03377 - Immunogenetics

Learning outcomes

At the end of the classes, the student shall have knowledge of the basic physiological mechanisms that regulate the functioning of the immune system as well as the capability to understand the different types of immune responses and their biological significance. In particular, the student: - will know about genetic strategies that allow the diversification of the immune responses to antigens; - will be able to understand the principle of the vaccine strategy; - will know about the main therapeutic strategies in which the immune system is involved: vaccines, use of monoclonal antibodies and immunosuppression in case of organ transplantation.

Course contents

• Introduction to Immunology. General features of the Immune Response (IR). Innate and acquired immunity. Cells and tissues of the Immune System. Lymphocytes, macrophages, granulocytes, dendritic cells. Haemogram with leucocyte populations count.
• Innate Immunity: general features. Components of the Innate Immunty: physical barriers, antimicrobial proteins, professional phagocytes, NK cells, gamma/delta lymphocytes. Mechanisms of phagocytosis and cytotoxicity NK. PAMPs, DAMPs and their recognition (by KIR receptors, Toll-like receptors, etc.).
• Antibodies: general features, structure and function of the different classes of antibodies (IgG, IgA, IgM, IgE and IgD); synthesis of monoclonal antibodies. Uses in diagnostics and clinic practice of monoclonal antibodies. Nomenclature CD. Immunophenotypization.
• Organization of genetic loci for the antibodies. Generation of antibodies repertoire: mechanisms of combinatorial differentiation (somatic recombination), junctional differentiation and for bases insertion.
• Lymphocytic activation and antibodies production. B-T cooperation. Distinction between thymus-dependent and thymus-dependent antigens. Isotypic shift; affinity increase and somatic hypermutation.
• Cell-mediated Immunity. T helper and Cytotoxic Lymphocytes. Th Subpopulations (Th1, Th2, Th17). Hints to Th functions (cytokine production, costimulation). Antigen presentation to T cell Receptor: MHC restriction. Biological significance of the restriction. Features of MHC molecules class I or II. Unusual MHC (HLA-E, G and DM). MHC in diagnostics: the tetramers.
• Organization of MHC genetic locus. Polymorphism of MHC genes. Genes for MHC I, II and III. HLA genotyping. Antigen presentation on MHC class I or II molecules. Antigen processing: intracellular antigens via proteasome and immunoproteasome; extracellular antigens via phagocytosis. Autophagy.
• Response to pathogens: bacteria, viruses, parasites. Humoral responses, functions of antibodies, primary and secondary responses. Hints to the complement system. Cell-mediated responses; DTH responses. Th1 or Th2 predominance. Escape mechanisms of pathogens.
• Cancer Immunology: immunological features of tumors. Cancer Antigens. Cancer Immunotherapy. Escape mechanisms from IR of tumors.
• Mechanisms of tolerance. Central Tolerance: negative and positive selection. Peripheral Tolerance: anergy, clonal deletion, suppressive cytokine production. T reg lymphocytes.
• Tolerance breakdown. Autoimmunity. Immunopathologiy: classification of hypersensitivities. Allergies: features and pathogeneic mechanisms; desensitising therapies towards allergens. Type II, III and IV hypersensitivities.
• Congenital and acquired immunodeficiencies. SCID and other immunodeficiencies of lymphocyte maturation. Innate immunity Immunodeficiencies. Acquired Immunodeficiencies due to immunosuppression, chemotherapy, malnutrition, viral infections. HIV virus and AIDS. Mechanisms of HIV infection. Cellular an molecular targets of HIV Bersagli cellulari e molecolari di HIV, replicative cycle of HIV. RIR to HIV infection.

Laboratory techniques in Immunology (immunohistochemistry, western blotting,flow cytometry, etc.)

Readings/Bibliography

Abbas-Lichtman-Pillai: Cellular and Molecular Immunology, sixth ed. or later. Elsevier-Masson ed.

Teaching methods

frontal lectures

Assessment methods

oral examination

Teaching tools

power point or pdf files

Office hours

See the website of Stefano Salvioli