Insights Into CD4 T Cell-Mediated Immunity to Influenza Viruses PDF Download
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Author: Anthony Thomas DiPiazza
Publisher:
ISBN:
Category :
Languages : en
Pages : 290
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Book Description
Influenza A viruses continue to pose a threat to human health worldwide and virusspecific CD4 T cells are key to protective immunity. The goal of the experiments within this thesis was to provide novel insight into elements within CD4 T cell responses that influence CD4 T cell specificity and function. Using a combination of novel reporter viruses, intravascular labeling in vivo, multi-parameter flow cytometry, and cytokine ELISpot procedures in two mammalian models, this work examined various stages of the developing immune response and the relationship between antigen acquisition, CD4 T cell fate choice, trafficking and compartmentalization within the inflamed lung, antigen specificity, and cytokine functionality. We found that pandemic 2009 H1N1 virus infection resulted in a broad pattern of viral antigen acquisition in the lung. Complex subpopulations of MHC class II-positive cells from both the hematopoietic and non-hematopoietic lineages were identified, with dynamic shifts over time. Our results demonstrated that antigen access occurs by uptake of exogenous antigen as well as infection. Finally, our results confirmed that many different cell types displayed peptide:MHC class II complexes in situ and possessed the capacity to stimulate influenza-specific CD4 T cells. These results correlated with differences in infection status, cell lineage, and MHC class II expression. These data suggest that there are many different types of antigen presenting cells in the lung that may impose additional checkpoints of CD4 T cell functionality and regulation. At the peak of the immune response, we found that lung CD4 T cells compartmentalized to vasculature and tissue. Antigen-experienced CD4 T cells were enriched in the tissue and expressed higher levels of molecules involved in trafficking to sites of pulmonary infection, damage, and repair. Surprisingly, we found similar representation in the fine specificity, immunodominance hierarchy, and polyfunctional potential of effector CD4 T cells in the two compartments. These results suggest that imprinting of CD4 effector programs in the priming lymph node plays a strong deterministic influence on CD4 function and fate. Also, we provide evidence of cellular intermediates in CD4 T cell trafficking in the lung. Finally, this thesis includes the first description of the CD4 and CD8 T cell repertoires in response to infection, a key step needed to advance the ferret model forward for future transmission and vaccine studies. Mechanistic studies of infection and vaccination in domestic ferrets may reveal novel links between antigen specificity and effector function, cellular correlates of protection, and the merits, consequences, and cellular heterogeneity of complex immunological memory.
Author: Anthony Thomas DiPiazza
Publisher:
ISBN:
Category :
Languages : en
Pages : 290
Get Book Here
Book Description
Influenza A viruses continue to pose a threat to human health worldwide and virusspecific CD4 T cells are key to protective immunity. The goal of the experiments within this thesis was to provide novel insight into elements within CD4 T cell responses that influence CD4 T cell specificity and function. Using a combination of novel reporter viruses, intravascular labeling in vivo, multi-parameter flow cytometry, and cytokine ELISpot procedures in two mammalian models, this work examined various stages of the developing immune response and the relationship between antigen acquisition, CD4 T cell fate choice, trafficking and compartmentalization within the inflamed lung, antigen specificity, and cytokine functionality. We found that pandemic 2009 H1N1 virus infection resulted in a broad pattern of viral antigen acquisition in the lung. Complex subpopulations of MHC class II-positive cells from both the hematopoietic and non-hematopoietic lineages were identified, with dynamic shifts over time. Our results demonstrated that antigen access occurs by uptake of exogenous antigen as well as infection. Finally, our results confirmed that many different cell types displayed peptide:MHC class II complexes in situ and possessed the capacity to stimulate influenza-specific CD4 T cells. These results correlated with differences in infection status, cell lineage, and MHC class II expression. These data suggest that there are many different types of antigen presenting cells in the lung that may impose additional checkpoints of CD4 T cell functionality and regulation. At the peak of the immune response, we found that lung CD4 T cells compartmentalized to vasculature and tissue. Antigen-experienced CD4 T cells were enriched in the tissue and expressed higher levels of molecules involved in trafficking to sites of pulmonary infection, damage, and repair. Surprisingly, we found similar representation in the fine specificity, immunodominance hierarchy, and polyfunctional potential of effector CD4 T cells in the two compartments. These results suggest that imprinting of CD4 effector programs in the priming lymph node plays a strong deterministic influence on CD4 function and fate. Also, we provide evidence of cellular intermediates in CD4 T cell trafficking in the lung. Finally, this thesis includes the first description of the CD4 and CD8 T cell repertoires in response to infection, a key step needed to advance the ferret model forward for future transmission and vaccine studies. Mechanistic studies of infection and vaccination in domestic ferrets may reveal novel links between antigen specificity and effector function, cellular correlates of protection, and the merits, consequences, and cellular heterogeneity of complex immunological memory.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 650
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Book Description
The immunobiology of respiratory virus infection is complex, and immunity depends upon the successful integration of contributions from the innate, humoral, and cell-mediated branches of the immune system. This dissertation focuses on cell-mediated immunity to respiratory viruses, and was motivated by 3 main questions 1) how and under what circumstances can the novel vaccine adjuvant Adjuplex® generate CD8 T-cell responses to non-replicating antigens, 2) what are the key gaps in our knowledge of anti-viral CD4 T-cell memory, and 3) can a systems biology analysis be used to elucidate the complex biology of ferret host responses to pandemic influenza viruses. We found that the vaccine adjuvant Adjuplex® can elicit potent CD8+ T-cell responses to non-replicating antigens in mice, and can be administered by multiple routes. We also found that systemic and intranasal vaccinations with Adjuplex® generate similar CD8+ T-cell recall responses in the lung after influenza challenge. However, only intranasal vaccines are protective, and protection correlates with increased effector and resident memory populations in the lung. Importantly, intranasal vaccination also results in potent heterosubtypic immunity. Mechanistically, Adjuplex® functions through complex interactions with innate cells in vivo and in vitro, including alterations in recruitment and activation of antigen-presenting cells, as well as antigen up-take and processing. Next, we identified important functionally distinct subsets of CD4 T cells that differ in their phenotype, trafficking patterns, and intrinsic abilities to differentiate into memory cells, and proposed a new integrated model for understanding CD4 T-cell memory generation that accounts for phenotypic plasticity. Lastly, we characterized and validated a complex systems-biology approach to analyzing host immune responses to infection with influenza, and in doing so identified new associations between histologic lesions, virus subtypes, gene expression patterns, and changes in abundance of lipids, metabolites, and proteins during the course of infection. This research provides critical insights into the mechanisms by which vaccine adjuvants can be used to generate protective CD8 T-cell immunity to non-replicating antigens, outlines a new model for understanding CD4 T cell memory generation, and validates the use of systems biology approaches to gain critical insights into the complex host responses to influenza virus infection.
Author: R. Ahmed
Publisher: Wiley-Blackwell
ISBN:
Category : Medical
Languages : en
Pages : 754
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Book Description
Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309220424
Category : Science
Languages : en
Pages : 200
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Book Description
For many years, experiments using chimpanzees have been instrumental in advancing scientific knowledge and have led to new medicines to prevent life-threatening and debilitating diseases. However, recent advances in alternate research tools have rendered chimpanzees largely unnecessary as research subjects. The Institute of Medicine, in collaboration with the National Research Council, conducted an in-depth analysis of the scientific necessity for chimpanzees in NIH-funded biomedical and behavioral research. The committee concludes that while the chimpanzee has been a valuable animal model in the past, most current biomedical research use of chimpanzees is not necessary, though noted that it is impossible to predict whether research on emerging or new diseases may necessitate chimpanzees in the future.
Author: Giovane R. Sousa
Publisher: Frontiers Media SA
ISBN: 2889763919
Category : Science
Languages : en
Pages : 298
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Book Description
Author: Richard W. Compans
Publisher: Springer
ISBN: 3319111558
Category : Medical
Languages : en
Pages : 442
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Book Description
This two-volume work covers the molecular and cell biology, genetics and evolution of influenza viruses, the pathogenesis of infection, resultant host innate and adaptive immune response, prevention of infection through vaccination and approaches to the therapeutic control of infection.. Experts at the forefront of these areas provide critical assessments with regard to influenza virology, immunology, cell and molecular biology, and pathogenesis. Volume I provides overviews of the latest findings on molecular determinants of viral pathogenicity, virus entry and cell tropism, pandemic risk assessment, transmission and pathogenesis in animal species, viral evolution, ecology and antigenic variation, while Volume II focuses on the role of innate and adaptive immunity in pathogenesis, development of vaccines and antivirals.
Author: John E. Bennett
Publisher: Elsevier Health Sciences
ISBN: 0323550274
Category : Medical
Languages : en
Pages : 5208
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Book Description
For four decades, physicians and other healthcare providers have trusted Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases to provide expert guidance on the diagnosis and treatment of these complex disorders. The 9th Edition continues the tradition of excellence with newly expanded chapters, increased global coverage, and regular updates to keep you at the forefront of this vitally important field. Meticulously updated by Drs. John E. Bennett, Raphael Dolin, and Martin J. Blaser, this comprehensive, two-volume masterwork puts the latest information on challenging infectious diseases at your fingertips. Provides more in-depth coverage of epidemiology, etiology, pathology, microbiology, immunology, and treatment of infectious agents than any other infectious disease resource. Features an increased focus on antibiotic stewardship; new antivirals for influenza, cytomegalovirus, hepatitis C, hepatitis B., and immunizations; and new recommendations for vaccination against infection with pneumococci, papillomaviruses, hepatitis A, and pertussis. Covers newly recognized enteroviruses causing paralysis (E-A71, E-D68); emerging viral infections such as Ebola, Zika, Marburg, SARS, and MERS; and important updates on prevention and treatment of C. difficile infection, including new tests that diagnose or falsely over-diagnose infectious diseases. Offers fully revised content on bacterial pathogenesis, antibiotic use and toxicity, the human microbiome and its effects on health and disease, immunological mechanisms and immunodeficiency, and probiotics and alternative approaches to treatment of infectious diseases. Discusses up-to-date topics such as use of the new PCR panels for diagnosis of meningitis, diarrhea and pneumonia; current management of infected orthopedic implant infections; newly recognized infections transmitted by black-legged ticks in the USA: Borrelia miyamotoi and Powassan virus; infectious complications of new drugs for cancer; new drugs for resistant bacteria and mycobacteria; new guidelines for diagnosis and therapy of HIV infections; and new vaccines against herpes zoster, influenza, meningococci. PPID continues its tradition of including leading experts from a truly global community, including authors from Australia, Canada and countries in Europe, Asia, and South America. Features more than 1,500 high-quality, full-color photographs—with hundreds new to this edition.
Author: Alexis M. Kalergis
Publisher: Frontiers Media SA
ISBN: 2889639185
Category :
Languages : en
Pages : 138
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Book Description
We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS
Author: Ofer Levy
Publisher: Frontiers Media SA
ISBN: 2889716589
Category : Medical
Languages : en
Pages : 335
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Book Description
Topic Editor Jay Evans is the co-founder, President and CEO of Inimmune Corporation. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Author: Tim Wreghitt
Publisher:
ISBN: 1009334409
Category : Medical
Languages : en
Pages : 334
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Book Description
Since the first edition was published in 2009, there have been significant advances in diagnostics and management of viral infections, as well as newly discovered viruses such as SARS-CoV-2 and Zika virus. This new edition provides up-to-date information on the key developments in clinical and diagnostic virology, especially molecular diagnosis, with guidance on new molecular and bedside tests. Effective antiviral treatments and novel combinations of treatments recently introduced are covered in depth. Infection control precautions and pandemic preparedness are discussed, with a focus on recent outbreaks. As with the first edition, coverage is succinct and practical with easily accessible information in algorithms and tables, and standardised chapter layouts organised from A to Z. This is an ideal introduction to complex topics for healthcare trainees, as well as a handy and easily accessible reference for more experienced hospital clinicians and primary care physicians.
