【Science you and me – Unlimited potential innate immune proteins】

The PGRP ( Tag7 ) protein activates the lymphoid immune cells of the organism to kill infected cells.
[Top] Activated lymphoid immune cells kill infected cells (infSC-1), but activated lymphoid immune cells do not pose a high risk to normal healthy cells.
[Bottom] Lymphatic immune cells activated by Tag7 protein are natural killer NK and CD8+ T cells.
In addition to its antibacterial effect, PGRP ( Tag7 ) protein also helps the body’s lymphoid immune cells to kill virus-infected cells.
If we can successfully use PGRP in the future, it is believed that it will have a significant positive effect on our medicine.

Tag7

[Science you and me – Everlasting innate immune proteins]

Innate immune proteins are antibacterial substances which have existed for millions of years. Their action sites are mainly directed to essential fragments of prokaryotes, so it’s difficult to develop drug-resistant strains.

PGRP is an innate immune protein that binds to peptidoglycan on the bacterial membrane, causing changes in oxidation, thiol or metal ions.

PGRP accelerates the TCA cycle and increases the formation of hydrogen peroxide (H2O2) and hydroxyl radicals (HO·).
PGRP may also cause the consumption of more than 90% of the thiol groups in the cell, which destroys the redox balance of the cells.
The third method of PGRP increases intracellular free Zn2+ and Cu+, which inactivates the enzyme or accelerates the consumption of thiol groups.
In contrast, antibiotics can only produce antibacterial effects in a single location; PGRP can use multiple pathways to inhibit bacteria, but PGRP research is not yet complete and there is currently no commercial PGRP for medical use in the future. If you can use PGRP in a large number of successful ways, it is believed that it will have a significant positive effect on our medicine.
Full paper : Dziarski, Roman, and Dipika Gupta. “How innate immunity proteins kill bacteria and why they are not prone to resistance." Current genetics 64.1 (2018): 125-129.

PGRP-S抗菌效果

 

 

Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre.

Front Microbiol. 2017 May 17;8:900. doi: 10.3389/fmicb.2017.00900. eCollection 2017.

Gould VMW1Francis JN2Anderson KJ2Georges B2Cope AV1Tregoning JS1.

 

Abstract

In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent. Volunteers were pre-selected with low haemagglutination inhibition (HAI) titres in order to ensure a higher proportion of infection; this allowed us to explore the role of other immune correlates. In spite of HAI being uniformly low, there were variable levels of H1N1 specific IgG and IgA prior to infection. There was also a range of disease severity in volunteers allowing us to compare whether differences in systemic and local H1N1 specific IgG and IgA prior to infection affected disease outcome. H1N1 specific IgG level before challenge did not correlate with protection, probably due to the pre-screening for individuals with low HAI. However, the length of time infectious virus was recovered from the nose was reduced in patients with higher pre-existing H1N1 influenza specific nasal IgA or serum IgA. Therefore, IgA contributes to protection against influenza and should be targeted in vaccines.

KEYWORDS:

Human Infection Challenge study; IgA; influenza; nasal; vaccine

 

 

Author information

1
Mucosal Infection and Immunity, Section of Virology, Imperial College LondonLondon, United Kingdom.
2
Altimmune, London BioScience Innovation CentreLondon, United Kingdom.

Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies.

Department of Medicine, University Hospitals of Cleveland, Case Western Reserve University, Ohio 44106.

J Virol. 1995 Feb;69(2):1339-43.

Mazanec MB1Coudret CLFletcher DR.

Abstract

Traditionally, immunoglobulin A (IgA) was thought to neutralize virus by forming complexes with viral attachment proteins, blocking attachment of virions to host epithelial cells. Recently we have proposed an intracellular action for dimeric IgA, which is actively transported through epithelial cells by the polymeric immunoglobulin receptor (pIgR), in that it may be able to bind to newly synthesized viral proteins within the cell, preventing viral assembly. To this effect, we have previously demonstrated that IgA monoclonal antibodies against Sendai virus, a parainfluenza virus, colocalize with the viral hemagglutinin-neuraminidase protein within infected epithelial cells and reduce intracellular viral titers. Here we determine whether IgA can interact with influenza virus hemagglutinin (HA) protein within epithelial cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the pIgR were infected on their apical surfaces with influenza virus A/Puerto Rico/8-Mount Sinai. Polymeric IgA anti-HA, but not IgG anti-HA, delivered to the basolateral surface colocalized with HA protein within the cell by immunofluorescence. Compared with those of controls, viral titers were reduced in the supernatants and cell lysates from monolayers treated with anti-HA IgA but not with anti-HA IgG. Furthermore, the addition of anti-IgA antibodies to supernatants did not interfere with the neutralizing activity of IgA placed in the basal chamber, indicating that IgA was acting within the cell and not in the extracellular medium to interrupt viral replication. Thus, these studies provide additional support for the concept that IgA can inhibit replication of microbial pathogens intracellularly.

PMID: 7815518   PMCID: PMC188717