopinath Rangam, Maria T. Simon, Sarah Maslen, et al. "A role for the RNA pol II–associated PAF complex in AID-induced immune diversification." Journal of Cell Biology 199, no. 1 (October 1, 2012): i1. http://dx.doi.org/10.1083/jcb1991oia1.

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Neuberger, M. S., J. E. Sale, S. J. Cumbers, C. J. Jolly, M. P. Bemark, M. R. Ehrenstein, A. Lanoue, et al. "Diversification and Selection Mechanisms for the Production of Protein Repertoires Lessons from the Immune System." Applied Biochemistry and Biotechnology 83, no. 1-3 (2000): 53–62. http://dx.doi.org/10.1385/abab:83:1-3:53.

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Hughes, Austin L. "Origin and diversification of the L-amino oxidase family in innate immune defenses of animals." Immunogenetics 62, no. 11-12 (September 28, 2010): 753–59. http://dx.doi.org/10.1007/s00251-010-0482-8.

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Bomblies, Kirsten. "Too much of a good thing? Hybrid necrosis as a by-product of plant immune system diversification." Botany 87, no. 11 (November 2009): 1013–22. http://dx.doi.org/10.1139/b09-072.

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Plants defend themselves against their enemies with an impressive arsenal of physical barriers, surveillance and defense proteins, enzymes, and toxic chemicals. Many different molecules are involved in the detection of invaders, suggesting that pathogen pressure selects for a broad array of defense strategies and a high diversity of recognition specificities in host species. Recent results in plants, however, show that immune system diversification can also have negative consequences; epistatic interactions among divergent immune system components can cause hybrid necrosis, a form of genetic incompatibility. This type of hybrid failure is frequently lethal, and characterized by the widespread induction of programmed cell death leading to tissue necrosis. In characterized examples, this is caused by hyperactivation of defense responses. Both the prevalence of hybrid necrosis in diverse plant taxa, and the growing indication that it may arise as a by-product of adaptation to the biotic environment, emphasize that it is likely a general factor in plant evolution. Since hybrid necrosis negatively impacts the progeny of certain crosses, divergence of the plant immune system may indirectly affect gene flow among populations, and perhaps contribute to the establishment or maintenance of species barriers.

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Boys, Ian N., Katrina B. Mar, and John W. Schoggins. "Functional-genomic analysis reveals intraspecies diversification of antiviral receptor transporter proteins in Xenopus laevis." PLOS Genetics 17, no. 5 (May 20, 2021): e1009578. http://dx.doi.org/10.1371/journal.pgen.1009578.

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The Receptor Transporter Protein (RTP) family is present in most, if not all jawed vertebrates. Most of our knowledge of this protein family comes from studies on mammalian RTPs, which are multi-function proteins that regulate cell-surface G-protein coupled receptor levels, influence olfactory system development, regulate immune signaling, and directly inhibit viral infection. However, mammals comprise less than one-tenth of extant vertebrate species, and our knowledge about the expression, function, and evolution of non-mammalian RTPs is limited. Here, we explore the evolutionary history of RTPs in vertebrates. We identify signatures of positive selection in many vertebrate RTP clades and characterize multiple, independent expansions of the RTP family outside of what has been described in mammals. We find a striking expansion of RTPs in the African clawed frog, Xenopus laevis, with 11 RTPs in this species as opposed to 1 to 4 in most other species. RNA sequencing revealed that most X. laevis RTPs are upregulated following immune stimulation. In functional assays, we demonstrate that at least three of these X. laevis RTPs inhibit infection by RNA viruses, suggesting that RTP homologs may serve as antiviral effectors outside of Mammalia.

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Fischer, Silke F., Philippe Bouillet, Kristy O'Donnell, Amanda Light, David M. Tarlinton, and Andreas Strasser. "Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells." Blood 110, no. 12 (December 1, 2007): 3978–84. http://dx.doi.org/10.1182/blood-2007-05-091306.

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Abstract T cell–dependent B-cell immune responses induce germinal centers that are sites for expansion, diversification, and selection of antigen-specific B cells. During the immune response, antigen-specific B cells are removed in a process that favors the retention of cells with improved affinity for antigen, a cell death process inhibited by excess Bcl-2. In this study, we examined the role of the BH3-only protein Bim, an initiator of apoptosis in the Bcl-2–regulated pathway, in the programmed cell death accompanying an immune response. After immunization, Bim-deficient mice showed persistence of both memory B cells lacking affinity-enhancing mutations in their immunoglobulin genes and antibody-forming cells secreting low-affinity antibodies. This was accompanied by enhanced survival of both cell types in culture. We have identified for the first time the physiologic mechanisms for killing low-affinity antibody-expressing B cells in an immune response and have shown this to be dependent on the BH3-only protein Bim.

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Bessonov, Nikolai, Gennady Bocharov, Andreas Meyerhans, Vladimir Popov, and Vitaly Volpert. "Nonlocal Reaction–Diffusion Model of Viral Evolution: Emergence of Virus Strains." Mathematics 8, no. 1 (January 12, 2020): 117. http://dx.doi.org/10.3390/math8010117.

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This work is devoted to the investigation of virus quasi-species evolution and diversification due to mutations, competition for host cells, and cross-reactive immune responses. The model consists of a nonlocal reaction–diffusion equation for the virus density depending on the genotype considered to be a continuous variable and on time. This equation contains two integral terms corresponding to the nonlocal effects of virus interaction with host cells and with immune cells. In the model, a virus strain is represented by a localized solution concentrated around some given genotype. Emergence of new strains corresponds to a periodic wave propagating in the space of genotypes. The conditions of appearance of such waves and their dynamics are described.

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Domingo, E., J. Diez, M. A. Martinez, J. Hernandez, A. Holguin, B. Borrego, and M. G. Mateu. "New observations on antigenic diversification of RNA viruses. Antigenic variation is not dependent on immune selection." Journal of General Virology 74, no. 10 (October 1, 1993): 2039–45. http://dx.doi.org/10.1099/0022-1317-74-10-2039.

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48

Tenzer, Stefan, Hayley Crawford, Phillip Pymm, Robert Gifford, Vattipally B. Sreenu, Mirjana Weimershaus, Tulio de Oliveira, et al. "HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification." Cell Reports 7, no. 2 (April 2014): 448–63. http://dx.doi.org/10.1016/j.celrep.2014.03.031.

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Nasution, Riven, Annisa Kesy Garside, and Dana Marsetiya Utama. "Penjadwalan Job Shop Dengan Pendekatan Algoritma Artificial Immune System." Jurnal Teknik Industri 18, no. 1 (August 24, 2017): 29. http://dx.doi.org/10.22219/jtiumm.vol18.no1.29-42.

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Production scheduling is an important activity in manufacturing. Optimal scheduling affects the time of completion of the work. PT. Interpack is a company that produces packaging machines. The job schedule of the product spare part still uses the random priority rules. Use of random rules makes a lot of time delay. Delay causes operator and machine idle. Delay also causes the total time of completion of the work (makespan) and delay the greater. So it needs to be rescheduled to work on the spare part of product. Job scheduling using the Artificial Immune System (AIS) algorithm. AIS was developed by Farmer et al. The AIS algorithm refers to the human immune system. The stages of the AIS algorithm begin with random initialization, antibody representation and gene classification, clone breeding, selection of donor antibodies, germ-line construction, gene fragment redesign, and ending with diversification of antibodies. AIS algorithm scheduling resulted in a more optimal new schedule. AIS algorithm scheduling generates a future of 6483.91 minutes. Company scheduling generates makespan of 7059.99 minutes. AIS Schedule finishes algorithm 4 days of the due date. AIS algorithm schedule increase machine utility by 1%.

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Khairuzzaman Mohamad Zamani, Mohamad, Ismail Musirin, Saiful Izwan Suliman, and Sharifah Azma Syed Mustaffa. "Chaotic Immune Symbiotic Organisms Search Algorithm for Solving Optimisation Problem." International Journal of Engineering & Technology 7, no. 3.15 (August 13, 2018): 73. http://dx.doi.org/10.14419/ijet.v7i3.15.17505.

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Achieving an optimal solution is very crucial while solving a problem. To achieve the optimality required, optimisation techniques can be implemented while solving the problem. The presence of classical optimisation techniques has enabled an optimal solution to be obtained. However, as the complexity of the optimisation problem increased, classical optimisation techniques faced difficulties in providing optimal solutions. Heuristics-based algorithms were introduced to counter the problem faced by classical optimisation techniques. Good performance of these heuristics-based algorithm has been implied through various implementation in solving optimisation problems. Despite the performance of these algorithms, the flaws of these algorithms hinder them from producing high-quality results. To mitigate the problem, this paper presents the development of Chaotic Immune Symbiotic Organisms Search algorithm which was inspired by the element of diversification as well as the increased capability of exploration. The performance of the proposed algorithm has been tested by solving several benchmark test functions. A comparative study was also conducted with respect to several other existing optimisation algorithms resulted in the superiority of the proposed algorithm in providing high-quality solutions.

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