scholarly journals Immune Response to Therapeutic Staphylococcal Bacteriophages in Mammals: Kinetics of Induction, Immunogenic Structural Proteins, Natural and Induced Antibodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Zuzanna Kaźmierczak ◽  
Joanna Majewska ◽  
Paulina Miernikiewicz ◽  
Ryszard Międzybrodzki ◽  
Sylwia Nowak ◽  
...  

Bacteriophages are able to affect the human immune system. Phage-specific antibodies are considered as major factors shaping phage pharmacokinetics and bioavailability. So far, general knowledge of phage antigenicity nevertheless remains extremely limited. Here we present comparative studies of immunogenicity in two therapeutic bacteriophages, A3R and 676Z, active against Staphylococcus aureus, routinely applied in patients at the Phage Therapy Unit, Poland. Comparison of the overall ability of whole phages to induce specific antibodies in a murine model revealed typical kinetics of IgM and IgG induction by these two phages. In further studies we identified the location of four phage proteins in the virions, with the focus on the external capsid head (Mcp) or tail sheath (TmpH) or an unidentified precise location (ORF059 and ORF096), and we confirmed their role as structural proteins of these viruses. Next, we compared the immune response elicited by these proteins after phage administration in mice. Similar to that in T4 phage, Mcp was the major element of the capsid that induced specific antibodies. Studies of protein-specific sera revealed that antibodies specific to ORF096 were able to neutralize antibacterial activity of the phages. In humans (population level), none of the studied proteins plays a particular role in the induction of specific antibodies; thus none potentially affects in a particular way the effectiveness of A3R and 676Z. Also in patients subjected to phage therapy, we did not observe increased specific immune responses to the investigated proteins.

1997 ◽  
Vol 39 (3) ◽  
pp. 322-328 ◽  
Author(s):  
TAHMEED AHMED ◽  
RYO SUMAZAKI ◽  
YOJI NAGAI ◽  
MASANAO SHIBASAKI ◽  
HITOSHI TAKITA

1989 ◽  
Vol 170 (2) ◽  
pp. 499-509 ◽  
Author(s):  
T Thepen ◽  
N Van Rooijen ◽  
G Kraal

A single intracheal dose of liposome-encapsuled dichloro-methylene-diphosphonate resulted in the elimination of alveolar macrophages (AM) from the lung, creating a model to study the in vivo role of AM in the pulmonary immune response. Using intratracheally administered trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH), the kinetics of the response, the location and number of TNP-specific antibody-forming cells, and the different Ig classes of the antibodies produced were studied in AM-depleted animals. The results show that AM elimination has a dramatic effect on the pulmonary immune responses against TNP-KLH. An increase in APC in lung-associated lymph nodes and a prolongation of the response is found, as well as an introduction of APC in lung tissue. In both experimental groups, the majority of the TNP-specific antibodies produced was IgG, followed by IgA and IgE, while very few IgM antibodies could be detected. We conclude from these results that AM are likely to play a role in controlling the pulmonary immune response in a suppressive way, thereby limiting the possible damage caused by severe immune responses in lung tissue.


Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 384 ◽  
Author(s):  
Utku M. Sonmez ◽  
Adam Wood ◽  
Kyle Justus ◽  
Weijian Jiang ◽  
Fatima Syed-Picard ◽  
...  

Gradients of soluble molecules coordinate cellular communication in a diverse range of multicellular systems. Chemokine-driven chemotaxis is a key orchestrator of cell movement during organ development, immune response and cancer progression. Chemotaxis assays capable of examining cell responses to different chemokines in the context of various extracellular matrices will be crucial to characterize directed cell motion in conditions which mimic whole tissue conditions. Here, a microfluidic device which can generate different chemokine patterns in flow-free gradient chambers while controlling surface extracellular matrix (ECM) to study chemotaxis either at the population level or at the single cell level with high resolution imaging is presented. The device is produced by combining additive manufacturing (AM) and soft lithography. Generation of concentration gradients in the device were simulated and experimentally validated. Then, stable gradients were applied to modulate chemotaxis and chemokinetic response of Jurkat cells as a model for T lymphocyte motility. Live imaging of the gradient chambers allowed to track and quantify Jurkat cell migration patterns. Using this system, it has been found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. The chemotaxis of the Jurkat cells was also found to be governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Distinct migratory behaviors in response to chemokine gradients in different contexts may be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Our approach demonstrates the feasibility of using a flow-free gradient chamber for evaluating cross-regulation of cell motility by multiple factors in different biologic processes.


2012 ◽  
Vol 279 (1746) ◽  
pp. 4505-4512 ◽  
Author(s):  
Hannah J. Tidbury ◽  
Alex Best ◽  
Mike Boots

Exposure to low doses of pathogens that do not result in the host becoming infectious may ‘prime’ the immune response and increase protection to subsequent challenge. There is increasing evidence that such immune priming is a widespread and important feature of invertebrate host–pathogen interactions. Immune priming clearly has implications for individual hosts but will also have population-level implications. We present a susceptible–primed–infectious model—in contrast to the classic susceptible–infectious–recovered framework—to investigate the impacts of immune priming on pathogen persistence and population stability. We describe impacts of immune priming on the epidemiology of the disease in both constant and seasonal environments. A key result is that immune priming may act to destabilize population dynamics. In particular, when the proportion of individuals becoming primed rather than infected is high, but this priming does not confer full immunity, the population may be strongly destabilized through the generation of limit cycles. We discuss the implications of our model both in the context of invertebrate immunity and more widely.


1973 ◽  
Vol 28 (1-2) ◽  
pp. 83-90
Author(s):  
Horst Mossmann ◽  
Dietrich K. Hammer

The reaction of bacteriophage T4 with 1-fluoro-2,4-dinitrobenzene resulted in a covalent binding of 2,4-dinitrophenyl (DNP) determinants to the phage. From the kinetics of inactivation reflecting the coupling process it is concluded that attachment of more than one DNP group to the critical site(s) of the phage is required for inactivation (multi-hit reaction). Contrary to this the neutralization of DNP-T4 by anti-DNP antibody turned out to be a first order reaction, until 80 %> neutralization fitting one-hit kinetics. If compared with native T4, the susceptibility of DNP-T4 to neutralization by anti-T4 antibody is considerably higher, indicating that attachment of DNP groups to T4 amplifies the sensitivity to neutralization by anti-T4. Comparing neutralization kinetics of DNP-T4 and native T4 by anti-DNP-T4 antibody it is suggested that native determinants and DNP groups, as well as determinants resulting from alteration due to the coupling process, all together may contribute as targets for neutralization. Three characteristics strengthen the view that the velocity of T4 conjugates in infecting the host strain is markedly decreased if compared with that of native T4: (a) considerable discrepancy between direct plating and decision technique (b) increasing variety of plaque size and (c) decreased velocity of the first step of reproduction. The kinetics of neutralization observed can be reconciled with a model proposed by Krummel and Uhr. The kinetics of reactivation of neutralized DNP-T4 by the presence cf DNP-BSA has been investigated and the problems involved in the reaction are discussed.


2020 ◽  
Vol 14 (6) ◽  
pp. 1928-1940
Author(s):  
Dieudonné Pascal Chuisseu Djamen ◽  
Roland Nankam Chimi ◽  
Arouna Njayou Ngapagna ◽  
Leonard Tedong ◽  
François-Marie Kanmangne ◽  
...  

The present work was to study the effects of Desmoduin adscendens, Khaya grandifoliola, Xylopia phloiodora extracts on growth parameters and selected blood parameters of broilers chickens. A total of 252 broiler chicks were randomly distributed into 4 groups. Chickens of control batch received commercial hepatoprotective (Hepaturyl 1 g/l) and the experimental groups received a formulation based on 3 extracts hepatoprotective plants at a concentration of 200, 100 and 50 mg/kg body weight. The mortality rate of control and experimental groups was 6.3% and 4.7% respectively. Average weight of batches at day 48 was, 2.6 for the control, 2.7 for the batch 2, 2.6 batch 3 and 2.5 kg batch 4 with an average consumption index ranging from 1.6 for the control and 1.7 for the experimental groups. Liver function in broilers was not altered (The values of alanine aminotransferase and aspartate aminotransferase were 5-25 IU/l and 50-350 IU/l respectively). Cholesterolemia, proteinemia and the triglyceridemia increased with the age of the animals (0.6- 4.1 mmol / l; 21-83 g / l; 0.3- 3.8 g / l respectively). The kinetics of the humoral immune response against infectious bursal disease was not influenced. This work has shown that the use of the formulation as hepatoprotective in chick drinking water shows results similar to those of commercial hepatoprotectors.Keywords: Broilers, hepatoprotective plants, hepatic functioning, growth performances, immune response


2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.


2021 ◽  
Vol 65 (04) ◽  
pp. 86-88
Author(s):  
Sevinc Nadir qızı Kerimova ◽  

The main prevention of rubella infection during pregnancy is to be vaccinated against this disease in preparation for pregnancy. Before you decide to get vaccinated against rubella, you need to have a special laboratory test to detect antibodies to the rubella virus in your blood to check if you are immune to this infection. The fact is that in some cases it is impossible to determine whether you are sick with rubella. Because in many cases, the disease can be latent or with a very limited number of symptoms, in which case, naturally, the body develops specific antibodies against the virus. Doctors believe that in this case, the body's immune response will be strengthened. It is recommended that the velvet vaccine be given at least 3 months before the planned date of pregnancy. Key words: pregnancy, rubella, fetus, infection


Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3102
Author(s):  
Kathleen M. Capaccione ◽  
Mikhail Doubrovin ◽  
Nikunj Bhatt ◽  
Akiva Mintz ◽  
Andrei Molotkov

The human immune system is a complex system which protects against invaders and maintains tissue homeostasis. It is broadly divided into the innate and adaptive branches. Granzyme B is serine protease that plays an important role in both and can serve as a biomarker for cellular activation. Because of this, a granzyme B PET agent (GZP) has recently been developed and has been shown to be able to monitor response to immunotherapy. Here, we evaluated the utility of granzyme B PET imaging to assess the innate immune response. We subcutaneously administered LPS to mice to induce inflammation and performed granzyme B PET imaging after 24 and 120 h. We dissected out tissue in the region of injection and performed granzyme B immunofluorescence (IF) to confirm specificity of the GZP radiotracer. Granzyme B PET imaging demonstrated increased uptake in the region of LPS injection after 24 h, which normalized at 120 h. Granzyme B immunofluorescence showed specific staining in tissue from the 24 h time point compared to the PBS-injected control. These findings support the use of granzyme B PET for imaging innate immunity. In certain clinical contexts, the use of GZP PET imaging may be superior to currently available agents, and we therefore suggest further preclinical studies with the ultimate goal of translation to clinical use.


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