scholarly journals The Immune System as Drug Target

2013 ◽  
Vol 5 ◽  
pp. III.S12145
Author(s):  
Darren R. Flower

The immune system is perhaps the largest yet most diffuse and distributed somatic system in vertebrates. It plays vital roles in fighting infection and in the homeostatic control of chronic disease. As such, the immune system in both pathological and healthy states is a prime target for therapeutic interventions by drugs–-both small-molecule and biologic. Comprising both the innate and adaptive immune systems, human immunity is awash with potential unexploited molecular targets. Key examples include the pattern recognition receptors of the innate immune system and the major histocompatibility complex of the adaptive immune system. Moreover, the immune system is also the source of many current and, hopefully, future drugs, of which the prime example is the monoclonal antibody, the most exciting and profitable type of present-day drug moiety. This brief review explores the identity and synergies of the hierarchy of drug targets represented by the human immune system, with particular emphasis on the emerging paradigm of systems pharmacology.

Author(s):  
bose Karthik

SARS-COV-2 is reported to be associated with severe immune dysregulation, delayed humoral responses and accelerated innate immune response mediated damages. As the pandemic is turning the world upside down, In order to address this disease we should first get an insight into the mechanism of action through which SARS-COV-2 is achieving the above said dysregulating or modulating effects on human immune system. T his article presents the basic or skeletal mechanism through which SARS-COV-2 dysregulates immune system by targeting innate immune system, adaptive immune system and different immune tolerance check points by dysregulating different miRNA’s and the preexisting conditions or comorbidities of the patients. This article comprises of the comparative and comprehensive literature review targeting all topics with the data available/reported till date in the scientific community.


2013 ◽  
Vol 191 (4) ◽  
pp. 1753-1764 ◽  
Author(s):  
Eva Billerbeck ◽  
Joshua A. Horwitz ◽  
Rachael N. Labitt ◽  
Bridget M. Donovan ◽  
Kevin Vega ◽  
...  

2016 ◽  
Vol 114 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Nina M. Høyland-Kroghsbo ◽  
Jon Paczkowski ◽  
Sampriti Mukherjee ◽  
Jenny Broniewski ◽  
Edze Westra ◽  
...  

CRISPR-Cas are prokaryotic adaptive immune systems that provide protection against bacteriophage (phage) and other parasites. Little is known about how CRISPR-Cas systems are regulated, preventing prediction of phage dynamics in nature and manipulation of phage resistance in clinical settings. Here, we show that the bacteriumPseudomonas aeruginosaPA14 uses the cell–cell communication process, called quorum sensing, to activatecasgene expression, to increase CRISPR-Cas targeting of foreign DNA, and to promote CRISPR adaptation, all at high cell density. This regulatory mechanism ensures maximum CRISPR-Cas function when bacterial populations are at highest risk for phage infection. We demonstrate that CRISPR-Cas activity and acquisition of resistance can be modulated by administration of pro- and antiquorum-sensing compounds. We propose that quorum-sensing inhibitors could be used to suppress the CRISPR-Cas adaptive immune system to enhance medical applications, including phage therapies.


2007 ◽  
Vol 292 (1) ◽  
pp. G6-G10 ◽  
Author(s):  
Ian R. Sanderson ◽  
W. Allan Walker

The innate immune system includes microbial pattern recognition receptors that detect bacteria and viral products at the cell surface, in vesicles, and within the cytoplasm. Transmembrane signaling occurs through Toll-like receptors (TLRs). Cytoplasmic receptors are generally members of the nucleotide-binding domain (NOD)-leucine-rich repeat (LRR) family (CATERPILLER family). They influence the effects of other family members and of TLRs. Most NOD-LRR members enhance signal transduction, but Monarch-1 counterbalances TLR activity. NOD-LRR family members also act within the adaptive immune system. The class II transactivator regulates major histocompatibility complex class II expression. In the intestine, it is developmentally regulated, and its expression depends on weaning and, independently, on age.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Gisa Ellrichmann ◽  
Christiane Reick ◽  
Carsten Saft ◽  
Ralf A. Linker

Huntington’s disease (HD) is characterized by a progressive course of disease until death 15–20 years after the first symptoms occur and is caused by a mutation with expanded CAG repeats in the huntingtin (htt) protein. Mutant htt (mhtt) in the striatum is assumed to be the main reason for neurodegeneration. Knowledge about pathophysiology has rapidly improved discussing influences of excitotoxicity, mitochondrial damage, free radicals, and inflammatory mechanisms. Both innate and adaptive immune systems may play an important role in HD. Activation of microglia with expression of proinflammatory cytokines, impaired migration of macrophages, and deposition of complement factors in the striatum indicate an activation of the innate immune system. As part of the adaptive immune system, dendritic cells (DCs) prime T-cell responses secreting inflammatory mediators. In HD, DCs may contain mhtt which brings the adaptive immune system into the focus of interest. These data underline an increasing interest in the peripheral immune system for pathomechanisms of HD. It is still unclear if neuroinflammation is a reactive process or if there is an active influence on disease progression. Further understanding the influence of inflammation in HD using mouse models may open various avenues for promising therapeutic approaches aiming at slowing disease progression or forestalling onset of disease.


1994 ◽  
Vol 180 (5) ◽  
pp. 1911-1920 ◽  
Author(s):  
R S Yeung ◽  
J M Penninger ◽  
T M Kündig ◽  
Y Law ◽  
K Yamamoto ◽  
...  

To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/-), after homologous recombination, have been generated. We report that expression of human CD4 molecule in mCD4/8-/- mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs. Upon vesicular stomatitis virus (VSV) challenge, the reconstituted mature T cell population effectively provide T help to B cells in immunoglobulin class switching from IgM to specific IgG-neutralizing antibodies. Human CD4+DQw6+ double transgenic mice are tolerant to DQw6 and the DQw6 molecule functions in antigen presentation, effectively generating a human MHC class II-restricted T cell response to streptococcal M6C2 peptide. These data show that both the hCD4 and DQw6 molecules are functional in mCD4/8-/- mice, fully and stably reconstituting this limb of the human immune system in mice. This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS).


2020 ◽  
Vol 3 (8) ◽  
pp. 25-43
Author(s):  
William de Jesús Ríos-Ríos ◽  
Jair Aguilar-Cruz

The human immune system has evolvedtoachieveahighlyefficient, specialized and specific immunity against particular molecular structures of each pathogenic microorganism and to develop mechanisms allowing to respond more quickly and efficiently to subsequent encounters with the same invading agent: the adaptive immune response. This paper describes the connection between the innate and adaptive immune response, as well as the cellular and humoral mechanisms of control and long-term protection of the adaptive immune response.


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.


2017 ◽  
Vol 41 (4) ◽  
pp. 578-593 ◽  
Author(s):  
François M. Abboud ◽  
Madhu V. Singh

The autonomic nervous system is a powerful regulator of circulatory adjustments to acute hemodynamic stresses. Here we focus on new concepts that emphasize the chronic influence of the sympathetic and parasympathetic systems on cardiovascular pathology. The autonomic neurohumoral system can dramatically influence morbidity and mortality from cardiovascular disease through newly discovered influences on the innate and adaptive immune systems. Specifically, the end-organ damage in heart failure or hypertension may be worsened or alleviated by pro- or anti-inflammatory pathways of the immune system, respectively, that are activated through neurohumoral transmitters. These concepts provide a major new perspective on potentially life-saving therapeutic interventions in the deadliest of diseases.


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