scholarly journals The Problem of Antigen Affinity Discrimination in B-Cell Immunology

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Subhadip Raychaudhuri

B and T lymphocytes activate the humoral and cellular arms of the adaptive immune system. The adaptive strategy works because receptors of adaptive immune cells can mount an immune response based on their affinity for antigens. Thus, affinity discrimination is central to adaptive immunity and has important biomedical ramifications. Due to its intricate connection to the affinity maturation process, affinity discrimination has a special significance in B-cell-mediated immune response. The role of affinity-matured high-affinity antibodies is increasingly recognized in vaccine development. In this paper, we discuss the recent progress made in mathematical and computational studies to explore the cellular and molecular mechanisms of B-cell affinity discrimination. Formation of B-cell receptor (BCR) oligomers and BCR-lipid rafts, upon antigenic stimulation, emerge to be key factors in B-cell affinity discrimination (at the level of single cells). It also provides a new way of thinking about kinetic proofreading and serial triggering, concepts that have been widely utilized to understand affinity discrimination in adaptive immune cells. Potential future applications of mathematical and computational modeling of affinity discrimination are discussed in the context of autoimmune disorders and vaccine design.

Author(s):  
Dr. Ahmed Al-Shukaili ◽  

In December 2019 a new type of coronaviruses appeared in China and named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the disease associated with this virus is called Coronavirus Disease 2019 or COVID-19. Currently, COVID19 is the main global health threat. In this review, we focus in the current knowledge of immune response to SARS-CoV-2. Dysregulation of immune system, such as elevation levels of proinflammatory mediators and their roles in disease progression and pathogenesis as well as imbalance between innate and adaptive immune cells, are discussed in this review.


2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Emina Hayashida ◽  
Zheng Lung Ling ◽  
Thomas M. Ashhurst ◽  
Barney Viengkhou ◽  
So Ri Jung ◽  
...  

Abstract Background Until the end of the twentieth century, Zika virus (ZIKV) was thought to cause a mostly mild, self-limiting disease in humans. However, as the geographic distribution of ZIKV has shifted, so too has its pathogenicity. Modern-day ZIKV infection is now known to cause encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome in otherwise healthy adults. Nevertheless, the underlying pathogenetic mechanisms responsible for this shift in virulence remain unclear. Methods Here, we investigated the contribution of the innate versus the adaptive immune response using a new mouse model involving intracranial infection of adult immunocompetent mice with a moderately low dose of ZIKV MR766. To determine the contribution of type I interferons (IFN-Is) and adaptive immune cells, we also studied mice deficient for the IFN-I receptor 1 (Ifnar1−/−) and recombination-activating gene 1 (Rag1−/−). Results We show that intracranial infection with ZIKV resulted in lethal encephalitis. In wild-type mice, ZIKV remained restricted predominantly to the central nervous system (CNS) and infected neurons, whereas astrocytes and microglia were spared. Histological and molecular analysis revealed prominent activation of resident microglia and infiltrating monocytes that were accompanied by an expression of pro-inflammatory cytokines. The disease was independent of T and B cells. Importantly, unlike peripheral infection, IFN-Is modulated but did not protect from infection and lethal disease. Lack of IFN-I signaling resulted in spread of the virus, generalized inflammatory changes, and accelerated disease onset. Conclusions Using intracranial infection of immunocompetent wild-type mice with ZIKV, we demonstrate that in contrast to the peripheral immune system, the CNS is susceptible to infection and responds to ZIKV by initiating an antiviral immune response. This response is dominated by resident microglia and infiltrating monocytes and macrophages but does not require T or B cells. Unlike in the periphery, IFN-Is in the CNS cannot prevent the establishment of infection. Our findings show that ZIKV encephalitis in mice is dependent on the innate immune response, and adaptive immune cells play at most a minor role in disease pathogenesis.


2020 ◽  
Author(s):  
Bhanwar Lal Puniya ◽  
Robert Moore ◽  
Akram Mohammed ◽  
Rada Amin ◽  
Alyssa La Fleur ◽  
...  

AbstractThe human immune system, which protects against pathogens and diseases, is a complex network of cells and molecules. The effects of complex dynamical interactions of pathogens and immune cells on the immune response can be studied using computational models. However, a model of the entire immune system is still lacking. Here, we developed a comprehensive computational model that integrates innate and adaptive immune cells, cytokines, immunoglobulins, and nine common pathogens from different classes of virus, bacteria, parasites, and fungi. This model was used to investigate the dynamics of the immune system under two scenarios: (1) single infection with pathogens, and (2) various medically relevant pathogen coinfections. In coinfections, we found that the order of infecting pathogens has a significant impact on the dynamics of cytokines and immunoglobulins. Thus, our model provides a tool to simulate immune responses under different dosage of pathogens and their combinations, which can be further extended and used as a tool for drug discovery and immunotherapy. Furthermore, the model provides a comprehensive and simulatable blueprint of the human immune system as a result of the synthesis of the vast knowledge about the network-like interactions of various components of the system.


2022 ◽  
Vol 11 (2) ◽  
pp. 400
Author(s):  
Aleksandra Kałużna ◽  
Paweł Olczyk ◽  
Katarzyna Komosińska-Vassev

Ulcerative colitis (UC) is a chronic inflammatory disease with an underlying excessive immune response directed against resident microbiota and/or dietary antigens. Both innate and adaptive immune cells play a crucial role in the pathogenesis of UC. In the case of innate immune response cells, neutrophils, dendritic cells, macrophages have a crucial impact on the development of the disease, as well as innate lymphoid cells, which have received a particular attention in recent years. On the other hand, mechanisms of the adaptive immune response involve cells such as: cytotoxic lymphocytes, regulatory lymphocytes Treg, or helper lymphocytes Th–Th2, Th9, Th17, Th22, among which significant discoveries about Th9 and Th17 lymphocytes have been made in recent years. Due to the presence of antibodies directed against resident microbiota or one’s own tissues, the influence of B lymphocytes on the development of UC is also highlighted. Additionally, the impact of cytokines on shaping the immune response as well as sustaining inflammation seems to be crucial. This review briefly describes the current state of knowledge about the involvement of the innate and adaptive immune systems in the pathogenesis of UC. The review is based on personal selection of literature that were retrieved by a selective search in PubMed using the terms “ulcerative colitis” and “pathogenesis of ulcerative colitis”. It included systematic reviews, meta-analyses and clinical trials. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents.


2020 ◽  
Vol 21 (15) ◽  
pp. 5203 ◽  
Author(s):  
Enyu Huang ◽  
Na Peng ◽  
Fan Xiao ◽  
Dajun Hu ◽  
Xiaohui Wang ◽  
...  

Tissue injury and inflammatory response trigger the development of fibrosis in various diseases. It has been recognized that both innate and adaptive immune cells are important players with multifaceted functions in fibrogenesis. The activated immune cells produce various cytokines, modulate the differentiation and functions of myofibroblasts via diverse molecular mechanisms, and regulate fibrotic development. The immune cells exhibit differential functions during different stages of fibrotic diseases. In this review, we summarized recent advances in understanding the roles of immune cells in regulating fibrotic development and immune-based therapies in different disorders and discuss the underlying molecular mechanisms with a focus on mTOR and JAK-STAT signaling pathways.


2020 ◽  
Vol 210 ◽  
pp. 06017
Author(s):  
Aleksandr Refeld ◽  
Anna Bogdanova ◽  
Evgeniya Prazdnova ◽  
Alexey Beskopylny ◽  
Anastasiya Olshevskaya ◽  
...  

Probiotics are becoming more and more common means of combating intestinal diseases of various origins: infectious pathologies, chronic inflammation, autoimmune disorders. The complex action, coupled with low side effects, makes probiotics promising drugs, especially in veterinary medicine, with an increasing trend towards the inefficient use of antibiotics in the livestock industry. One of the main mechanisms of probiotics action - modulation of host immunity - is perhaps the most difficult and, at the same time, the most actively studied since it is crucial for therapy. Immunobiotics (probiotics that modulate the host's immune response) interact with various innate and adaptive immune cells, changing the expression of pro- and anti-inflammatory cytokines. This action is provided by both the cellular components of probiotic microorganisms and their metabolites and is primarily associated with the host's immunocompetent cells' pattern-recognition receptors, although other molecular mechanisms also exist. This review aims to briefly describe both the molecular mechanisms of immunomodulation by probiotics and the prospects for their use in veterinary medicine.


Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo

Background: Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. Objectives: The participation of platelets in inflammatory processes will be discussed also in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Conclusion: Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.


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