scholarly journals Long-lived Memory T Lymphocyte Responses After Hantavirus Infection

2002 ◽  
Vol 196 (5) ◽  
pp. 579-588 ◽  
Author(s):  
Heather L. Van Epps ◽  
Masanori Terajima ◽  
Jukka Mustonen ◽  
T. Petteri Arstila ◽  
Elizabeth A. Corey ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Acute Infection ◽  
Public Health Problem ◽  
T Cell Response ◽  
Hantavirus Infection ◽  
Important Public Health Problem ◽  
Virus Persistence ◽  
Ctl Epitopes ◽  
N Protein ◽  
Ctl Responses

Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal syndrome (HFRS), which is an important public health problem in large parts of Europe. We examined the memory cytolytic T lymphocyte (CTL) responses in 13 Finnish individuals who had HFRS between 1984 and 1995. In seven of these donors, we detected virus-specific CTL responses against the PUUV nucleocapsid (N) protein after in vitro stimulation with PUUV. Six novel CD8+ CTL epitopes were defined on the N protein and were found to be restricted by various HLA alleles including A2, A28, B7, and B8. This is the first demonstration of PUUV-specific CTL responses in humans, and the first identification of CTL epitopes on PUUV. In addition, this study provides one of the few characterizations of a human antiviral memory T cell response, without the complicating issues of virus persistence or reinfection. Interferon (IFN)-γ ELISPOT analysis showed that memory CTL specific for these epitopes were present at high frequency in PUUV-immune individuals many years after acute infection in the absence of detectable viral RNA. The frequencies of PUUV-specific CTL were comparable to or exceeded those found in other viral systems including influenza, EBV and HIV, in which CTL responses may be boosted by periodic reinfection or virus persistence.

scholarly journals Identification of Dominant Optimal HLA-B60- and HLA-B61-Restricted Cytotoxic T-Lymphocyte (CTL) Epitopes: Rapid Characterization of CTL Responses by Enzyme-Linked Immunospot Assay

2000 ◽  
Vol 74 (18) ◽  
pp. 8541-8549 ◽  
Author(s):  
Marcus A. Altfeld ◽  
Alicja Trocha ◽  
Robert L. Eldridge ◽  
Eric S. Rosenberg ◽  
Mary N. Phillips ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Cytotoxic T Lymphocyte ◽  
Hla Class I ◽  
Peripheral Blood Mononuclear ◽  
Antiviral Immune Response ◽  
Ctl Epitopes ◽  
Hla Class I Molecules ◽  
Hiv 1 ◽  
Ctl Responses

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses play a major role in the antiviral immune response, but the relative contribution of CTL responses restricted by different HLA class I molecules is less well defined. HLA-B60 or the related allele B61 is expressed in 10 to 20% of Caucasoid populations and is even more highly prevalent in Asian populations, but yet no CTL epitopes restricted by these alleles have been defined. Here we report the definition of five novel HLA-B60-restricted HIV-1-specific CTL epitopes, using peripheral blood mononuclear cells in enzyme-linked immunospot (Elispot) assays and using CTL clones and lines in cytolytic assays. The dominant HLA-B60-restricted epitope, Nef peptide KEKGGLEGL, was targeted by all eight subjects with B60 and also by both subjects with B61 studied. This study additionally establishes the utility of the Elispot assay as a more rapid and efficient method of defining novel CTL epitopes. This approach will help to define new CTL epitopes that may play an important role in the immune control of HIV-1.

scholarly journals Acute Resolving Woodchuck Hepatitis Virus (WHV) Infection Is Associated with a Strong Cytotoxic T-Lymphocyte Response to a Single WHV Core Peptide

2007 ◽  
Vol 81 (13) ◽  
pp. 7156-7163 ◽  
Author(s):  
Ina Frank ◽  
Claudia Budde ◽  
Melanie Fiedler ◽  
Uta Dahmen ◽  
Sergei Viazov ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cell Response ◽  
Cytotoxic T Lymphocyte ◽  
Hepatitis Virus ◽  
Immunological Response ◽  
T Cell Response ◽  
Woodchuck Hepatitis Virus ◽  
Core Peptide ◽  
Ctl Responses

ABSTRACT Woodchucks infected with woodchuck hepatitis virus (WHV) are an excellent model for studying acute, self-limited and chronic hepadnaviral infections. Defects in the immunological response leading to chronicity are still unknown. Specific T-helper cell responses to WHV core and surface antigens (WHcAg and WHsAg, respectively) are associated with acute resolving infection; however, they are undetectable in chronic infection. Up to now, cytotoxic T-lymphocyte (CTL) responses could not be determined in the woodchuck. In the present study, we detected virus-specific CTL responses by a CD107a degranulation assay. The splenocytes of woodchucks in the postacute phase of WHV infection (18 months postinfection) were isolated and stimulated with overlapping peptides covering the whole WHcAg. After 6 days, the cells were restimulated and stained for CD3 and CD107a. One peptide (c96-110) turned out to be accountable for T-cell expansion and CD107a staining. Later, we applied the optimized degranulation assay to study the kinetics of the T-cell response in acute WHV infection. We found a vigorous T-cell response against peptide c96-110 with peripheral blood cells beginning at the peak of viral load (week 5) and lasting up to 15 weeks postinfection. In contrast, there was no T-cell response against peptide c96-110 detectable in chronically WHV-infected animals. Thus, with this newly established flow cytometric degranulation assay, we detected for the first time virus-specific CTLs and determined one immunodominant epitope of WHcAg in the woodchuck.

scholarly journals Maintenance or Emergence of Chronic Phase Secondary Cytotoxic T Lymphocyte Responses after Loss of Acute Phase Immunodominant Responses Does Not Protect SIV-Infected Rhesus Macaques from Disease Progression

2010 ◽  
Vol 2010 ◽  
pp. 1-9
Author(s):  
M. Shannon Keckler ◽  
Vida L. Hodara ◽  
Laura M. Parodi ◽  
Luis D. Giavedoni
Keyword(s):  
Disease Progression ◽  
T Lymphocyte ◽  
Vaccine Development ◽  
Cytotoxic T Lymphocyte ◽  
Rhesus Macaques ◽  
Viral Evolution ◽  
Critical Role ◽  
Chronic Phase ◽  
Ctl Epitopes ◽  
Ctl Responses

The simian immunodeficiency virus- (SIV-) infected rhesus macaque is the preferred animal model for vaccine development, but the correlates of protection in this model are not completely understood. In this paper, we document the cytotoxic T lymphocyte (CTL) response to SIV and its effects on viral evolution in an effort to identify events associated with disease progression regardless of MHC allele expression. We observed the evolution of epitopes targeted by CTLs in a group of macaques that included long-term nonprogressing (LTNP), slowly progressing (SP), normally progressing (NP), and rapidly progressing (RP) animals. Collectively, our data (1) identify novel CTL epitopes from an SP animal that are not restricted by known protective alleles, (2) illustrate that, in this small study, RP and NP animals accrue more mutations in CTL epitopes than in SP or LTNP macaques, and (3) demonstrate that the loss of CTL responses to immunodominant epitopes is associated with viral replication increases, which are not controlled by secondary CTL responses. These findings provide further evidence for the critical role of the primary cell-mediated immune responses in the control of retroviral infections.

scholarly journals Hepatitis B Surface Antigen Vector Delivers Protective Cytotoxic T-Lymphocyte Responses to Disease-Relevant Foreign Epitopes

2006 ◽  
Vol 80 (8) ◽  
pp. 3975-3984 ◽  
Author(s):  
Wai-Ping Woo ◽  
Tracy Doan ◽  
Karen A. Herd ◽  
Hans-Jürgen Netter ◽  
Robert W. Tindle
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Hepatitis B Surface Antigen ◽  
Dna Encoding ◽  
Ctl Epitopes ◽  
Syncytial Virus ◽  
Ctl Responses

ABSTRACT Although hepatitis B surface antigen (HBsAg) per se is highly immunogenic, its use as a vector for the delivery of foreign cytotoxic T-lymphocyte (CTL) epitopes has met with little success because of constraints on HBsAg stability and secretion imposed by the insertion of foreign sequence into critical hydrophobic/amphipathic regions. Using a strategy entailing deletion of DNA encoding HBsAg-specific CTL epitopes and replacement with DNA encoding foreign CTL epitopes, we have derived chimeric HBsAg DNA immunogens which elicited effector and memory CTL responses in vitro, and pathogen- and tumor-protective responses in vivo, when the chimeric HBsAg DNAs were used to immunize mice. We further show that HBsAg DNA recombinant for both respiratory syncytial virus and human papillomavirus CTL epitopes elicited simultaneous responses to both pathogens. These data demonstrate the efficacy of HBsAg DNA as a vector for the delivery of disease-relevant protective CTL responses. They also suggest the applicability of the approach of deriving chimeric HBsAg DNA immunogens simultaneously encoding protective CTL epitopes for multiple diseases. The DNAs we tested formed chimeric HBsAg virus-like particles (VLPs). Thus, our results have implications for the development of vaccination strategies using either chimeric HBsAg DNA or VLP vaccines. HBsAg is the globally administered vaccine for hepatitis B virus infection, inviting its usage as a vector for the delivery of immunogens from other diseases.

Case-fatality From Orally-transmitted Acute Chagas Disease: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Eduardo G Bruneto ◽  
Miguel M Fernandes-Silva ◽  
Cristina Toledo-Cornell ◽  
Silvia Martins ◽  
João M B Ferreira ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Case Fatality Rate ◽  
Meta Analysis ◽  
Acute Infection ◽  
Case Fatality ◽  
Public Health Problem ◽  
First Year ◽  
Important Public Health Problem ◽  
Oral Transmission ◽  
Acute Chagas Disease

Abstract Orally-transmitted acute Chagas disease (CD) is emerging as an important public health problem. The prognosis of acute infection following oral transmission is unknown. The aim of this study was to analyze and summarize data on orally-transmitted acute CD. We searched for publications from 1968 to 31 January 2018. We included studies and unpublished data from government sources that reported patients with acute orally-transmitted CD. We identified 41 papers and we added 932 unpublished cases. In all, our study covered 2470 cases and occurrence of 97 deaths. Our meta-analysis estimated that the case-fatality rate was 1.0% (95% CI 0.0–4.0%). Lethality rates have declined over time (P = .02). In conclusion, orally-transmitted acute CD has considerable lethality in the first year after infection. The lethality in symptomatic cases is similar to that from other routes of infection. The lethality rate of orally-acquired disease has declined over the years.

scholarly journals B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction

2018 ◽  
Vol 115 (12) ◽  
pp. 3126-3131 ◽  
Author(s):  
Ling Chen ◽  
Takeshi Azuma ◽  
Weiwei Yu ◽  
Xu Zheng ◽  
Liqun Luo ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Response ◽  
Tumor Escape ◽  
Immune Functions ◽  
Adaptive Resistance ◽  
Multiple Tumor ◽  
Ctl Responses

Induced B7-H1 expression in the tumor microenvironment initiates adaptive resistance, which impairs immune functions and leads to tumor escape from immune destruction. Antibody blockade of the B7-H1/PD-1 interaction overcomes adaptive resistance, leading to regression of advanced human cancers and survival benefits in a significant fraction of patients. In addition to cancer cells, B7-H1 is expressed on dendritic cells (DCs), but its role in DC functions is less understood. DCs can present multiple antigens (Ags) to stimulate dominant or subdominant T cell responses. Here, we show that immunization with multiple tumor Ag-loaded DCs, in the absence of B7-H1, vastly enhances cytotoxic T lymphocyte (CTL) responses to dominant Ag. In sharp contrast, CTL responses to subdominant Ag were paradoxically suppressed, facilitating outgrowth of tumor variants carrying only subdominant Ag. Suppressed CTL responses to subdominant Ag are largely due to the loss of B7-H1–mediated protection of DCs from the lysis of CTL against dominant Ag. Therefore, B7-H1 expression on DCs may help maintain the diversity of CTL responses to multiple tumor Ags. Interestingly, a split immunization approach, which presents dominant and subdominant Ags with different DCs, promoted CTL responses to all Ags and prevented tumor escape in murine tumor models. These findings have implications for the design of future combination cancer immunotherapies.

Suicide on the Indian Subcontinent

Crisis ◽  
2002 ◽  
Vol 23 (3) ◽  
pp. 104-107 ◽  
Author(s):  
Murad M. Khan
Keyword(s):  
Sri Lanka ◽  
Mental Health Professionals ◽  
Indian Subcontinent ◽  
Interpersonal Relationship ◽  
Public Health Problem ◽  
Elderly Subjects ◽  
Important Public Health Problem ◽  
Policy Makers ◽  
Formidable Challenge ◽  
Causative Factors

Summary: The Indian subcontinent comprises eight countries (India, Pakistan, Bangladesh, Nepal, Sri Lanka, Afghanistan, Bhutan, and the Maldives) and a collective population of more than 1.3 billion people. 10% of the world's suicides (more than 100,000 people) take place in just three of these countries, viz. India, Sri Lanka, and Pakistan. There is very little information on suicides from the other four countries. Some differences from suicides in Western countries include the high use of organophosphate insecticides, larger numbers of married women, fewer elderly subjects, and interpersonal relationship problems and life events as important causative factors. There is need for more and better information regarding suicide in the countries of the Indian subcontinent. In particular, studies must address culture-specific risk factors associated with suicide in these countries. The prevention of this important public health problem in an area of the world with myriad socio-economic problems, meager resources, and stigmatization of mental illness poses a formidable challenge to mental health professionals, policy makers, and governments of these countries.

Study of the efficacy of Pathadi Ghanavati with Lajamanda in the management of Aamatisara

2019 ◽  
Vol 4 (03) ◽  
Author(s):  
Madhura Jadhav ◽  
P. D. Londhe
Keyword(s):  
Acute Diarrhoea ◽  
Public Health Problem ◽  
World Health ◽  
Important Public Health Problem ◽  
Loose Motion ◽  
Economic Class ◽  
Watery Stool ◽  
Health Organization ◽  
Effective Remedy ◽  
Trial Drug

Acute Diarrhoea is an important public health problem worldwide. The World Health Organization estimates that there are more than 1000 million cases of Acute Diarrhoea. Loose motion less than 2 weeks that labelled as Acute Diarrhoea. Diarrhoea is described in Ayurvedic classics with the name of ‘Atisara’. It means passing of excessive flow of watery stool through anus. Most important factor in the pathogenesis of Aamatisara is Mandagni. In present study 50 patients of Aamatisara were selected from OPD and IPD of Kayachikitsa department. For the clinical study Pathadi Ghanavati and Lajamanda was selected as the trial drug which was given for the duration of 7 days in the dose of 1gm twice a day. It was observed that 32% patients were from the age group 51-60 years, 70% were females, 62% were from lower-middle socio economic class. Sama Jivha was found in all the patients. Among results loose motion showed 98.75% relief, 97.82% showed improvement in Udarashoola, 97.43% improvement in Agnimandya and Daurbalya each, 100% relief was seen in Aruchi. All the symptoms showed highly significant results. Hence it can be concluded that Pathadi Ghanavati and Lajamanda is very effective remedy in the patients of Aamatisara.

scholarly journals Sarcopenic Obesity in Liver Cirrhosis: Possible Mechanism and Clinical Impact

2021 ◽  
Vol 22 (4) ◽  
pp. 1917
Author(s):  
Hiroki Nishikawa ◽  
Hirayuki Enomoto ◽  
Shuhei Nishiguchi ◽  
Hiroko Iijima
Keyword(s):  
Liver Cirrhosis ◽  
Current Knowledge ◽  
Protein Energy Malnutrition ◽  
Public Health Problem ◽  
Diagnostic Value ◽  
Sarcopenic Obesity ◽  
Important Public Health Problem ◽  
Alcoholic Fatty Liver ◽  
Protein Energy ◽  
Clinical Consequences

The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle–liver–adipose tissue axis. Here, we overview the current knowledge of Sa-O, especially focusing on LC.

scholarly journals The gut at war: the consequences of enteropathogenic Escherichia coli infection as a factor of diarrhea and malnutrition

2000 ◽  
Vol 118 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Ulysses Fagundes-Neto ◽  
Isabel Cristina Affonso Scaletsky
Keyword(s):  
Escherichia Coli ◽  
Diarrheal Disease ◽  
Driving Forces ◽  
Public Health Problem ◽  
Clinical Aspects ◽  
Small Intestinal Mucosa ◽  
Enteropathogenic Escherichia Coli ◽  
Important Public Health Problem ◽  
The Impact

Diarrheal disease is still the most prevalent and important public health problem in developing countries, despite advances in knowledge, understanding, and management that have occurred over recent years. Diarrhea is the leading cause of death in children under 5 years of age. The impact of diarrheal diseases is more severe in the earliest periods of life, when taking into account both the numbers of episodes per year and hospital admission rates. This narrative review focuses on one of the major driving forces that attack the host, namely the enteropathogenic Escherichia coli (EPEC) and the consequences that generate malnutrition in an early phase of life. EPEC serotypes form dense microcolonies on the surface of tissue-culture cells in a pattern known as localized adherence (LA). When EPEC strains adhere to epithelial cells in vitro or in vivo they cause characteristic changes known as Attaching and Effacement (A/E) lesions. Surface abnormalities of the small intestinal mucosa shown by scanning electron microscopy in infants with persistent diarrhea, although non-specific, are intense enough to justify the severity of the clinical aspects displayed in a very young phase in life. Decrease in number and height of microvilli, blunting of borders of enterocytes, loss of the glycocalyx, shortening of villi and presence of a mucus pseudomembrane coating the mucosal surface were the abnormalities observed in the majority of patients. These ultrastructural derangements may be due to an association of the enteric enteropathogenic agent that triggers the diarrheic process and the onset of food intolerance responsible for perpetuation of diarrhea. An aggressive therapeutic approach based on appropriate nutritional support, especially the utilization of human milk and/or lactose-free protein hydrolyzate-based formulas and the adequate correction of the fecal losses, is required to allow complete recovery from the damage caused by this devastating enteropathogenic agent.

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