Module Code: Module Title: IMM III Autoimmunity and Principles of Transplantation Immunology Module Convenors: Emeritus Professor Jennifer Rolland and Dr Karla Lemmert Discipline: Professor Allan Cripps Committee: Dr Karla Lemmert Emeritus Professor Jennifer Rolland Date Module Outline reviewed: November 17, 2006 Date Module Outline modified: May 5, 2007 Date Module Outline modified: May 17, 2011 Date Module Outline modified: December 3, 2013 Page 1
A. Objectives This Module is designed to provide the candidate with a sound knowledge of the immunological basis of autoimmunity and allograft rejection and the diagnostic procedures for the diagnosis of autoantibodies and for tissue typing. For candidates undertaking the Immunology Fellowship Program it is necessary to successfully complete Module I Principles of Human Immunology. For candidates from other programs taking this module as an elective it is essential that they familiarise themselves with the content of Module I and undertake additional study on Immune Tolerance and Histocompatibility Antigens. B. Interrelationship of the Module to Other Modules This Module builds on the basic knowledge gained in Module IMM I and develops an understanding of alterations in the normal immunological state which predispose to disease states. This Module is the second component of the Diagnostic Modules: C. Brief Description Module IMM II Human Immunodeficiency Disorders & Lymphoid Neoplasias Module IMM III Autoimmunity and Principles of Transplantation Immunology Module IMM IV Infectious Disease and Tumor Immunology This Module covers immune mechanisms associated with autoimmune disease and allograft rejection. The Module emphasizes the diagnostic methods used to detect autoantibodies and assay procedures for tissue typing. The interpretation of results, limitations of the assays and quality assurance systems is also a requirement. D. Content 1. Immune Tolerance and Apoptosis The concept of central and peripheral tolerance T cell tolerance AIRE transcription factor and self antigen expression in the thymus B cell tolerance Oral tolerance Apoptosis Functional tolerance Mechanisms for maintaining self tolerance Objective: This section requires an understanding of the detailed immunological concepts involved in tolerance and apoptosis. Candidates should build on their knowledge gained in Module I (Principles of Human Immunology). 2. The Histocompatibility Complex Candidates should revise section 2.1 from Module I (The Principles of Human Immunology) prior to commencing section 3 or 5.1 of this Module. 3. Immune Mechanisms of Autoimmunity and Autoimmune Disease What is autoimmunity? Factors [breakdown of functional T cell anergy, genetics, infection, exposure to normally hidden antigens, new epitopes] which give rise to autoimmune disorders Page 2
. Mechanisms of tissue damage in autoimmunity o Type 1 hypersensitivity o Type 2 hypersensitivity o Type 3 hypersensitivity o Type 4 hypersensitivity The immunological dysfunction and tissue specificity/target autoantigen/s of the following autoimmune disorders: o Ankylosing spondylitis o Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis o Antiphospholipid syndrome o Autoimmune anaemia o Autoimmune hepatitis o Coeliac disease o Goodpasture s syndrome o Graves disease o Hashimoto s thyroiditis o Idiopathic thrombocytopenia purpura o Inflammatory bowel disease (Crohn s disease and ulcerative colitis) o Insulin-dependent diabetes mellitus o Multiple sclerosis o Myasthenia gravis o Pemphigius vulgaris o Pernicious anemia o Rheumatoid arthritis o Scleroderma o Sjogren s syndrome o Systemic lupus erythematosus Objective: To understand what autoimmunity is and the mechanisms/factors which can result in the breakdown of self tolerance leading to autoimmune disease. Candidates are expected to have a sound understanding of the laboratory diagnosis of autoimmune disorders. In addition, they should have basic knowledge of the general clinical features and genetic associations of the disorders listed above. 4. Laboratory diagnosis of autoimmune disease Knowledge of the laboratory procedures and their diagnostic specificity and sensitivity for the autoimmune disorders given in 3 (above) is expected. Candidates will need to be able to clearly articulate an understanding of issues relating to standardisation and quality control/assurance for each of the diagnostic technologies, for example immunofluorescence, enzyme linked immunoassay, radioimmunoassay, agglutination and so on. Objective: To develop a theoretical basis around the procedures, technology, quality assurance and limitations of laboratory diagnostics for detecting autoimmunity in patients. 5. Transplantation Immunology 5.1 Common organs and tissues transplanted 5.2 Targets for allograft rejection ABO blood group antigens Major histocompatibility antigens (HLA structure and polymorphisms) Page 3
The nature and role of minor histocompatability antigens in allograft rejection 5.3 Immune mechanisms of allograft rejection Hyperacute, acute and chronic rejection The role of T lymphocytes, antibodies and cytokines in allograft rejection 5.4 Graft-versus-host (GVH) disease in recipients who receive allogenic bone marrow transplants 5.5 Pregnancy as a privileged graft Objective: To understand the immunological basis of allograft recognition and rejection. 6. Laboratory procedures for tissue typing for allograft transplantation and monitoring transplant rejection Serological typing of major histocompatibility antigens (MHC) Molecular MHC typing T cell activation assays o Proliferation assay (mixed lymphocyte culture [MLC]) o Elispot assay to determine cytokine responses o Limiting dilution assays (LDA) to determine the frequency of T cell precursors o Assays for typing of minor histocompatibility antigens Testing for preformed HLA antibodies Objective: To develop a theoretical basis for the procedures, technology, quality assurance and limitations of tissue typing procedures for transplantation. E. Rationale for Content The diagnostic laboratory plays a key role in the detection and monitoring of autoimmune disorders. The laboratory findings are often critical in the differential diagnosis between disorders. An understanding of the immunological mechanisms underpinning disease, as well as the application of diagnostic technology and its limitations is crucial in the clinical setting. Successful transplantation is dependent on the best possible tissue match despite major advances in chemotherapy to prevent graft rejection. It is the role of the tissue typing laboratory to undertake and interpret the results of the various assays currently available for typing. It is essential that the laboratory scientist has expert knowledge of the immunological basis of allograft rejection, a theoretical understanding of the basis of the tests conducted in the laboratory, including their limitations and quality assurance requirements in addition to technical competencies. F. Examination Under the Fellowship Regulations, a 3-hour written examination will be held at the completion of each Module. Each examination will contain a mixture of short answer questions and essay style questions. In some examinations, clinical and laboratory management case based scenarios will be include in the question mix. Examination for this Module will focus on an overall understanding of the immunological basis for the autoimmunity and transplantation, the clinical presentation and diagnosis of each disorder and the respective diagnostic tests and quality assurance for diagnosing and monitoring therapies. Page 4
Questions will be evenly divided across the 2 topic themes: Autoimmune Disorders Transplantation Immunology The examination will consist of: Two essay questions, each with a total value of 35 marks; suggested time allocation 30 minutes per essay total 60 minutes. Twenty short answer questions, each worth five marks total value for the short answer questions 100 marks; suggested time allocation five minutes per question total 100 minutes. Twenty minutes for re-reading and review. There will be an initial reading time of fifteen minutes, during which no writing will be permitted. G. Texts and Supporting Material The following texts all provide an excellent resource for this module. It is suggested that you glance through the texts and select one that appeals to you and you purchase that text. You should, from time to time, consult the other texts in the library to broaden your reading. 1. Abbas A and Lichtman A, editors Basic Immunology: Functions and Disorders of the Immune System (3 rd edn) Philadelphia, Elsevier Inc, 2010 ISBN: 9781416055693 2. Coico R and Sunshine G Immunology: A Short Course. (5 th edn) New Jersey, John Wiley & Sons, 2009 ISBN: 9780470081587 3. Longo D, Fauci A, Kasper D, Hauser S, Jameson J and Loscalzo J, editors Harrison s Principles of Internal Medicine (18 th edn) New York, McGraw-Hill, 20 ISBN: 9780071 4. Mak T, Saunders M, editors The Immune Response: Basic and Clinical Principles London, Elsevier Inc, 2006 ISBN: 9780120884513 5. Male D, Brostoff J, Roth D and Roitt I Immunology (8 th Edn) Saunders, 2012 ISBN: 9780323080583 6. Detrick B, Hamilton RG, Folds JD, editors Manual of Molecular and Clinical Laboratory Immunology (7 th Edn) ASM Press Washington, 2006 ISBN: 155581364 7. Keogan MT, Wallace EM, O Leary P Page 5
Concise Clinical Immunology for Healthcare Professionals Routledge Press, 2006 ISBN: 9780415298292 8. Kindt TJ, Goldsby RA, Osborne BA Kuby Immunology (6 th Edn) WH Freeman and Company, 2007 ISBN: 1429202114 H. Appointment of a Mentor Each candidate is required to nominate a mentor for the Module at the time of application for entry and into the Fellowship Program. If a candidate is unable to nominate a mentor then the candidate should contact the Module Convenor for assistance. The appointment of a mentor is made by the Examinations Council. I. Module Communications Module Convenors: Emeritus Professor Jennifer Rolland Department of Immunology Monash University Level 2, Monash University Building, AMREP Melbourne VIC 3004 Phone +61 3 9903 0480 email: jennifer.rolland@monash.edu Dr Karla Lemmert Hunter Area Pathology Service Immunology Department Locked Bag #1 Hunter Region Mail Centre, NSW 2310 Phone +61 2 4921 4022 Email: karla.lemmert@hnehealth.nsw.gov.au Discipline Committee: Professor Allan Cripps Dr Karla Lemmert Emeritus Professor Jennifer Rolland J. Candidate Feedback Immediately following notification of the examination result each candidate will be asked to complete a feedback questionnaire on the Module. However, feedback at anytime during the study of the Module is encouraged through the mentor or directly to the Module Convenor. Page 6