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Australasian Society for Immunology Incorporated
Infection Immunity and Immunogenetics Unit,
Pathology and Laboratory Medicine, University of Western Australia
Can a HIV patient who once progressed to AIDS ever regain a normal immune system on antiretroviral therapy (ART)? Why do some HIV patients beginning ART have an uneventful immune recovery, whilst others develop immune restoration disease? Are the effects of CMV similar in HIV patients, transplant recipients and healthy aging? Why is HCV disease more severe in HIV patients and what determines how HCV patients respond to therapy? Patricia Price and Martyn French manage the Infection Immunity and Back Row LtoR: Martyn French (Clinical co-ordinator), James Taylor (research assistant) Immunogenetics Unit of the School of Middle Row LtoR: Sonia Fernandez (Scientist), Sara Tanascovic (PhD student), Samantha Bunt & Alfred Laiman (Honours students) Pathology and Laboratory Medicine Front Row LtoR: Silvia Lee (Scientist) Lilian Cha, Nandini Makwana, Laila Abudulai, Henny of the University of Western Australia Saraswati, Jacquita Affandi (PhD students), Patricia Price (Research co-ordinator). based at Royal Perth Hospital, with Henny is completing her PhD within our project in Jakarta. post-doctoral scientists, Silvia Lee and Sonia Fernandez. Projects addressing identifi ed two important factors. Firstly, CD4+ the outcome of infection with HIV, T cell defi ciency parallels lower naïve CD4+ T CMV, HCV and mycobacteria include cell counts and is associated with evidence of a small or inactive thymus. Secondly, CD4+ Infection Immunity & Immunogenetics investigations of the effects of T cell defi ciency is closely associated with Unit, University of WA pathogen-specifi c immune responses, persistently increased immune activation host genotype and drug treatments. which may induce CD4+ T cell senescence They are designed to answer some and increase rates of apoptosis. Sonia Obituary: Emeritus Prof. Gordon Ada 8 important questions. Fernandez demonstrated that the effects of Obituary: Dr William (Bill) Boyle immune activation are most evident on the How does immune activation infl uence
naïve CD4+ T cell population, particularly Honorary Secretary's News immune reconstitution in HIV patients
in individuals with a small thymus. We Student News given ART?
are now characterising defi ciencies in the immune system of patients with low CD4+ T Councillors' News Up to 30% of HIV patients receiving ART cell recovery and investigating the causes of Visiting Speaker Program fail to achieve a normal CD4+ T cell count. immune activation. Projects include:Such individuals are at an increased risk of Upcoming Conferences death and experience higher rates of cancer, The causes of persistent immune activation. Travel Award Conference Reports cardiovascular disease and kidney disease. Lines of investigation include the roles Our comparisons between patients with poor of type I interferons and underlying viral Publications List or good CD4+ T cell recovery on ART have infections such as CMV.
ASI Inc. Newsletter December 2012
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ASI Inc. Newsletter December 2012
One aspect of the role of Newsletter Editor is hard to anticipate and diffi cult to describe. The Newsletter plays an important role in reporting the death of Immunologists who are members of ASI or their colleagues. In this edition we report the death of two signifi cant immunologists – Gordon Ada and Bill Boyle. I knew neither of them personally, but the respect and affection of their colleagues is palpable in their obituaries. As Editor, I read the obituaries and usually fi nd myself researching further on the Web and this is always a humbling and inspirational experience: humbling because of the volume and signifi cance of the work (and the inverse then apparent in my own career) and inspirational because it seems they achieved their greatness by being good. By that I mean that they were good scientifi cally and professionally and those are two things we can all strive for. In this issue we have reprinted two articles Gordon Ada wrote as unsolicited submissions to the Newsletter in 2004 (there were three published in 2004). I urge you to have a look online at the transcript of an interview with Gordon Ada by Frank Fenner on the Australian Academy of Science website. This gives a tremendous insight into the personality of Gordon and his fascinating career. So, although the passing of friends and colleagues is a sad event, it is a time for recognising their achievement and the role of the Newsletter (with mixed emotions) is to bring their stories and inspiration to the wider ASI community.
I wish everyone a safe and relaxing holiday season and hope you come back invigorated and ready to submit your next grant.
Simon Apte ASI Inc. Newsletter December 2012
Infection Immunity and Immunogenetics predicted IRD. This is consistent with the CMV may have long-term effects in HIV
Unit, Pathology and Laboratory Medicine, notion that IRD develop when there are high patients. Treatment of systemic CMV
University of Western Australia (cont.)
levels of antigen when the patients begin disease is expensive and protracted, so ART. Studies of T-cell responses to HCV prophylaxis is suspended once patients Homeostatic maintenance of the peripheral that may associate with IRD are nearing are stable on ART. CMV reactivation is naïve CD4+ T cell pool in HIV patients completion.
triggered by inflammatory mediators, on long-term ART. This study looks at including TNF. Immune activation in HIV the proliferative potential of CD4+ T cells disease increases levels of this cytokine, so (particularly naïve cells) in response to both What is the lasting footprint of CMV
frequent subclinical reactivation of CMV general stimuli and IL-7.
is expected. We investigated HIV patients The effects of interferon-α on homeostasis Cytomegalovirus (CMV) infection is who began antiretroviral therapy (ART) with of CD4+ T cells and memory B cells. Our usually asymptomatic, but can cause extreme immunodefi ciency and maintained data associate low CD4+ T cell counts after a mononucleosis-like illness in some a virological response until they were >50 long-term ART with increased interferon individuals years old. One can assume that they had activity. IFN-α appears to alter CD4+ T cell . CMV disease can manifest as a
syndrome or as an acute infection of an organ a high burden of CMV pre-ART as many homeostasis by interfering with the IL-7 or tissue. CMV retinitis is prevalent in 46% had experienced CMV retinitis. These HIV mediated pathway of proliferation. The of patients with untreated HIV infection, patients retained high titres of antibody work also addresses memory B cells, as this and remains a common cause of blindness reactive with CMV after 14 (13-16) years population is also defi cient in some HIV in resource limited settings. This will be on ART and displayed elevated IFNγ patients responding to ART.
addressed in our new project in Indonesia.
responses to an immediate early peptide of CMV (unpublished data). This constitutes Why do some HIV patients experience
In considering the role of CMV in human a "heavy footprint" of CMV likely arising Immune Restoration Disease?
health, many studies have overlooked the from frequent reactivations. CMV and fact that 50-90% of all populations are thymic insuffi ciency may be synergistic in I m m u n e r e s t o r a t i o n d i s e a s e i s seropositive. As the virus has the capacity their effects on T-cell profi les. It may be a clinical phenomenon seen in some for latency and is known to be reactivated by important that HIV disease also depresses immunocompromised HIV patients whose "stress" (immunosuppression), most people NK cell function – these mechanisms are immune function is restored after starting harbour latent virus ART. It is characterised by exaggerated or . Sensitive PCR-based
viral load assays are available, but these are atypical infl ammatory reactions or worsening only routinely applied in patients likely to CMV remains an important pathogen of pre-existing infectious disease. Worldwide have acute disease. There is little probability after renal transplantation. In Australia, the most important IRD associated with of detecting latent CMV. We are working prophylaxis (valganciclovir) is routinely on a tool to evaluate the lifelong effects of administered for 12-26 weeks after CMV on human health – the "footprint" of transplantation, according to a formula Our studies in Cambodia, India, South CMV. The footprint may include: that considers donor and recipient CMV Africa and Malaysia provided evidence seropositivity and clinical risk. CMV remains that T-cell and innate immune responses 1. CMV DNA detected by a sensitive PCR a signifi cant cause of graft loss despite contribute to the immunopathology of assay of blood, saliva or urine.
prophylaxis and in the longer term, CMV IRD associated with M. tuberculosis or 2. CMV-peptide/HLA tetramer positive reactivations are implicated in deterioration cryptococcal infection. Increased T-cell in renal function, exhaustion or senescence and/or dendritic cell responses to M. 3. IFNγ responses of CD4 and CD8 T-cells of T-cells and cardiovascular disease. We are tuberculosis or cryptococcal antigens could to CMV antigens.
now addressing this in a cross-sectional study be demonstrated in many patients with 4. Anti-CMV antibody detected by focussing on the role of NK cells in resistance ‘paradoxical' exacerbations of partially to CMV. The resulting holistic view of treated tuberculosis but were not diagnostic. 5. Enhanced expression of NK receptors the immune response in man will identify Patients also displayed perturbations of on NK cells and T-cells.
phenotypes associated with protection and chemokine levels. Interestingly low levels of those individuals who will benefi t most from CCL2 pre-ART show promise as a marker of In older CMV-seropositive adults, up to CMV prophylaxis. risk, whereas immunogenetic markers show 23% of the T-cell population can be CMV- no consistent pattern across ethnicities. Low specifi c. Their accumulation correlates with CCL2 levels may generate a high bacterial Can a response to HCV therapy be
immunologic aging or ‘‘immunosenescence'' load pre-ART – this is likely a key component evident in the entire T-cell population of risk. A study of cryptococcosis-associated assayed ex vivo. Repeated sub-clinical CMV Dr Silvia Lee has a programme of research IRD undertaken in Durban, South Africa has infections may expand CMV-specifi c T- investigating the correlation between demonstrated the importance of CD4+ T-cell cells clones until they suppress homeostatic treatment outcome, disease status and defi ciency and high pathogen load.
expansion of other T-cells. CMV infects immunological status during hepatitis C virus endothelial cells in acute stages of infection. (HCV) infection. These studies have resulted Our research in Indonesian HIV patients The resulting infl ammation may lead to from ongoing collaborations with clinicians starting ART is centred on HCV IRD. Dr Evy atherosclerosis. at Royal Perth Hospital (Dr James Flexman Yunihastuti (PhD completed 2010) showed and Dr Wendy Cheng) and researchers at that low levels of anti-HCV antibodies ASI Inc. Newsletter December 2012
Murdoch University and Fremantle Hospital by immunohistochemistry for inhibition of analysed the role of TNF block haplotypes as (Dr Mark Watson and Dr Jane Allan). Recent HCV infectivity in a hepatoma cell line. a predictor of risk for sensory neuropathy in projects include: HIV patients. Constance reconstructed 38- Why do some HIV patients experience
SNP haplotypes in healthy control cohorts The effects of HCV and IFN-based therapy of different ethnic backgrounds. Haplotypes on DC responses. Therapy impaired IL-12 associated with SN in Caucasian, Malay and and IFNα production by DCs and reduced HIV-associated sensory neuropathy (HIV- Chinese patients were determined.
production of IFNα by PBMC after SN) is a length-dependent peripheral stimulation with ligands for TLR3, TLR7/8, neuropathy that is frequently painful and is To extend this work, 404 Black HIV-TLR9 and RIG-I. This was independent a common complication of HIV infection. positive Africans from the Virology Clinic of a patients' response to therapy and was HIV-SN is defi ned as present if the patient of the Charlotte Maxeke Academic Hospital not accompanied by reduced expression had both symptoms and signs of peripheral Johannesburg in collaboration with Ms of pertinent TLR on dendritic cells. These neuropathy detected using the AIDS Clinical Antonia Wadley (PhD submitted 2012) data implicate TLR signaling pathways in Trials Group (ACTG) Brief Peripheral and Prof Peter Kamerman (University immune dysfunction associated with HCV Neuropathy Screen. SN can be caused of Witwatersrand). Of those exposed to disease and its treatment.
by HIV itself, but symptoms can also be stavudine, 57% had HIV-SN and 74% of triggered by ART. This is most common in these people described the syndrome as The effects of HCV and IFN-based therapy patients receiving older nucleoside analogue painful. SNPs and haplotypes from TNF on natural killer (NK) cells and T-cells. reverse transcriptase medications (usually and adjacent genes from the MHC were Frequencies of CD56dim NK cells expressing stavudine), but neuropathy is also seen in assessed. There was no association with perforin and CD16 were lower on therapy, Australians with HIV. My collaborator, Dr TNF-1031, but the haplotypes incorporating irrespective of outcome, whilst proportions of Kate Cherry, confi rmed that 44% of patients TNF-1031 and associated with SN in Asians effector CD4 and CD8 T-cells only declined treated at the Alfred Hospital (Melbourne) and Caucasians were not found in Africans. in patients who achieved a virological are affected.
Hence critical haplotypes are slightly better response. Similarly production of IFNγ to defi ned and TNF-1031 itself is exonerated. HCV antigens declined in responders but I established collaborations in SE Asia and Novel associations were identifi ed between not in non-responders. Therapy may promote South Africa to address why some patients HIV-SN protection and fi ve other SNPs found the expansion of NK cells able to produce suffer SN whilst others do not when treated in a single haplotype block were associated cytokines, whilst decreased HCV-specifi c with the antiretroviral drug stavudine. This with SN for the fi rst time. We also found CD4 T-cell responses during therapy may be will help clinicians decide which patients novel associations with minor alleles of associated with reduction in effector memory may be treated safely with stavudine and polymorphisms in IL4. These data support CD4 T-cells in the circulation of patients with who should be prioritized for expensive an infl ammatory etiology to HIV-SN.
a sustained virological response.
alternatives. The South African Department of Health now recommends use of tenofovir The search for immunological correlates The potential of genotype cross-reactive HCV as fi rst line treatment, but many people of SN: Learning from the genes. Confocal neutralising antibody. We are interested in remain on stavudine and or live with the microscopy was used to visualise CD14+ the ability of antibody to neutralise HCV side effects. Stavudine is still prescribed in macrophages and TNF production in infectivity using the HCV genotype 2a virus other resource-poor countries.
skin biopsies from HIV patients with (JFH1) cell culture model. Plasma samples active (painful) and "burned-out" (numb) were collected from 108 chronic HCV- Genetic studies in Australian, Asian and neuropathy. 50uM sections were triple- infected patients prior to therapy. All patients African cohorts. Disordered infl ammation stained to mark PGP9.5+ dermal and had antibodies that reacted to the JFH-1 may be central to the pathogenesis of SN. epidermal nerves (red), CD14+ macrophages antigen by ELISA and 96% of patients had Our fi rst study found that alleles of TNFA (green) and cell nuclei (blue). Parallel detectable neutralising antibodies. We now and IL12B (encoding TNFα and IL-12p40) sections were stained to mark TNF (green). plan to examine neutralising antibody titres distinguished Australian patients who Images derived from 15-40 focal planes were in samples collected during and after therapy developed SN within six months of ART compiled, so nerve fi bres could be followed and assess antigen recognition by western from those who did not. We then tested through the tissue. In active neuropathy, blot. This includes patients co-infected with HIV patients in Jakarta and Kuala Lumpur, biopsies from the ankle and thigh displayed HIV receiving ART.
confi rming that neuropathy is common dense infi ltrates of CD14+ macrophages, with among Asian patients. We showed that a distribution consistent with migration from With Kathy Davern (Monoclonal Antibody increasing patient height and increasing age dermal blood vessels to concentrate around Facility, WAIMR), Silvia is producing human are risk factors for SN. damaged nerves. In late-stage neuropathy, monoclonal antibodies that can neutralize ankle biopsies demonstrated extensive focal HCV infection. This is important for the Initial genotyping of Indonesian patients nerve damage (often with no nerves visible) management of transplant recipients and confi rmed an association with TNFA-1031*2, and few macrophages. The results suggest for prophylaxis. Using cryopreserved cells an allele associated with SN in Australians. that activated macrophages producing from chronic HCV-infected patients fused to This provided a link with alleles in the TNF TNF may instigate epidermal nerve fi bre a human myeloma cell line, hybridomas have haplotype block, but linkage disequilibrium damage.
been prepared. Supernatants were tested by of this region hampers disease association ELISA for recognition of HCV antigen and studies. Constance Chew (PhD student) fi rst
ASI Inc. Newsletter December 2012
Patricia Price Sylvia Lee Sonia Fernandez Studies of HIV in the majority world:
Key members of the team at UWA
are infected with HIV and/or HCV and the JakCCANDO project
the effects of antiviral therapy. She has Patricia Price (PhD,1985) runs several published several articles which utilised
ART is becoming more widely available in projects investigating HIV disease with a real-time PCR to evaluate mRNA expression
Asia, so many HIV patients with advanced focus on the consequences of beginning ART of viral genes and critical cytokines in viral
disease (AIDS) and untreated opportunistic with very low CD4 T-cell counts, as this is infections. More recently she has focussed
infections are starting therapy. JakCCANDO reality for many patients worldwide. To this on characterisation of humoral responses
stands for Jakarta CMV, Cardiovascular, end, she has initiated and run collaborations to HCV and has developed and exploited a
Antiretroviral, Neuropathy, Dental, with institutions in Africa and Asia. Patricia novel assay for neutralising antibody.
Ophthalmology. It is our third and largest is now returning to a long-standing interest
project based in the Cipto Mangunkusomo in CMV in relation to human disease; Sonia Fernandez completed her PhD in
Hospital affi liated with the University of specifi cally the varied manifestations of 2007. Since then she has continued to work
Indonesia. We will investigate the recovery CMV infection and how consequences in the fi eld of HIV immunology. Her main
of immune function and the role of CMV in arise from the infection of so few cells. The research interest is the immune recovery of
HIV patients beginning ART. Preliminary characterization of CMV genes encoding HIV infected patients receiving antiretroviral
data shows antibody responses to HIV are proteins homologous to components of therapy with a focus on the immunological
extremely high in Indonesian patients with human infl ammatory pathways presents mechanisms that underlie immune activation.
a signifi cant (but undocumented) burden many avenues for study. These can now be Current projects include the role of IFNα
of disease. This project will support four applied to real clinical situations – evaluating in immune activation and characterisation
Clinical/Biomedical PhD projects (at UI), the roles of immune activation, CMV burden of T-cell and B-cell homeostasis in HIV
plus graduate students enrolled through UI and T-cell competency in HIV patients, patients.
and UWA. Studies of candida immunology renal transplant recipients and healthy aging
are a new initiative.
Ben Oliver completed his PhD in 2012. His
thesis investigated whether plasma biomarkers
Evidence of repeated CMV reactivation Martyn French is a Winthrop Professor may inform about the immunopathogenesis
(the "footprint" of CMV) will include CMV in Clinical Immunology in the School of immune restoration disease associated
DNA (by PCR), antibodies and CD8 T-cell of Pathology and Laboratory Medicine with Mycobacterium tuberculosis (TB-IRD)
responses. This will be correlated with .
of UWA and also a Consultant Clinical or have a role in prediction and diagnosis. Immunologist/Immunopathologist at Royal He found that infl ammatory mediators of a) immune activation, immunosenescence Perth Hospital. He has had a research and the innate immune system may infl uence and T-cell homeostasis clinical interest in primary and secondary the immunopathogenesis of TB-IRD, while b) c l i n i c a l o u t c o m e s p r e v i o u s l y immunodefi ciency disorders for over 30 T cell responses may aid in diagnosis.
associated with CMV in other contexts, years. His current research is focused on
specifi cally ocular, cardiovascular and immune restoration disease in patients Constance Chew completed her PhD in
neurological sequelae assessed by expert commencing ART, immune activation and 2012. She analysed the role of TNF block
dysfunction in patients on long-term ART haplotypes as a predictor of risk for sensory and phagocytosis-inducing antibodies in the neuropathy in Caucasian, Malay, Chinese and Natural killer cells will be considered as a control of HIV infection. He also contributes South African HIV patients. Genotypes were mechanism affecting the "footprint" of CMV, to multi-centre research studies on the then reconstructed into TNF block haplotypes including an evaluation of the importance molecular pathology and genetics of primary and their effects on HIV-SN disease of genetically-determined variations in NK antibody defi ciency disorders.
were determined. Constance identified chemokines as molecules likely to mediate Silvia Lee completed her PhD in 2004 neuropathy and used confocal microscopy
and has continued a focus on research into to visualise infi ltrating macrophages around
the immune responses of patients who the damaged nerves.
ASI Inc. Newsletter December 2012
Sara Tanaskovic & Zayd Aghafar Naamah Laila Abudulai Sara Tanaskovic is in the fi nal year of a Nandini Makwana is a fi rst year PhD student
PhD investigating naive T-cell homeostasis investigating if (and how) persistent CMV
in HIV patients responding to ART. She infections induce changes in Natural Killer
demonstrated the importance of the thymus (NK) cell function and phenotype and drive
in the generation of naive T-cells, naive T-cell NK and T cell immunosenescence in renal
homeostasis and apoptosis as a cause of naive transplant recipients. She will correlate
T-cell loss. Data based on Stat5 implicate the CMV footprint with NK genotype
perturbations to IL-7 signalling. The and phenotype, including investigations
associated reduced expression of CD27 and of NK senescence. Whilst this has been
CD28 may impede CD4+ T-cell homeostasis described in elderly individuals and CMV
or compound the functional defi cit.
is known to promote senescence in T-cells, it is unclear whether CMV drives NK Lilian Cha Laila Abudulai is a third year PhD student immunosenescence.
addressing the impairment of memory B-cell
IgG isotype switching as a cause of decreased Zayd Aghafar is an MSc student addressing
phagocytosis-enhancing antibody responses KIR diversity and the role of NK cells in
in chronic HIV Infection. The impairment CMV infection. NK genotypes may infl uence
of IgG subclass diversifi cation by blocking CMV disease in HIV patients but do not
isotype switching may be a mechanism affect susceptibility to HIV. To assess NK used by the HIV virus to evade the immune cell function, purifi ed NK cells activated system and impede phagocytosis-enhancing with IL-2 are co-cultured with CMV-infected ASI Inc acknowledges the antibody responses. Therefore, stimulating or uninfected human fibroblasts. CMV support of the following IgG2 antibody production might be a means down-regulates NK activation assessed sustaining member: of developing a novel HIV vaccine. with CD107a. Factors infl uencing this down regulation are under investigation. • Jomar Bioscience Lilian Cha has recently started her PhD
investigating IFNα and immune activation in
HIV patients receiving ART. She is building
on evidence that IFN-α may be involved in
ICB Online Manuscript
HIV pathogenesis, with a positive correlation between chronic immune activation and levels of IFNα and interferon-stimulated Online manuscr ipt submission for Immunology and Cell Biology now genes. Lilian will investigate the effect of PO Box 7108,
IFNα on CD4 T-cell and memory B cell Upper Ferntree Gully,Vic. 3156
homeostasis, and examine the expression of the type I interferon pathway transcriptome All manuscript submissions to ICB should in future be made online via this web site Tel: +61 3 9756 0128
in HIV patients with good and poor recovery to speed up the reviewing and acceptance Fax: +61 3 9753 6372
of CD4 T-cells.
Gabrielle Belz, Editor-in-Chief Immunology and Cell Biology ASI Inc. Newsletter December 2012
Obituary – Emeritus Professor Gordon L. Ada
Professor Sir Gustav Nossal
This piece appeared originally as an obituary In 1968, Professor Frank Fenner invited for the Members of the Australian Academy Ada to Canberra to head the Department of of Science. Microbiology of the John Curtin School of Medical Research of the Australian National Gordon L. Ada died peacefully on 25 University. Here, Ada surrounded himself September after a brief illness, aged 89. His with an outstanding group of colleagues. wife Jean pre-deceased him by several years; He managed to combine the disciplines our sympathy goes out to his children and of virology and immunology in a creative grandchildren.
fashion. Helped by Robert Blanden, this created the atmosphere within which Peter Ada, a Sydney University graduate in science, Doherty and Rolf Zinkernagel were able to began his career at the Commonwealth Serum make their Nobel Prize-winning discovery Laboratories in Melbourne. In 1948, Sir of how T lymphocytes "saw" antigenic Macfarlane Burnet recruited him to The peptides in association with "self" molecules Walter and Eliza Hall Institute of Medical of the major histocompatibility complex. Research to work on biochemical aspects of The author was privileged to be at a Brook the infl uenza virus under Alfred Gottschalk Lodge Symposium in 1974 where Ada gave (later FAA). His most important discovery this amazing discovery its fi rst international was that infl uenza virus was an RNA, not airing. Curiously, it caused little stir – it was DNA virus, very novel at that time. just too novel – but the world pretty soon Ada was also actively involved in the caught on. Ada continued to give exemplary Australian Society of Immunology and the Initially just plain Mr Ada, Gordon eschewed leadership to the group until his retirement. Australian Academy of Science amidst his the normal PhD pathway but submitted his He was also very infl uential in education in many editorial and administrative duties. He published work for a DSc which he received immunology, through reviews and popular was universally admired for his gentle and and shortly after which he was elected to the books.
gentlemanly leadership and his impeccably high standards of scientific rigour and Ada's retirement was clouded by a serious integrity. He will be sorely missed.
Burnet changed the Institute's direction from and prolonged illness of his beloved wife virology to immunology in 1957, but Ada was Jean. He looked after her with loving care GJV Nossal slow to follow. In the early 1960s he teamed to the very end.
The University of Melbourne up with the author of this note and began a felicitous fi ve year collaboration, the purpose of which was to determine how antigen exerted its stimulatory action through tracing radioactively-labelled antigen through the body (in the rat) using autoradiography, including electron-microscopic detection. This resulted in about 20 publications, the most important of which discovered the follicular dendritic cell. This extraordinary cell type had the capacity to capture antigen and hold it on the surface of long dendritic processes for prolonged periods (up to at least nine months). B lymphocytes were attracted to the vicinity and a germinal centre was set up, which was critical to the process of immunological memory. Another important fi nding was that single antibody-producing cells did not contain antigen (even where four molecules could have been detected). This disproved the direct template hypothesis of antibody formation.
Emeritus Professor Frank Fenner (left) relaxing with Gordon Ada Thanks to Geeta Chaudhri for providing all Gordon Ada photographs used in this tribute
ASI Inc. Newsletter December 2012
What does it take to be a great scientist?
Originally published in ASI Newsletter, June 2004
The next talk after mine at the meeting was Because of his high standing, none of my US What does it take to be a great scientist? It given by Albert Sabin, the virologist who colleagues wished to criticise Sabin; would takes brilliance of course and persistence, and developed the oral poliovirus vaccine (OPV). I do something about it? Back in Canberra, this can involve being prepared to fi ght very For this he was almost revered in the USA. Bob Blanden and Arno Mullbacher joined hard for your ideas and beliefs. The extent to But he was recognised to be a somewhat me in writing a short article gently pointing which this can be pursued was brought home diffi cult person: a young scientist, having out the fl aws in Sabin's paper. We were also to me by a brief interaction with virologist worked with him once, rarely repeated the concerned that it might inhibit research aimed Albert Sabin very late in his career.
experience. Shortly after he started his talk, he at developing HIV vaccines. Our article was stopped, glared at me sitting in the third row published in Nature under the heading – HIV: After I retired in 1987, I spent three years at at this large meeting, and said in a very loud to vaccinate or not to vaccinate (2). There Johns Hopkins School of Hygiene and Public voice – "DR ADA, YOU MUST IMMUNISE was no immediate response. In March, 1993, Health in Baltimore and became Director of AT THE SITE OF INFECTION." I felt like Sabin died and was buried in the Arlington a Center for AIDS Research. This brought creeping under the chair in front of me. I National Cemetery. Almost to the day, Nature me into close contact with the AIDS Program learnt later that he had spent much time advised me that they had just received a scientists at the NIH in Washington and I seeing if he could vaccinate young children statement for publication sent by Dr Sabin was invited to give talks at various meetings with measles vaccine by the respiratory route before his death in which he stated he did not there. Shortly after I returned to Canberra, rather than by injection. This was possible accept our arguments mainly because we had I was asked to join a new NIH committee but not feasible on a large scale. But how not actually shown such cells being destroyed – an HIV Vaccine Working Group which could I respond? in the recipients. Did I want to reply? I said was to meet three or four times a year in there was now no point in replying; let Dr Washington. I was the only non-USA citizen Early in 1992, a paper appeared in the Sabin rest in peace. But I thought that I had on the committee and was appointed because Proceedings of the National Academy yet to meet an immunologist who would I was thought to know something about of Sciences (1) by Dr Sabin in which he disagree with our argument.
cell-mediated immune responses generated stressed the improbability of being able following vaccination. I was also invited to vaccinate against HIV infecting by the Postscript: The WHO polio eradication to give talks at various scientifi c meetings vaginal route. The reason was because campaign was initiated in 1988, but the time usually held at NIH. At one meeting – a infected semen contained latently infected limit was fi nally extended to 2005. The year Bob Gallo meeting – I gave a talk on what cells (containing only viral DNA but no 1994 may go down in medical history as the is called the common mucosal immune viral particles) which could persist in the time when the last case of natural infection sytem. There was increasing evidence that recipient indefi nitely and later initiate an worldwide was detected. Though many stimulating at one mucosal site could result infection. At the next meeting of the HIV countries have now switched to the use of in a specifi c immune response at another Vaccine group, I pointed out the fl aws in this the inactivated virus vaccine (IPV), the use of site. For example, adenovirus infects via the argument – mainly that such cells would, in the OPV was absolutely crucial in achieving respiratory tract, but the adenoviral vaccine is nearly all recipients, be recognised as foreign the great success to date.
administered orally and gives good protection and very rapidly destroyed by the recipient's from a subsequent respiratory challenge. immune system (host-versus graft reaction). (1) Sabin, A. B. Proc. Nat. Acad. Sci., USA. 89: It had become clear that increasing numbers (2) Ada, G., Blanden, B., Mullbacher,A. Nature of women became infected after unprotected sexual intercourse with HIV-infected partners. It was known that the female vagina is not well endowed with lymphoid tissue. In fact, the vaginal fl ora can include seven different non-pathogenic bacteria, fi ve pathogenic bacteria and seven pathogenic viruses, and yet they induce poor immune responses. Normally, the non-pathogenic Gordon Ada, winner of the fi rst bacteria induce an environment which award for best newsletter article inhibits other infections. So in my talk, I for three contributions published in stressed the need to fi nd out whether an 2004 newsletters, two of which are HIV vaccine might be effective if given reprinted here via another mucosal site (we now know the respiratory tract can be quite effective as an immunisation route for this purpose). ASI Inc. Newsletter December 2012
The Importance of Mother's Milk
Originally published in ASI Newsletter, June 2004
On becoming Director of the Walter and Eliza So in the mid 1950s I started such a the bacteria then removed by centrifugation Hall Institute in 1942, Macfarlane Burnet and programme, using a crude broth as the and the supernatant given to Eric French colleagues began a major investigation of the culture fl uid for the Cholera organisms and for assaying. Some hours later, Eric burst infl uenza virus with the hope that they might Eric French agreed to carry out the assays into my room, exclaiming, "Gordon, lots of be able to learn how to control an infl uenza for RDE activity. Despite using adsorption RDE activity!" My wife then kindly agreed pandemic like the one which killed at least to RBCs at 4oC followed later by the elution to my having another small sample of her 20 million people after the First World War. of the enzyme at 37oC as an important step milk. This I dialysed against some of the The virus was grown in embryonated chicken in the purifi cation, the enzyme preparation synthetic medium, then added the bacteria eggs. When harvesting the allantoic fl uid was still not pure enough. An important to the dialysate and incubated it. Fortunately, from the infected eggs, Burnet noticed that visitor to the Institute in 1956-7 was Joshua most of the active factor(s) was dialysable the red blood cells (RBCs) were often in Lederberg, who in 1958 was to share the and (later), one component was found to be clumps (agglutinated). But it was George Nobel Prize in Physiology or Medicine for sialyl lactose. Hirst in New York who found that after his work on the genetic properties of bacteria. incubating such agglutinated cells at 37oC On telling him of my frustration, he said, We found bovine colostrum to be a rich for a few hours, the clumps of cells broke up, "Gordon, you must grow the bacteria in a source of the dialysable active factors and and adding more of the same virus no longer purely synthetic medium." This I achieved, this led to my being able to produce enough caused those cells to agglutinate. Hirst thus but - you've guessed it, absolutely no RDE and subsequently to obtain crystals of the showed that the infl uenza virus contained an was secreted. RDE was thus an inducible enzyme. Burnet was told about it before enzyme which would destroy a receptor for enzyme! (It would be fascinating to know he left on an overseas trip. As I wanted the virus on the RBC. Burnet soon confi rmed how the decision is made to secrete or to be absolutely sure my technique was this, but remembered a paper published years not secrete the enzyme.) At this stage, the reproducible, I prepared crystals of the earlier which showed that V. cholerae grown specifi city of RDE was unknown. So, where enzyme (now called neuraminidase) from in culture secreted a factor which affected would I fi nd a rich source of an appropriate three successive batches before we submitted the properties of RBCs. Burnet then showed substrate which desirably would have a low a paper to Nature with pictures of the crystals. that RBCs incubated in such a culture could molecular weight, and thus make purifi cation It was accepted but one week before the no longer be agglutinated by the infl uenza of the enzyme easier? paper came out in 1959, Nature published virus. Thus, the culture was shown to contain a paper with German authors claiming an infl uenza virus-like receptor-destroying My wife had recently had her fourth (and last) crystallization of the enzyme, but showing enzyme (RDE) and this became a very baby and as I was watching her breastfeeding no pictures. I became a world supplier of the important tool in the infl uenza virus work. him one day, it suddenly struck me – her pure enzyme for about three years before Alfred Gottschalk in the Institute then started milk must be an extraordinarily rich source Sigma became a supplier. Graeme Laver in work to elucidate the nature of the bond split of a great variety of different substances in the Department of Microbiology in the John by RDE which eventually he achieved. I order for the baby to survive and grow so Curtin School isolated and crystallized the thought his work would be facilitated if the quickly. My wife agreed to my having a neuraminidase (sialidase) from the virus enzyme could be purifi ed.
small sample of her milk which I added to the about 20 years later. This led in due course synthetic culture medium. The bacteria were to the synthesis of a compound which added and the culture incubated overnight, neutralised the neuraminidase activity of the infl uenza virus.
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ASI Inc. Newsletter December 2012
Obituary – Dr William (Bill) Boyle
Ian Mackenzie & Sandra Uren
On Friday 9 November, one of our former he developed the Immunology major for colleagues and ASI member William "Bill" Science students at Melbourne University. Boyle passed away. Bill was Associate He also provided medical students with an Professor and Reader in Immunology introduction to immunology that provided a in the Department of Microbiology and framework for the new paradigms that they Immunology at the University of Melbourne would encounter in the future. from 1970 until his retirement in 1998. After Bill retired from Melbourne University, Bill was born in Glasgow in 1933, and he took up a part-time consulting role at the undertook a Science degree with fi rst class Austin Research Institute (ARI) at the Austin honours, and subsequently his PhD from Hospital until the Institute merged with the Glasgow University. He worked with Allan Burnet Institute at the Alfred Hospital. At the Davies on mouse tissue cell antigens at the ARI, Bill was most closely associated with Microbiological Research Establishment Prof Mauro Sandrin's Transplantation Lab in England where he was Senior Research where he was warmly welcomed by all. At Offi cer. In 1963 he joined the Division of the ARI, Bill was also a consultant for Prima Immunology at Duke University Medical Biomed Ltd – a public company commercial- Centre where he worked with Bernard Amos. izing the ARI's inventions – where Bill was During this time he pioneered the use of an active member of the Scientifi c Advisory several now routine techniques including the Board (SAB) and he was also a member of isolation of leucocyte populations by Ficoll the SAB for Roche's CARG grants. Mark barrier centrifugation, and the use of the 51Cr program for many years. He was also PhD Hogarth, Director of the ARI at the time, release assay for cytotoxicity. supervisor for many students, including recalled that of all the lecturers he had at Keryn Williams, Anne Kelso, Bill Heath, Melbourne Uni, Bill's were the only ones By 1970 he and his wife Mary had three Robyn Sutherland and Andrew Nash. Bill he remembered! young children, and they decided that the served on NHMRC Assignor's panels and best opportunities for their young family Regional Grants Committees and was an Indeed, it is as a teacher and mentor that Bill were to be found in Australia. He joined active member of many professional societies, will be most remembered and sadly missed. the Department of Microbiology (as it was including the Australian Tissue Typing His enthusiasm for all aspects of immunology then known) at the University of Melbourne, Association (ATTA), the Transplantation and cell biology was palpable and infectious, where his research interests included the Society of Australia and New Zealand and his approach to science was thoughtful areas of T cell activation, histocompatibility (TSANZ) and ASI, where he was Chair of and rigorous. Bill's contributions to both antigens and transplantation, and macrophage the Education Committee in 1993-4. research and teaching to a generation biology. His work was published in many of science and medical students leave a journals including Nature and J Exp Med. Bill also took a major role in teaching to lasting legacy that many of us have much He supervised a large number of Honours undergraduate students where, together with to be grateful for. He leaves behind his wife and Masters students and was a very expert Christina Cheers and Ian Mackenzie (in Mary, four children and fi ve (nearly six) co-ordinator of the department's Honours the Department of Pathology until 1995), grandchildren.
ASI Inc. Newsletter December 2012
ASI Inc. Newsletter December 2012
HONORARY SECRETARY'S NEWS
ASI International travel award recipients
the conference dinner at the MCG which ASI Travel Bursaries
We received a large number of excellent we hope will be a highlight. Members of There were a large number of applications applications for the October round of the the Local Organising Committee include from students and early post-docs for travel ASI international Travel Awards, and the Frank Alderuccio (meeting treasurer), bursaries to attend the ASI 2012 annual following awards of $3000 each were Meredith O'Keeffe, Nicole La Gruta, Stuart scientific meeting in Melbourne. The made: Mannering, Su Heinzel, Daniel Layton, following were selected for funding:Phil Hodgkin, and Edwin Hawkins. The Owen Siggs (University of Oxford); IgN student reps for 2012 are Julia Marchingo Dino Tan (UWA)Winter School, Singapore and Maria Demaria, and they have done a Malcolm Starkey (Newcastle University) Mehmet Yabas (ANU); Keystone Symposia great job with organising the student dinner. Sumaira Hasnain (Mater Institute) "B cell Development and Function", Others involved in the SIGs and workshops Colorado, USA include John Stambas, Nicole Haynes and Alison Carey (Griffi th University) Emma Grant (Postgraduate Symposium), Erika Duan (Monash University); American Seth Masters (Infection and Immunity SIG), Michelle Vo (Centenary Institute)Association of Immunology Centennial Odilia Wijburg (Mucosal Immunity SIG) and Alvin Pratama (ANU) meeting, Honolulu, USA Phil Darcy (Tumour Immunology SIG).
Md Ashik Ullah (University of Sydney) Connie Duong (Peter Mac); Keystone
Symposium: Cancer Immunology and Election of new council members
Sally Mujaj (QIMR) Immunotherapy, Vancouver, Canada There was a call for nominations for the positions of state/regional councillors for Zahra Sabouri (ANU) Stephen Mattarollo (University of WA, SA/NT and ACT in October, as well as Taryn Osmond (Malaghan Institute, NZ) Queensland); Keystone Symposium: for the executive position of ASI Treasurer. Cancer Immunology and Immunotherapy, After nominations were received and a Brooke Dobson (University of Otago, NZ) Vancouver, Canada ballot conducted the following new council James Q. Wang (ANU) Jason Waithman (Telethon Institute for members were elected; Roy Ramiscal (ANU) Child Health/UWA); Keystone Symposium: Understanding Dendritic Cell Biology to WA: Dr Andrew Currie Connor O'Meara (QUT) Advance Disease Therapies, Colorado SA/NT: Dr Cara Fraser Fatima El-Assaad (University of Sydney) ASI 2012 conference
ACT: Dr Anselm Enders Meru Sheel (QIMR) At time of writing, preparations are nearly Marie Kharkrang (Victoria University, complete for the ASI 2012 annual scientifi c ASI Treasurer: Dr John Stambas meeting, which will be held in Melbourne from 2-6 December at the new Melbourne We would like to take the opportunity Cameron S Field (Malaghan Institute, NZ)Convention and Exhibition Centre. We have to express our sincere gratitude to the Tessa Gargett (University of Adelaide) had a great response with more than 550 outgoing state/regional councillors – Dr abstracts and over 700 registrants to date. Alec Redwood, Dr Michele Grimbaldeston Megan Ives (Garvan Institute)Many thanks to my co-chair Prof Steve and Dr Stephen Daley (ACT) – who have Aline Nocon (University of Sydney) Turner from the University of Melbourne, worked so hard over the past three years to who has presided over the scientifi c program represent the ASI members in their region, Michael Wong (ANU)for the meeting, and all of the members of and organise branch activities and annual Pallave Dasari (University of Adelaide)the local organising committee who have meetings. Special thanks should also go Sarrabeth Stone (Victoria University, NZ) worked so hard behind the scenes to secure to the outgoing ASI Treasurer Dr Pablo sponsorship, review abstracts, assist in Silveira, who has done a fantastic job in the Jason Lynch (University of Queensland)programming and budgeting, and helping quite onerous position of Treasurer for the Laura Cook (UNSW) to prepare the social program, including past three years.
Roland Ruscher (University of Queensland) Rose Ffrench ASI Inc. Newsletter December 2012
ASI STUDENT NEWS
That time of year has come. The ASI conference is all over and the student function held at The Common Man was a great success and enjoyed by all. We just wanted to give a big thank you to the student committee who helped us organize this great event: Emma Grant, Eleanor Livingston Jones, Aislin Meehan, Rangsima Reantragoon and Alison West. And of course, thank you to all of you who attended for making it a night to remember! For photos of the night don't forget to visit our ASI student facebook page "Student members of the Australasian Society for Immunology".
As we head towards the end of year break we thought we'd give you a comic or two to help you brains unwind for the year.
For another great procrastination tool or just something to help you get through a tough day in the lab visit http://whatshouldwecallgradschool.tumblr.com/ for a guaranteed laugh.
Thanks for having us as your students reps for 2012. We've had a great time putting together the quarterly newsletter articles, running the student facebook page and organizing the student function. We hope to see you at future ASI events! Julia Marchingo and Maria Demaria Image from http://xkcd.com/ ASI Inc. Newsletter December 2012
ASI Councillors' News
The mid career scientists invited to speak Victorian News
were: Dr Shelley Gorman (Sunlight, In an effort to enhance communications The highlight of 2012 for Immunology infl ammation and obesity-related metabolic and collaborations for our Queensland- in Victoria/Tasmania is undoubtedly the diseases: a hypothesis), Dr Andrew Lucas based ASI members, and immunologists in 42nd Annual Meeting of the Australasian (Abacavir hypersensitivity, poster child general, September saw the formation of iQ Society of Immunology, which runs from for the altered peptide generation), Dr (Immunology Queensland). This ASI sub- December 2-6 at the Melbourne Convention John Waitman (Immuno-surveillance of committee consists of 10-15 student and post- and Exhibition Centre. The organising melanoma by dendritic cells) and Dr Anna doc ASI members from various immunology committee, headed by Stephen Turner and Johansson (Tumour targeted TFNα improves hubs across Brisbane, the Gold Coast and Rose Ffrench, have been working hard all vessel function and enhances active immune Townsville (UQ, QUT, Griffi th University, this year and they all deserve a great deal of QIMR, MMRI, JCU) and will organise events credit for the work they have done to make of interest to local immunologists. the conference a huge success. Student presentation were selected from abstracts; the four selected speakers were Given the location of the Annual Meeting The following positions were appointed: Scott Cornwall (The Effect of Mesothelioma in Melbourne, the Immunology Group of Chairperson: Dr Ashraful Haque, on Dendritic Cell Subsets), Laila Abudulai Victoria did not hold their normal annual Secretary: Dr Danielle Stanisic, and (Diversifi cation of IgG Antibody Responses retreat. However, IgV was still heavily Treasurer: Marcela Gatica-Andrades. to Pneumococcal Polysaccharides in involved in other activities, including HIV Patients), Shruti Krishnan (Tumour providing signifi cant fi nancial support to iQ can be contacted through the secretary eradication and induction of memory local members attending the ASI conference. d.stanisic@griffi th.edu.au. against murine mesothelioma by combined Many IgV members are also heavily involved immunotherapy) and, finally, Joanne in organising the national meeting. This year iQ has already been very busy with two Gardner who took out the Western Australian saw IgV run a competition to design a new Brisbane-based events planned for the fi rst Institute of Medical Research Student Oral logo, with the winner to be announced at the half of next year. The fi rst event is a night of Presentation Award for her presentation ASI conference.
"Immunology Speed Dating" on Friday 8th entitled "Mesothelioma tumours modulate February for immunology students. It will dendritic cell lipid content, phenotype and This year Victoria hosted a visit by Prof Pam be a fun and informal way to meet students function". ASI also supported a student Schwartzberg who was sponsored by the ASI from other institutions, to hear about what poster prize and this was awarded to Dino Tan Visiting Speakers Program. Pam was a very they are doing and to think about how best for an excellent poster describing the study popular speaker and next year ASI visiting to communicate one's research in a few "Treg function and induction of CTLA-4 are speakers will include John Wherry (visiting short minutes. Cash prizes will be awarded impaired in patients with chronic obstructive in February, hosted by Scott Mueller), Branch to the students who can best impress their pulmonary disease".
Moody (visiting in March – Dale Godfrey "immunology dates" with a summary of hosting), Ed Palmer (hosted by Su Heinzel) At this stage we plan to run concurrent and Mark Jenkins. Please contact the hosts sessions with CBSM every two years, if you would like to meet the speakers and iQ's second event will be open to the general interspersed with our P.I.G meetings. If let me know if you have nominations for public, and will coincide with the Day of anyone has another view please let me know, international speakers to visit Victoria or Immunology in late April. Watch this space but we on your local committee thought Tasmania under this program, or if your for more details in the next newsletter. the initiative with CBSM worked very well institute wants to host a seminar by one of Ashraful Haque this year.
the aforementioned speakers.
Councillor This is my last official duty as State Next year will see the return of the IgV Councillor for WA. To be honest, I was a little conference as well as the other initiatives W.A. News
reticent about taking on the role when fi rst that support immunology, including approached, it seemed a lot of extra work. sponsored seminars, the Masterclass, Day The WA branch of ASI has had a busy 2012. And while there have been moments where of Immunology and student and postdoctoral In association with the Combined Biological things got a bit hectic, the experience has travel awards to visit conferences and deliver Sciences Meeting (CBSM), we introduced been well worth it. I have had an opportunity seminars interstate and overseas. I will advise immunology sessions into the annual CBSM to meet and work with other Councillors and members about all these events as they meeting. CBSM is an institution in WA and the Executive and it really has been a great draw near. Please contact me if you have has been running annual scientifi c meetings pleasure and, to be honest, a privilege. It has any suggestions or queries. Renewal forms in Perth for the past 22 years. We were been an experience to see how our society accompany this newsletter so please renew very fortunate to be able to convince David works and to meet the people who ensure it ASAP so that you receive all the updates Tarlinton to come over to Perth and give our continues. So thanks to ASI and welcome to and notifi cations about ASI and IgV. Please keynote address. This excellent talk was then the new State Councillor.
let your new students and colleagues know backed up by two full immunology sessions about signing up too! for mid career researchers and students. Alec Redwood Stuart Berzins ASI Inc. Newsletter December 2012
opportunities for them to network with the Fraser, Erin Lousberg, Susan Christo, ASI student body in Adelaide. Nicole Christie, Dave Yip, Natasha 8th Adelaide Immunology Retreat (AIR-7)
Kolesnikoff, Houng Taing, Kevin Fenix, 2012 Report
In addition to the very high standard of Yuka Harata-Lee, Natalie Stevens and Iain Once again, the Adelaide Immunology Retreat science presented, we also participated Comerford – for all their hard work and (AIR) for PhD students, Honours students and in wine tasting at the historic Seven Hills enthusiasm for the meeting. Also a BIG research assistants was a great success. It was Winery. This was a very popular function thank you to all our sponsors: Miltenyi, held at the Comfort Inn in the lovely surrounds – not only due to the quality juice of the vine Sapphire Bioscience, Jomar, Uni SA, of the Clare Valley on 7-8 September. The sampled but also because of the interesting Adelaide Uni, Roche Diagnostics Australia, retreat was opened with a terrifi c seminar history of the winery – it was set up in BioRad, AdeLab Scientifi c, Karl Zeiss, by Prof Lynn Corcoran (WEHI, Vic), our the 1800s by Catholic monks to provide Geneworks, BD Biosciences, Genesearch, invited national speaker. This was followed sacramental wine for parishes throughout Life Technologies, Epitope Technologies, by presentations from PhD students, South Australia. Qiagen, Australian Bioscience, Beckman Honours students and research assistants. Coulter and STEMCELL Technologies. Overall the standard of the presentations Finally, I would like to thank the AIR-8 Without their generous fi nancial support the was exceptional. Congratulations go to the organizing committee members – Cara event each year could not be held. following students and research assistant who received awards: Nicole Christie (AIR-8 Best PhD
Tessa Gargett and Heidi Neubauer (both
received the award of 2nd PhD Presentation
Nikhil Thyagaraja (Best Honours
Bianca Van Dierman and Lih Tan
(both received the award of 2nd Honours
Presentation Prize) and
Daniella Penko (Best Research Assistant/
To strengthen links between SA and NT, our invited ‘local' speaker was Dr Gabi Minigo (Menzies, NT). Next year we are hoping to sponsor at least two Northern Territory students to attend AIR-9 in order to provide Above: AIR-8 award winners
Below: AIR-8 participants
ASI Inc. Newsletter December 2012
Out with the Old and in with the New attached to her nomination form. Cara will accommodation, catering and transport and
SA/NT State Branch Councillor
make a terrifi c councillor and I look forward receiving registrations. In 2009 Dr Fraser My term as the ASI SA/NT State Branch to supporting her in this role. Congratulations participated in school visits promoting Councillor will come to an end at the on your appointment, Cara! understanding of immunology for the World Melbourne ASI Annual Meeting. I have Day of Immunology. greatly enjoyed my time as councilor – it Cara Fraser Bio
has been a privilege to serve the Society Dr Cara Fraser has been an active member Dr Fraser's research interests include tumour
and the SA/NT membership in this capacity. of the ASI since 2004, during which time immunology and immunotherapy, kinase
Highlights have been convening the Adelaide she has made an increasingly substantial inhibition, adjuvants, vaccines and infectious
Immunology Retreats for the past three years contribution to national and local Society diseases. Currently Dr Fraser manages the
and also taking on the task of the Program activities. In 2010/2011 Dr Fraser was a Experimental Therapeutics Laboratory,
Chair at the 41st ASI Annual Meeting that member of the organising committee for the which requires liaison between the RAH, SA
was held last year in Adelaide. It has been 41st Annual Scientifi c Meeting of the ASI Pathology, UniSA, and UA for everything
extremely rewarding interacting with the ASI and was the sole convenor of the Tumour from OGTR, ethics, fi nancial reconciliation
SA student body during the AIR meetings and Immunology Workshop. This involved and student co-supervision. Collectively,
watching their burgeoning careers develop inviting international and national speakers, Dr Fraser's past involvement with ASI,
over each subsequent year I convened the compiling the program, liaising with managerial experience and diverse research
meeting. It is with this in mind that I hand delegates and chairing sessions. Dr Fraser has interests afford her the necessary skills to
over the councillor position to Dr Cara Fraser, also participated in organizing fi ve Adelaide make a positive contribution to ASI as the
who is the new incumbent for the next three Immunology Retreats, progressively SA/NT ASI Councillor.
years. Cara has always impressed me with taking on more responsibility and gaining
her enthusiasm and dedication to the Society. experience in all aspects of event organisation
Below, I have included her short bio that she including obtaining sponsorship, organising The 4th Annual NSW/ACT retreat was held in co-hosting a very couth trivia contest (apart Question asking prize: Yogesh Jeelall idyllic surrounds at Bowral on 23–24 August. from the risqué bits).
Seventy-six delegates attended this year's Thank you so much to our wonderful meeting and enjoyed fantastic presentations The recipients of awards were: meeting sponsors: BD Biosciences, Miltenyi, all round. As always, it was a great meeting Jomar Bioscience, Stemcell Technologies, and hopefully fruitful in terms of forming Honours Student prize (shared): Felix Marsh- Australian Biosearch, Life Technologies and new links and collaborations. Wakefi eld (USyd) and David McDonald In Vitro. Their support allows us to bring you (Centenary Institute) the meeting at a very reasonable price and For their keynote presentations, we would invite some great plenary speakers. like to warmly thank Professor Tony PhD student prizes:Cunningham, Dr Michele Grimbaldeston, 1st Hannes Bergmann (JCSMR) We look forward to seeing you all at the Professor Tony Basten, and Dr Adrian 2nd Manu Singh (JCSMR) Zahra Sabouri (JCSMR) Marcel Batten (NSW Councillor) Thanks also to Scott Byrne for helping to Post Doc Prize ($500 voucher from Stephen Daley (ACT Councillor) organize the program, Marian Fernandez for Invitrogen): Ian Parish (JCSMR)organizing the judging and Julie Wheway for Back row LtoR: Hannes Bergmann (PhD talk prize), Ian Parish (Early Career Researcher Prize), Dr Adrian Smith (Plenary), Zahra Sabouri (PhD talk prize), Michele Grimbaldeston (Plenary), Marcel Batten (NSW Councillor). Front row LtoR: David McDonald (Honours prize), Manu Singh (PhD talk prize), Felix Marsh-Wakefi eld (Honours prize) and Stephen Daley (ACT Councillor) ASI Inc. Newsletter December 2012
THE ASI VISITING SPEAKER PROGRAM 2012
The opportunity to establish or to strengthen Melbourne, 18th – 20th
Huang S, Cheng TY, Young DC, Layre E,
collaborations with leading immunologists Sydney, 21st & 22nd
Madigan CA, Shires J, Cerundolo V, Altman
abroad y greatly encouraged by the ASI Wellington, 25th
JD, Moody DB. Discovery of deoxyceramides
Visiting Speaker Program. It allows bringing and diacylglycerols as CD1b scaffold lipids among key overseas players in the various fi elds of Dr Moody has been investigating the cellular diverse groove-blocking lipids of the human CD1 system. Proc Natl Acad Sci U S A. 2011 Nov research in Immunology for them to interact mechanisms by which CD1 proteins, MHC 29;108(48):19335-40. with local groups. During 2012, the ASI class II proteins and Toll-like receptors Kasmar AG, van Rhijn I, Cheng TY, Turner
VSP facilitated the visits by JoAnne Flynn control T cell activation. CD1 proteins M, Seshadri C, Schiefner A, Kalathur RC,
from the University of Pittsburgh (hosted are a family of evolutionarily conserved Annand JW, de Jong A, Shires J, Leon L,
by Michael Good) and Pam Schwartzberg antigen presenting molecules that bind lipid Brenner M, Wilson IA, Altman JD, Moody
from the NIH (hosted by Stuart Tangye). antigens for presentation to T cells. Using DB. CD1b tetramers bind αβ T cell receptors to
Both visits were very well received in the mass spectrometry to study the lipid content identify a mycobacterial glycolipid-reactive T
of the cell wall of M. tuberculosis, his team cell repertoire in humans. J Exp Med. 2011 Aug has discovered lipid ligands for CD1a, 29;208(9):1741-7. Yakimchuk K, Roura-Mir C, Magalhaes KG,
We already have a good line-up of speakers CD1b, CD1c and CD1d proteins. They are de Jong A, Kasmar AG, Granter SR, Budd
for 2013 and will let you know details as studying the cellular mechanisms of lipid R, Steere A, Pena-Cruz V, Kirschning C,
they become available. However, we are loading onto CD1 proteins in endosomal Cheng TY, Moody DB. Borrelia burgdorferi
always eager to receive your proposals for compartments of dendritic cells and the infection regulates CD1 expression in human
new speakers and are willing to accommodate roles of Toll-like receptors in promoting cells and tissues via IL1-β. Eur J Immunol. 2011
your suggestions. We do look forward to cellular antigen presentation. They are using Mar;41(3):694-705.
hearing from you with your proposals. these lipids to study the function of CD1- de Jong A, Peña-Cruz V, Cheng TY, Clark RA,
For details on the process, visit the ASI restricted T cells in human patients with Van Rhijn I, Moody DB. CD1a-autoreactive
tuberculosis, autoimmune thyroiditis and T cells are a normal component of the human αβ T cell repertoire. Nat Immunol. 2010 drug hypersensitivity reactions.
Dec;11(12):1102-9. Selected Recent Publications
A/Professor E. John Wherry, University of
Layre E, Moody DB. Lipidomic profiling
Pennsylvania, Department of Microbiology, of model organisms and the world's major Professor Marc Jenkins, Distinguished
Philadelphia, PA, USA pathogens. Biochimie. 2012 Aug 23. doi: McKnight University Professor, Department Hosted by Scott Mueller, University of pii: S0300-9084(12)00336-7. 10.1016/ j.biochi.2012.08.012. of Microbiology, University of Minnesota, Hong S, Cheng TY, Layre E, Sweet L, Young Minneapolis, MN. USA
DC, Posey JE, Butler WR, Moody DB.
Hosted by David Tarlinton, WEHI Sydney, 1st
Ultralong C100 mycolic acids support the Brisbane. 4th & 5th
assignment of Segniliparus as a new bacterial Melbourne, 6th – 8th
genus. PLoS One. 2012;7(6):e39017. Zeissig S, Murata K, Sweet L, Publicover J,
Hu Z, Kaser A, Bosse E, Iqbal J, Hussain MM,
Balschun K, Röcken C, Arlt A, Günther R,
Hampe J, Schreiber S, Baron JL, Moody DB,
Liang TJ, Blumberg RS. Hepatitis B virus-
Dr Branch Moody, MD. Brigham and induced lipid alterations contribute to natural
Women's Hospital, Harvard University, killer T cell-dependent protective immunity. Nat Med. 2012 Jul;18(7):1060-8. Hosted by Dale Godfrey, University of Madigan CA, Cheng TY, Layre E, Young DC,
McConnell MJ, Debono CA, Murry JP, Wei
JR, Barry CE 3rd, Rodriguez GM, Matsunaga
I, Rubin EJ, Moody DB.
Lipidomic discovery of deoxysiderophores reveals
a revised mycobactin biosynthesis pathway in
Mycobacterium tuberculosis. Proc Natl Acad Sci
U S A. 2012 Jan 24;109(4):1257-62.
Layre E, Sweet L, Hong S, Madigan CA, Prof. Jenkins will visit Melbourne, Sydney
Desjardins D, Young DC, Cheng TY, Annand
and Canberra between May 18 and 26;
JW, Kim K, Shamputa IC, McConnell detailed dates to be defi ned.
MJ, Debono CA, Behar SM, Minnaard
AJ, Murray M, Barry CE 3rd, Matsunaga Mark has made many outstanding
I, Moody DB. A comparative lipidomics contributions to both T and B cell activation
platform for chemotaxonomic analysis of Mycobacterium tuberculosis. Chem Biol. 2011 and differentiation. Recently he has perfected Dec 23;18(12):1537-49.
the detection of rare, antigen specifi c B and ASI Inc. Newsletter December 2012
T cells in the naive repertoire and followed Quantitative impact of thymic selection on UPCOMING
their entry into the immune response. This Foxp3+ and Foxp3- subsets of self-peptide/MHC has led to some striking insights into the class II-specifi c CD4+ T cells. PNAS U S A. requirements for immunity and the capacity 2011;108(35):14602-7.
of these cells to sustain themselves as Pepper M, Jenkins MK. Origins of CD4(+) Lorne Infection & Immunity Conference
effector and central memory T cells. Nat Immunol. memory cells. Mark has also applied this 2011 Jun;12(6):467-71. 20-22 February 2013 technology to follow CD4 T cell responses Pape KA, Taylor JJ, Maul RW, Gearhart PJ, Mantra Lorne, Victoria
to intracellular pathogens. Jenkins and his Jenkins MK. Different B cell populations mediate www.lorneinfectionimmunity.org
colleagues investigate CD4+ helper T and early and late memory during an endogenous B cell activation in vivo at a level that can immune response. only be achieved by directly tracking antigen- March 11–12, 2013 specifi c cells. Using gene-targeted recipients Chu HH, Moon JJ, Kruse AC, Pepper M, Barcelona, Spain
or antibody blocking approaches, they Jenkins MK. Negative selection and peptide http://www2.kenes.com
identify molecules that are critical for in vivo chemistry determine the size of naive foreign peptide-MHC class II-specifi c CD4+ T cell popu- T and B cell signal transduction, proliferation, lations. J Immunol. 2010;185(8):4705-13.
lymphokine production, survival, and Jenkins MK, Chu HH, McLachlan JB, Moon World Immune Regulation Meeting
differentiation. The goal is to achieve a basic JJ. On the composition of the preimmune "Innate and Adaptive Immune Response
understanding of these processes so that they repertoire of T cells specifi c for Peptide-major and Role of Tissues in Immune Regula- can be manipulated to improve vaccines and histocompatibility complex ligands. Annu Rev tion" Immunol. 2010;28:275-94. Review.
March 13–16, 2013 Catron DM, Pape KA, Fife BT, van Rooijen N,
Davos, Switzerland Selected Recent Publications
Jenkins MK. A protease-dependent mechanism
Email: [email protected] for initiating T-dependent B cell responses to Jenkins MK, Moon JJ. The role of naive T cell
precursor frequency and recruitment in dictating large particulate immune response magnitude. J Immunol. 2012 antigens. J Immunol. 2010;184(7):3609-17.
Pepper M, Linehan JL, Pagán AJ, Zell T, Immunology 2013
Dileepan T, Cleary PP, Jenkins MK.Different
Taylor JJ, Pape KA, Jenkins MK.A germinal
center-independent pathway generates unswitched
routes of bacterial infection induce long-lived Honolulu, Hawaii, USA memory B cells early in the primary response. J TH1 memory cells and short-lived TH17 cells. www.immunology2013.orgExp Med. 2012;209(3):597-606.
Nat Immunol. 2010; 11(1):83-9.
Chu HH, Moon JJ, Takada K, Pepper M,
Pepper M, Pagán AJ, Igyártó BZ, Taylor JJ,
30 Years of HIV Science – Imagine the Molitor JA, Schacker TW, Hogquist KA,
Jenkins MK. Opposing signals from the Bcl6
transcription factor and the interleukin-2 receptor Jameson SC, Jenkins MK. Positive selection May 21-23, 2013
generate T helper 1 central and effector memory optimizes the number and function of MHCII- restricted CD4+ T cell clones in the naive Paris, France cells. Immunity. 2011;35(4):583-95.
polyclonal repertoire. Proc Natl Acad Sci U S http://www.pasteur.fr 15th International Moon JJ, Dash P, Oguin TH 3rd, McClaren
Congress of Immunology JL, Chu HH, Thomas PG, Jenkins MK
August 22–27, 2013Rome, [email protected] An invitation and a request to all ASI members
6th Asian Congress of AutoimmunityNovember 21-23, 2013 to contribute copy that they think might be interesting, useful, historical, humorous or thought provoking.
¾ We invite our student membership to voice their views on issues that interest or directly concern them.
Email: [email protected] ¾ It's our newsletter, so let's support it and strive to make it even better.
¾ The ASI newsletter comes out 4 times a year and we welcome your The Walter and Eliza Hall
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ASI Inc. Newsletter December 2012
TRAVEL AWARD CONFERENCE REPORTS
7th International EMBO Workshop on Antigen Presentation and Processing
Monash University, Melbourne
The 7th International EMBO Workshop on More informal than most conferences, For me, one of the most valuable experiences Antigen Presentation and Processing was the workshop also included daily forums was being able to talk to leaders from around held in the beautiful city of Amsterdam this with open discussion. The fi rst day's topic the world during breaks, as well as getting year (24–27 April) and I was lucky enough to was commercial and clinical demands on constructive feedback during the poster be able to attend thanks to help from a special scientists, and inspired lots of impassioned session. Spread throughout the fi rst two days, travel award. The opening address by Paul comments that arguments over funding came the posters were also eligible for invited Roche set the tone of the conference with at the cost of patients' lives. After thanking the talks on the last day. Although I missed him threatening to hit anyone who spoke too organizers with books (one on how to write out, fellow Australian Hannah Siddle was long with a convenient gavel, and introduced clearly met with much laughter), the second selected, giving a fascinating presentation on everyone with comical pictures (no doubt day's forum included the two extremely Tasmanian devil facial tumour disease. from previous conferences). The workshop's controversial topics of the contribution of tradition dictates that all presentations must DRiPs to antigen presentation, and the main Overall, not only was the conference highly be on data that has not yet been published, source of in vivo cross presentation. Truly, if educational and entertaining, the experience leading to some happy embarrassment on in a less civilized setting, there might have allowed me to gain insight into many facets Thursday, when Nilabh Shastri had to change been a brawl, with both topics encouraging of antigen presentation and meet some of his topic at the last minute when his paper loud and vigorous discussions (at one point the most well respected (for good reasons!) was accepted to Nature Immunology on the one very prominent member of the fi eld was members of the fi eld, all made possible by weekend. The tradition, and a decision on the heard to exclaim: "You're wrong!" to be met the support of ASI.
part of the selection committee, also meant with cries of "Maybe he needs a book on an unusually strong showing of early career manners!"). The third day's forum, hosted researchers, including Eva Huber, Alex by a number of students in the fi eld, was Theodossis and Mariolina Salio. perhaps a more polite ending. Eleanor enjoying a fresh stroopwafel, a national dish of the Netherlands One of the tables at the conference dinner involved in lively discussion ASI Inc. Newsletter December 2012
Tuberculosis Vaccines for the World 2012 International Conference
Malaghan Institute of Medical Research, Wellington, New Zealand
I recently attended the Tuberculosis Vaccines for the World 2012 International Conference (TBV 2012) in Orlando, Florida, US. Although TBV2012 was a small meeting, it was packed full of infl uential talks by some of the worlds leading TB scientists and clinicians. The meeting was opened with a very informative talk by David Murray addressing the so-called "myths" surrounding the TB vaccine BCG. Highlights included the presentation of preliminary clinical trial results by Dr Helen McShane and Dr Willem Hanekom, and a fantastic talk by Dr Andrea Cooper delineating the role of IL-17 and IL-27 in immunity to TB.
Meeting at Aeras with Lew Barker, Director I was very fortunate to have the opportunity an amazing experience being able to present of Clinical Development, Aeras (left), Lindsay to present my research to such an impressive and defend my research to such high caliber Ancelet, Frank Aldwell, Head of Research and Director, Immune Solutions Ltd (right). audience. My talk focused on the ability of scientists. The meeting was very successful, a novel lipid-formulated oral BCG vaccine and Aeras agreed to trial our vaccine in a to induce long-term CD4+ memory T cell novel natural infection study alongside their responses in the lung. My presentation top candidate TB vaccines.
was well received, and gave me an excellent opportunity to network with TB Finally, I presented a seminar of my work Contributions sought
immunologists, and gain valuable feedback at the Vaccine and Infectious Disease on my research. Organization/International Vaccine Center for the ASI online
(VIDO/InterVac) in Saskatoon Canada. I was While in the US I also travelled to Washington fortunate to be given a very escorted tour of DC where I visited Dr Robert Seder at the the brand new, world-leading $140 million As part of World Day of Vaccine Research Center at the National Containment Level 3 facility, which was due Immunology events, we have Institute of Health. I was given a tour of the to open the following week.
developed an online NIH and his laboratory and gave a seminar immunology quiz (see http://www.
presentation of my research.
My attendance at TBV 2012 conference, lab visits in the US and Canada, as well as Along with my collaborators from Immune my meeting with Aeras, made this trip very on the ASI website. This quiz is Solutions Ltd, the inventors of the oral busy and exciting. I was able to network targeted at the general public, but vaccine, we presented our oral BCG and form future collaborations with leading it would be good to add a few vaccine research platform to the TB vaccine vaccine researchers, which is critical to my more questions (especially some partnership Aeras. I presented my research success as a young scientist. I felt very proud with an Australian fl avour), and fi ndings to the Aeras senior leadership team to present New Zealand research to such an maybe even add an "Advanced and staff, which included the Chief Scientifi c international audience and am extremely Level", with questions that Offi cer, Dr Tom Evans, and the Vice President grateful to ASI for providing me with such undergrad students might fi nd of Scientifi c Affairs, Dr Ann Ginsberg. It was a brilliant opportunity.
useful for revising for exams. All that's needed now are the questions and answers.
If you would like to contribute any multiple choice questions for either the general quiz or an advanced version, please send them to Judith Greer at ASI Inc. Newsletter December 2012
4th Annual Antigen Processing and Presentation Workshop, Amsterdam, 2012
Ludwing Institute for Cancer Research, Victoria
The 4th annual Antigen Processing and also reported, highlighting the importance presented from several lab groups using a Presentation Workshop was held alongside of saposin facilitation of lipid binding in similar degradation/peptide rescue approach, the beautiful canals of Amsterdam, The endosomal compartments. The important investigating the contribution of DRiPs to the Netherlands. The meeting was attended mechanism of cross presentation of antigens overall peptide pool. While it was agreed that by a broad range of scientists from our was unanimously agreed upon that it does DRiPs do exist, further research is required immunological niche ranging from stalwarts exist, however the underlying mechanisms as to their exact contribution to the overall in the fi eld to young and upcoming scientists, behind the phenomenon are still yet to be peptide pool, in a range of antigenic scenarios. with the calibre of research presented of a fully described and more investigation is However, it is clear that new and exciting continuous high standard. required. The exact contribution of cross instalments into this debate will arise shortly presentation versus directly presented in the future. A large proportion of the research presented antigens is also an elusive topic that remains focused on a major trend in the fi eld of to be fully understood. The demonstration of From this data and other exciting observations trying to understand more detail about the visualising this phenomenon in vivo using presented at this workshop, it is evident that peptide loading complex (PLC) and how imaging techniques was highlighted as a the Antigen Processing and Presentation fi eld peptides are loaded into the MHC cleft. This goal for the future. is strong and will be fruitful in the future. included analysis of the crystal structures of This meeting provided me personally with various parts of the complex, the importance Indeed most controversial of all, the debate new insights into the fi eld and the directions of specific residues for binding to the of the DRiP hypothesis remains a hot topic. into which current research is headed. I'd Class II DO and DM proteins, the exact This hypothesis suggests that a major like to thank the ASI for the Travel Grant I protein composition of the PLC, as well proportion of peptides are generated from received for both the intellectual stimulation as timelines for the peptide binding and Defective Ribosomal Products (DRiPs) I received as well as the chance to talk to loading processes. Data involving alternate rather than from degradation of correctly fellow researchers and pioneers in the fi eld presenting molecules such as CD1s were folded stable proteins. Confl icting data was about my scientifi c work.
SPF MICE AND RATS
MAINTENANCE OF STRAINS
IMPORT AND EXPORT
PO Box 1180 Canning Vale DC, Western Australia 6970
Telephone: (08) 9332 5033 Fax: (08) 9310 2839
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ASI Inc. Newsletter December 2012
3rd European Congress of Immunology, Glasgow
Malaghan Institute of Medical Research, Wellington, New Zealand
On 5-8 September 2012, for the third time dying cells. Eric Vivier presented his immunologists from all over Europe gathered recent fi ndings on the tuning of NK cell at one big conference to present and discuss functions via NKp46, where blocking their latest research. The range of topics was of this activating receptor leads to extremely diverse with sessions covering hyperresponsiveness of NK cells. innate and adaptive immune responses, therapy, regulation, signalling, infectious Matthew Albert's contribution diseases as well as autoimmunity and cancer. "Biomarkers lie!" initiated a lively Up to 12 concurrent sessions spoilt the discussion about the validation, delegates for choice. benefi ts and clinical implementation of biomarkers. In addition, his With over 4000 participants, this was identifi cation of a dominant-negative the largest conference I have attended cleavage variant of CXCL10 shed so far. In addition, it was also my fi rst light on the paradoxical correlation Sabine in front of the "Armadillo", part of the Scottish paperless meeting. Going green, the of high CXCL10 levels with impaired Exhibition and Conference Centre in Glasgow, where conference organisers provided free wifi hepatitis C clearance and highlighted the meeting was held and a smartphone app to search for abstracts, the caveat of common detection kits instead of a printed monster of a conference that cannot distinguish the two CXCL10 to meet Doug Fearon, Ken Smith, Paul programme. While technical hiccups led to forms. A study presented by Panayotis Klenerman, Vincenzo Cerundolo and their some spontaneous gatherings around one of Verginis identifi ed decreased recruitment and groups. I was impressed with the diversity of the few printed programmes, the paperless functional alteration of infl ammatory DCs their projects and learned much about their idea is defi nitely worthwhile, especially for as a mechanism of Treg mediated immune- brilliant research in the regulation of immune such a large meeting. suppression. This finding particularly responses in infection, autoimmunity and intrigued me as I observed a correlation cancer. I also had the opportunity to present The symposium sessions and workshops between the accumulation of infl ammatory my own work on the use of adjuvants featured many impressive presentations DCs and increased anti-tumour immune for tumour-immunotherapy, leading to by postdoctoral fellows and distinguished responses after adjuvant treatment in my interesting discussions and providing me laboratory heads. Among my personal work.
with valuable feedback.
highlights was Caetano Reis e Sousa's talk. Earlier this year, both his team and Ken Overall, I found the presentations at the On my way back to New Zealand I stopped Shortman and Mireille Lahoud's groups ECI meeting very informative. In addition, over in Singapore to meet Christiane Ruedl from Australia identifi ed F-actin as the it also provided a great overview of the and discuss a collaborative project. Jean- ligand for the receptor DNGR-1 (Clec9A). exciting immunology research in Europe Pierre Abastado shared insights into his Investigating the down-stream effects of and the opportunity to interact with other spontaneous melanoma model and kindly this interaction in more detail, he showed delegates during the poster sessions and gave me the opportunity to give a talk at the data indicating that DNGR-1 binding of coffee breaks. Singapore Immunology Network (SIgN). F-actin initiates syk-signalling, which in turn alters endosome traffi cking, increasing Fitting in several laboratory visits before A big thank you to ASI, as well as the NZ antigenicity rather than adjuvanticity of and after the conference, I had the pleasure Cancer Society and the Kathleen Stewart Scholarship for making this invaluable experience possible for me.
Glaswegian pipers getting everyone into the spirit at the ECI opening ASI Inc. Newsletter December 2012
23rd Annual Scientifi c Meeting of the Australasian Society of Clinical Immunology
and Allergy (ASCIA)
Wai Yan (Kiwi) Sun
Centre for Cancer Biology, SA Pathology, Adelaide
I was very delighted to be awarded the ASI The next part of my trip was to attend the skin allergies wherein the ratio of specifi c Postgraduate International Travel Grant conference and workshop. It was well IgE and total IgE was often not considered to travel to New Zealand for (1) visiting organized and divided into sessions which and thereby causing misleading test results. laboratories and presenting at the Malaghan covered (1) primary immune defi ciency, He also showed that the levels of IgE in Institute, (2) attending the 23rd Annual (2) allergy prevention, (3) infl ammatory serum do not correlate with the severity Scientifi c Meeting of the Australasian eye disease, (4) immunotherapy, (5) of allergic symptoms and advised that a Society of Clinical Immunology and autoimmunity, (6) food allergy, (7) sensitivity test alone should not be used as Allergy (ASCIA) on 5-8 September 2012 anaphylaxis and (8) vitamin D and the only read out system to defi ne allergy in Wellington, and (3) visiting the "Kiwi the immune system. There were 300 in clinic.
delegates from both clinical and research backgrounds who contributed to the There were about 50 posters, mainly The ASCIA conference is a top tier programme and discussions. All sessions by students and trainees. I presented a conference for me to attend as my PhD were interesting and informative. I was poster based on my current PhD work focuses on using a small molecule as a particularly attracted to the work of and was honoured to be selected for new therapy to treat allergic infl ammation. A/Prof Mimi Tang (Paediatric Clinical further discussion on the third day of the Thus, meeting with the top scientists in this Immunologist, Melbourne) who presented conference. At the discussion session, I had fi eld is highly benefi cial for my study and on Oral Immunotherapy and Tolerance. She the opportunity to talk to some clinicians future direction. To start off my journey, I discussed the roles of Treg cells in terms of and researchers where I received very visited a few laboratories at the Malaghan tolerance and desensitization in response to positive feedback as well as excellent ideas Institute in Wellington, where I met with a a single high dose antigen changelle versus for future directions. number of senior postdoc researchers and multiple low dose antigen changelle. Her PhD students from the Allergic Diseases work showed that only the multiple low At the end of my trip, I went to visit the Research Lab led by Prof Graham Le dose administration can upregulate the cute little Kiwi birds. I have always wanted Gros, the Immune Cell Biology Lab led by inducible Treg cells, which suggests a to meet this unique bird as we share the Prof Franca Ronchese and the Arthritis & better immunotherapeutic approach to same name, Kiwi. I was so excited when Infl ammation Lab led by Dr Jacquie Harper. induce oral tolerance. I saw one Kiwi and had to stop myself I was fortunate enough to present and share from touching it. But I know it is virtually my PhD work with them and as a result I Another highlight of this conference impossible … why? Because Kiwi birds received a lot of valuable comments, which included the impressive presentation by Dr can run very fast, up to 45 mph (which is will help with my current research and Jorg Kleine-Tebbe (Allergy and Asthma almost as fast as a car on a road)! They are furture career.
Centre, Berlin, Germany). He discussed small but very powerful!!the current issue of IgE testing for food and Overall, the conference was well attended with outstanding presentations, venue and catering. I learnt a lot of new information about allergy, not only scientifi c but also clinical. This was an excellent experience for me and will greatly aid the completion of my PhD. Finally, I would like to sincerely thank ASI for providing me with this opportunity to present and attend the ASCIA conference in New Zealand.
ASI Inc. Newsletter December 2012
Congratulations to ASI members who have published their following work in the last three months (articles with an ePub date between July and September 2012) Londrigan SL, Tate MD, Brooks AG, Reading PC. Kang SS, Kim HJ, Jang MS, Moon S, In Lee S, Jeon Duarte J, Carrie N, Oliveira VG, Almeida C, Agua-Doce Cell-surface receptors on macrophages and dendritic
JH, Baik JE et al. Gene expression profi le of human
A, Rodrigues L, Simas JP et al. T cell apoptosis and
cells for attachment and entry of infl uenza virus. J
peripheral blood mononuclear cells induced
induction of Foxp3+ regulatory T cells underlie the
Leukoc Biol 2012; 92(1): 97.
by Staphylococcus aureus lipoteichoic acid. Int
therapeutic effi cacy of CD4 blockade in experimental
Hamilton JA, Davis J, Pobjoy J, Cook AD. Immunopharmacol 2012; 13(4): 454.
autoimmune encephalomyelitis. J Immunol 2012;
is not essential for optimal fertility or for weight
Jalilian I, Peranec M, Curtis BL, Seavers A, Spildrejorde control. Cytokine 2012; 57(1): 30.
M, Sluyter V, Sluyter R. Activation of the damage-
Kelly PN, Grabow S, Delbridge AR, Adams JM, Strasser Tan SY, Cavanagh LL, d'Advigor W, Shackel N, Fazekas associated molecular pattern receptor P2X7 induces
A. Prophylactic treatment with the BH3 mimetic
de St Groth B, Weninger W. interleukin-1beta release from canine monocytes. Vet
ABT-737 impedes Myc-driven lymphomagenesis in
Phenotype and functions
Immunol Immunopathol 2012; 149(1-2): 86.
mice. Cell Death Differ 2012.
of conventional dendritic cells are not compromised
in aged mice. Immunol Cell Biol 2012; 90(7): 722.
Scott NM, Ng RL, Strickland DH, Bisley JL, Bazely Patel O, Pellicci DG, Gras S, Sandoval-Romero ML, Sheng YH, Hasnain SZ, Png CW, McGuckin MA, SA, Gorman S, Norval M et al. Toward homeostasis:
Uldrich AP, Mallevaey T, Clarke AJ et al. Recognition
regulatory dendritic cells from the bone marrow of
of CD1d-sulfatide mediated by a type II natural
Techniques for assessment of interactions
mice with infl ammation of the airways and peritoneal
killer T cell antigen receptor. Nat Immunol 2012;
of mucins with microbes and parasites in vitro and
cavity. Am J Pathol 2012; 181(2): 535.
in vivo. Methods Mol Biol 2012; 842: 297.
Song KD, Hwang S, Yun CH. Fernandez CS, Cameron G, Godfrey DI, Kent SJ. Ex-
Oldenburg M, Kruger A, Ferstl R, Kaufmann A, Nees T cell receptor signaling
vivo alpha-galactosylceramide activation of NKT
G, Sigmund A, Bathke B et al. TLR13 recognizes
that regulates the development of intrathymic
cells in humans and macaques. J Immunol Methods
bacterial 23S rRNA devoid of erythromycin
natural regulatory T cells. Immune Netw 2011;
2012; 382(1-2): 150.
resistance-forming modification. Science 2012;
Song KD, Kim DJ, Lee JE, Yun CH, Lee WK. Wolyniec K, Shortt J, de Stanchina E, Levav-Cohen Y, Alsheich-Bartok O, Louria-Hayon I, Corneille V et Gupta P, Reid RC, Iyer A, Sweet MJ, Fairlie DP. Towards
transforming growth factor-beta-inducible early
al. E6AP ubiquitin ligase regulates PML-induced isozyme-selective HDAC inhibitors for interrogating
gene 1, acts as a tumor suppressor. Biochem Biophys
Res Commun 2012;
senescence in Myc-driven lymphomagenesis. Blood
disease. Curr Top Med Chem 2012; 12(14): 1479.
2012; 120(4): 822.
Melville JM, Bischof RJ, Meeusen EN, Westover Etto T, de Boer C, Prickett S, Gardner LM, Voskamp Ancelet L, Rich FJ, Delahunt B, Kirman JR. Dissecting
A, Davies JM, O'Hehir RE et al. Unique and Cross-
Changes in fetal thymic immune
memory T cell responses to TB: concerns using
Reactive T Cell Epitope Peptides of the Major Bahia
cell populations in a sheep model of intrauterine
adoptive transfer into immunodeficient mice.
Grass Pollen Allergen, Pas n 1. Int Arch Allergy
infl ammation. Reprod Sci 2012; 19(7): 740.
Tuberculosis (Edinb) 2012; 92(5): 422.
Immunol 2012; 159(4): 355.
O'Keeffe M, Fancke B, Suter M, Ramm G, Clark J, Wu L, Hochrein H. Dudgeon K, Rouet R, Kokmeijer I, Schofi eld P, Stolp Cook AD, Pobjoy J, Sarros S, Steidl S, Durr M, Lacey Nonplasmacytoid, high IFN-alpha-
J, Langley D, Stock D et al. General strategy for the
DC, Hamilton JA. Granulocyte-macrophage colony-
producing, bone marrow dendritic cells. J Immunol
generation of human antibody variable domains with
stimulating factor is a key mediator in infl ammatory
increased aggregation resistance. Proc Natl Acad Sci
and arthritic pain. Ann Rheum Dis 2012.
Kang SS, Jeon JH, Woo SJ, Yang JS, Kim KW, Yun U S A 2012; 109(27): 10879.
Kin NW, Stefanov EK, Dizon BL, Kearney JF. IFN-gamma renders human intestinal
Ma CS, Deenick EK, Batten M, Tangye SG. The origins,
Antibodies generated against conserved antigens
epithelial cells responsive to lipopolysaccharide of
function, and regulation of T follicular helper cells.
expressed by bacteria and allergen-bearing fungi
Vibrio cholerae by down-regulation of DMBT1. Comp
Immunol Microbiol Infect Dis 2012;
J Exp Med 2012; 209(7): 1241.
suppress airway disease. J Immunol 2012; 189(5):
Jeon JH, Kim SK, Baik JE, Kang SS, Yun CH, Chung Sutton VR, Sedelies K, Dewson G, Christensen ME, Bird PI, Johnstone RW, Kluck RM et al. Ng HI, Fernando GJ, Kendall MA. Induction of potent
Lipoteichoic acid of Staphylococcus
Granzyme B triggers a prolonged pressure to die
CD8(+) T cell responses through the delivery of
aureus enhances IL-6 expression in activated human
in Bcl-2 overexpressing cells, defi ning a window of
subunit protein vaccines to skin antigen-presenting
basophils. Comp Immunol Microbiol Infect Dis 2012;
opportunity for effective treatment with ABT-737.
cells using densely packed microprojection arrays.
Cell Death Dis 2012; 3: e344.
J Control Release 2012; 162(3): 477.
Good-Jacobson KL, Tarlinton DM. Multiple routes to
Lim YC, Roberts TL, Day BW, Harding A, Kozlov S, Hansen DS, Stewart CR, Jaworowski A, de-Koning Ward B-cell memory. Int Immunol 2012; 24(7): 403.
Kijas AW, Ensbey KS et al. A role for homologous TF. Advances in infection and immunity: from bench
Lacey DC, Achuthan A, Fleetwood AJ, Dinh H, Roiniotis recombination and abnormal cell-cycle progression
to bedside. Immunol Cell Biol 2012; 90(8): 751.
J, Scholz GM, Chang MW et al. Defi ning GM-CSF- and
in radioresistance of glioma-initiating cells. Mol
Crequer A, Troeger A, Patin E, Ma CS, Picard C, macrophage-CSF-dependent macrophage responses
Cancer Ther 2012; 11(9): 1863.
Pedergnana V, Fieschi C et al. Human RHOH
by in vitro models. J Immunol 2012; 188(11): 5752.
Krautler NJ, Kana V, Kranich J, Tian Y, Perera D, defi ciency causes T cell defects and susceptibility
Huynh J, Kwa MQ, Cook AD, Hamilton JA, Scholz Lemm D, Schwarz P et al. Follicular dendritic cells to EV-HPV infections. J Clin Invest 2012; 122(9):
GM. CSF-1 receptor signalling from endosomes emerge from ubiquitous perivascular precursors. 3239.
mediates the sustained activation of Erk1/2 and Akt
Cell 2012; 150(1): 194.
Slape CI, Saw J, Jowett JB, Aplan PD, Strasser A, in macrophages. Cell Signal 2012; 24(9): 1753.
Spero D, Petrovsky N, De Groot A. Report from the
Jane SM, Curtis DJ. Inhibition of apoptosis by BCL2
Woodberry T, Minigo G, Piera KA, Amante FH, fi eld: Fifth vaccine renaissance in Providence RI. prevents leukemic transformation of a murine
Pinzon-Charry A, Good MF, Lopez JA et al. Low-level
Hum Vaccin Immunother 2012; 8(7): 1006.
myelodysplastic syndrome. Blood 2012; 120(12):
Plasmodium falciparum blood-stage infection causes
Tu E, Ang DK, Bellingham SA, Hogan TV, Teng 2475.
dendritic cell apoptosis and dysfunction in healthy
MW, Smyth MJ, Hill AF et al. Both IFN-gamma Griffi n PE, Roddam LF, Belessis YC, Strachan R, Beggs
volunteers. J Infect Dis 2012; 206(3): 333.
and IL-17 are required for the development of
S, Jaffe A, Cooley MA. Expression of PPARgamma
Cliffe ST, Bloch DB, Suryani S, Kamsteeg EJ, Avery severe autoimmune gastritis. Eur J Immunol 2012;
and paraoxonase 2 correlated with Pseudomonas
DT, Palendira U, Church JA et al. Clinical, molecular,
aeruginosa infection in cystic fi brosis. PLoS One
and cellular immunologic findings in patients
Seidel P, Hostettler K, Hughes J, Tamm M, Roth M. 2012; 7(7): e42241.
with SP110-associated veno-occlusive disease with
Dimethylfumarate inhibits CXCL10 via heme-
Teng MW, Vesely MD, Duret H, McLaughlin N, Towne immunodefi ciency syndrome. J Allergy Clin Immunol
oxygenase-1 in airway smooth muscle. Eur Respir
JE, Schreiber RD, Smyth MJ. Opposing roles for
IL-23 and IL-12 in maintaining occult cancer in an
equilibrium state. Cancer Res 2012; 72(16): 3987.
ASI Inc. Newsletter December 2012
Kerr JB, Hutt KJ, Cook M, Speed TP, Strasser A, Findlay in a mouse model of myeloproliferative disease driven
JK, Scott CL. Cisplatin-induced primordial follicle
O'Sullivan T, Saddawi-Konefka R, Vermi W, Koebel by enhanced wild-type Flt3 signaling. Blood 2012;
oocyte killing and loss of fertility are not prevented
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INTERNATIONAL JOURNAL OF ENVIRONMENTAL CHEMISTRY & CHROMATOGRAPHY VOL. 1 ISSUE 1, 2015; 8 – 14; http://ijeec.sbtjournals.com SBT JOURNALS RESEARCH ARTICLE rimidines, which are essential for DNA synthesis and cell multiplication. This leads to the failure of nuclear divi- sion. Several RP-HPLC4,5,6,9-12 , Spectrophotometric meth-ods1-3,7 & HPTLC Methods8 have been reported for simul-