Immunology of Infectious Disease Commons^™

Exploring Immune System Through Computational Modeling: A Comprehensive Study Of Lymph Nodes And Immune Response Scaling, Vaccine Efficacy, And Large-Scale Extreme First Passage Time, Jannatul Ferdous

Computer Science ETDs

The adaptive immune response is a complex defense mechanism that develops over time to recognize and eliminate pathogens with remarkable precision and durability. This dissertation investigates the dynamics, scaling, and efficiency of the adaptive immune response through a synthesis of computational modeling, mathematical analysis, and agent-based simulations. First, we analyze the topology of the lymphatic network and investigate the T cell search time to find the lymph node that is containing the matching dendritic cell. Second we show how the scaling of lymph node number and volume with body mass, leads to scale-invariant search times for T cells locating antigen-bearing …

Alfred Russel Wallace Notes 37. What About Wallace On Vaccination . . . ?, Charles H. Smith

Faculty/Staff Personal Papers

Best known for his natural history studies on evolution and biogeography, Alfred Russel Wallace (1823−1913) had a significant second career as a social critic. One of his most controversial stances was his position on (smallpox) vaccination. Anti-vaxxers of the present frequently bring up his name as a resource for their side, but the situation is not so easily reducible to that.

Macrophage Heterogeneity And Function In The Lung, Xin Li

Dartmouth College Ph.D Dissertations

Macrophages are critical custodians of the lung, orchestrating immune surveillance, maintaining tissue homeostasis, and coordinating both innate and adaptive responses. This dissertation examines their heterogeneity and specialized functions, focusing on IMs, which reside in the lung interstitium, and AMs, which occupy the airspace. Through comprehensive single-cell transcriptomic profiling of murine and human samples, we identify multiple IM and AM subsets defined by distinct chemokine, cytokine, receptor, and innate immune gene signatures. These subsets display clear divisions of labor, contributing to immune cell recruitment, tertiary lymphoid structure formation, and alveolar homeostasis.

In IMs, coordinated chemokine programs not only recruit inflammatory cells …

Investigating Regulation Of Neutrophil-Mediated Inflammation In Mycoplasma Pneumoniae Infection, Nathan D. Velazquez

University Scholar Projects

No vaccine exists for Mycoplasma pneumoniae (Mp) infections, largely due to the

gap in understanding in the virulence and immunopathogenesis of this bacterium.

We have recently demonstrated that neutrophils are maladaptive in the context of

Mp infection, and drive disease severity while also impairing bacterial clearance.

Furthermore, we observed that B cells play a regulatory role in limiting disease

severity by modulating neutrophilic inflammation. We investigated this

phenomenon further to elucidate the mechanisms by which B cells regulate

neutrophilic inflammation. We utilized a monoclonal antibody to deplete B cells

during Mp infection and found that B-cell-depleted mice had elevated neutrophil …

Impact Of Temperature And Microbial Infection On The Honey Bee Hemocytes, Michael E. Oeth

Master's Theses

Introduction

Honey bees (Apis mellifera) rely on hemocytes for immunity, wound healing, and hemolymph homeostasis. While 32°C reflects optimal hive conditions, suboptimal temperatures (22°C) and stressors like pathogens (Varroa destructor, bacteria) or pesticides impair hemocyte function. Using clodronate liposomes (CLD) to deplete hemocytes, we assessed how immune suppression interacts with these stressors.

Methods

Newly emerged (5-day-old) and older (15-day-old) bees were assigned to: CLD, control liposomes (LP), PBS, injection wound, or no treatment. Cohorts were exposed to 32°C (optimal) or 22°C (stressful for non-immunosuppressed bees). Fifteen-day-old bees were challenged with Escherichia coli or Staphylococcus aureus. Survival, hemolymph volume, and hemocyte …

Which Costimulatory Domains In Chimeric Antigen Receptor T Cells Induce Cytokine Responses That Are Linked To A More Toxic Car T Cell Therapy In Acute Lymphocytic Leukemia?, Elisabeth Cohen

Longwood Senior Thesis Proposal

No abstract provided.

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

African Sleeping Sickness: From Basic Biology To Future Directions, Riddhi R. Patel

All Theses

African Sleeping Sickness is a Neglected Tropical Disease (NTD) which poses a significant health risk to impoverished populations in 36 Sub-Saharan African countries. It is a devastating disease caused by the protozoan parasite Trypanosoma brucei, which is transmitted to mammals via the bite of infected tsetse flies. The disease manifests in two stages: the hemolymphatic stage and the meningoencephalitic stage. In the latter stage, it invades the Central Nervous System (CNS) and can be fatal if left untreated. It is caused by morphologically indistinguishable species of Trypanosoma brucei in both humans and animals, where in humans it is known as …

Does A Waiting Room Increase Same-Day Treatment For Sexually Transmitted Infections Among Pregnant Women? A Quality Improvement Study At South African Primary Healthcare Facilities, Ranjana M. Gigi, Mandisa M. Mdingi, Lukas Bütikofer, Chibuzor M. Babalola, Jeffrey D. Klausner, Andrew Medina-Marino, Christina A. Muzny, Christopher M. Taylor, Janneke H. Van De Wijgert, Remco P. Peters, Nicola Low

School of Medicine Faculty Publications

BACKGROUND: Same-day testing and treatment of curable sexually transmitted infections (STI) is a strategy to reduce infection duration and onward transmission. South African primary healthcare facilities often lack sufficient waiting spaces. This study aimed to assess the proportion of, and factors influencing, pregnant women waiting for on-site STI test results before and after the installation of clinic-based waiting rooms. METHODS: We conducted an observational quality improvement study at 5 public primary healthcare facilities in South Africa from March 2021 to May 2023. The intervention was the installation of a waiting room in two clinics. Three clinics were used as comparators: …

Clinical Characteristics And Outcomes Of Pediatric Staphylococcal Scalded Skin Syndrome (Ssss) At An Inner-City Tertiary Care Center, Nina Kb Gust Md, Ashley Frei Bs, Rebecca M. Adams Bs, Elika Ridelman Phd, Christina Shanti Md, Ronald Thomas Phd, Jocelyn Y. Ang Md

Medical Student Research Symposium

Introduction

Staphylococcal Scalded Skin Syndrome (SSSS) is a blistering skin condition caused by a toxin-producing staphylococcus species. Epidemiologic studies on pediatric SSSS in the United States are limited, with a reported incidence of 7.67 cases per million children and 45.1 per million infants. Immature renal function, lack of protective antibodies, and increased exotoxin target desmoglein-1 are hypothesized to increase incidence in younger children. We aimed to determine clinical and microbiological characteristics of pediatric SSSS and factors that could help predict disease severity.

Methods

A retrospective chart review was performed for admitted patients under 18 years old diagnosed with SSSS from …

Soluble Cd13 Is A Potential Mediator Of Neutrophil-Induced Thrombogenic Inflammation In Sars-Cov-2 Infection, Pei-Suen Tsou, Ramadan A. Ali, Chenyang Lu, Gautam Sule, Carmelo Carmona-Rivera, Serena Lucotti, Yuzo Ikari, Qi Wu, Phillip L. Campbell, Mikel Gurrea-Rubio, Kohei Maeda, Sharon E. Fox, William D. Brodie, Megan N. Mattichak, Caroline Foster, Ajay Tambralli, Srilakshmi Yalavarthi, M Asif Amin, Katarina Kmetova, Bruna Mazetto Fonseca, Emily Chong, Yu Zuo, Michael D. Maile, Luisa Imberti, Arnaldo Caruso, Francesca Caccuri, Virginia Quaresima, Alessandra Sottini, Douglas B. Kuhns, Et Al

School of Medicine Faculty Publications

The soluble variant of the ectopeptidase CD13 (sCD13), released from the cell surface by matrix metalloproteinase 14 (MMP14), is a potent pro-inflammatory mediator, displaying chemotactic, angiogenic, and arthritogenic properties through bradykinin receptor B1 (B1R). We revealed a link between sCD13 and amplified neutrophil-mediated inflammatory responses in SARS-CoV-2 infection. sCD13 was markedly elevated in patients with COVID-19 and correlated with disease severity and variants, ethnicity, inflammation markers, and neutrophil extracellular trap formation (NETosis). Neutrophils treated with sCD13 showed heightened NETosis and chemotaxis, which were inhibited by sCD13 receptor blockade. Meanwhile sCD13 did not induce platelet aggregation. Single-cell analysis of COVID-19 lungs …

Neutrophil Inflammatory Death Regulation By Bacterial Type Iii Secreted Effectors, Arianna D. Reuven

Dartmouth College Ph.D Dissertations

Yersinia and Pseudomonas use a T3SS to secrete effectors into host cells that inhibit phagocytosis and modulate immune responses, such as inflammasome activation. Inflammasomes promote the activation of the proinflammatory protease caspase-1. The activation of an inflammasome sensor in response to a signal or ligand initiates the assembly of the inflammasome leading to activation of caspase-1 which cleaves GSDMD and pro-inflammatory cytokines IL-1β and IL-18 into their mature forms. As neutrophils are recruited in large quantities to sites of infection, they are excellent candidates to drive inflammasome dependent responses. Neutrophils have been shown to produce multiple inflammasomes, like pyrin and …

Confounding Factors Of Cervical Carcinogenesis And Cervical Cancer Health Disparity, Vivek Kumar Kashyap, Namita Sinha, Nadeem Zafar, Murali M. Yallapu, Santosh Kumar, Everardo Cobos, Subhash C. Chauhan

Research Symposium

Clinical studies show that cervical cancer is the most frequently detected cancer in women living with human immunodeficiency virus (HIV), which has been defined as an acquired immunodeficiency syndrome (AIDS). Women living with HIV are 6 times more likely to develop cervical cancer compared to the general population, and an estimated 5% of all cervical cancer cases are attributable to HIV. Studies suggest that several genes are involved in different molecular pathways, which can influence the vulnerability, severity, or advancement of cervical cancer in the presence of HIV and human papillomavirus (HPV) co-infection. Clinical studies have also shown levels of …

Development Of A Multi-Epitope Peptide Vaccine Against Monkeypox Virus: Immunoinformatics Analysis For South East Asian Hla Alleles, Nelson Chandra, Mochammad Aqilah Herdiansyah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit

Makara Journal of Science

The monkeypox virus (MPXV), a DNA virus causing zoonotic disease, poses major global public health challenges, with mortality rates between 3%–6%. Although smallpox vaccines provide partial cross-protection, there is a critical need for a dedicated, effective monkeypox (mpox) vaccine. This study aimed to design a multi-epitope peptide-based vaccine specifically adapted to the HLA allele profiles common in Southeast Asian populations, where MPXV cases are rising. Using immunoinformatics, we screened for and detected B and T cell epitopes from the MPXV cell surface antigen and IFN-alpha/beta receptor proteins. The vaccine design was validated through a rigorous evaluation of its antigenicity, immunogenicity, …

Survey Of Mosquito Larval Habitats At The Ksu Field Station, Rose Sofia, Eli Lovvorn, Aspen Hartman, Andrew Haddow

Symposium of Student Scholars

The greater Atlanta metropolitan area hosts numerous mosquito species that are nuisance biters and can transmit arthropod-borne diseases to humans. We surveyed the Kennesaw State University (KSU) Field Station – an incredibly biodiverse location – where student, staff, and faculty-led groups engage in outdoor research and teaching activities. The KSU Field Station located in Cobb County, GA is a heavily trafficked 25-acre property that may attract various mosquito species capable of transmitting pathogens to humans and animals alike. On August 27th, 2024, our team investigated the KSU Field Station to quantify and record potential water-holding containers that serve as mosquito …

Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …

Comprehensive Sumo Proteomic Analyses Identify Hiv Latency-Associated Proteins In Microglia., Fergan Imbert, Dianne Langford

Rowan-Virtua School of Osteopathic Medicine Departmental Research

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at …

Characterizing Malaria Infections In Caribbean Lizards: Parasite Niche Expansion & Host Response, Sarah J. Pangburn

Dissertations, Theses, and Capstone Projects

Malaria is historically one of the most severe parasitic human diseases and is still responsible for over half a million deaths annually. Plasmodium species, the causative agents of malaria, are often characterized by two hallmark features of their asexual stages: the invasion of vertebrate red blood cells and the presence of hemozoin pigment as a byproduct of host hemoglobin digestion. Despite their evolutionary relatedness to mammalian Plasmodium, wildlife malaria parasites are understudied, leaving their vast genetic diversity to be explored. Lizard-infective malaria parasites, for example, include over 100 species of Plasmodium and present a diverse array of phenotypes, some …

Inflammatory Hyperplastic Mass Mimicking Local Recurrence Following Endoscopic Submucosal Dissection Of A Colonic Adenoma, Isiah Gonzalez, Linda K Green, Salmaan Jawaid, Wasseem Skef

Faculty, Staff and Students Publications

This case presents a hyperplastic inflammatory mass at the resection site of a colorectal tubular adenoma. A 65-year-old man with a history of alcohol-associated liver cirrhosis, >10 lifetime polyps, and a CHEK2 mutation underwent hybrid endoscopic submucosal dissection of a 3 cm lateral spreading tumor, nongranular, Paris 0-IIa polyp in the ascending colon. Postresection pathology confirmed tubular adenoma with negative margins (R0). Six-month surveillance colonoscopy in the community identified a mass at the resection site, initially suspected to be local recurrence. Repeat colonoscopy demonstrated a mass which appeared inflammatory, with a Kudo type II hyperplastic pit pattern on narrow-band imaging …

Immuno-Bioinformatics Study Of Secondary Metabolites From Watercress Nasturtium Officinale As Immunostimulant In Whiteleg Shrimp Litopenaeus Vannamei By Targeting Peroxinectin And Scavenger Receptor Class B, Qurrota A’Yunin, Muhaimin Rifa’I, Maftuch Maftuch, Yoga Dwi Jatmiko, Muhammad Hermawan Widyananda, Triyanto Triyanto, Muhammad Tegar Handrianto

Karbala International Journal of Modern Science

The viral disease affects the whiteleg shrimp (Litopenaeus vannamei) and causes losses. Immunostimulants are recognized as a more environmentally friendly approach to disease management and antimicrobial properties of aquatic organisms. Watercress (Nasturtium officinale) is an aquatic plant species that contains antioxidant properties that can protect the organism from disease and boost the immune system. Shrimp rely heavily on innate immunity to combat infectious agents due to their absence of adaptive immunity. Peroxinectin and scavenger receptor class B (SRB) play essential roles in the shrimp defense system. This research employs a bioinformatic to assess the immunostimulatory potential …