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P53 and The Immune Response: 40 Years of Exploration-A Plan for the Future.

ABSTRACT: The p53 field was born from a marriage of the techniques of cancer virus research and immunology. Over the past 40 years, it has followed the path of cancer research. Now cancer treatments are turning to immunotherapy, and there are many hints of the role of the p53 protein in both the regulation of the innate immune system and as an antigen in adaptive immune responses. The p53 gene and protein are part of the innate immune system, and play an important role in infectious diseases, senescence, aging, and the surveillance of repetitive DNA and RNAs. The mutant form of the p53 protein in cancers elicits both a B-cell antibody response (a tumor antigen) and a CD-8 killer T-cell response (a tumor-specific transplantation antigen). The future will take the p53-immune response field of research into cancer immunotherapy, autoimmunity, inflammatory responses, neuro-degeneration, aging, and life span, and the regulation of epigenetic stability and tissue regeneration. The next 40 years will bring the p53 gene and its proteins out of a cancer focus and into an organismic and environmental focus.

SUBMITTER: Levine AJ

PROVIDER: S-EPMC7013403 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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P53 and The Immune Response: 40 Years of Exploration-A Plan for the Future.

Levine Arnold J AJ

International journal of molecular sciences 20200115 2

The <i>p53</i> field was born from a marriage of the techniques of cancer virus research and immunology. Over the past 40 years, it has followed the path of cancer research. Now cancer treatments are turning to immunotherapy, and there are many hints of the role of the p53 protein in both the regulation of the innate immune system and as an antigen in adaptive immune responses. The <i>p53</i> gene and protein are part of the innate immune system, and play an important role in infectious diseases ...[more]

PMID: 31952115

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Project description:The fungal skin disease, chytridiomycosis (caused by Batrachochytrium dendrobatidis and B. salamandrivorans), has caused amphibian declines and extinctions globally since its emergence. Characterizing the host immune response to chytridiomycosis has been a focus of study with the aim of disease mitigation. However, many aspects of the innate and adaptive arms of this response are still poorly understood, likely due to the wide range of species' responses to infection. In this paper we provide an overview of expected immunological responses (with inference based on amphibian and mammalian immunology), together with a synthesis of current knowledge about these responses for the amphibian-chytridiomycosis system. We structure our review around four key immune stages: (1) the naïve immunocompetent state, (2) immune defenses that are always present (constitutive defenses), (3) mechanisms for recognition of a pathogen threat and innate immune defenses, and (4) adaptive immune responses. We also evaluate the current hot topics of immunosuppression and immunopathology in chytridiomycosis, and discuss their respective roles in pathogenesis. Our synthesis reveals that susceptibility to chytridiomycosis is likely to be multifactorial. Susceptible amphibians appear to have ineffective constitutive and innate defenses, and a late-stage response characterized by immunopathology and Bd-induced suppression of lymphocyte responses. Overall, we identify substantial gaps in current knowledge, particularly concerning the entire innate immune response (mechanisms of initial pathogen detection and possible immunoevasion by Bd, degree of activation and efficacy of the innate immune response, the unexpected absence of innate leukocyte infiltration, and the cause and role of late-stage immunopathology in pathogenesis). There are also gaps concerning most of the adaptive immune system (the relative importance of B and T cell responses for pathogen clearance, the capacity and extent of immunological memory, and specific mechanisms of pathogen-induced immunosuppression). Improving our capacity for amphibian immunological research will require selection of an appropriate Bd-susceptible model species, the development of taxon-specific affinity reagents and cell lines for functional assays, and the application of a suite of conventional and emerging immunological methods. Despite current knowledge gaps, immunological research remains a promising avenue for amphibian conservation management.

Project description:Abundance-occupancy (A-O) relationships are widely documented for many organismal groups and regions, and have been used to gain an understanding of regional population and community trends. Monitoring changes in abundance and occupancy over time may be what is required to document changes in conservation status and needs for some species, communities, or areas.We hypothesize that if there is a higher proportion of declining species in one group of species compared with another (e.g., migratory species vs. permanent residents), then a consequence of that difference will be vastly different abundance-occupancy relationships. If this difference persists through time, then the resulting A-O relationships between the groups will continue to diverge.For neotropical migrants, short-distance migrants, and permanent resident birds of North America, we assess the numbers of declining species over 1969-2009. We further test for differences in the A-O relationship across these three groups, and in rates of change in abundance and occupancy separately.We find significant differences in numbers of declining species across the migratory groups, a significant decline in the A-O relationship for permanent residents, a significant increase for Neotropical migrants, and a nonsignificant decline for short-distance migrants over the 40 years. Further, abundances are not changing at different rates but occupancies are consistently greater over time for neotropical migrants versus permanent residents, likely driving the changes in A-O relationships observed.In these analyses, we documented changing A-O trends for different groups of species, over a relatively long time period for ecological studies, one of only a few studies to examine A-O relationships over time. Further, we have shown that a temporally unvarying abundance-occupancy relationship is not universal, and we posit that variability in A-O relationships is due to human impacts on habitats, coupled with variation in species' abilities to respond to human impacts.

Dataset Information

P53 and The Immune Response: 40 Years of Exploration-A Plan for the Future.

Publications

P53 and The Immune Response: 40 Years of Exploration-A Plan for the Future.

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