Evolution of Adaptive Immunity
适应性免疫的进化
基本信息
- 批准号:9899205
- 负责人:
- 金额:$ 38.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-07-15 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdoptedAdultAffinityAmphibiaAnimalsAntibodiesAntibody ResponseAntigen PresentationAntigen ReceptorsAntigen-Presenting CellsAntigensAreaAutoimmunityB-Lymphocyte SubsetsB-LymphocytesBacteriaBindingBinding SitesBirdsBloodCarbohydratesCellsCommunicable DiseasesCrystallizationDataDendritic CellsDevelopmentEvolutionFishesFollicular Dendritic CellsGenesGrowthHistocompatibility Antigens Class IIHumanHumoral ImmunitiesImmuneImmune responseImmune systemImmunityImmunizationImmunoglobulin GenesImmunoglobulin MImmunoglobulinsImmunologyJawLampreysLicensingLicensing FactorLightLymphocyteLymphoid TissueMajor Histocompatibility ComplexMalignant NeoplasmsMalpighian corpusclesMammalsModelingMovementMucosal ImmunityMusNewborn AnimalsOsteichthyesPhenotypeRanaReptilesResearchSharkSpecificityStructureSurfaceT-Cell ReceptorT-LymphocyteTestingTimeTissuesTumor Necrosis Factor-BetaVertebratesWorkadaptive immune responseadaptive immunitybasechemokinecold blooded vertebratecomparativefightingjuvenile animalprospectiveresponse
项目摘要
SUMMARY
Studies of nonmammalian vertebrates (fish, amphibians, reptiles, and birds) have provided
essential discoveries in adaptive immunity, especially regarding lymphocyte lineages, origins of
the major histocompatibility complex (MHC), mucosal immunity, and antigen receptors. From
work that we have done in sharks, the oldest living vertebrates with immunoglobulins, T cell
receptors and the MHC, we hypothesize that the mammalian B1 cell paradigm is operable in
neonatal and young animals. Sharks also have antibodies with invariant binding sites (germline-
joined gene-encoded antibodies), which are expressed in secretory B cells but not in naïve B
cells. The antibody is modeled to have an unusual binding site, it binds to self tissues and
bacteria, and it is proposed to be a model for B1-derived antibodies in mammals. A second
wave of shark B cells with a unique immunoglobulin repertoire (also B1-like, with little N-region
addition) forms the nascent splenic white pulp, also proposed to be the paradigm for all
vertebrates, which we will test in mice and amphibians. Regarding humoral immune responses,
it is well known that nonmammalian vertebrates have poor affinity maturation of the antibody
response and seem to lack follicular dendritic cells (FDC); thus the mechanism of how native
antigen is presented to B cells is poorly understood. We have re-identified an antigen presenting
cell (APC) in frogs that expresses high levels of MHC class II, and yet presents native antigen
on its surface in the center of B cell follicles relatively late after immunization. We hypothesize
that these APC perform a `double-duty,' presenting antigen to both T cells and B cells. Our data
suggest that T cells are stimulated by these APC early in a response, and then the activated T
cells license the APC to stop degrading antigen, upregulate B cell chemokines (cxcl13), and
enter the follicle to present antigen to specific B cells. We hypothesize that this cell represents
the paradigm for humoral responses in cold-blooded vertebrates, and that conventional
mammalian DC can take on this `double-duty' phenotype in particular immune responses.
总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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Martin F Flajnik其他文献
The last flag unfurled? A new immunoglobulin isotype in fish expressed in early development
最后一面旗帜展开了吗?鱼类早期发育中表达的一种新的免疫球蛋白同种型
- DOI:
10.1038/ni0305-229 - 发表时间:
2005-03-01 - 期刊:
- 影响因子:27.600
- 作者:
Martin F Flajnik - 通讯作者:
Martin F Flajnik
All GOD's creatures got dedicated mucosal immunity
所有上帝的造物都有专门的黏膜免疫。
- DOI:
10.1038/ni0910-777 - 发表时间:
2010-09-01 - 期刊:
- 影响因子:27.600
- 作者:
Martin F Flajnik - 通讯作者:
Martin F Flajnik
Martin F Flajnik的其他文献
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{{ truncateString('Martin F Flajnik', 18)}}的其他基金
Highly Stable, Anthrax-specific Shark Antibody Fragment
高度稳定的炭疽特异性鲨鱼抗体片段
- 批准号:
6771109 - 财政年份:2003
- 资助金额:
$ 38.63万 - 项目类别:
Highly Stable, Anthrax-specific Shark Antibody Fragment
高度稳定的炭疽特异性鲨鱼抗体片段
- 批准号:
6675141 - 财政年份:2003
- 资助金额:
$ 38.63万 - 项目类别:
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