2010-2011 academic year
Immunology (20420)
Qualification/course: bachelor's degree in Human Biology
Year: third
Term: second
Number of ECTS credits: 4 credits
Student commitment: 100 hours
Teaching language or languages: Spanish and Catalan
Teaching staff: Miguel López-Botet Arbona (UPF), José Aramburu Beltrán (UPF), Cristina López Rodríguez (UPF), Maria Buxadé (UPF)
1. Introduction to the subject
Immunology is a compulsory third year subject in the bachelor's degree in Medicine (UAB-UPF), with 4 ECTS credits, taught jointly with the bachelor's degree in Biology (UPF) during the second term of the third year.
2. Competences to be acquired
During the teaching in the subject, students should obtain the competences required by the educational authorities and stipulated in the degree syllabus, which can be summarised as follows:
• Understand the structure and function of the immune system. Be able to describe the main cellular and molecular factors involved in the various immune response processes in mammals.
• Be aware of the general principles governing interaction between the immune system and pathogens, transplant and tumours.
• Be aware of the basic principles of physiopathology of the main types of immune system alterations, and the appropriate diagnostic and therapeutic approaches.
• Learn the foundations of the various analytical applications of the antigen-antibody reaction and the use of basic techniques the immunology laboratory.
General learning objectives
The teaching project in the subject aims to:
• Provide students with knowledge of the physiology of the immune system and the main cellular and molecular components involved in immune and inflammatory responses.
• Enable students to understand the processes of defence against pathogens and parasites, and responses to to transplants and tumours.
• Provide students with the knowledge necessary for understanding the physiopathology of immunodeficiencies and chronic autoimmune and allergic inflammatory diseases.
• Instruct students on the principles of the main diagnostic, therapeutic and preventive applications of immunology.
Specific objectives
The specific objectives of each topic will be announced as the programme takes place during the academic year, by means of the virtual classroom. These will be the focus of assessment of the students's academic performance.
3. Contents
Lectures syllabus
Subject 1. Introduction: Basic concepts of the immune system
General concepts. Humoural and cellular immunity. Innate and adaptive immunity. Main cellular and molecular elements of the immune system. Pathogen-associated molecular patterns (PAMPs) pattern recognition receptors. Antigen receptors: clonal distribution. Organs and tissues of the immune system.
Subject 2. Introduction: basic concepts of immune and inflammatory responses
Phases of the immune response. Activation and memory of the immune system. Tolerance. Immunity and inflammation. Immune evasion mechanisms. Immunopathology. Immunotherapy. Study methodology. Historical perspective.
Subject 3. Immunoglobulins: structure and function
Structure of the immunoglobulin molecule (Ig). Ig isoptypes and subclasses. Allotypes and idiotypes. Configuration of the point of interaction with antigen. Physical-chemical and biological properties of the Igs. Effector functions: neutralisation, opsonisation, complement activation, antibody-dependent cellular cytotoxocity. Ig as B-lymphocyte antigen receptors. Ig secretion in mucus.
Subject 4. Immunoglobulins: genetics
Chromosome location and organisation of genes in heavy (H) and light (L) chains. Ig gene reordering mechanisms. Allelic exclusion. Ig diversity generation. Changes in Ig isotype synthesis. Somatic hypermutation. Transcriptional regulation of Ig genes and their expression. Ig superfamily molecules: general concepts.
Subject 5. Antigens
General concepts: antigen, immunogen, antigenic determinant (epitope), immunocomplex. Non-protein antigens. Haptens. Physical-chemical bases of Ig-antigen interaction. Cross reactivity. Interaction of antigens with T-cells and B-cells. Antigen processing and presentation. Adjuvants. Polyclonal activators.
Subject 6. The complement system (I)
General concepts. Structure and relationship of the components. Activation pathways: classic, alternative and lectin-dependent. Regulating factors.
Subject 7. The complement system (II)
Structure, tissue distribution and functions of the C factor receptors. Biological functions: cytolysis, opsonisation, elimination of immune complexes. Role in inflammation and regulation of the immune response. Interrelation with other plasmatic enzymatic systems.
Subject 8. Applications of immunoglobulins analytical techniques
Antigen-antibody reaction detection methods: general principles. Techniques based on immunocomplex precipitation. Agglutination. Complement fixation. Immunotransfer. Immunoprecipitation and affinity chromatography. Immunoselection. Radio immunoassay and enzyme immunoassay. Immunofluorescence and immunohistochemistry. Antiserums and monocolonal antibodies (AcM). Technology for obtaining AcMs. AcMs as reagents to identify and characterise leukocyte molecules (clusters of differentiation or CDs).
Subject 9. Major Histocompatibility Complex or MHC): structure and genetics
Basic concepts and terminology. Human MHC: the HLA system. Classification of components of MHC. Structure of class I and II MHC molecules. Genomic organisation. Other MHC molecules. Tissue distribution and regulation of class I and II molecule expression. Genetics of MHC: allelic polymorphism; haplotypes and linkage disequilibrium. Involvement of MHCs in the rejection of homografts (allografts). Methods for studying the HLA system and practical applications. HLA-disease association.
Subject 10. Major histocompatibility complex (MHC): functions
Antigen processing and presentation. Presentation of cytosolic endocytosed/phagocytised antigens by MHC class II molecules. Presentation of cytosolic antigens class I by MHC molecules. Cross-presentation Presentation of non-protein antigens.
Subject 11. Cellular and molecular elements of the innate immune response (I)
Phagocytic cells: polymorphonucleated and macrophages. Main phenotype and functional properties. Phagocytosis mechanism and phases. Chemotaxis. Involvement of Ig and C-factors: surface receptors involved. Other surface receptors in myelomonocytic cells. Dendritic cells: types and functions.
Subject 12. Cellular and molecular elements of the innate immune response (II)
Pathogen-associated molecular patterns (PAMPs) pattern recognition receptors. Toll-like receptors as a paradigm. Other PAMPs receptors. Signal transduction mechanisms. Interrelation of innate and adaptive responses.
Subject 13. Natural cytotoxic cells (NKs)
NK (natural killer) cells: phenotypical and functional characteristics. Physiological role. Regulation of NK cell activity by interaction with MHC class I molecules: receptors involved. Other NK receptors. Transmission of inhibitor and activator signals by NK receptors. Leukocyte receptors with an inhibitory function.
Subject 14. T (I) lymphocytes
Biochemical structure of antigen receptors (TcR). Molecular genetics of antigen receptors. Structural organisation, chromosome location and somatic recombination mechanisms (gene reordering). TCR diversity generation mechanisms. TcR complex coupling.
Subject 15. T (II) lymphocytes
Restriction of antigen recognition by MHCs. Alloantigen response. Superantigens and non-protein antigens. T-lymphocyte activation mechanisms. Subpopulations of T-lymphocytes and their functional specialisation. Markers. T-cell differentiation: states of maturation. TcR positive and negative repertoire selection. Memory T cells.
Subject 16. B lymphocytes
B cell cytological characteristics and markers. Igs as part of the B-lymphocyte receptor (BcR). BcR complex coupling. B cell subpopulations. B cell activation. T-lymphocyte-independent and -dependent responses. Regulation of Ig proliferation and secretion. B cell differentiation: states of maturation. BcR repertoire selection.
Subject 17. Lymphocyte activation mechanisms
Metabolic pathways involved in signal transduction by antigen receptors (TcR and BcR) and auxiliary molecules. Transcriptional regulator factor activation. Regulation of proliferation (clonal expansion) of lymphocytes. Targets for immunosuppressant drugs.
Subject 18. Mechanisms affecting the immune response: cellular cytotoxicity and cytokines (I)
Types of cytotoxic cells. Phases in the process. Characteristics of granulosomes. Molecular elements involved: perforin and granzymes. Apoptosis as a cytotoxic mechanisms. General properties of cytokines. Cytokines involved in natural immunity and the inflammatory response. Chemokines.
Subject 19. Mechanisms affecting the immune response: cellular cytotoxicity and cytokines (II)
Cytokines involved in the regulation of the specific immune response. Cytokines regulating hematopoiesis. Molecular characteristics, receptors and signalling mechanisms. Main biological effects. New therapies with cytokines and antagonists.
Subject 20. Leukocytosis traffic during immune and inflammatory responses
Functional organisation of the immune system organs and tissues. Interaction of the leukocytes with the endothelium and the extracellular matrix. Regulation of transendothelial migration: adhesion and chemotaxis. Molecules involved (selectins, integrins, cytokines, chemokines, etc.). Role in the formation of inflammatory infiltrates and the location of lymphocytes in tissues.
Subject 21. Regulation of the immune response
Central and peripheral tolerance mechanisms. Anergy and clonal deletion. Apoptosis. Bases for the immune system memory. Helper T lymphocytes. Cytokines.
Subject 22. Immune response to microbial pathogens and parasites
Paradigms in the host-pathogen relationship. Extra- and intracellular pathogens. Opportunist infections. Acute and chronic infection. Persistent infections: latency. Immune evasion mechanisms.
Subject 23. Vaccination
Historical background. General principles of vaccination. Types of vaccines. Impact on infectious pathology. Strategies and limitations in the design of new vaccines.
Subject 24. Immunodeficiencies
Classification of immunodeficiencies. Paradigm of the various types of primary immunodeficiencies. Diagnostic criteria and therapeutic principles. Autoinflammatory syndromes.
Subject 25. Basic mechanisms in immunopathology: hypersensitivity reactions (II)
Gell-Coombs classification. Immediate hypersensitivity (type I). Cellular elements and main participating molecular mediators. Biological effects. Physiological role in defence against pathogens. Clinical expression of immediate hypersensitivity. Concepts of anaphylaxis, allergy and atopy.
Subject 26. Basic mechanisms in immunopathology: hypersensitivity reactions (II) IgE-and immune complex-mediated reactions (type II and III). Secondary reactions to the agonist or antagonist action of surface receptor-specific antibodies. T cell-mediated hypersensitivity (type IV).
Seminars
Four seminars will be organised (2 hours, 30 students per group) with complementary content to the lectures, which will also be subject to final assessment. The appropriate material for preparing the seminar (articles, script...) will be distributed in advance in each case. The lecturer will focus the subject in the first part, and the most relevant points based on the established script will subsequently be debated.
Seminar 1. Immune response in transplants
Immunology of solid organ transplants. Renal transplant as a paradigm. Mechanisms and types of rejection. Importance of histocompatibility antigens. Therapeutic control and prophylaxis of transplant complications. Transplantation of hematopoietic progenitors. Varieties. Rejection mechanisms. Physiopathology of graft reaction against the host.
Seminar 2. Autoimmunity
Basic concepts. Autoimmunity induction mechanisms. Experimental hypotheses and models. Genetics and autoimmunity. Other etiological factors. Lesion mechanisms in autoimmune pathology. Diagnostic and therapeutic principles.
Seminar 3. Immune response, inflammation and cancer. Antitumour immunotherapy
Historical development. Experimental models. Types of tumour antigens. Application as markers. Response to tumours. Tumour immune evasion mechanisms. Immune deficiency and cancer: immunosuppression and autoimmune paraneoplastic syndromes. Inflammation and cancer. Antitumour immunotherapy: monocolonal antibodies, cell therapy and vaccination. Clinical results. Limitations.
Seminar 4. New biological therapies with immunoglobulins and derivatives
Generation of monocolonal antibodies and others Ig derivatives for therapeutic use. Action mechanisms. Applications in the treatment of inflammatory diseases and cancer. Clinical results: limitations and secondary effects.
Practical syllabus
The programme will take place over five consecutive sessions (3 hours, 15 students per group) with the following content:
Practical session 1. Agglutination and complement fixation
Practical session 2. Enzyme immunoassay (EIA)
Practical session 3. Leukocyte separation techniques
Practical session 4. Analysis of lymphocyte markers for immunofluorescence with monocolonal antibodies (AcM)
Practical session 5. Flow cytometry applications for analysis of leukocyte subpopulations. Data analysis and interpretation.
4. Assessment
a) Assessment methods. Assessment will be carried out by multiple choice tests (MCT), essay tests, short questions and practical problems in the classroom.
b) Type and number of evaluations. Impact on the final mark
A partial accreditative assessment (in MCT format) will take place during the course, covering all the theoretical content taught up to that point. There will also be continuous evaluation of the contents of the practical sessions and the seminars (short questions).
The final accreditative assessment of the theoretical content will include questions on all the topics in the lectures and seminars (in MCT, essay and short question format). There will also be a multiple choice test on the planned objectives in the practical sessions in the format of practical problems in the classroom.
The impact on the final mark will be as follows:
- partial accreditative (15%)
- continuous in practical sessions and/or seminars (15%)
- Final accreditation, MCT (30%)
- Final accreditation, essay and short questions (30%)
- Final accreditation, practical session (10%)
c) Criteria for passing the subject and qualitative notes
Student must obtain a mark of 5 points or higher to pass the subject. A grade of good requires at least 7 points and an excellent grade requires 9.
5. Bibliography and teaching resources
5.1. Basic bibliography
Available in the Library
• Cellular and molecular immunology / Abul K. Abbas, Andrew H. Lichtman, Shiv Pillai Philadelphia: Saunders Elsevier, cop. 2007 6th ed.
• Immunology / Thomas J. Kindt, Richard A. Goldsby, Barbara A. Osborne New York: W.H. Freeman, cop. 2007 6th ed.
Translations into Spanish
• Inmunología celular y molecular / Abul K. Abbas, Andrew H. Lichtman, Shiv Pillai Barcelona: Elsevier, cop. 2008. 6th ed.
• Inmunología de Kuby / Thomas J. Kindt, Richard A. Goldsby, Barbara A. Osborne Mexico: McGraw-Hill, cop. 2007
6. Methodology
Lectures
They will be taught to the students on the Medicine and Biology courses at the same time, and materials will be provided in advance (presentations).
Seminars
Four seminars will be organised (2 hours, 30 students per group) with complementary content to the lectures, which will also be subject to assessment. In each case, the appropriate material for preparing for the seminar (presentations, articles and script) will be distributed in advance. The lecturer will provide a conceptual focus for the subject, and the most relevant points will subsequently be debated according to the established script. Students should have some basic knowledge to take maximum advantage of the seminars. The programming will be concentrated at the end of the term.
Practical programme
The programme is designed so that students personally use some of the basic techniques of immunology in the laboratory, beginning with the critical interpretation of results and laying the foundations bases for problem solving. It will take place over five consecutive sessions (3 hours, 15 students per group).
7. Programme of activities
Students will be informed in due course.