Lecture Overview
In his first lecture, Dustin explains that adaptive immunity allows an individual to specifically recognize and respond to a vast number of molecules. B cells recognize intact antigens and produce neutralizing antibodies. T cells, on the other hand, have receptors on their surface that recognize very small antigen fragments bound to MHC on the surface of antigen presenting cells (APC). Dustin explains that T cells overcome the challenges of finding and binding to the APCs with the help of a multitude of adhesion molecules. Once the T cell receptor has bound a peptide antigen, an immunological synapse, with its typical bulls-eye structure, is formed resulting in T cell activation.
In Part 2, Dustin describes how a reconstituted system has allowed the immunological synapse to be studied in molecular detail. It is possible to visualize the localization of signaling molecules such as kinases, and determine the role of the actin cytoskeleton in regulating this localization. Dustin also touches on the role of the immunological synapse in autoimmune disease and cancer.
In his last lecture, Dustin presents work from his lab showing that T cell receptor enriched vesicles are generated in the immunological synapse. These vesicles can be transferred to B cells leading to activation of the B cells and, potentially, the production of higher specificity antibodies.
Speaker Bio
Michael Dustin is Professor of Immunology and Director of Research at The Kennedy Institute of Rheumatology at the University of Oxford. Prior to joining the Kennedy Institute, Dustin was a faculty member at the Skirball Institute of Biomolecular Medicine at New York University from 2001-2013 and at Washington University School of Medicine from 1993-2000. Dustin received his BA in Biology from Boston University and his PhD in Cell and Developmental Biology from Harvard University.
As described in his iBioSeminar, Dustin’s lab studies the molecular events that take place at the immunological synapse. Future research will focus on developing therapies targeted to the immunological synapse to cure chronic inflammatory illnesses such as rheumatoid arthritis.
Dustin is an active participant in the immunology community; he is a member of numerous grant review committees and journal editorial boards. His research has been recognized with many awards including the 2000 Presidential Early Career Award in Science and Engineering and the 2012 DART-NYU Biotechnology Achievement Award.
Medical and Patient education videos
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Title
Description
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Video interview with patient with an aspergilloma and chronic pulmonary aspergillosis, diagnosed after coughing up blood who later developed azole resistance on voriconazole. Patient History This patient had severe kyphoscoliosis as a child with insertion of spinal rods in early adulthood. She is a life-long non-smoker. She first presented in 2001 with an irritating cough and several treatments with antibiotics failed to alleviate it. After 2 years the cough worsened and she developed a fever. She was investigated but results were inconclusive. She then coughed up large amounts of blood (haemoptysis) and had a very severe bleed which was treated with embolisation and oral tranexamic acid. She continued to cough and produce green sputum and lose weight. Aspergillus precipitin titre was high and she was initially diagnosed with chronic pulmonary aspergillosis with one cavity containing an aspergilloma. Treatment with itraconazole did not alleviate her symptoms (despite adequate blood levels) and she started voriconazole and considerable improvement was seen initially and she gained some weight. She continued voriconazole for 2 years. However her Aspergillus titre remained high and her cough continued. Further tests showed her trough plasma levels of voriconazole to be more than 0.5mg/L, however isolates revealed that her Aspergillus fumigatus was drug resistant to itraconazole, voriconazole and posaconazole. The patient has now commenced amphotericin B therapy. We thank the patient for kindly providing this interview.
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Video Interview with long-term ABPA patient who coughed up large sputum plugs. This patient had several episodes of pneumonia and developed bronchiectasis after diagnosis for a collapsed left lung. She was treated with inhaled corticosteroids and bronchodilators and progressed well. She was later diagnosed with possible ABPA (aspergillus precipitins were negative), after producing a large sputum plug which was positive for aspergillus hyphae. Her main symptoms were severe coughing with production of clear sputum. In December 04 her coughing became very severe and she coughed badly for 7 months. Her treatment was modified to include itraconazole (400mg/day solution- she required a higher dose than normal as she was taking other medication which reduced it’s absorption). 8 weeks later she started very severe bouts of coughing over 3 days – which produced a large number of small mucous plugs, finally a very large plug (resembling a piece of grey chewing gum) was coughed up. After this, the coughing subsided and the patient felt well and a chest X-ray at this time showed a significant improvement with clearing of shadows from the right lower lobe. Itraconazole levels have been reduced to 300mg per day and steroid intake reduced. The patient remained well in July 2007. We thank the patient for kindly providing this interview.
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Video interview with patient with childhood asthma and ABPA, who showed a marked improvement in her ABPA and asthma when she commenced nebulised Amphotericin B. Her medication was changed from itraconazole at this time to allow for her to try for pregnancy. Two types of nebuliser – VentStream and the Pari LC system are discussed in the interview. Her condition is still stable using inhaled amphotericin B. We thank the patient for kindly providing this interview
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Video interview with this patient with childhood asthma and ABPA. After persistent chest infections and continuous steroids and a bad productive cough, Aspergillus was cultured from sputum in 2002. After successfully taking itraconazole, the patient developed peripheral neuropathy (tingling and loss of sensation) in the hands. After stopping itraconazole – persistent chest infections requiring antibiotics and prednisolone were common. The patient at this point had a high IgE level and positive RAST tests. Voriconazole was then prescribed – which has successfully treated the aspergillus infection – no steroids are required and the cough is greatly reduced with the patient feeling well. However an unfortunate side effect of voriconazole has been a photosensitive rash on any exposed skin. Despite using complete sunscreen – the rash continues. The patient is continuing to take voriconazole.
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Video interview with patient JW with childhood asthma and subsequent ABPA, describes his experience with 3 different azole types of antifungal drugs and who showed a marked improvement when taking posaconazole.
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Video interview with Catherine, who developed severe invasive aspergillosis following a kidney transplant. Fortunately, she was successfully treated with antifungal drugs. We thank the patient for kindly providing this interview and Pfizer for supporting the production of this video.
