Show simple item record

dc.contributor.advisorWetzler, Lee M.en_US
dc.contributor.advisorHenderson, Andrewen_US
dc.contributor.authorLisk, Christina Marieen_US
dc.date.accessioned2020-02-14T18:45:13Z
dc.date.available2020-02-14T18:45:13Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/2144/39410
dc.description.abstractVaccines are credited with saving millions of lives, yet there still remain infectious diseases with no effective vaccine. Subunit vaccines contain specific components from pathogens, which, cannot stimulate the immune system alone, necessitating the inclusion of an immunostimualtory adjuvant. Toll-like receptor (TLR) ligands, due to their immunostimualliting ability are being explored as potential adjuvants. To further advance vaccine development, thorough investigations need to be performed to characterize cellular interactions within the immune system after stimulation and how adjuvants affect this process including antigen distribution within the draining lymph node. Our studies have focused on a TLR2/TLR1-ligand based adjuvant, PorB, the major outer membrane protein from Neisseria meningitidis. We hypothesized that TLR adjuvants would increase antigen deposition onto follicular dendritic cells (FDC) which would enhance high affinity antibody production and that depletion or knockouts of subcapsular sinus CD169+ macrophages would negatively affect antibody production. We demonstrated that PorB increased FDC frequency and antigen deposition on these FDCs. Further studies examined the role of CD169+ macrophages in PorB adjuvanticity using low-dose clodronate treated mice (which preferentially removes CD169+ macrophages), or CD169 knockout mice. Compared to wildtype controls, low-dose clodronate mice and CD169 knockout mice had greatly decreased antibody response with the use or PorB as an adjuvant along with decreased antigen deposition on FDCs. Together, these data emphasize the effect of adjuvant stimulation on cellular interactions antigen distribution in lymph nodes along with the unique ability of PorB to affect this process.en_US
dc.language.isoen_US
dc.subjectImmunologyen_US
dc.subjectAdjuvantsen_US
dc.subjectImmunologyen_US
dc.subjectPorin Ben_US
dc.subjectTLR agonistsen_US
dc.subjectVaccinesen_US
dc.titleCD169+ subcapsular sinus macrophages are necessary for adjuvant activity of TLR ligands and antigen deposition onto follicular dendritic cellsen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2020-01-30T17:06:23Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineMolecular and Translational Medicineen_US
etd.degree.grantorBoston Universityen_US
dc.identifier.orcid0000-0001-6217-4063


This item appears in the following Collection(s)

Show simple item record