Microbiology Commons^™

Examining Early Interactions Between Innate Airway Resident Immune Cells And Mtb-Specific Factors During Pulmonary Infection With Mycobacterium Tuberculosis, Micah D. Dunlap

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis (Mtb) is the leading cause of death by an infectious agent in the world today, infecting roughly one quarter of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized.

Lung resident Alveolar Macrophages (AMs) are the first host contact with Mtb bacilli after inhalation and are thus key mediators of the early pulmonary immune response. AMs are generally believed to reside entirely in the airway, but it was recently demonstrated that they have the capacity to egress and enter into granulomas during pulmonary infection with hypervirulent Mtb. Furthermore, …

Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh

Arts & Sciences Electronic Theses and Dissertations

Protective immune responses to Mycobacterium tuberculosis (Mtb) must induce bactericidal functions while minimizing damage to the lung. Such responses require precise control of pro- and anti-inflammatory factors to regulate the recruitment and function of protective immune cells but the mechanisms by which this control is exerted remain incompletely defined. Basic helix-loop-helix family, member e40 (Bhlhe40) is a transcription factor known to regulate production of pro- and anti-inflammatory cytokines that affect protective immunity to Mtb. Immune-responsive Gene 1 (Irg1) is an enzyme that generates itaconate, a metabolite with potential anti-inflammatory and antibacterial roles during Mtb infection. The impact of Bhlhe40 and …

The Role Of Bhlhe40 In Autoimmune Neuroinflammation And Mycobacterial Infection, Chih-Chung Lin

Arts & Sciences Electronic Theses and Dissertations

The mammalian immune system is composed of innate and adaptive compartments, which cooperate with each other to maintain homeostasis and protect the host from the invasion by a variety of pathogens. The tight control of immune responses is extremely important for all individuals. Here, we discovered that the transcription factor basic helix-loop-helix family, member e40 (Bhlhe40) is a critical protein that regulates the autoimmune ("against self") and anti-microbial ("against non-self") responses of myeloid cells and T lymphocytes. Multiple sclerosis (MS) is a human neuroinflammatory disease in the central nervous system with an autoimmune etiology. We have reported that Bhlhe40 positively …

Tuberculosis In Vulnerable Populations In Eastern Mediterranean Region-Implications For Control, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objectives: Socially and economically disadvantaged or "vulnerable" people are at high risk of tuberculosis (TB) and also contribute to active chains of TB transmission. Included in such vulnerable populations are children, women, prisoners, people living with human immunodeficiency virus, the homeless, and displaced people. The ongoing active transmission of TB among such populations is made more difficult to assess and control by difficult access, health inequities, poverty, and other chronic and debilitating health conditions at individual, domestic, and community levels.
Methods: The 22 Eastern Mediterranean Region member states encompass diverse sociopolitical and socioeconomic situations with far-reaching effects on vulnerable populations …

Drug Resistant Tuberculosis: Challenges Of Urbanization, Rumina Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

Histologic Findings In Biopsies/Resection Specimens From The Small Intestine With Special Emphasis On Celiac Disease: Experience From A Developing Country In South Asia, Huma Arshad, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Biopsies from the small intestine especially the duodenum are now being performed much more frequently than in the past. The most frequent reason for performing duodenal biopsies is to evaluate for malabsorption. In the last few years, increased awareness has resulted in more biopsies sent for evaluation of malabsorption, especially celiac disease (CD). In the duodenum, features of malabsorption (increased intraepithelial lymphocytes, villous shortening, and atrophy) were the most common histologic finding seen in 63.4% of cases. Serum tTG levels were available for correlation in 52.8% of cases. In patients with confirmed CD, 53.4% were MARSH IIIb, and 29.5% were …

Line Probe Assay For Detection Of Rifampicin And Isoniazid Resistant Tuberculosis In Pakistan, Joveria Qais Farooqi, Erum Khan, Syed Muhammed Zaheer Alam, Asho Ali, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective:
To assess the efficacy of a line-probe assay delta (LiPA) as rapid diagnostic test for early detection of drug-resistant tuberculosis compared to conventional susceptibility methods in Pakistan.
Methods:
Resistance to rifampicin (RIF) and isoniazid (INH) in 108 smear-positive pulmonary tuberculosis samples was detected using a line-probe assay [GenoType MTBDRplus (Hain Lifescience, GmbH, Nehren, Germany)] at the clinical microbiology laboratory of Aga Khan University Hospital in May, 2009. Results were compared with susceptibilities performed while using agar proportion.
Results:
In comparison to the agar proportion method, the detection rate and specificity of resistance using MTBDR plus was 92.5% and 98.2% …

Presence Of Rd149 Deletions In M. Tuberculosis Central Asian Strain 1 Isolates Affect Growth And Tnfalpha Induction In Thp-1 Monocytes., Akber Kanji, Zahra Hasan, Mehnaz Tanveer, Raunaq Mahboob, Sana Jafri, Rumina Hasan

Department of Pathology and Laboratory Medicine

Central Asian Strain 1 (CAS1) is the prevalent Mycobacterium tuberculosis genogroup in South Asia. CAS1 strains carry deletions in RD149 and RD152 regions. Significance of these deletions is as yet unknown. We compared CAS1 strains with RD149 and concurrent RD149-RD152 deletions with CAS1 strains without deletions and with the laboratory reference strain, M. tuberculosis H37Rv for growth and for induction of TNFα, IL6, CCL2 and IL10 in THP-1 cells. Growth of CAS1 strains with deletions was slower in broth (RD149; p = 0.024 and RD149-RD152; p = 0.025) than that of strains without deletions. CAS1 strains with RD149 deletion strains …

Esat6-Induced Ifngamma And Cxcl9 Can Differentiate Severity Of Tuberculosis., Zahra Hasan, Bushra Jamil, Mussarat Ashraf, Muniba Islam, Muhammad S Yusuf, Javaid A Khan, Rabia Hussain

Department of Pathology and Laboratory Medicine

Background: Protective responses against Mycobacterium tuberculosis are dependent on appropriate T cell and macrophage activation. Mycobacterial antigen six kDa early secreted antigenic target (ESAT6) and culture filtrate protein 10 (CFP10) can detect M. tuberculosis specific IFNgamma responses. However, most studies have been performed in non-endemic regions and to study pulmonary tuberculosis (PTB). We have studied ESAT6 and CFP10 induced cytokine and chemokines responses in PTB and extrapulmonary (EPul) TB.
Methodology: IFNgamma, IL10, CXCL9 and CCL2 responses were determined using an ex vivo whole blood assay system in PTB (n = 30) and EPulTB Patients with limited (LNTB, n = …

Cytokine Gene Polymorphisms Across Tuberculosis Clinical Spectrum In Pakistani Patients., Ambreen Ansari, Najeeha Talat, Bushra Jamil, Zahra Hasan, Tashmeem Razzaki, Ghaffar Dawood, Rabia Hussain

Department of Pathology and Laboratory Medicine

Background:Pakistan ranks 7(th) globally in terms of tuberculosis (TB) disease burden (incidence 181/100000 pop./yr, prevalence of 329/pop./yr). Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuberculosis clinical severity is multi-factorial and cytokines play a pivotal role in the modulation of disease severity. We have recently reported that the ratio of two key cytokines (IFNgamma and IL10) show significant correlation with the severity spectrum of tuberculosis. The objective of the current study was to analyze the frequency of cytokine gene polymorphisms linked to high and low responder phenotypes (IFNgamma +874 T(hi)-->A(lo) …