Disruption of T Cell Tolerance to Self-Immunoglobulin Causes Polyclonal B Cell Stimulation Followed by Inactivation of Responding Autoreactive T Cells

Choudhury, Arpita; Mukherjee, Paushali; Basu, Sandip K.; George, Anna; Rath, Satyajit; Bal, Vineeta

doi:10.4049/jimmunol.164.4.1713

Cited by 8 publications

(3 citation statements)

References 54 publications

(37 reference statements)

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“…However, over time it usually broadens, affecting other tissues and organs and representing a variety of different antibodies. At this stage, a so-called polyclonal B-cell activation has occurred [69], primarily the consequence of autoreactive B cells being found more frequently in the mature peripheral cell repertoire than autoreactive T cells [69].…”

Section: 'Classic' Autoimmunitymentioning

confidence: 99%

Female infertility due to abnormal autoimmunity: frequently overlooked and greatly underappreciated. Part I

Gleicher¹,

Weghofer²,

Barad³

2007

Expert Review of Obstetrics & Gynecology

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When the impact of abnormal autoimmune function on female fertility is objectively examined, an unexpectedly large contribution is (auto)immune related. This may be surprising since many authorities have been dismissive of (auto)immune-associated infertility. In this article, we therefore summarize the link between abnormal autoimmune function and female infertility, based on literature searches. Abnormal autoimmune function affects female fertility at numerous levels of the reproductive process. As with autoimmune conditions in general, abnormal autoimmune function affecting fertility is often difficult to diagnose since it frequently presents subclinically, without overt clinical symptoms. It also demonstrates other characteristics of abnormal autoimmunity, such as familial occurrence and genetic predisposition, environmental cofactors contributing to phenotypic expression of genetic risk and cyclicity of occurrence, often characterized by gestational exacerbation patterns. Proven treatments for autoimmune-associated infertility have not been established to date. This fact should, however, not preclude efforts to reach correct diagnoses, since only accurate diagnoses can lead to appropriately conducted clinical trials.Expert Rev. Obstet. Gynecol. 2(4), 453-464 (2007) "Fashions are the only induced epidemics, proving that epidemics can be induced by tradesmen." Bernard Shaw Bernard Shaw's quotation astutely comments on both the fickleness of fashion and the general fickleness of thought. By utilizing epidemics as acronyms for periodic, irrational behavior, he reminds us that fashionable behavior permeates all spheres of life, including, of course, the science of medicine.The thinking on autoimmune abnormalities in reproductive medicine is a good example. A highly popular topic during the 1980s and early 1990s, autoimmunity fell out of fashion by the end of the last decade. Some prominent individuals [1,2] and professional organizations [3] succeeded to a large degree in relegating the concept that abnormal autoimmune function can adversely affect female fertility to the dustbin of undistinguished, and failed, ideas. This article aims to balance an, at times quite opinionated, discourse [2,4]. As this twopart series of articles will demonstrate, abnormal autoimmune function can indeed interfere with successful human reproduction at quite a number of different levels.

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Section: 'Classic' Autoimmunitymentioning

confidence: 99%

Female infertility due to abnormal autoimmunity: frequently overlooked and greatly underappreciated. Part I

Gleicher¹,

Weghofer²,

Barad³

2007

Expert Review of Obstetrics & Gynecology

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“…Investigations in the past 50 years have revealed that Staphylococcus aureus is able to invade and survive inside mammalian cells, primarily phagocytes and neutrophils, preventing their clearance. , Meanwhile, incomplete clearance of intracellular S. aureus sees the host infected cells as “Trojan horses” to disseminate the bacteria away from the initial site to the new “land of happiness” for infection . This “Trojan horses” phenomenon results in significant enhancement of the antibiotic minimum inhibitory concentration (MIC) for intracellular bacteria, causing failure of the antibiotics in vitro and in vivo. ,, Thus, the development of antibacterial agents with intracellular activity against S. aureus poses challenges in antimicrobial therapy.…”

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confidence: 99%

Macrophage-Instructed Intracellular Staphylococcus aureus Killing by Targeting Photodynamic Dimers

Cai

Fei

et al. 2018

ACS Appl. Mater. Interfaces

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The survival of Staphylococcus aureus inside phagocytes is considered to be the sticking point of long-term chronic inflammation. Here, we fabricate peptide-chlorophyll-based photodynamic therapy (PDT) agents with "sandwich" dimeric structure to enhance the PDT effect and active targeting property to eliminate intracellular infections, which could be seen as prospective antibacterial agents for inflammation.

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“…These observations may provide a lead for manipulating immune responses to generate new generation vaccines and immunotherapeutics. Furthermore, they recently showed that the H-dThd uptake delivery of autologous serum albumin to scavenger receptors leads to a breakdown of T cell tolerance in mice to self-albumin, offering a new tool to dissect mechanisms of immune tolerance and the etiopathogenesis of autoimmunity [115,119].…”

Section: To Modulate Immune Responsesmentioning

confidence: 99%

Intracellular Delivery of Drugs to Macrophages

Mukhopadhyay

Basu

2003

Advances in Biochemical Engineering/Biotechnology

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Toxic side effects which often complicate successful therapy in a number of diseases possibly arise due to the fact that at therapeutically effective concentrations the non-target cells in the body are also exposed to the cytotoxic effects of the drugs. Minimization of such adverse reactions might be feasible through drug delivery modalities that would reduce the uptake of the drugs by non-target cells and selectively deliver the drug only to the target cells (and/or intracellular sites) at relatively low extracellular concentrations. The current generic approach to site-specific drug delivery consists of attaching the therapeutic agent to a carrier recognized only by the cells where the pharmacological action is desired. Two types of recognition elements on the surface of target cells are being exploited for this purpose, viz., (i) antigens capable of generating specific, non-cross reactive antibodies, and (ii) receptors on the cell surface capable of efficient transport of the ligands. In general, incomplete specificity for the target cells and poor internalization of antibody-drug conjugates still limit the usefulness of antibodies for site-specific drug delivery applications necessitating exploration of alternatives. The alternate possibility is to exploit the exquisite cell type specificity and high efficiency of endocytosis of macromolecules mediated by specific receptors present on the surface of target cells for delivering drugs. A large number of infectious, metabolic, and neoplastic diseases are associated with macrophages leading to morbidities and mortalities to millions of people worldwide, thus an appropriate design of a drug delivery system to macrophages will be of tremendous help.

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Disruption of T Cell Tolerance to Self-Immunoglobulin Causes Polyclonal B Cell Stimulation Followed by Inactivation of Responding Autoreactive T Cells

Cited by 8 publications

References 54 publications

Female infertility due to abnormal autoimmunity: frequently overlooked and greatly underappreciated. Part I

Female infertility due to abnormal autoimmunity: frequently overlooked and greatly underappreciated. Part I

Macrophage-Instructed Intracellular Staphylococcus aureus Killing by Targeting Photodynamic Dimers

Intracellular Delivery of Drugs to Macrophages

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