scholarly journals Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2991
Author(s):  
Martyna Cieślik ◽  
Natalia Bagińska ◽  
Andrzej Górski ◽  
Ewa Jończyk-Matysiak

Studies described so far suggest that human β-defensin 2 is an important protein of innate immune response which provides protection for the human organism against invading pathogens of bacterial, viral, fungal, as well as parasitical origin. Its pivotal role in enhancing immunity was proved in infants. It may also be considered a marker of inflammation. Its therapeutic administration has been suggested for maintenance of the balance of systemic homeostasis based on the appropriate composition of the microbiota. It has been suggested that it may be an important therapeutic tool for modulating the response of the immune system in many inflammatory diseases, offering new treatment modalities. For this reason, its properties and role in the human body discussed in this review should be studied in more detail.

2021 ◽  
Vol 15 ◽  
Author(s):  
Omar Mossad ◽  
Thomas Blank

The immune system is crucial for defending against various invaders, such as pathogens, cancer cells or misfolded proteins. With increasing age, the diminishing immune response, known as immunosenescence, becomes evident. Concomitantly, some diseases like infections, autoimmune diseases, chronic inflammatory diseases and cancer, accumulate with age. Different cell types are part of the innate immunity response and produce soluble factors, cytokines, chemokines, and type I interferons. Improper maturation of innate immune cells or their dysfunction have been linked to numerous age-related diseases. In parallel to the occurrence of the many functional facets of the immune response, a symbiotic microbiota had been acquired. For the relevant and situation-dependent function of the immune system the microbiome plays an essential role because it fine-tunes the immune system and its responses during life. Nevertheless, how the age-related alterations in the microbiota are reflected in the innate immune system, is still poorly understood. With this review, we provide an up-to-date overview on our present understanding of the gut microbiota effects on innate immunity, with a particular emphasis on aging-associated changes in the gut microbiota and the implications for the brain innate immune response.


2021 ◽  
pp. 1-10
Author(s):  
Bader Alshehri

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.


2021 ◽  
Author(s):  
Raphaël Jami ◽  
Emilie Mérour ◽  
Julie Bernard ◽  
Annie Lamoureux ◽  
Jean K. Millet ◽  
...  

Salmonid alphavirus (SAV) is an atypical alphavirus, which has a considerable impact on salmon and trout farms. Unlike other alphaviruses such as the chikungunya virus, SAV is transmitted without an arthropod vector, and does not cause cell shut-off during infection. The mechanisms by which SAV escapes the host immune system remain unknown. By studying the role of SAV proteins on the RIG-I signaling cascade, the first line of defense of the immune system during infection, we demonstrated that non-structural protein 2 (nsP2) effectively blocks the induction of type I interferon (IFN). This inhibition, independent of the protease activity carried by nsP2, occurs downstream of IRF3 which is the transcription factor allowing the activation of the IFN promoter and its expression. The inhibitory effect of nsP2 on the RIG-I pathway depends on the localization of nsP2 in the host cell nucleus which is linked to two nuclear localization sequences (NLS) located in its C-terminal part. The C-terminal domain of nsP2 by itself is sufficient and necessary to block IFN induction. Mutation of the NLS of nsP2 is deleterious to the virus. Finally, nsP2 does not interact with IRF3, indicating that its action is possible through a targeted interaction within discrete areas of chromatin, as suggested by its punctate distribution observed in the nucleus. These results therefore demonstrate a major role for nsP2 in the control by SAV of the host cell’s innate immune response. Importance The global consumption of fish continues to rise and the future demand cannot be met by capture fisheries alone due to limited stocks of wild fish. Aquaculture is currently the world’s fastest growing food production sector with an annual growth rate of 6-8 %. Recurrent outbreaks of SAV result in significant economic losses with serious environmental consequences on wild stocks. While the clinical and pathological signs of SAV infection are fairly well known, the molecular mechanisms involved are poorly described. In the present study, we focus on the non-structural protein nsP2 and characterize a specific domain containing nuclear localization sequences that are critical for the inhibition of the host innate immune response mediated by the RIG-I pathway.


2021 ◽  
Vol 28 ◽  
Author(s):  
Xiao-Yang Chen ◽  
Puay Hoon Tan

: Despite diagnostic and therapeutic advances in breast cancer, it remains the most frequently diagnosed malignancy in females, with the highest cancer-related mortality rate in women globally. With an improved understanding of the complex interactions between breast cancer and the immune system, immunotherapy has shown great potential in clinical management, potentially adding to current treatment modalities. These immunotherapeutic approaches include adoptive cell transfer therapy, cancer vaccination, monoclonal antibody therapy, and oncolytic virus therapy. Depending on the immune cells and cytokines present, the tumour microenvironment (TME) can be immunosuppressive or favourable for mounting an immune response. Effector lymphocytes play an essential role during an anticancer immune response, but their activities can be suppressed by the hostile TME. Many studies have made good progress in the modulation of the immune response to allow the identification and elimination of tumour cells. However, the efficacy of these immunotherapies is patient-specific and highly dependent on the immunological profile of the tumour and its TME. This review will give an overview of breast cancer, the immune system as well as their complex relationship. Strategies and approaches that can harness the potential of immunotherapy that engages lymphocytes in the treatment of breast cancer, along with their current challenges, will also be discussed.


Author(s):  
Paul Klenerman

How does the immune system know when to respond? ‘First responders: the innate immune response’ considers this fundamental question that is central to understanding both normal (e.g. to infections) and abnormal (e.g. in auto-immune diseases) responses; and designing vaccines and new therapies in cancer and infectious diseases. It looks at how ‘danger’ is sensed by the immune system through pathogen-associated molecular patterns and damage-associated molecular patterns. Having been alerted, it is important that rapid action is taken to limit the spread of a pathogen. A number of responses can be initiated immediately, forming a critical part of our innate immunity, which are followed by the acute phase response.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1776 ◽  
Author(s):  
Sofie Bliddal ◽  
Claus Henrik Nielsen ◽  
Ulla Feldt-Rasmussen

Autoimmune thyroid disease (AITD) is often observed together with other autoimmune diseases. The coexistence of two or more autoimmune diseases in the same patient is referred to as polyautoimmunity, and AITD is the autoimmune disease most frequently involved. The occurrence of polyautoimmunity has led to the hypothesis that the affected patients suffer from a generalized dysregulation of their immune system. The present review summarizes recent discoveries unravelling the immunological mechanisms involved in autoimmunity, ranging from natural autoimmunity to disease-specific autoimmunity. Furthermore, the clinical grounds for considering AITD in a setting of polyautoimmunity are explored. A better understanding of these may pave the way for designing new treatment modalities targeting the underlying immune dysregulation when AITD appears in the context of polyautoimmunity.


Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 836
Author(s):  
Eileen A. Moran ◽  
Susan R. Ross

Retroviruses are major causes of disease in animals and human. Better understanding of the initial host immune response to these viruses could provide insight into how to limit infection. Mouse retroviruses that are endemic in their hosts provide an important genetic tool to dissect the different arms of the innate immune system that recognize retroviruses as foreign. Here, we review what is known about the major branches of the innate immune system that respond to mouse retrovirus infection, Toll-like receptors and nucleic acid sensors, and discuss the importance of these responses in activating adaptive immunity and controlling infection.


2019 ◽  
Vol 49 (2) ◽  
Author(s):  
Francesca Millanta ◽  
Simona Sagona ◽  
Maurizio Mazzei ◽  
Mario Forzan ◽  
Alessandro Poli ◽  
...  

ABSTRACT: The innate immune system of honeybees mainly consists in antimicrobial peptides, cellular immunity and melanisation. In order to investigate the immune response of honeybees to immune stressors, three stress degrees were tested. Newly emerged bees naturally DWV-infected were collected from a Varroa mite-free apiary and divided into three experimental groups: naturally DWV infected bees, PBS injected bees, and artificially DWV super infected bees. Phenoloxidase activity and haemolymph cellular subtype count were investigated. Phenoloxidase activity was highest (P<0.05) in DWV-superinfected bees, and the haemocyte population differed within the three observed groups. Although, immune responses following DWV infection have still not been completely clarified, this investigation sheds light on the relation between cell immunity and the phenoloxidase activity of DWV-naturally infected honeybees exposed to additional stress such as injury and viral superinfection.


2019 ◽  
Vol 12 (581) ◽  
pp. eaax3521 ◽  
Author(s):  
Nelson O. Gekara ◽  
Hui Jiang

Cyclic cGMP-AMP synthase (cGAS) alerts the innate immune system to the presence of foreign or damaged self-DNA inside the cell and is critical for the outcome of infections, inflammatory diseases, and cancer. Two studies now demonstrate that cGAS activation is regulated by differential subcellular localization through its non-enzymatic, N-terminal domain.


2020 ◽  
Vol 21 (2) ◽  
pp. 541 ◽  
Author(s):  
Arnold J. Levine

The p53 field was born from a marriage of the techniques of cancer virus research and immunology. Over the past 40 years, it has followed the path of cancer research. Now cancer treatments are turning to immunotherapy, and there are many hints of the role of the p53 protein in both the regulation of the innate immune system and as an antigen in adaptive immune responses. The p53 gene and protein are part of the innate immune system, and play an important role in infectious diseases, senescence, aging, and the surveillance of repetitive DNA and RNAs. The mutant form of the p53 protein in cancers elicits both a B-cell antibody response (a tumor antigen) and a CD-8 killer T-cell response (a tumor-specific transplantation antigen). The future will take the p53-immune response field of research into cancer immunotherapy, autoimmunity, inflammatory responses, neuro-degeneration, aging, and life span, and the regulation of epigenetic stability and tissue regeneration. The next 40 years will bring the p53 gene and its proteins out of a cancer focus and into an organismic and environmental focus.


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