Topic Review
T Lymphocyte
Exosomes are extracellular vesicles (EV) of endosomal origin (multivesicular bodies, MVB) constitutively released by many different eukaryotic cells by fusion of MVB to the plasma membrane. However, inducible exosome secretion controlled by cell surface receptors is restricted to very few cell types and a limited number of cell surface receptors. Among these, exosome secretion is induced in T lymphocytes and B lymphocytes when stimulated at the immune synapse (IS) via T-cell receptor (TCR) and B-cell receptor (BCR), respectively. IS formation by T and B lymphocytes constitutes a crucial event involved in antigen-specific, cellular and humoral immune responses. Upon IS formation by T and B lymphocytes with antigen-presenting cells (APC) the convergence of MVB towards the microtubule organization center (MTOC), and MTOC polarization to the IS, are involved in polarized exosome secretion at the synaptic cleft. This specialized mechanism provides the immune system with a finely-tuned strategy to increase the specificity and efficiency of crucial secretory effector functions of B and T lymphocytes. Since inducible exosome secretion by antigen-receptors is a critical and unique feature of the immune system this entry considers the study of the traffic events leading to polarized exosome secretion at the IS and some of their biological consequences.
  • 1.8K
  • 29 Oct 2020
Topic Review
Gastrointestinal Diseases in Primary Immunodeficiencies
In recent years, the incidence of immune-mediated gastrointestinal disorders, including celiac disease (CeD) and inflammatory bowel disease (IBD), is increasingly growing worldwide. It is well established that primary immunodeficiencies (PIDs) exhibit gastrointestinal manifestations and mimic other diseases, including CeD and IBD. The most common PIDs in adults are the selective immunoglobulin A deficiency (SIgAD) and the common variable immunodeficiency (CVID). However, some differences concerning diagnostics and management between enteropathy/colitis in PIDs, as compared to idiopathic forms of CeD/IBD, have been described. There is an ongoing discussion whether CeD and IBD in CVID patients should be considered a true CeD and IBD or just CeD-like and IBD-like diseases. This review addresses the current state of the art of the most common primary immunodeficiencies in adults and co-occurring CeD and IBD.
  • 1.7K
  • 29 Oct 2020
Topic Review
Epigenetic Regulations of T Cell Differentiation
T cell differentiation is a tightly regulated process. Recent studies have shown that epigenetics plays a significant role at all stages of the differentiation process.  The different stages of T cell differentiation are introduced and recent findings on the epigenetic regulation of this process will be discussed. The epigenetic modifications associated with T cell differentiation related to cancer are discussed as well.
  • 1.6K
  • 18 Jul 2022
Topic Review
CAR-T Cells in Pancreatic cancer
Pancreatic cancer has the worst prognosis and lowest survival rate among all types of cancers and thus, there exists a strong need for novel therapeutic strategies. Chimeric antigen receptor (CAR)-modified T cells present a new potential option after successful FDA-approval in hematologic malignancies, however, current CAR T cell clinical trials in pancreatic cancer failed to improve survival and were unable to demonstrate any significant response. The physical and environmental barriers created by the distinct tumor microenvironment (TME) as a result of the desmoplastic reaction in pancreatic cancer present major hurdles for CAR T cells as a viable therapeutic option in this tumor entity. Cancer cells and cancer-associated fibroblasts express extracellular matrix molecules, enzymes, and growth factors, which can attenuate CAR T cell infiltration and efficacy. Recent efforts demonstrate a niche shift where targeting the TME along CAR T cell therapy is believed or hoped to provide a substantial clinical added value to improve overall survival.
  • 1.6K
  • 16 Oct 2020
Topic Review
Balancing Immune System to Treat Rheumatoid Arthritis
Rheumatoid arthritis (RA) and other autoimmune inflammatory diseases are examples of imbalances within the immune system (disrupted homeostasis) that arise from the effects of an accumulation of environmental and habitual insults over a lifetime, combined with genetic predispositions. The Ligand Epitope Antigen Presentation System (LEAPS) therapies are capable of inhibiting ongoing disease progression in animal models. Whereas DMARDs ablate or inhibit specific proinflammatory cytokines or cells and JAK inhibitors (jakinibs) inhibit the receptor activation cascade for expression of proinflammatory cytokines, the LEAPS therapeutic vaccines specifically modulate the ongoing antigen-specific, disease-driving, proinflammatory T memory cell responses. This decreases disease presentation and changes the cytokine conversation to decrease the expression of inflammatory cytokines while increasing the expression of regulatory cytokines. 
  • 1.6K
  • 09 May 2022
Topic Review
CD19-CAR-T Cells
CD19-targeted chimeric antigen receptor (CAR) T (CD19-CAR-T) cell therapy usually causes B cell aplasia because of “on-target off-tumor” toxicity. The aim of the study was to assess the concept that the introduction of an inhibitory CAR (iCAR) into CAR-T cells could alleviate the side effect of CD19-CAR-T cell therapy. The results showed that CD19-CAR-T cells with a novel KIR/PD-1-based inhibitory CAR (iKP-19-CAR-T) exhibited more naïve, less exhausted phenotypes and preserved a higher proportion of central memory T cells (TCM). Furthermore, iKP-19-CAR-T cells exerted the similar level of cytotoxicity on CD19+HLA-C1- Burkitt’s lymphoma cells compared to CD19-CAR-T cells while sparing CD19+HLA-C1+ healthy human B cells both in vitro and in the xenograft model. Our data demonstrates that the KIR/PD-1-based inhibitory CAR can be a promising strategy to avoid B cell aplasia caused by CD19-CAR-T cell therapy.  
  • 1.6K
  • 26 Oct 2020
Topic Review
Vaccine Technology in Bovine Theileriosis
Theileriosis is a blood piroplasmic disease that adversely affects the livestock industry, especially in tropical and sub-tropical countries. It is caused by haemoprotozoan of the Theileria genus, transmitted by hard ticks and which possesses a complex life cycle. The infection and treatment method (ITM) is currently used in the control and prevention of T. parva infection, and recombinant vaccines are still under evaluation. The use of gene gun immunization against T. parva infection has been recently evaluated.
  • 1.6K
  • 26 Oct 2020
Topic Review
Rational Vaccine Design
Vaccines are the most effective medical intervention due to their continual success in preventing infections and improving mortality worldwide. Early vaccines were developed empirically however, rational design of vaccines can allow us to optimise their efficacy, by tailoring the immune response. Establishing the immune correlates of protection greatly informs the rational design of vaccines. This facilitates the selection of the best vaccine antigens and the most appropriate vaccine adjuvant to generate optimal memory immune T cell and B cell responses. This review outlines the range of vaccine types that are currently authorised and those under development. We outline the optimal immunological correlates of protection that can be targeted. 
  • 1.5K
  • 29 Apr 2021
Topic Review
The Alveolar Epithelium at Homeostasis
The alveolar epithelium serves as a barrier between the body and the external environment. To maintain efficient gas exchange, the alveolar epithelium has evolved to withstand and rapidly respond to an assortment of inhaled, injury-inducing stimuli. Alveolar damage can lead to loss of alveolar fluid barrier function and exuberant, non-resolving inflammation that manifests clinically as acute respiratory distress syndrome (ARDS).
  • 1.5K
  • 21 Sep 2022
Topic Review
Cardiac Glycosides
Cardiac glycosides (CG’s) are naturally occurring biologically active small molecules, used to diagnose a diversity of heart diseases such as congestive heart failure and cardiac arrhythmia. The story of CG’s started over 100 years ago when Sir William Withering reported the use of foxglove plant for treating “dropsy” associated with congestive heart failure and the foxglove plant (Digitalis purpurea) was still in the use for the extraction of Digoxin, a cardiac glycoside used to treat congestive heart failures (Johnson., 2012). The core structure of CGs comprises a steroid nucleus attached to a five-membered lactone ring (cardenolide) or six-membered lactone rings (bufadienolides) along with sugar moieties. Major plant-derived CGs were obtained from plant families of Apocynaceae, Scrophulariaceae, and Asparagaceae (Thevitia neriifolia, Neerium oleander, Digitalis purpurea, Digitalis lanata, Urginea maritime, and Strophanthus kombe). Structurally, all these contain a core steroid nucleus connected with sugar moiety at C3 position and lactone moiety at C17 position (Figure 1.3). The pharmacological significance of all the CG’s lies in the core steroid confirmation that contains A/B and C/D cis- portions and the properties such as pharmacokinetics and pharmacodynamics lie between the confined sugars molecules (Pongrakhananon., 2013). Apart from the plant sources, CG’s were also isolated from several animal species such as bufadienolide was isolated from frogs, and also mammalian tissues contain a cardiac glycoside which is similar to endogenous digitalis (Melero et al., 2000). Quite a few studies have conveyed that the human body does contain a lot more CG’s in different parts. For example, the plasma membrane contains Ouabain and Proscillaridin A and human urine contains digoxin and marinobufagenin whereas human lenses consist of 19-norbufalin (Schoner and Scheiner-Bobis., 2007). In the year 1785, William Withering was the first person to use a digitalis compound from Digitalis purpurea to treat congestive heart failures. Currently, Digoxin is used for treating congestive heart failures. The mechanism of action of Digoxin is that it can inhibit the sodium-potassium pump (Na+/K+-ATPase). Living organisms maintain more percentage of K+ within the cell and less percentage of Na+. However, the scenario at the outside of the cell is quite opposite to the intracellular conditions where a high percentage of Na+ and less percentage of K+ will be maintained. Hence, there is a concentration incline that exists between the outside and inside cellular environments, which will be maintained by sodium-potassium pump. The Na+/K+-ATPase is recognized as a transmembrane protein whose functions are to maintain ionic balance in the heart tissue. Na+/K+-ATPase utilizes ATP as the whole energy source, to exchange two K+ ions inside the cell and pushes three Na+ ions outside to maintain intra cellular homeostasis. Also, Na+/K+-ATPase transports glucose and amino acids by keeping less concentration of Na+ within the cell and helps in the maintenance of electrochemical incline. The increment of the Na+ level inside the cell retort to CGs fortifies the ion exchange mechanism. This leads to the expansion of intracellular Ca2+ percentage which therefore promotes organelle instances such as myocardial contractibility, and generates optimistic inotropic effects in the heart cell with CGs (Kaplan., 2002).  
  • 1.5K
  • 12 Aug 2020
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