Mystery mast cells under scanner again

Mast Cells are the most neglected immune cells to be studied yet are the most important amongst them. They are the classical mediators of allergic reactions. When the antigen-specific IgE binds to an antigen (usually allergen), it triggers mast cell activation by binding to high-affinity Fc epsilon receptor I. This leads to the release of mast cell mediators such as histamine, chymotryptase, tryptase, TNF etc. To protect the mast cells from activation induced death, the CD200R is induced. CD200R inhibits mast cell activation through ITIM (immunoreceptor tyrosine-based inhibition motif ).

Recent evidence shows that Mast cellos sense pathogens through toll-like receptor mediated pathways. In addition, the receptors for IgG2a and Ig light chains have been identified. However, the receptor for IgLC is yet to be characterised. Added to this is the concept of MCregs (regulatory mast cells). Mast cells are identified in the triumvirate along with Tregs and Th17. While the tregs inhibit mast cells, mast cells in turn activate the Th17 cells. The complete mechanisms underlying this three-way interactions is to be explore.

Basophils: The neglected minority gains a new respect as antigen presenting cells

To function as an antigen-presenting cell, the cell must fulfill a number of criteria. Upon antigen exposure, the candidate cell must express MHC class II and co-stimulatory molecules. It must be able to take up and process antigen and localize to draining lymph nodes, where efficient T cell–antigen-presenting cell interactions take place. Ideally, the candidate cell would also express the relevant cytokines required for T cell differentiation, although other accessory cells may provide the required cytokines. Finally, the candidate cell must be able to induce CD4⁺ T cell proliferation and differentiation in in vitro and in vivo assays.
Differentiation of naïve CD4⁺ T cells into Th2 cells requires three signals: T cell receptor triggering through peptide antigen recognition in the context of MHC class II molecule, amplification of T cell receptor signaling via co-stimulatory molecules and the presence of appropriate cytokine. For Th2 cell differentiation, however, dendritic cells are not the one-stop shop for all three required signals since dendritic cells do not produce IL-4, the cytokine necessary for Th2 cell differentiation. This observation implies that other antigen-presenting cells, in addition to dendritic cells, may contribute to Th2 cell differentiation.
The studies by Artis and colleagues (Perrigoue et al, Nat Immunol 2009), Medzhitov and colleagues (Sokol al, Nat Immunol 2009), and Nakanishi and colleagues (Yoshimoto al, Nat Immunol 2009), use three different models and elegantly demonstrate that basophils meet the criteria for antigen-presenting cells for Th2 cell differentiation.
Artis and colleagues studied the intestinal helminth parasite Trichuris muris. They showed that CD11c-restricted expression of MHC class II was not sufficient to generate a Th2 inflammatory response. Medzhitov and colleagues investigated the role of basophils in Th2 response to protease antigen papain and OVA. They demonstrated that MHC expression on basophils was sufficient to drive Th2 cell differentiation. Nakanishi and colleagues focused on the role of basophils in augmentation of Th2 responses by antigen–IgE immune complexes.
With basophils added to the list of cells capable of antigen presentation to naïve CD4⁺ T cells, the question arises as to what is the dominant antigen-presenting cell in Th2 inflammatory responses. Four approaches were used to highlight the dominant role of basophils.
First, the authors showed that basophil depletion through treatment with a monoclonal antibody to FceRI significantly diminished Th2 cell differentiation. The second approach used diphtheria toxin in CD11c-DTR mice and demonstrated that depletion of dendritic cells did not alter Th2 cell differentiation in response to OVA plus papain Th2 immunity to T. muris. The third approach demonstrated that CD11c-restricted expression of MHC class II was not sufficient to induce Th2 cell differentiation in response to OVA plus papain or to protect against infection with T. muris. In the fourth approach, mice were immunized in the ear with papain and the ear was either left intact or removed after two hours in order to remove the source of tissue resident dendritic cells. The authors observed Th2 cell differentiation, albeit at lower levels, in the draining lymph node, despite removal of skin resident dendritic cells.
The idea that the basophil is the dominant antigen-presenting cell for Th2 cell differentiation is certainly intriguing, but its validation requires further investigation.

What discriminates danger signals from pathogens with that of damage to tissues

The immune system protects against infection by pathogenic microorganisms, but it also recognizes when the body has been injured. Burns, radiation exposure, and bruises all involve the immune system when responding to damaged tissue. Which signaling pathways recognize tissue damage and keep the resulting inflammatory response from getting out of hand? Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. In seminal paper in Science (Vol. 323. no. 5922, pp. 1722 - 1725, March 2009), Chen and colleagues demonstrated an unique mechanisms by which the body differentiates between self- and non-self signals during danger.
They that CD24-deficient mice exhibit increased susceptibility to danger- (DAMPs) but not pathogen-associated molecular patterns (PAMPs). CD24 associates with high mobility group box 1 (HMGB1), heat shock protein 70 (HSP70), and heat shock protein 90 (HSP90), negatively regulates their stimulatory activity, and inhibits nuclear factor-kappa B (NF-B) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec-G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns. Through association with and inhibition of the molecules that are released after tissue damage, CD24 and Siglec-G protected mice from an otherwise lethal inflammatory response.

After a long time

Sorry friends for not being active in the previous months. Unfortunately, my India visit and subsequent work load contributed to the lack of time for the blog.
I request the contributors to keep posting messages not only about the opportunities but also about science.

Zurich Ph.D. Program in Microbiology and Immunology

The Zurich Ph.D. Program in Microbiology and Immunology is a joint program of the University of Zurich and ETH Zurich, two highly prestigious Swiss universities with excellent research facilities. The program offers research and education opportunities in a stimulating international environment for ambitious students who wish to work towards a Ph.D. Microbiology, immunology, biochemistry, microbiology, genetics, cell, developmental, molecular, systems and structural biology are covered by the program.

Accepted students perform their research project in one of the participating research groups of their choice, according to their scientific interest. Advanced teaching and training courses are offered throughout the curriculum. Students will obtain their Ph.D. from either the University of Zurich or ETH Zurich and receive a graded certificate from the program.

The program language is English throughout.

• Browse the participating research groups
• Check infos on applications & deadlines

Sir RATAN TATA Scholarships for Studies in the UK-Deadline July 2

The British Council invites applications for Sir Ratan Tata
Scholarships for Indian students planning to study in the UK.The Sir
Ratan Tata Trust (SRTT) has set up this new scholarship scheme in
Development Studies and will offer three scholarships of up to £20,000
each.

The programme is aimed at students interested in studying for a full
time Masters degree in the disciplines of Developmental Economics and
Science and Technology. Students can take advantage of this
scholarship to study courses that are inter-disciplinary like the
following and more.
* Development studies
* Development Economics;
* Studies in Science, Society and Development;
* Economic Development;
* Science, Technology, Medicine and Society;
* Social Informatics and Management;
* Public Health;
* Environment, Science and Society

Eligibility criteria, application form with the guidance can be
downloaded from http://www.britishcouncil.org/india-scholarships-sirratantata.htm

To find research opportunities in France

Mant research students in France invariably need the help of Association Bernard Gregory. This association has a website that posts opportunities for research (PhD, postdoc, technicians etc). To search for research opportunities in France, click on the link below.
http://www.abg.asso.fr/offre_rechercher.php?nature=1&mz=1&lg=en


About ABG:

Founded in 1980, the Association Bernard Gregory promotes the value of training through research to the non-academic world and helps the entry of young PhDs from any discipline into business.

Mission

The mission of the ABG is to promote the placement of PhDs into companies through:

• information, professionalisation initiatives and individual support programmes for job seekers,
• promoting training through research within the business world,
• matching the skills of new and recent PhDs to job offers in companies.

Initiatives

The actions of the ABG are complentary to research institutions' and doctoral schools'. They include:

• Continuous information for PhD students, new and recent PhDs and postdocs on the job market and opportunities for professional contact, through a website that receives 400,000 visits per month, 'Docteurs&Co' quarterly newsletter, around a hundred interventions at PhD student forums and a European guide 'From PhD to Employment' (170,000 copies downloaded in 2004) available in French and in English.
• Professionalisation initiatives: Doctoriales and the 'Adding value to skills – a new chapter in the thesis' programme (170 PhD students involved in 2004).
• A network of 300 correspondents who provide individual support to new PhDs in structuring their career plans, in writing a CV aimed at the non-academic sector, and who follow them through to recruitment.
• An online CVs database validated by ABG correspondents (1,000 CVs) and a database of company job offers (750 in 2004).
• Coordinating a network of companies and partner research organizations: offering arenas (web and press) to communicate their initiatives and their actions in support of jobs for new and recent PhDs; organizing regular meetings of the Business Club that deal with new and recent PhDs and with companies.

EMBO Lifesciences Mobility Portal

The European Molecular Biology Organisation (EMBO) is a prominent body involved in molecular biology research. It funds research in molecular biology that involves chemistry, physics, bioinformatics that support molecular biology. One of the initiatives of EMBO is the "EMBO Lifesciences Mobility Portal". It can be accessed here
http://mobility.embo.org/

PhD fellowships from Wellcome trust

Visit the following website for the PhD student fellowships from Wellcome trust.
http://www.wellcome.ac.uk/Funding/Biomedical-science/Grants/PhD-programmes-and-studentships/WTD004384.htm

Support is provided for four years and includes:

• a stipend
• PhD registration fees at UK/EU student rate
• contribution towards laboratory rotation expenses in the first year
• research expenses for years two to four
• contribution towards travel
• contribution towards transferable-skills training.

Students are recruited annually by the individual Programmes for uptake in October each year. Recruitment begins in the preceding December. If you are interested in applying you should contact the relevant Programme. Currently 27 Programmes based in centres of excellence throughout the UK with specialised training provided in a range of important biomedical research areas are supported:

• developmental biology and cell biology
• genetics, statistics and epidemiology
• immunology and infectious disease
• molecular and cellular biology
• neuroscience
• physiological sciences
• structural biology and bioinformatics.