Immune recovery vitritis

Introduction Immune recovery vitritis (IRV) is symptomatic vitritis of > 1+ severity associated with inactive cytomegalovirus (CMV) retinitis. It is an opportunistic infection of the eye, in the patients who suffer from AIDS, and is treated with a highly active antiretroviral therapy (HAART). As a result of this therapy, there is an immune reconstitution in the body and inflammation of the vitreous body. Objective The aim of the study was to show the incidence of IRV in patients treated with HAART. Method A retrospective study was conducted in patients who suffered from CMV retinitis. Twenty-one were treated with HAART and had the diagnosis of CMV retinitis, as well. All of them were examined by the same ophthalmologist who peformed slit lamp examination with mydriasis and indirect ophthalmoscopy. Results Nine of 21 patients developed IRV as a complication of HAART, two had cystoid macular edema (CMO). Conclusion CMV retinitis develops when the number of CD4+ T lymphocytes drops below 50/mm3. This results in necrotic retinitis which, if untreated, leads to complete loss of vision. With the introduction of HAART, we learned that the reconstitution of immune status was achieved as well as life expectancy, but there was a dramatic decline in the opportunistic infection, including CMV retinitis, as well. With the immune reconstitution, the inflammation develops in the eye, known as IRV. Sometimes, it is necessary to treat this condition, but in the case of our patients, the inflammation was mild, and no treatment was necessary

Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host

The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell. Our model explains the experimentally observed shortening of a second infection when cross-reactivity is present, and shows that memory in the cellular adaptive immune response is necessary to protect against a second infection.Comment: 35 pages, 12 figure

Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum.

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus

African Trypanosomes undermine humoral responses and vaccine development : link with inflammatory responses?

African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i) early parasite diagnosis, (ii) anti-trypanosome (drugs) treatment, and (iii) anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination

Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease.

Sexual transmission of Ebola virus (EBOV) has been demonstrated more than a year after recovery from the acute phase of Ebola virus disease (EVD). The mechanisms underlying EBOV persistence and sexual transmission are not currently understood. Using the acute macaque model of EVD, we hypothesized EBOV would infect the reproductive tissues and sought to localize the infection in these tissues using immunohistochemistry and transmission electron microscopy. In four female and eight male macaques that succumbed to EVD between 6 and 9 days after EBOV challenge, we demonstrate widespread EBOV infection of the interstitial tissues and endothelium in the ovary, uterus, testis, seminal vesicle, epididymis, and prostate gland, with minimal associated tissue immune response or organ pathology. Given the widespread involvement of EBOV in the reproductive tracts of both male and female macaques, it is reasonable to surmise that our understanding of the mechanisms underlying sexual transmission of EVD and persistence of EBOV in immune-privileged sites would be facilitated by the development of a nonhuman primate model in which the macaques survived past the acute stage into convalescence

Immunological Changes after Cancer Treatment and Participation in an Exercise Program

Purpose: The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on T-cell number and function, and to determine the role of a mixed type, moderate intensity exercise program in facilitating the recovery of T-cell number and function. Methods: Immunological measures of white blood cell, lymphocyte, CD3+, CD4+, and CD8+ counts, and CD3+ cell function were assessed pretransplant (PI), immediately posttransplant (PII), and 1 month (I1), 2 months (I2) and 3 months (PIII) posttransplant. After PII, 12 patients were divided equally into a control group (CG) or exercise intervention group (EG). Results: Lower total T-cell, helper T-cell, and suppressor T-cell counts (P < 0.01), as well as lower T-cell function (P < 0.01), when compared with normative data, were found at PI. More specifically, 88% of the group had CD3+, CD4+, and CD8+ counts that were more than 40%, 20%, and 50% below normal at PI, respectively. Undertaking a PBST caused further adverse changes to the total leukocyte, lymphocyte, CD3+, CD4+ and CD8+ count, and the helper/suppressor ratio. Although CD8+ counts had returned to normal by PIII, CD3+, CD4+, and the CD4+/CD8+ ratio remained significantly lower than normative data (P < 0.01), with 66%, 100%, and 100% of the subject group reporting counts and ratios, respectively, below the normal range. Conclusion: The PBST patients were immunocompromised before undertaking the transplant, and the transplant procedure imposed further adverse changes to the leukocyte and lymphocyte counts. The leukocyte and CD8+ counts returned to normal within 3 months posttransplant; however, the other immunological parameters assessed demonstrated a delayed recovery. Although participation in the exercise program did not facilitate a faster immune cell recovery, neither did the exercise program hinder or delay recovery

Mathematical models for vaccination, waning immunity and immune system boosting: a general framework

When the body gets infected by a pathogen or receives a vaccine dose, the immune system develops pathogen-specific immunity. Induced immunity decays in time and years after recovery/vaccination the host might become susceptible again. Exposure to the pathogen in the environment boosts the immune system thus prolonging the duration of the protection. Such an interplay of within host and population level dynamics poses significant challenges in rigorous mathematical modeling of immuno-epidemiology. The aim of this paper is twofold. First, we provide an overview of existing models for waning of disease/vaccine-induced immunity and immune system boosting. Then a new modeling approach is proposed for SIRVS dynamics, monitoring the immune status of individuals and including both waning immunity and immune system boosting. We show that some previous models can be considered as special cases or approximations of our framework.Comment: 18 pages, 1 figure keywords: Immuno-epidemiology, Waning immunity, Immune status, Boosting, Physiological structure, Reinfection, Delay equations, Vaccination. arXiv admin note: substantial text overlap with arXiv:1411.319

Immunotronics - novel finite-state-machine architectures with built-in self-test using self-nonself differentiation

A novel approach to hardware fault tolerance is demonstrated that takes inspiration from the human immune system as a method of fault detection. The human immune system is a remarkable system of interacting cells and organs that protect the body from invasion and maintains reliable operation even in the presence of invading bacteria or viruses. This paper seeks to address the field of electronic hardware fault tolerance from an immunological perspective with the aim of showing how novel methods based upon the operation of the immune system can both complement and create new approaches to the development of fault detection mechanisms for reliable hardware systems. In particular, it is shown that by use of partial matching, as prevalent in biological systems, high fault coverage can be achieved with the added advantage of reducing memory requirements. The development of a generic finite-state-machine immunization procedure is discussed that allows any system that can be represented in such a manner to be "immunized" against the occurrence of faulty operation. This is demonstrated by the creation of an immunized decade counter that can detect the presence of faults in real tim

HIV-Infected Subjects With Poor CD4 T-Cell Recovery Despite Effective Therapy Express High Levels of OX40 and α4β7 on CD4 T-Cells Prior Therapy Initiation

Background HIV-infected subjects with suboptimal CD4 restoration despite suppressive combined antiretroviral treatment (cART) (immunodiscordant subjects) have been classically characterized after a variable period of time under cART. Recently, we have reported that an increased frequency of proliferating CD4 T-cells in these subjects is already present before the cART onset. The potential contribution of peripheral compensatory homeostatic proliferation (HP) is yet unknown. We aimed to analyze the expression of HP-related cellular markers on CD4 T-cells of immunodiscordant subjects before cART. Go to: Methods We analyzed the expression of OX40 and α4β7 on peripheral CD4 T-cells from immunodiscordant and control subjects (n = 21 each group) before cART initiation, and also on available follow-up samples (after 24 month of suppressive cART). Additionally, we tested the expression of these markers in an in vitro system for the study of human HP processes. Go to: Results Immunodiscordant subjects showed increased levels of OX40 and α4β7 on CD4 T-cells before cART initiation. While the cART tended to reduce these levels, immunodiscordant subjects still maintained comparatively higher levels of OX40 and α4β7 after 24 months under suppressive cART. These HP-related markers were upregulated in vitro during the human HP, especially during the fast HP. Go to: Conclusion Our results are compatible with exacerbated HP processes in immunodiscordant subjects, already before the cART onset.Fondo de Investigación Sanitaria FIS PI14/01693 PI13/0796 PI16/0503Fondos Europeos para el Desarrollo Regional (FEDER) CTS2593Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo CTS2593AGAUR 2017SGR948GILEAD GLD14/293The Spanish AIDS Research Network of Excellence RD12/0017/0029 RD16/0025/0019 RD16/0025/0006Junta de Andalucía. Consejería de Salud y Bienestar Social C-0013-201