Inflammation and Immunity Research Unit

Publications

Diagnostic services

During the past year we have continued with our programme of automation and expansion of the repertoire of serodiagnostic services offered to our clients, especially serodiagnosis of auto immune diseases.  This has proved to be a particularly successful initiative, which has resulted in significant improvements in turnaround times and increased referrals from other regions.  Other service-rendering activities which have been improved through introduction of new technologies and/or expansion of the range of services offered include tissue typing and immunophenotyping of leukaemias.

Research programmes

The major research programmes of the Department of Immunology progressed extremely well during the past year.  These are infectious diseases research and research focused on the immunopathogenesis and therapy of acute and chronic inflammatory diseases of non-infective origin.

• Infectious diseases research: Tuberculosis, HIV/AIDS, and severe pneumococcal disease are the major research focus areas.  Tuberculosis research is focussed on the potassium (K+) transporters of Mycobacterium tuberculosis (MTB), especially their role in bacterial virulence, and potential to serve as novel targets for drugs/vaccines.  The primary objective of HIV/AIDS research is to establish the effects of HIV infection on regional T-lymphocyte colonization and macrophage activation in the gastrointestinal tract, as well as the effects of antiretroviral therapy on reconstitution of various sub-populations of T-lymphocytes, macrophage activation status, and privileged viral reservoirs, especially in relation to anatomical site and drug resistance.  Novel insights into HIV immunopathogenesis of this type are essential for discerning approaches to drug and vaccine design.  Pneumococcal diseases research continues to focus on pneumolysin, the major protein virulence factor of this microbial pathogen, by using strategies which target the production and/or cytotoxic and pro-inflammatory activities of the toxin.

• Inflammatory diseases of non-infective origin: In the case of acute/chronic inflammatory diseases of non-infective origin, our efforts are targeted primarily at identifying the mechanisms which initiate mobilisation of calcium during receptor-mediated activation of inflammatory cells, particularly the neutrophil, as well as those which restore Ca2+ homeostasis to the cells.  This research has identified several novel Ca2+-handling-based targets for anti-inflammatory therapy.  The second component in this research programme involves identification of the mechanisms by which heavy metals of environmental/industrial significance (cobalt, manganese, palladium, platinum, palladium) trigger and /or potentate harmful inflammatory responses.

Teaching and training

Undergraduate

The Department of Immunology provides teaching/training in basic/applied immunology to students medical technicians/technologists, undergraduate medical and dental students, as well as to students enrolled in various BSc courses.

Postgraduate

Training is offered at the BSc Hons, MSc and PhD levels, while Registrars/Clinical Assistants from other departments (Medical Microbiology/Virology, Haematology), as well as Clinical Pathology Registrars, rotate through the department’s research and service laboratories. It is also the policy of the department to provide access to both equipment and supervision to researchers from other departments and academic institutions.

Honours bestowed on staff members

• Prof S Cassol was awarded a substantial European Union research grant for HIV-1 drug resistance surveillance.
• Following intensive external review, the MRC Unit for Inflammation with Prof R. Anderson director was granted a fifth and final 5 year cycle commencing on 1 May 2009.

Research Outputs

*=Invited contribution

• Feldman C, Anderson R.  Therapy for pneumococcal bacteremia: monotherapy or combination therapy.  Current opinion in Infectious Diseases 2009; 22:137-142.
• Venter M, Burt FJ, Blumberg L, Fickl H, Paweska J, Swanepoel R.  Cytokine induction after laboratory-acquired West Nile Virus infection.  New England Journal of Medicine 2009; 360:1260-1262 (letter).
•    Cholo MC, Van Rensburg EJ, Anderson R.  Potassium-uptake systems of Mycobacterium tuberculosis: genomic and protein organization and potential roles in microbial pathogenesis and chemotherapy.  South African Journal of Epidemiology and Infection 2009: Vol 13-16.
• *Feldman C, Anderson R.  New insights into pneumococcal disease.  Respirology 2009: 14:167-179.
• Anderson R, Theron AJ, Gravett CM, Steel HC, Tintinger GR, Feldman C.  Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism.  British Journal of Pharamacology 2009; 156: 105-115.
• Theron AJ, Gravett CM, Steel HC, Tintinger GR, Feldman C, Anderson R. Leukotrienes C4 and D4 sensitize human neutrophils for hyperreactivity to chemoattractants. Inflammation Research 2009; 57: 1-6.
• Mabeta P, Pepper MS.  A comparative study on the anti-angiogenic effects of DNA-damaging and cytoskeletal-disrupting agents.  Angiogenesis 2009; DOI 10.1007/s10456-009-9134-8.
• Pathak AP, Hochfeld WE, Goodman SL, Pepper MS. Circulating and imaging markers for angiogenesis. Angiogenesis 2008; 11: 321-335.
• Steel HC, Tintinger GR, Anderson R.  Comparison of the anti-inflammatory activities of imidazole anti-mycotics in relation to molecular structure.  Chemical Biology and Drug Design 2008; 72: 225-228.
• Boy SJ, Van Heerden MB, Wolfaardt M, Cockeran R, Gema E, Van Heerden WF.  An investigation of the role of oral epithelial cells and Langerhans cells as possible HIV viral reservoirs.  Journal of Oral Pathology and Medicine 2008; 38: 114-119.
• Smit E, Pretorius E, Anderson R, Oommen J, Potjo M.  Differentiation of human monocytes in vitro following exposure to Canova in the absence of cytokines.  Ultrastructural Pathology 2008; 32: 147-152.
• *Tintinger GR, Steel HC, Theron AJ, Anderson R.  Pharmacological control of neutrophil-mediated inflammation: strategies targeting calcium handling by activated polymorphonuclear leukocytes.  Drug Design, Development and Therapy 2008; 2: 95-104.
• Lourens NA, Bosenberg LH, Tintinger GR, Ker JA, Fickl H, Sharp C, Van Zyl M, Anderson R.  Soluble triggering receptor expressed on myeloid cells in patients with suspected meningitis, peritonitis, or pleuritis. Infectious Diseases in Clinical Practice 2008; 16: 157-162.
• Olivier BJ, Schoenmaker T, Mebius R, Everts V, Mulder CJ, Van Nieuwkerk KM, De Vries TJ, Van der Merwe SW.  Increased osteoclast formation and activity by peripheral blood mononuclear cells in chronic liver disease patients with osteopenia.  Hepatology 2008; 47: 259-267.
• Schlaudraff KU, Bezzola T, Montandon D, Pepper MS, Pittet B.  Mixed arterio-venous insufficiency in random skin flaps in the rat: Is the application of medicinal leeches beneficial?  Journal of Surgical Research 2008; 150: 85-91.
• Beck IA, Crowell C, Kittoe S, Cassol S, et al.  Optimization of the oligonucleotide ligation assay, a rapid and inexpensive test for detection of HIV-1 drug resistance mutations for non-North American variants.  Journal of the Acquired Immunodeficiency Syndrome 2008; 48: 418-427.
• Mosam A, Hurkchand HP, Cassol E, Page T, Cassol S, et al.  Characteristics of HIV-associated Kaposi’s sarcoma among women and men in South Africa.  Journal of STD and AIDS 2008; 19: 400-405.

Book Chapter
Richards GA, Anderson R.  Whole blood chemiluminescence in the measurement of the proinflammatory effects of cigarette smoke and the response to administration of nutrient antioxidants.  In: Handbook of chemiluminescent methods, Eds: I Popov, G Lewin, Transworld Research Network, kerala, India (ISBN:978-81-7895-334-2) 2009, pp1-24.

Peer-reviewed published conference abstracts
 1.  Anderson R, Theron AJ, Gravett C M, Steel HC, Tintinger GR, Feldman C.      Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism.  American Journal of Respiratory and Critical Care Medicine 2008; 177:A2711 (presented at the American Thoracic Society Congress, Toronto, Canada, May 2008).

*2. Hodkinson B, Meyer P, Ally M, Musenge E, Wadee A, Anderson R, Tikly M.  Anti-CCP antibodies in early rheumatoid arthritis in South Africa.  European League Against Rheumatism (EULAR) Congress, Paris, France, 11-14 June 2008.

*3. Hodkinson B, Meyer P, Ally M, Musenge E, Wadee A, Anderson R, Tikly M.  A prospective study of early rheumatoid arthritis in South Africa: Response to traditional DMARDS in an improvershed setting EULAR Congress, Paris, France, 11-14 June 2008.

*4. Hodkinson B, Meyer P, Ally M, Musenge E, Wadee A, Anderson R, Tikly M.  Mutated citrullinated vimentin antibodies in early rheumatoid arthritis.  EULAR Congress, Paris, France, 11-14 June 2008.

*All 3 abstracts were published in the Annals of Rheumatic Diseases, Eular Issue, 2008: AB0197, FR10052, THU0198.

Invited plenary/keynote conference lecture
Cassol S. “Virus molecular research in developing countries,” 14th International Workshop on Virus Evolution and Molecular Epidemiology, Cape Town, South Africa, 31 August-5 September, 2008.

Invited congress presentation
Cholo MC, “What prevents clofazimine from being a good TB drug” South African TB Conference, Durban, South Africa, 2-4 July 2008.

Conference presentations/posters
Anderson R, Theron AJ, Gravett CM, Steel HC, Tintinger GR.  “Montelukast in hibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism,” Combined Congress of the South African Thoracic and Critical Care Societies, Cape Town, South Africa, August 208.  NB This oral presentation was awarded the prize for the best overall presentation at this congress.

Dissertation (MSc)
Stivaktas P. “Comparison of cyclosporine A, ionizing radiation and mitomycin C as inactivators of stimulator cells in the one-way mixed lymphocyte reaction.”  Degree awarded by the University of Pretoria in November 2008.

Professional Development
The following training courses were presented in the Department of Immunology/MRC Unit during 2008.  Most involved training by overseas experts, and most were open to interested parties from other academic institutions:

• NucliSENS HIV-1 Viral load
• TruGENE HIV-1 Drug Resistance Phenotype
• Luminex suspension bead array technology for tissue typing applications organised by Tepnel Life Science and One Lambda
• Cytochrome P450 genotyping using microarray gene chip technology (Affymetrix).  This involved 2x2 day training sessions, as well as 1 day on the theory of research and diagnostic applications

Mr G Malherbe spent 2 weeks at the Children’s Hospital and Research Institute, University of Washington, Seattle, USA, training in the oligonucleotide ligation assay (OLA) for the detection and quantification of HIV-1 drug resistance mutations.  In addition several members of the department attended PLG/CD4 training courses offered by the NHLS.