Lymphocyte recirculation, exercise, and immune responses

1998 ◽  
Vol 76 (5) ◽  
pp. 490-496 ◽  
Author(s):  
John B Hay ◽  
William N Andrade
Keyword(s):  
Immune Responses ◽  
Cell Tracking ◽  
Lymphocyte Subsets ◽  
Blood Pool ◽  
Exercise Stress ◽  
Lymphocyte Migration ◽  
Blood Samples ◽  
Lymphocyte Recirculation ◽  
Afferent Lymph

Alterations in leukocyte concentrations in the blood are associated with exercise, stress, and other pathophysiological perturbations. The continuous migration and redistribution of cells of the recirculating lymphocyte pool between the blood and lymphatic systems can be influenced by a variety of physiological, immunological, and pathological processes. The phenotypic distribution of lymphocyte subsets is not the same in blood, afferent lymph, and efferent lymph, and cell-tracking experiments have shown that lymphocytes vary in their migratory properties. The most comprehensive physiological studies tracking these cells in vivo have been done in sheep. It has been shown that lymph-derived cells have different migratory capacities than blood-derived lymphocytes, that antigenic challenge of a single lymph node can first reduce the output of lymphocytes from the node and then markedly increase the recruitment from the blood and subsequently the output into efferent lymph. In most mammals, the blood pool of lymphocytes represents only about 1% of the total lymphocytes and only a small fraction of the recirculating lymphocyte pool. Therefore, testing the effects of exercise on lymphocyte recirculation by examining blood samples only requires considerable deduction and inference to interpret multicompartmental effects.Key words: lymphocyte migration, blood, lymph, lymph nodes.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Maria S. Salvato ◽  
C. Cameron Yin ◽  
Hideo Yagita ◽  
Toshihiro Maeda ◽  
Ko Okumura ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Immune Responses ◽  
Persistent Infection ◽  
Lymphocyte Subsets ◽  
Hiv Disease ◽  
Viral Immunity ◽  
Acute Hiv ◽  
Fas Pathway ◽  
Cell Subpopulations

Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4-lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander) cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203). Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

scholarly journals In vivo modulation of CD1 and MHC class II expression by sheep afferent lymph dendritic cells. Comparison of primary and secondary immune responses.

1989 ◽  
Vol 170 (4) ◽  
pp. 1303-1318 ◽  
Author(s):  
J Hopkins ◽  
B M Dutia ◽  
R Bujdoso ◽  
I McConnell
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Lines ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Primary Response ◽  
Secondary Response ◽  
Afferent Lymph

The experiments described in this article characterize the phenotypic and functional changes in afferent lymph cell populations that occur as a result of in vivo immune stimulation. During the primary immune response (in antigen-naive sheep) there are very transient increases in level of CD1 expression by subpopulations of dendritic cells (DC) but no alterations in cell kinetics or MHC class II expression. In contrast, secondary antigenic challenge (in primed sheep) into the drainage area of an afferent lymphatic causes profound changes in the cell output, characterized by a greater than threefold drop in total cell output on days 1-3 followed by an approximate fivefold rise on day 5. There is also a substantial increase in both the proportion of MHC class II-positive T lymphocytes (from 28 to 54%) and in the quantitative expression of class II by both DC and lymphocytes. Class II expression by DC increases five- to sixfold by day 5, while the level of expression of class II on lymphocytes approximately doubles. The increase in CD1 expression during the secondary response is more prolonged than during the primary response, being detectable between days 2 and 6 after challenge. The rise in class II affects the whole DC population, in contrast to CD1 where the increase affects only a subpopulation of cells. In terms of functional properties, afferent lymph DC isolated during a primary response show no alteration of their activity, whereas DC taken 4-5 d after secondary challenge are up to fivefold more active in their ability to present soluble antigen to primed autologous T cells and to antigen-specific cell lines as well as to stimulate in the MLR. The relative expression of class II correlates temporally with an increased capacity of DC to present antigen. Monoclonal anti-class II antibodies totally inhibit the in vitro assays but anti-CD1 antibodies have no effect. The previous paper has demonstrated that afferent DC can associate with antigen in vivo and can present that antigen to antigen-specific T cells. This article extends our knowledge of DC biology and demonstrates that DC, activated during secondary in vivo immune responses, have an enhanced ability to present an antigen, unrelated to that used for challenge, to specific T cell lines. This enhancement correlates directly with quantitative variation of expressed class II and not CD1 and suggests that this variation in class II expression plays a physiological role in in vivo immune regulation.

Infection and transformation of dendritic cells from bovine afferent lymph by Theileria annulata

Parasitology ◽  
2002 ◽  
Vol 124 (5) ◽  
pp. 485-493 ◽  
Author(s):  
S. A. STEPHENS ◽  
C. J. HOWARD
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Lines ◽  
Protozoan Parasite ◽  
Theileria Annulata ◽  
Phenotypic Analysis ◽  
Proliferating Cells ◽  
Afferent Lymph ◽  
Proliferating Cell

Following incubation with sporozoites of the protozoan parasite Theileria annulata, dendritic cells (DC), extracted from bovine afferent lymph, became infected and transformed into large, rounded, continuously proliferating cell lines. Phenotypic analysis of the transformed cells by immunostaining and flow cytometry revealed that they expressed MHC class I and II antigens, the myeloid marker MyD1 (SIRPα) and the bovine WC6 (workshop cluster 6) molecule. Transformed DC cell lines differed from those produced from infection of macrophages and B cells in that some lines expressed CD21 and a proportion of cells continued to express the antigen stained by the mAb CC81, a marker which defines a subpopulation of DC in afferent lymph. Both of the main populations of DC that have been identified in bovine afferent lymph appeared to be equally permissive for infection and transformation with T. annulata. These findings raise the possibility that the transformed proliferating cells characteristic of in vivo infections could be derived from DC as well as macrophages. This could have consequences for understanding the pathogenesis of the disease and for developing methods to manipulate immune responses to eliminate the parasite.

Hemophilic Bledding Evaluated by Blood Pool Scanning

1981 ◽  
Vol 45 (03) ◽  
pp. 208-210 ◽  
Author(s):  
D Green ◽  
S M Spies ◽  
N A Rana ◽  
J W Milgram ◽  
R Mintzer
Keyword(s):  
Blood Volume ◽  
Blood Pool ◽  
Invasive Technique ◽  
Scintillation Camera ◽  
Knee Prostheses ◽  
Hemophilic Patient ◽  
Chronic Arthropathy ◽  
Image Density ◽  
Regional Blood Volume

SummaryThe technique of blood pool scanning was used to examine 15 hemophilic subjects. Employing an in vivo method for erythrocyte labeling with Technetium-99 m, a dynamic perfusion sequence is obtained using a scintillation camera positioned over the area to be examined. This demonstrates the vascularity of the tissue. Subsequently, equilibrium blood pool images of the area are obtained and analyzed with a densitometer to assess relative regional blood volume. In patients who were not bleeding but had chronic arthropathy, vascularity was not increased, and the blood volume of comparable joints was similar. By contrast, marked increases in vascularity and image density were observed in studies of acutely bleeding joints. Chronic hemarthroses were associated with persistent, but less marked increases in joint perfusion. Transient increases in joint vascularity were demonstrated after insertion of knee prostheses. In a patient with a thigh hematoma, the dimensions of the hemorrhage were clearly delineated. Since only a tracer dose of nuclide is infused intravenously, there are no allergic reactions or other side effects of the procedure. Blood pool scanning is a safe, non-invasive technique that augments clinical and radiographic evaluations, and provides a new dimension in the assessment of the hemophilic patient.

The Effect of Alimentary Hyperlipemia on Thrombolysis in vivo

1960 ◽  
Vol 04 (02) ◽  
pp. 149-166 ◽  
Author(s):  
Nils U. Bang ◽  
Eugene E. Cliffton
Keyword(s):  
Fibrinolytic Activity ◽  
Fibrinolytic Enzyme ◽  
Enzyme Treatment ◽  
Enzyme Therapy ◽  
Fasting State ◽  
Fatty Meal ◽  
Complete Dissolution ◽  
Blood Samples ◽  
Specific Inhibitors

Summary1. The effect of a standard, potent fibrinolytic enzyme therapy has been compared in fasting and lipemic dogs.2. The standard fibrinolytic regimen resulted in the complete dissolution of all clots produced experimentally in the fasting state in 10 dogs.3. Clots formed during alimentary lipemia exhibited a markedly increased resistance to the standard fibrinolytic regimen in 6 dogs.4. An increase in anti plasmin fibrinolytic titer with concomitant decrease in spontaneous fibrinolytic activity was observed in 15 dogs following the administration of a fatty meal. No difference in fibrinolytic activity and APF titer was demonstrable in fasting and lipemic blood samples obtained during fibrinolytic enzyme treatment.5. The possibility of the presence of specific inhibitors against the fibrinolytic enzyme in clots formed during lipemia has been investigated and the evidence to support this theory is discussed.

scholarly journals Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ai-Ling Tian ◽  
Qi Wu ◽  
Peng Liu ◽  
Liwei Zhao ◽  
Isabelle Martins ◽  
...  
Keyword(s):  
Stress Response ◽  
Immune Responses ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Serine Residue ◽  
Eif2α Phosphorylation ◽  
Lysosomotropic Agents ◽  
Cultured Human Cells

AbstractThe integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger eIF2α phosphorylation in vitro (in cultured human cells) and, as validated for hydroxychloroquine, in vivo (in mice). Cells bearing a non-phosphorylatable eIF2α mutant (S51A) failed to accumulate autophagic puncta in response to azithromycin, chloroquine, and hydroxychloroquine. Conversely, two inhibitors of eIF2α dephosphorylation, nelfinavir and salubrinal, enhanced the induction of such autophagic puncta. Altogether, these results point to the unexpected capacity of azithromycin, chloroquine, and hydroxychloroquine to elicit the integrated stress response.

scholarly journals Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España
Keyword(s):  
Positron Emission Tomography ◽  
Blood Sample ◽  
Pet Imaging ◽  
Spectroscopic Analysis ◽  
Gamma Spectroscopy ◽  
Emission Tomography ◽  
Blood Samples ◽  
Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

scholarly journals Predicting chromosome damage in astronauts participating in international space station missions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alan Feiveson ◽  
Kerry George ◽  
Mark Shavers ◽  
Maria Moreno-Villanueva ◽  
Ye Zhang ◽  
...  
Keyword(s):  
International Space Station ◽  
Dose Response ◽  
Ex Vivo ◽  
Space Station ◽  
Space Radiation ◽  
Blood Samples ◽  
International Space ◽  
Significant Difference ◽  
Subject Specific

AbstractSpace radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose–response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose–response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.

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