Immunology

Several workers have observed that there is an extremely close immunological resemblance between the serum albumins of apes and man. Our studies with the quantitative micro-complement fixation method confirm this observation. To explain the closeness of the resemblance, previous workers suggested that there has been a slowing down of albumin evolution since the time of divergence of apes and man. Recent evidence, however, indicates that the albumin molecule has evolved at a steady rate. Hence, we suggest that apes and man have a more recent common ancestry than is usually supposed. Our calculations lead to the suggestion that, if man and Old World monkeys last shared a common ancestor 30 million years ago, then man and African apes shared a common ancestor 5 million years ago, that is, in the Pliocene era.

@article{sarich1967immunological,
    author = "Sarich, Vincent M. and Wilson, Allan C.",
    title = "Immunological Time Scale for Hominid Evolution",
    year = "1967",
    journal = "Science",
    abstract = "Several workers have observed that there is an extremely close immunological resemblance between the serum albumins of apes and man. Our studies with the quantitative micro-complement fixation method confirm this observation. To explain the closeness of the resemblance, previous workers suggested that there has been a slowing down of albumin evolution since the time of divergence of apes and man. Recent evidence, however, indicates that the albumin molecule has evolved at a steady rate. Hence, we suggest that apes and man have a more recent common ancestry than is usually supposed. Our calculations lead to the suggestion that, if man and Old World monkeys last shared a common ancestor 30 million years ago, then man and African apes shared a common ancestor 5 million years ago, that is, in the Pliocene era.",
    url = "https://doi.org/10.1126/science.158.3805.1200",
    doi = "10.1126/science.158.3805.1200",
    number = "3805",
    openalex = "W2048918147",
    pages = "1200-1203",
    volume = "158",
    references = "doi101002ajpa1330260211, doi1010160002934366901458, doi101016s006532330860128x, doi101038202147a0, doi101038205135a0, doi101038213155a0, doi101073pnas581142, doi101126science147365368, doi101159000155026, doi1043249781315081083"
}

@misc{sarich1967immunological1,
    author = "Sarich, V. and Wilson, A",
    title = "Immunological Time Scale for Homonid Evolution",
    year = "1967",
    howpublished = "Science, v. 158, p. 1200-1203",
    note = "talkorigins\_source = {true}; raw\_reference = {Sarich, V., and Wilson, A., 1967, Immunological Time Scale for Homonid Evolution: Science, v. 158, p. 1200-1203.}"
}

We discuss published molecular evidence concerning the relationship of man to African apes and Old World monkeys. Quantitative comparisons of their serum albumins, transferrins, hemoglobins, and DNA show that man is genetically much more similar to the African apes than to the Old World monkeys. The amino acid sequences of hemoglobins from humans, chimpanzees, gorillas, and rhesus monkeys are consistent with the hypothesis that the probability of an amino acid substitution occurring in a given interval of time is the same for every hemoglobin lineage. This allows the use of these data as a hemoglobin evolutionary clock, just as we have previously done with the albumins. It is shown that concordance exists between the hemoglobin and albumin results and that both support the suggestion that the human lineage diverged from that leading to the African apes far more recently than is generally supposed. Considering both the albumin and hemoglobin data, we would set the most probable date at 4 to 5 million years.

@article{doi101073pnas6341088,
    author = "Wilson, Allan C. and Sarich, Vincent M.",
    title = "A MOLECULAR TIME SCALE FOR HUMAN EVOLUTION",
    year = "1969",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "We discuss published molecular evidence concerning the relationship of man to African apes and Old World monkeys. Quantitative comparisons of their serum albumins, transferrins, hemoglobins, and DNA show that man is genetically much more similar to the African apes than to the Old World monkeys. The amino acid sequences of hemoglobins from humans, chimpanzees, gorillas, and rhesus monkeys are consistent with the hypothesis that the probability of an amino acid substitution occurring in a given interval of time is the same for every hemoglobin lineage. This allows the use of these data as a hemoglobin evolutionary clock, just as we have previously done with the albumins. It is shown that concordance exists between the hemoglobin and albumin results and that both support the suggestion that the human lineage diverged from that leading to the African apes far more recently than is generally supposed. Considering both the albumin and hemoglobin data, we would set the most probable date at 4 to 5 million years.",
    url = "https://doi.org/10.1073/pnas.63.4.1088",
    doi = "10.1073/pnas.63.4.1088",
    openalex = "W2031209673",
    references = "doi101007bf02476695, doi1010160022283668902945, doi101038217624a0, doi1010382191335a0, doi101073pnas581142, doi101126science15137171530, doi101126science1613841529, doi101146annurevbi37070168003455, doi101515bchm219613251283, sarich1967immunological"
}

@article{bauer1970an,
    author = "Bauer, Klausdieter",
    title = "An immunological time scale for primate evolution consistent with fossil evidence",
    year = "1970",
    journal = "Human Genetics",
    url = "https://doi.org/10.1007/bf00278772",
    doi = "10.1007/bf00278772",
    number = "4",
    openalex = "W1999884902",
    pages = "344-350",
    volume = "10",
    references = "doi1010382191335a0, doi101073pnas6341088, doi101111j174966321969tb20453x, doi101126science1683931578, doi101159000313795, doi101159000391318, doi101159000391328, openalexw2565219170, openalexw788933220, sarich1967immunological"
}

Although there seems to be a regular relation of protein change versus time via an exponential equation of the form ID =e(kt), nevertheless, examination of the data indicates that such an exponential fit may be premature. Two other models, ID = kt + b and ID = bt(k) + c represent better fits. Without better data none of the models appears convincing.

@article{doi101126science1683931578,
    author = "Read, Dwight and Lestrel, Pete E.",
    title = "Hominid Phylogeny and Immunology: A Critical Appraisal",
    year = "1970",
    journal = "Science",
    abstract = "Although there seems to be a regular relation of protein change versus time via an exponential equation of the form ID =e(kt), nevertheless, examination of the data indicates that such an exponential fit may be premature. Two other models, ID = kt + b and ID = bt(k) + c represent better fits. Without better data none of the models appears convincing.",
    url = "https://doi.org/10.1126/science.168.3931.578",
    doi = "10.1126/science.168.3931.578",
    openalex = "W2079424709",
    references = "doi101016b9780123955623x50012, doi101126science15137171530, doi1043249781315081083, openalexw616142447"
}

Recalculation of the time of divergence of the Pongidae and Hominidae after correction of immunological distance by inclusion of generation length yields minimum dates of approximately 14 million years ago.

@article{doi101126science1764036803,
    author = "Lovejoy, C. Owen and Burstein, Albert H. and Heiple, Kingsbury G.",
    title = "Primate Phylogeny and Immunological Distance",
    year = "1972",
    journal = "Science",
    abstract = "Recalculation of the time of divergence of the Pongidae and Hominidae after correction of immunological distance by inclusion of generation length yields minimum dates of approximately 14 million years ago.",
    url = "https://doi.org/10.1126/science.176.4036.803",
    doi = "10.1126/science.176.4036.803",
    openalex = "W1997728089",
    references = "doi101126science1683931578"
}

@article{doi101007bf00273638,
    author = "Bauer, Klausdieter",
    title = "Age determination by immunological techniques of the last common ancestor of man and chimpanzee",
    year = "1973",
    journal = "Human Genetics",
    url = "https://doi.org/10.1007/bf00273638",
    doi = "10.1007/bf00273638",
    openalex = "W2070816758",
    references = "doi101007bf00281036"
}

@article{doi101126science17940781144,
    author = "Sarich, Vincent M. and Wilson, Allan C.",
    title = "Generation Time and Genomic Evolution in Primates",
    year = "1973",
    journal = "Science",
    url = "https://doi.org/10.1126/science.179.4078.1144",
    doi = "10.1126/science.179.4078.1144",
    openalex = "W2092437348",
    references = "doi101007bf01659390, doi101007bf01659392, doi101007bf01659396, doi101038202147a0, doi101038224149a0, doi101073pnas581142, doi101073pnas6341088, doi101126science1553760279, doi101126science15838051200, doi101146annurevmi23100169002415, uzzell1971phyletic"
}

@article{mettler1984immunological,
    author = "Mettler, L. and Paul, S.",
    title = "Immunological Aspects of Pathological Pregnancy (Infertility Immunology)",
    year = "1984",
    journal = "Gynecologic and Obstetric Investigation",
    url = "https://doi.org/10.1159/000299094",
    doi = "10.1159/000299094",
    number = "6",
    openalex = "W2049106428",
    pages = "281-288",
    volume = "18"
}

@article{howard1985cellular,
    author = "Howard, Jonathan C.",
    title = "Cellular immunology: Immunological help at last",
    year = "1985",
    journal = "Nature",
    url = "https://doi.org/10.1038/314494a0",
    doi = "10.1038/314494a0",
    number = "6011",
    openalex = "W1969798121",
    pages = "494-495",
    volume = "314",
    references = "doi101002eji1830010104, doi101016s0065277608609190, doi101038314537a0, doi101073pnas791175, doi101084jem1582303, doi101084jem16041102, doi104049jimmunol12061809, doi104049jimmunol12631075, doi104049jimmunol12751869, openalexw1530422829"
}

@article{soni1990immunology,
    author = "Soni, N",
    title = "Immunology, immunological mediators and AIDS",
    year = "1990",
    journal = "Current Opinion in Anaesthesiology",
    url = "https://doi.org/10.1097/00001503-199006000-00026",
    doi = "10.1097/00001503-199006000-00026",
    number = "3",
    openalex = "W2033462912",
    pages = "444-448",
    volume = "3"
}

There is increasing evidence for variation in rates of nucleotide substitution among divergent taxonomic groups. Here, we summarize published rate data and show a strong relationship between substitution rate and body size. For instance, rates of nuclear and mtDNA evolution are slow in whales, intermediate in primates, and fast in rodents. A similar relationship exists for poikilothermic vertebrates. However, these taxa have slower mtDNA substitution rates overall than do homeotherms of similar size. A number of physiological and life history variables are highly correlated with body size. Of these, generation time and metabolic rate explain some patterns of rate heterogeneity equally well. In many cases, however, differences in metabolic rate explain important exceptions to the generation time model. Correlation between metabolic rate and nucleotide substitution may be mediated by (i) the mutagenic effects of oxygen radicals that are abundant by-products of aerobic respiration, and (ii) increased rates of DNA synthesis and nucleotide replacement in organisms with higher metabolic rates. Both of these factors increase mutation rate by decreasing the "nucleotide generation time," the average length of time before a nucleotide is copied either through replication or repair. Reconsideration of the generation time hypothesis to include physiological effects such as metabolic rate improves the theoretical underpinnings of molecular evolution.

@article{doi101073pnas9094087,
    author = "Martin, A. P. and Palumbi, Stephen R.",
    title = "Body size, metabolic rate, generation time, and the molecular clock.",
    year = "1993",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = {There is increasing evidence for variation in rates of nucleotide substitution among divergent taxonomic groups. Here, we summarize published rate data and show a strong relationship between substitution rate and body size. For instance, rates of nuclear and mtDNA evolution are slow in whales, intermediate in primates, and fast in rodents. A similar relationship exists for poikilothermic vertebrates. However, these taxa have slower mtDNA substitution rates overall than do homeotherms of similar size. A number of physiological and life history variables are highly correlated with body size. Of these, generation time and metabolic rate explain some patterns of rate heterogeneity equally well. In many cases, however, differences in metabolic rate explain important exceptions to the generation time model. Correlation between metabolic rate and nucleotide substitution may be mediated by (i) the mutagenic effects of oxygen radicals that are abundant by-products of aerobic respiration, and (ii) increased rates of DNA synthesis and nucleotide replacement in organisms with higher metabolic rates. Both of these factors increase mutation rate by decreasing the "nucleotide generation time," the average length of time before a nucleotide is copied either through replication or repair. Reconsideration of the generation time hypothesis to include physiological effects such as metabolic rate improves the theoretical underpinnings of molecular evolution.},
    url = "https://doi.org/10.1073/pnas.90.9.4087",
    doi = "10.1073/pnas.90.9.4087",
    openalex = "W2074097929"
}

Amino acid sequence data from 57 different enzymes were used to determine the divergence times of the major biological groupings. Deuterostomes and protostomes split about 670 million years ago and plants, animals, and fungi last shared a common ancestor about a billion years ago. With regard to these protein sequences, plants are slightly more similar to animals than are the fungi. In contrast, phylogenetic analysis of the same sequences indicates that fungi and animals shared a common ancestor more recently than either did with plants, the greater difference resulting from the fungal lineage changing faster than the animal and plant lines over the last 965 million years. The major protist lineages have been changing at a somewhat faster rate than other eukaryotes and split off about 1230 million years ago. If the rate of change has been approximately constant, then prokaryotes and eukaryotes last shared a common ancestor about 2 billion years ago, archaebacterial sequences being measurably more similar to eukaryotic ones than are eubacterial ones.

@article{doi101126science2715248470,
    author = "Doolittle, Russell F. and Feng, Da-Fei and Tsang, Simon K. and Cho, Glen and Little, Elizabeth",
    title = "Determining Divergence Times of the Major Kingdoms of Living Organisms with a Protein Clock",
    year = "1996",
    journal = "Science",
    abstract = "Amino acid sequence data from 57 different enzymes were used to determine the divergence times of the major biological groupings. Deuterostomes and protostomes split about 670 million years ago and plants, animals, and fungi last shared a common ancestor about a billion years ago. With regard to these protein sequences, plants are slightly more similar to animals than are the fungi. In contrast, phylogenetic analysis of the same sequences indicates that fungi and animals shared a common ancestor more recently than either did with plants, the greater difference resulting from the fungal lineage changing faster than the animal and plant lines over the last 965 million years. The major protist lineages have been changing at a somewhat faster rate than other eukaryotes and split off about 1230 million years ago. If the rate of change has been approximately constant, then prokaryotes and eukaryotes last shared a common ancestor about 2 billion years ago, archaebacterial sequences being measurably more similar to eukaryotic ones than are eubacterial ones.",
    url = "https://doi.org/10.1126/science.271.5248.470",
    doi = "10.1126/science.271.5248.470",
    openalex = "W1970473208",
    references = "doi101007bf02101113, doi101007bf02111276, doi101007bf02603120, doi1010160022283670900574, doi101016b9781483227344500176, doi101016b9781483232119500097, doi101038202147a0, doi101038361219a0, doi101073pnas86239355, doi101126science1604319, doi101126science17940781144, doi101126science2605108640, doi101128mr5749539941993, doi1023072412448, doi107312nei92038"
}

Abstract The first third (ca. 1200 bp) of exon 1 of the nuclear gene encoding the interstitial retinoid‐binding protein (IRBP) has been sequenced for 12 representative primates belonging to Lemuriformes, Lorisiformes, Tarsiiformes, Platyrrhini, and Catarrhini, and combined with available data (13 other primates, 11 nonprimate placentals, and 2 marsupials). Phylogenetic analyses using maximum likelihood on nucleotides and amino acids robustly support the monophyly of primates, Strepsirrhini, Lemuriformes, Lorisiformes, Anthropoidea, Catarrhini, and Platyrrhini. It is interesting to note that 1) Tarsiidae grouped with Anthropoidea, and the support for this node depends on the molecular characters considered; 2) Cheirogaleidae grouped within Lemuriformes; and 3) Daubentonia was the sister group of all other Lemuriformes. Study of the IRBP evolutionary rate shows a high heterogeneity within placentals and also within primates. Maximum likelihood local molecular clocks were assigned to three clades displaying significantly contrasted evolutionary rates. Paenungulata were shown to evolve 2.5–3 times faster than Perissodactyla and Lemuriformes. Six independent calibration points were used to estimate splitting ages of the main primate clades, and their compatibility was evaluated. Divergence ages were obtained for the following crown groups: 13.8–14.2 MY for Lorisiformes, 26.5–27.2 MY for Lemuroidea, 39.6–40.7 MY for Lemuriformes, 45.4–46.7 MY for Strepsirrhini, and 56.7–58.4 MY for Haplorrhini. The incompatibility between some paleontological and molecular estimates may reflect the incompleteness of the placental fossil record, and/or indicate that the variable IRBP evolutionary rates are not fully accommodated by local molecular clocks. Am J Phys Anthropol, 2003. © 2003 Wiley‐Liss, Inc.

@article{doi101002ajpa10322,
    author = "Poux, Céline and Douzery, Emmanuel",
    title = "Primate phylogeny, evolutionary rate variations, and divergence times: A contribution from the nuclear gene IRBP",
    year = "2003",
    journal = "American Journal of Physical Anthropology",
    abstract = "Abstract The first third (ca. 1200 bp) of exon 1 of the nuclear gene encoding the interstitial retinoid‐binding protein (IRBP) has been sequenced for 12 representative primates belonging to Lemuriformes, Lorisiformes, Tarsiiformes, Platyrrhini, and Catarrhini, and combined with available data (13 other primates, 11 nonprimate placentals, and 2 marsupials). Phylogenetic analyses using maximum likelihood on nucleotides and amino acids robustly support the monophyly of primates, Strepsirrhini, Lemuriformes, Lorisiformes, Anthropoidea, Catarrhini, and Platyrrhini. It is interesting to note that 1) Tarsiidae grouped with Anthropoidea, and the support for this node depends on the molecular characters considered; 2) Cheirogaleidae grouped within Lemuriformes; and 3) Daubentonia was the sister group of all other Lemuriformes. Study of the IRBP evolutionary rate shows a high heterogeneity within placentals and also within primates. Maximum likelihood local molecular clocks were assigned to three clades displaying significantly contrasted evolutionary rates. Paenungulata were shown to evolve 2.5–3 times faster than Perissodactyla and Lemuriformes. Six independent calibration points were used to estimate splitting ages of the main primate clades, and their compatibility was evaluated. Divergence ages were obtained for the following crown groups: 13.8–14.2 MY for Lorisiformes, 26.5–27.2 MY for Lemuroidea, 39.6–40.7 MY for Lemuriformes, 45.4–46.7 MY for Strepsirrhini, and 56.7–58.4 MY for Haplorrhini. The incompatibility between some paleontological and molecular estimates may reflect the incompleteness of the placental fossil record, and/or indicate that the variable IRBP evolutionary rates are not fully accommodated by local molecular clocks. Am J Phys Anthropol, 2003. © 2003 Wiley‐Liss, Inc.",
    url = "https://doi.org/10.1002/ajpa.10322",
    doi = "10.1002/ajpa.10322",
    openalex = "W1969394126",
    references = "doi101111j109583121997tb01480x"
}

@article{knapp2003evolution,
    author = "Knapp, Leslie A.",
    title = "Evolution and immunology",
    year = "2003",
    journal = "Evolutionary Anthropology: Issues, News, and Reviews",
    url = "https://doi.org/10.1002/evan.10077",
    doi = "10.1002/evan.10077",
    number = "S1",
    openalex = "W2111901725",
    pages = "140-144",
    volume = "11",
    references = "doi101034j139900392000550314x, doi101038335167a0, doi101038352595a0, doi101038352619a0, doi101038360434a0, doi101038nm0496405, doi101073pnas863958, doi101073pnas952011745, doi101093oxfordjournalsmolbeva040626, doi103201eid0303970301"
}

@article{inman2009cattle,
    author = "Inman, Charlotte and Hudson, Chris",
    title = "Cattle immunology: vaccination and immunological testing",
    year = "2009",
    journal = "Livestock",
    url = "https://doi.org/10.1111/j.2044-3870.2009.tb00295.x",
    doi = "10.1111/j.2044-3870.2009.tb00295.x",
    number = "4",
    openalex = "W1979274972",
    pages = "35-39",
    volume = "14",
    references = "doi101111j204438702009tb00208x"
}

@article{shay2013immunological,
    author = "Shay, Tal and Kang, Joonsoo",
    title = "Immunological Genome Project and systems immunology",
    year = "2013",
    journal = "Trends in Immunology",
    url = "https://doi.org/10.1016/j.it.2013.03.004",
    doi = "10.1016/j.it.2013.03.004",
    number = "12",
    openalex = "W2171711783",
    pages = "602-609",
    volume = "34",
    references = "doi101002j153873051948tb01338x, doi101016jcell201101004, doi101016jcell201209016, doi101038nature11247, doi101038ni10081091, doi101038ni2370, doi101038ni2416, doi101038ni2419, doi10106313067010, doi101126science1198704"
}

@article{wu2014t,
    author = "Wu, Xiuli and Przybylski, Grzegorz K. and Yang, Qintai and Liu, Qifa",
    title = "T Cells Immunology in the Immunological Diseases",
    year = "2014",
    journal = "Journal of Immunology Research",
    url = "https://doi.org/10.1155/2014/690324",
    doi = "10.1155/2014/690324",
    openalex = "W2090644321",
    pages = "1-2",
    volume = "2014"
}

Primates have long been a test case for the development of phylogenetic methods for divergence time estimation. Despite a large number of studies, however, the timing of origination of crown Primates relative to the Cretaceous-Paleogene (K-Pg) boundary and the timing of diversification of the main crown groups remain controversial. Here, we analysed a data set of 372 taxa (367 Primates and 5 outgroups, 3.4 million aligned base pairs) that includes nine primate genomes. We systematically explore the effect of different interpretations of fossil calibrations and molecular clock models on primate divergence time estimates. We find that even small differences in the construction of fossil calibrations can have a noticeable impact on estimated divergence times, especially for the oldest nodes in the tree. Notably, choice of molecular rate model (autocorrelated or independently distributed rates) has an especially strong effect on estimated times, with the independent rates model producing considerably more ancient age estimates for the deeper nodes in the phylogeny. We implement thermodynamic integration, combined with Gaussian quadrature, in the program MCMCTree, and use it to calculate Bayes factors for clock models. Bayesian model selection indicates that the autocorrelated rates model fits the primate data substantially better, and we conclude that time estimates under this model should be preferred. We show that for eight core nodes in the phylogeny, uncertainty in time estimates is close to the theoretical limit imposed by fossil uncertainties. Thus, these estimates are unlikely to be improved by collecting additional molecular sequence data. All analyses place the origin of Primates close to the K-Pg boundary, either in the Cretaceous or straddling the boundary into the Palaeogene.

@article{doi101093sysbiosyy001,
    author = "dos Reis, Mario and Gunnell, Gregg F. and Barba‐Montoya, Jose and Wilkins, Alex and Yang, Ziheng and Yoder, Anne D.",
    title = "Using Phylogenomic Data to Explore the Effects of Relaxed Clocks and Calibration Strategies on Divergence Time Estimation: Primates as a Test Case",
    year = "2018",
    journal = "Systematic Biology",
    abstract = "Primates have long been a test case for the development of phylogenetic methods for divergence time estimation. Despite a large number of studies, however, the timing of origination of crown Primates relative to the Cretaceous-Paleogene (K-Pg) boundary and the timing of diversification of the main crown groups remain controversial. Here, we analysed a data set of 372 taxa (367 Primates and 5 outgroups, 3.4 million aligned base pairs) that includes nine primate genomes. We systematically explore the effect of different interpretations of fossil calibrations and molecular clock models on primate divergence time estimates. We find that even small differences in the construction of fossil calibrations can have a noticeable impact on estimated divergence times, especially for the oldest nodes in the tree. Notably, choice of molecular rate model (autocorrelated or independently distributed rates) has an especially strong effect on estimated times, with the independent rates model producing considerably more ancient age estimates for the deeper nodes in the phylogeny. We implement thermodynamic integration, combined with Gaussian quadrature, in the program MCMCTree, and use it to calculate Bayes factors for clock models. Bayesian model selection indicates that the autocorrelated rates model fits the primate data substantially better, and we conclude that time estimates under this model should be preferred. We show that for eight core nodes in the phylogeny, uncertainty in time estimates is close to the theoretical limit imposed by fossil uncertainties. Thus, these estimates are unlikely to be improved by collecting additional molecular sequence data. All analyses place the origin of Primates close to the K-Pg boundary, either in the Cretaceous or straddling the boundary into the Palaeogene.",
    url = "https://doi.org/10.1093/sysbio/syy001",
    doi = "10.1093/sysbio/syy001",
    openalex = "W2762173626",
    references = "doi101016jympev201402023, doi101038nature14120, doi101093sysbiosyv080, doi101126science1683931578"
}

Understanding protective influenza immunity and identifying immune correlates of protection poses a major challenge and requires an appreciation of the immune system in all of its complexity. While adaptive immune responses such as neutralizing antibodies and influenza-specific T lymphocytes are contributing to the control of influenza virus, key factors of long-term protection are not well defined. Using systems immunology, an approach that combines experimental and computational methods, we can capture the systems-level state of protective immunity and reveal the essential pathways that are involved. New approaches and technological developments in systems immunology offer an opportunity to examine roles and interrelationships of clinical, biological, and genetic factors in the control of influenza infection and have the potential to lead to novel discoveries about influenza immunity that are essential for the development of more effective vaccines to prevent future pandemics. Here, we review recent developments in systems immunology that help to reveal key factors mediating protective immunity.

@article{tomic2021systems,
    author = "Tomic, Adriana and Pollard, Andrew J. and Davis, Mark M.",
    title = "Systems Immunology: Revealing Influenza Immunological Imprint",
    year = "2021",
    journal = "Viruses",
    abstract = "Understanding protective influenza immunity and identifying immune correlates of protection poses a major challenge and requires an appreciation of the immune system in all of its complexity. While adaptive immune responses such as neutralizing antibodies and influenza-specific T lymphocytes are contributing to the control of influenza virus, key factors of long-term protection are not well defined. Using systems immunology, an approach that combines experimental and computational methods, we can capture the systems-level state of protective immunity and reveal the essential pathways that are involved. New approaches and technological developments in systems immunology offer an opportunity to examine roles and interrelationships of clinical, biological, and genetic factors in the control of influenza infection and have the potential to lead to novel discoveries about influenza immunity that are essential for the development of more effective vaccines to prevent future pandemics. Here, we review recent developments in systems immunology that help to reveal key factors mediating protective immunity.",
    url = "https://doi.org/10.3390/v13050948",
    doi = "10.3390/v13050948",
    number = "5",
    openalex = "W3161006937",
    pages = "948",
    volume = "13",
    references = "doi1010020471142727mb2129s109, doi101016s0140673617332932, doi101038nature08182, doi101038ni1688, doi101038nrg3920, doi101038s4157301900245, doi101038s4157601900937, doi101056nejmoa2001017, doi101126science1198704, doi101161circulationaha115001593"
}