Posts Tagged Human Biology

Discovery of new white blood cell reveals target for better vaccine design


ScienceDaily (July 27, 2012) — Researchers in Newcastle and Singapore have identified a new type of white blood cell which activates a killing immune response to an external source — providing a new potential target for vaccines for conditions such as cancer or Hepatitis B.

Publishing in the journal Immunity, the team of researchers from Newcastle University in collaboration with A*STAR’s Singapore Immunology Network (SIgN) describe a new human tissue dendritic cell with cross-presenting function.

Dendritic cells (DCs) are a type of white blood cell that orchestrate our body’s immune responses to infectious agents such as bacteria and viruses, as well as cancer cells. They are also very important for eliciting the immune response generated by vaccines.

DCs kick start an immune response by presenting small fragments of molecules from micro-organisms such as bacteria and viruses, or from vaccines or tumours, called antigens on their surface. This leads to activation of another white blood cell subset called T cells, which specialise in killing cells and are crucial for eliminating cancerous or infected cells. Most cells are only able to present antigens from within themselves, and so will only elicit an immune response if they are infected themselves. Only a specialised subset of DCs is able to generate a response to an external source of antigen, for example bacteria, vaccines and tumours.

The identity of human tissue DCs that are capable of presenting external antigen to activate the cell-killing response by T cells — a process termed ‘cross-presentation’ — has remained a mystery. Their discovery, as revealed by this research, will help scientists to design better targeted vaccine strategies to treat cancer and infections such as Hepatitis B.

“These are the cells we need to be targeting for anti-cancer vaccines,” said Dr Muzlifah Haniffa, a Wellcome Trust Intermediate Fellow and Senior Clinical Lecturer at Newcastle University. “Our discovery offers an accessible, easily targetable system which makes the most of the natural ability of the cell.” The researchers also showed for the first time that dendritic cell subsets are conserved between species and have in effect created a map, facilitating the translation of mouse studies to the human immune system.

“The cross-species map is in effect a Rosetta stone that deciphers the language of mouse into human,” explains Matthew Collin, Professor of Haematology from Newcastle University.

In the paper the researchers describe how the cross-presenting DCs were first isolated from surplus plastic surgery skin which was digested to melt the gelatinous collagen to isolate the cells. This research will have significant impact on the design of vaccines and other targeted immunotherapies.

The Rosetta Stone of our immune system: Mapping Human and Mouse dendritic cells

The Newcastle University team in collaboration with A*STAR’s Singapore Immunology Network (SIgN) have for the first time ever aligned the dendritic cell subsets between mouse and humans allowing the accurate translation of mouse studies into the human model for the first time.

The researchers isolated the dendritic cells from human blood and skin and those from mouse blood, lung and liver. Using gene expression analysis, they identified gene signatures for each human dendritic cell subset. Mouse orthologues of these genes were identified and a computational analysis was performed to match subsets across species.

This provides scientists for the first time with an accurate model to compare DCs between species. Professor Matthew Collin explains: “This is in effect a Rosetta stone that deciphers the language of mouse into human. It can put into context the findings from the extensive literature using mouse models to the human settings.”

Dr. Haniffa added: “These gene signatures are available in a public repository accessible for all researchers to benefit from the data. It will allow detailed knowledge of individual human dendritic cell subsets to enable specific targeting of these cells for therapeutic strategy.”

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The above story is reprinted from materials provided by Newcastle University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Muzlifah Haniffa, Amanda Shin, Venetia Bigley, Naomi McGovern, Pearline Teo, Peter See, Pavandip Singh Wasan, Xiao-Nong Wang, Frano Malinarich, Benoit Malleret, Anis Larbi, Pearlie Tan, Helen Zhao, Michael Poidinger, Sarah Pagan, Sharon Cookson, Rachel Dickinson, Ian Dimmick, Ruth F. Jarrett, Laurent Renia, John Tam, Colin Song, John Connolly, Jerry K.Y. Chan, Adam Gehring, Antonio Bertoletti, Matthew Collin, Florent Ginhoux. Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103 Nonlymphoid Dendritic Cells. Immunity, 2012; 37 (1): 60 DOI: 10.1016/j.immuni.2012.04.012

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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‘Diving board’ sensors key to DNA detection


ScienceDaily (July 27, 2012) — A tiny vibrating cantilever sensor could soon help doctors and field clinicians quickly detect harmful toxins, bacteria and even indicators of certain types of cancer from small samples of blood or urine. Researchers from Drexel University are in the process of refining a sensor technology that they developed to measure samples at the cellular level into an accurate method for quickly detecting traces of DNA in liquid samples.

According to lead researcher Dr. Raj Mutharasan, a professor in Drexel’s College of Engineering, the group’s unique application of lead zirconate titanate (PZT) to current piezoelectric-excited cantilever sensor technology has created a way to conduct more sensitive and timely tests for DNA. This DNA test will allow for quick identification of harmful cells and bacteria.

“I equate this new technology to authorities trying to catch a criminal using latent fingerprints rather than a mug shot,” Mutharasan said. “It is more precise, selective and sensitive. With the PZT sensor we can potentially detect DNA derived from a much smaller number of pathogens and in a much shorter period of time than current methods.”

Cantilever Sensor Uses Electric Current for More Sensitive Measurements

Cantilever sensor technology, which has been around for a little over a decade, detects its minute targets using a method that is relatable to a springboard bouncing with the movements of a diver. The “board” -or cantilever in this application- vibrates at a higher frequency when the diver jumps off and his or her mass is removed. Conversely, the vibration frequency of a cantilever would decrease when weight is added to it. Measuring the difference in frequency of mass-free versus mass-loaded vibrations allow researchers to detect cells or, in this case, DNA, in samples.

Mutharasan and his group combined the PZT material to the cantilever in an innovative design, which allows researchers to initiate the “springboard” effect by applying an electric current. This is an upgrade over the classical cantilever method which requires an external stimulus -a flick of the diving board- to set the system into motion.

Because PZT sensors are completely controllable, Mutharasan’s group has discovered high-order vibration modes in certain designs that are sensitive to very small mass changes, on the order of one-billionth of a microgram, in liquid samples.

“Such high sensitivity enables us to measure biological molecules at a million-fold more sensitive than what is currently feasible,” Mutharasan said

A Second Advantage: Rapid Room-Temperature Replication of DNA

The PZT cantilever device is dually useful because it speeds up the process of replicating DNA in a sample. Replication is a necessary step in the testing process in order to improve the quality of the sample and positively identify the bacteria or cell of its origin, much like growing bacterial culture. Muthrasan’s research group will conduct simultaneous amplification and detection of DNA that is expected to be carried out at room temperature and in a short time frame.

Typical replication can be time-consuming because the sample needs to be heated in order to begin the process. The advantage of the cantilever sensor is that double-stranded DNA can be unwound by vibrating the sensor at the proper frequency. This procedure essential step for replication can cut a typical detection process, which could take several hours, down to less than an hour.

The National Science Foundation recently awarded the team a grant to continue research into simultaneous DNA replication and detection using these piezoelectric vibrations. The key discovery that Mutharasan’s team is building upon is its observation that DNA can be “melted” -a term describing the process of unwinding a DNA strand for replication- by application of mechanical energy to sensor surface via PZT.

With the PZT sensor’s unique ability to test samples in liquids and at room temperature, Mutharasan can foresee applications in detecting food and water contamination, as well as use in the medical field. In early testing the PZT sensor has successfully detected DNA indicators for prostate cancer in urine samples, toxin-producing genes in pathogenic E. coli and an identifying gene of malaria-causing Plasmodium falciparum in patient blood samples. The technology is still likely to be three-to-five years from becoming commercially available for medical and environmental uses, according to Mutharasan.

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The above story is reprinted from materials provided by Drexel University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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