Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Prions, vCJD and the Immune System Relay

Published: Friday, December 06, 2013
Last Updated: Friday, December 06, 2013
Bookmark and Share
BBSRC is helping to shed new light on variant Creutzfeldt-Jakob disease.

Despite more than a decade's worth of research, many aspects of variant Creutzfeldt-Jakob disease (vCJD) still remain a mystery. This fatal neurodegenerative disease of the brain is often referred to as the human form of bovine spongiform encephalopathy (BSE), known to most as 'mad cow disease'.

vCJD was first described in 1986 and was attributed to humans eating meat from infected cattle. The exact root of the disease is still unknown, but proteins known as prions are believed to be the causative agent. A build up of misfolded prions in the brain causes the progressive death of neurons, for which there is no cure. The brains of people that have died of the disease look sponge-like when viewed under a microscope, hence the word 'spongiform' in BSE.

Misfolding proteins

The way that a prion infection spreads is debated. The prion mode of action is very different to bacteria and viruses as they are simply proteins, devoid of any genetic material. Once a misfolded prion enters a healthy person – potentially by eating infected food – it converts correctly-folded proteins into the disease-associated form. To date, nobody knows quite how this happens.

vCJD is by no means the only form of prion disease in humans. Sporadic CJD (sCJD) is the most common, causing around 1-2 deaths per 1,000,000 people in the UK each year, generally in those over the age of 60. vCJD is also rare – despite an estimated 400-500,000 BSE infected cattle entering the food chain in the 1980's – with only 177 definite or probable cases having been reported to date. Unlike sCJD, the majority of those affected were young (~26 years old).

Initially, this age discrepancy was thought to be related to dietary habits, with young people more likely to be eating food with a high risk of contamination. No strong evidence for this was found (old people eat pies and burgers, too).

The immune system relay

New research from scientists at The Roslin Institute – which is strategically-funded by BBSRC – and published in the Journal of General Virology, is helping us to understand why vCJD appears to mainly affect the young.

Having a healthy immune system seems to be central to vCJD development. Indeed, mice that lack a functional immune system have a lower susceptibility to prion disease. The misfolded prions appear to hijack the defence system that protects against bacterial and viral infection, using it to gain access to the nervous system and, ultimately, the brain.

Dr Neil Mabbott, one of the co-authors of the study, describes the movement of the prions as 'a relay', which begins in the small intestine.

In order to ascertain whether there are any pathogens in the small intestine and, if so, what response needs to be mounted, the body uses an 'antigen sampling' system (kind of a built in dipstick) to see what is present.

This system is the point of entry for the misfolded prions, allowing them to slip in the body's lymphatic system. Once there, they attach to the surface of immune cells known as follicular dendritic cells (FDCs), and replicate by causing normal prion proteins to misfold into the disease-causing version.

Through methods unknown, the misfolded prions escape the surface of the FDCs, moving into the nerves, and spread through the spinal cord and vagus nerve to the brain where the real damage begins.

The new research studied two groups of mice: 32 between six and eight weeks of age and 29 around ninety weeks old (very old for a mouse). These two groups of mice were injected with prions from a cow known to have been infected with BSE.

Dropping the baton?

Within a few months, prions had accumulated in the lymph nodes and spleen of the young mice, although they did not show any signs of disease. Over a year later, the majority of those tested showed classic signs of prion neurodegeneration.

In contrast, none of the old mice developed any clinical disease, all died of natural age-related diseases. Only one of the 29 older aged mice showed any sign of having prions in its brain and this was only in a small, localised area. Given that most of these adult mice died before the time it takes to develop prion disease, it can't be ruled out that they would have developed an infection if they'd lived long enough, although there was no evidence of any prion-related neurodegeneration.

Despite there being no evidence of prions in the elderly mice's brains, there were detectable levels in their spleens, albeit at lower levels than in the younger mice. Dr Mabbott suggests that this may be because one of the relay steps is missing, or working less efficiently, in the older mice.

The research, funded by the BBSRC and the  European Commission: Seventh Framework Programme (FP7) , builds on previous work that showed how the microarchitecture of the mice's spleen – part of the antigen sampling system – deteriorates with age, as do the numbers of FDCs, leaving less for the prions to replicate on.

Error bars

While this study does provide us with further background into vCJD, a disease that remains much of a mystery, we need to remember that the mice being used in the study are clearly not humans, so any parallels drawn between the two species must be done carefully. That said, recent research published in the BMJ suggests that levels of abnormal vCJD prions in humans appear to be higher than we previously thought.

Researchers investigated over 30,000 stored appendix samples, removed during operations in the UK between 2000 and 2012, of which 16 showed evidence of abnormal prions. Although a small number, the authors of the paper suggest that this indicates a prevalence of 493 people per million in the UK with abnormal prions, higher than the total number of confirmed vCJD cases (177) to date.

In addition to showing the importance of ageing to susceptibility of prion disease, Dr Mabbott's work has also uncovered the effects that getting old has on the immune system. He has recently been awarded a grant from the BBSRC to further investigate the mechanisms that cause the immune system to break down, which may ultimately help to improve people's health as they get older.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Expanding the DNA Alphabet: 'Extra' DNA Base Found to be Stable in Mammals
A rare DNA base, previously thought to be a temporary modification, has been shown to be stable in mammalian DNA, suggesting that it plays a key role in cellular function.
Thursday, June 25, 2015
Global Food Security (GFS) Develops New Funding Programme
New programme of research to tackle resilience of the food system.
Tuesday, June 02, 2015
£4M to Fund Important Food Crops from BBSRC and NERC
Research projects designed with industry partners to maximize impact.
Tuesday, June 02, 2015
Controlling Leaf Blotch Disease In Wheat
Scientists have found a genetic mechanism that could stop the spread of a "devastating" disease threatening wheat crops.
Thursday, February 05, 2015
Rising Temperatures Predicted to Lower Wheat Yields
An international consortium of researchers has used big data sets to predict the effects climate change on global wheat yields.
Friday, December 26, 2014
New Test For Detecting Horse Meat
New test compares differences in chemical compositions of the fat found in meats.
Tuesday, December 02, 2014
UK And India Collaborate On Future-Proof Crops
Drought-tolerant tomatoes, improved wheat and grass pea could provide crops for the future.
Friday, November 28, 2014
Drugs Used to Treat Lung Disease Work With the Body Clock
Scientists from The University of Manchester have discovered why medication to treat asthma and pneumonia can become ineffective.
Thursday, August 14, 2014
Researchers Use ‘Big Data’ Approach to Map the Relationships Between Human and Animal Diseases
EID2 database used to prevent and tackle disease outbreaks around the globe.
Thursday, July 17, 2014
TGAC at the Forefront of Next Generation Sequencing Capability
The Genome Analysis Centre adds two Illumina HiSeq 2500 machines to its platform suite.
Thursday, June 26, 2014
UK Diet and Health Research Awarded £4M
Funding awarded to six projects investigating diet and health to enable the food and drink industry to meet the needs of UK consumers.
Wednesday, June 25, 2014
Better Understanding of Disease Resistance Genes in Crops
Effector-triggered defence concept describes how plants protect themselves against the apoplast.
Friday, June 06, 2014
Investment Provides Access to the World’s Most Advanced Crystallography Technology
The UK community will benefit thanks to a £5.64M investment from UK research funders.
Tuesday, June 03, 2014
Public-private Research Partnership to Support Sustainable Agricultural Systems
The partnership will support projects that will help provide solutions to key challenges affecting the sustainability of the UK crop and livestock sectors.
Friday, May 23, 2014
Protective Proteins Reduce Damage to Blood Vessels
Proteins found blood have been shown to reduce damage caused to blood vessels as we age, and in conditions such as atherosclerosis and arthritis.
Thursday, May 22, 2014
Scientific News
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Lab-on-a-Chip Offers Promise for TB and Asthma Patients
A device to mix liquids using ultrasonics is the first and most difficult component in a miniaturized system for low-cost analysis of sputum from patients with pulmonary diseases such as tuberculosis and asthma.
Intracellular Microlasers Could Allow Precise Labeling of up to a Trillion Individual Cells
MGH investigators have induced structures incorporated within individual cells to produce laser light at wavelengths that differ based on the size, shape and composition of each microlaser, allowing precise labeling of individual cells.
Real-Time Imaging of Lung Lesions During Surgery
Targeted molecular agents cause lung adenocarcinomas to fluoresce during surgery, according to pilot report.
Watching a Tumour Grow in Real-Time
Researchers from the University of Freiburg have gained new insight into the phases of breast cancer growth.
Protein Related to Long Term Traumatic Brain Injury Complications Discovered
NIH-study shows protein found at higher levels in military members who have suffered multiple TBIs.
Childhood Cancer Cells Drain Immune System’s Batteries
Cancer cells in neuroblastoma contain a molecule that breaks down a key energy source for the body’s immune cells, leaving them too physically drained to fight the disease.
Self-Assembling, Biomimetic Membranes May Aid Water Filtration
A synthetic membrane that self assembles and is easily produced may lead to better gas separation, water purification, drug delivery and DNA recognition, according to an international team of researchers.
Researchers Discover Immune System’s 'Trojan Horse'
Oxford University researchers have found that human cells use viruses as Trojan horses, transporting a messenger that encourages the immune system to fight the very virus that carries it.
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!