Immunity Commons^™

Bmp Signaling Co-Regulation Of Immune Response And Lipid Metabolism, Katerina K. Yamamoto

Dissertations, Theses, and Capstone Projects

The Bone Morphogenetic Proteins (BMPs) are secreted peptide ligands of the Transforming Growth Factor beta (TGF-β) family, initially identified for their roles in development and differentiation across animal species. They are now increasingly recognized for their roles in physiology and infectious disease. In the nematode Caenorhabditis elegans, the BMP ligand DBL-1 controls fat metabolism and immune response, in addition to its roles in body size regulation and development. DBL-1 regulates classical aspects of innate immunity, including the induction of anti-microbial peptides. We theorized that BMP-dependent regulation of fat metabolism could also promote resilience against microbial pathogens. We found that …

Tgf-B Signaling Mechanisms In Caenorhabditis Elegans Response To Bacterial Pathogens, Emma J. Ciccarelli

Dissertations, Theses, and Capstone Projects

When exposed to infection, the nematode C. elegans mounts an innate immune response through secretion of antimicrobial peptides (AMPs). Different signaling pathways in the worm regulate release of these AMPs. One highly conserved pathway is the C. elegans BMP like pathway – regulated by the ligand DBL-1. The DBL-1 pathway is noted for its significant role in development but has also been shown to regulate many post-developmental processes within the worm, including the immune response. We are interested in determining how DBL-1 signaling can mediate a response specific to immunity, separate from its other functions in the worm. Through survival …

Function Of Atm And Msh2 During Dna Repair And Recombination, Emily Sible

Dissertations, Theses, and Capstone Projects

Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm^-/- mice …

Innate Antibodies, Murine Models, And Evolution: A Study Of Trypanosome Lytic Factor Functions And Their Translational Applications, Joseph P. Verdi

Dissertations, Theses, and Capstone Projects

Trypanosome lytic factors (TLFs) are primate-specific antimicrobial protein complexes that lyse African trypanosome parasites by delivering the channel-forming toxin APOL1 to the invading microorganisms. Human serum contains two TLFs that are delivered to the parasite by separate mechanisms, only one of which has been characterized. TLF1 is endocytosed by a receptor that is typically blocked by other serum factors in vivo, suggesting that TLF2 is the more relevant lytic factor in the context of trypanosome immunity. TLF2 is non-covalently associated with polyclonal immunoglobulin M (IgM) antibodies, which we report here to be involved in the uptake mechanism. The TLF2-IgMs …

Characterization Of Immunomodulatory Microbial Factors In Medicinal Plants, Kriti Kalpana

Dissertations, Theses, and Capstone Projects

Medicinal plants are one of the biggest sources of natural products with therapeutic importance. There are currently over 28,000 plants with putative medicinal values. Plant-derived compounds have been explored extensively for various biological activities ranging from anti-cancer, immune-boosting to anti-inflammatory and anti-oxidant. Some of the most important therapeutic agents are of plant-origin, such as paclitaxel from Pacific yew (Taxus brevifolia) and artemisinin from qinghao su (a Chinese medicinal herb; a.k.a. Artemisia annua) to name a few.

The study presented in this thesis started out as classical pharmacognosy research, which focused on the identification of immunostimulatory factors in …

Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee

Dissertations, Theses, and Capstone Projects

Glioblastoma (GBM) is one of the most deadly forms of cancer with a mean 5-year survival rate of ≤5%. We have used the non-invasive strategy of long-term intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of murine GBM cell line GL261-implanted mice to study the therapeutic effect of CC on GBM remission. The treatment caused GBM tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate (60%) was also achieved through long-term intraperitoneal (i.p) infusion of a highly bioavailable phosphotidylcholine (PC)-encapsulated formulation of CC, Curcumin Phytosome Meriva (CCP), into the GL261-implanted GBM …