dc.contributor.advisor | Dixit, Narendra M | |
dc.contributor.author | Garg, Amar Kumar | |
dc.date.accessioned | 2021-09-29T06:27:07Z | |
dc.date.available | 2021-09-29T06:27:07Z | |
dc.date.submitted | 2018 | |
dc.identifier.uri | https://etd.iisc.ac.in/handle/2005/5355 | |
dc.description.abstract | Passive immunization has been used classically to rapidly clear antigen
and reduce disease burden. Surprisingly, recent studies have found passive
immunization to induce lasting improvements in the humoral response, pre-
senting a novel strategy to elicit potent antibodies against pathogens includ-
ing HIV-1. How passive immunization alters the humoral response is poorly
understood. Here, we hypothesized that administered antibodies raise the
selection stringency in germinal centres (GCs) by preferentially forming im-
mune complexes with antigen and letting only B cells with higher affinities
acquire antigen and survive. We performed stochastic simulations of the
GC reaction based on this hypothesis. Our simulations recapitulated sev-
eral independent experimental observations, presenting successful tests of
the hypothesis. Further, the simulations unravelled a quality-quantity trade-
o constraining the GC response. Greater selection stringency yielded fewer
surviving B cells but with higher affinity for antigen. Increasing antigen avail-
ability relaxed the constraint. Comprehensively exploring parameter space,
our simulations identi fied passive immunization protocols that exploited the
quality-quantity trade-off and maximized the GC output. Together, our
study presents a new conceptual understanding of the GC reaction and a
robust computational framework for the rational optimization of passive im-
munization strategies. | en_US |
dc.language.iso | en_US | en_US |
dc.relation.ispartofseries | ;G29309 | |
dc.rights | I grant Indian Institute of Science the right to archive and to make available my thesis or dissertation in whole or in part in all forms of media, now hereafter known. I retain all proprietary rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part
of this thesis or dissertation | en_US |
dc.subject | immunization | en_US |
dc.subject | Passive immunization | en_US |
dc.subject | antibodies | en_US |
dc.subject | Immune complexes | en_US |
dc.subject | germinal centres | en_US |
dc.subject.classification | Research Subject Categories::TECHNOLOGY::Chemical engineering | en_US |
dc.title | Quality-quantity trade off during antibody production and the design of optimal passive immunization protocols | en_US |
dc.type | Thesis | en_US |
dc.degree.name | MTech (Res) | en_US |
dc.degree.level | Masters | en_US |
dc.degree.grantor | Indian Institute of Science | en_US |
dc.degree.discipline | Engineering | en_US |