COURSE: BASIC IMMUNOLOGY Subject 1: Introduction to Immunology: Innate and acquired immunity; Cells and organs in the immune system Lecturer: Prof. Yona Keisari Type of presentation: Lecture Duration: 2 hours Summary: A. Protective mechanisms a. Innate Immunity b. Adaptive Immunity B. Functions of the immunocompetent system Immunology as an independent discipline dealing with specific reactions initiated by a highly specialized system of cells and organs. a. Protection against pathogens and toxic agents b. Preservation of normal structures in the body: removal of damaged cells c. Wound healing d. Pathological function of the immunocompetent system C. Cells tissues and organs of the Immune systaem. a. Innate immunity and inflammatory cells: Phgocytes, NK cells. b. Cells of the adaptive immune response: lymphocytes and antigen presenting cells c. Central lymphoid organs: Bone marrow; thymus d. Peripheral lymphoid organs: Lymph nodes, spleen, mucosa associated lymphoid tissue. e. Circulation of lymphoid cells: The lymphatic system Literature: Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch. 1, pp. 1-22; ch. 2, pp. 23-51. 1 Subject 2: Innate immunity Lecturer: Dr. Gal Markel Type of Presentation: Lecture Duration: 3 hours Summary: A. Definition of Innate Immunity B. Pathogen associated molecular patterns (PAMP) C. Pattern regognition receptors (PRR) D. Cells of the innate immune response E. Relations between Innate and Adaptive Imunity I. Pattern Recognition receptors a. mannose receptor b. receptor for manose-binding protein d. scavenger receptors c. receptors for chemotactic factors (formylated peptides, chemokines, leukotriene B4) II. Toll-like receptors (TLRs): a. structure of TLRs b. classification of TLRs c. ligands for TLRs d. TLR dimerization e. responses to TLR stimulation and signal transduction from TLRs f. TLR4 and endotoxic shock Literature: Kuby, Immunology (6th ed., 2007) Goldsby, Kindt and Osborne, eds. Freedman & Co. ch 3, pp. 52-75. 2 Subject 3: Innate Immunity: Phagocyte migration; Intracellular killing mechanisms; Inflammation Lecturer: Dr. Gal Markel Type of Presentation: Lecture Duration: 3 hours Summary: A. Origin of Phagocytes: a. Bone marrow origin and differentiation of neutrophils and macrophages b. Functional and biochemical changes in the course of differentiation c. Colony stimulating factors (CSFs) B. Cell Biology of phagocytic cells (neutrophils, macrophages, eosinophils): a. Neutrophils 1. Neutrophil granules – Heterogeneity 2. Degranulation 3. Granules “pathology” b. Eosinophils and their granules c. Monocytes and macrophages 1. Distribution within the host 2. Recruitment to tissues 3. Receptors and membranal molecules 4. The secretory products of macrophages C. Inflammation: Acute and chronic inflammation a. Initiation of inflammation b. Cell migration and Chemotaxis 1. Adherence and activation 2. Diapedesis 3. Chemotaxis: chemotactic factors and chemokines c. Phagocytosis; Receptors and mechanisms. 1. Structure and function of macrophage receptors 2. Lysosomes, phagocytic vacuoles, fusion d. Killing of microbial agents. 1. Oxidative killing of pathogens 2. Non-oxidative killing mechanisms D. Phagocyte disorders. Literature: 1. Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. Ch 2, 23-30, 35-40. Ch. 3, ch. 13, pp. 327-343. 3 Subject 4: Regulation of the Innate Immune response: Cytokines, Arachidonic acid metabolites. Lecturer: Dr. Gal Merkel Type of Presentation: Lecture Duration: 3 hours Summary: A. The concept of cytokines B. General properties of cytokines: a. Common functional properties b. Common systemic activities c. Common cell sources and cascading events d. Common receptor molecules C. Functional categories of cytokines: a. Cytokines that regulate immune responses b. Cytokines that facilitate innate immune responses and activate inflammatory responses c. Chemokines: Cytokines that affect leukocyte movement d. Cytokines that stimulate hematopoiesis D. Cytokine receptors: a. Cytokine receptor families b. Common γ Chain E. Regulation of inflammation by cytokines a. Proinflammatory cytokines:IL-1, IL-6, TNF-alpha. b. Antiinflammatory cytokines: IL-10, TGF-beta. c. Acute phase response. d. Fever. e. Hemopoiesis. F. Role of cytokines and cytokine receptors in diseases: a. Toxic shock syndrome b. Bacterial septic shock G. Arachidonic acid metabolites: Prostaglandins, Leukotriens, Thromboxane Literature: 1. Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch.12, pp. 302-326. Ch. 13, 338-346. 4 Subject 5: Adaptive Immune response. Cells and organs of the Adaptive immune response Lecturer: Dr. Michal Besser Type of presentation: Lecture Duration: 2 hours Summary: A. Introduction to Adaptive Immunity: B cells and T cells B. Lymphoid cells: B and T cell biology and development 1. T-Cell Differentiation and Maturation a. T helper cells (Th), T cytotoxic cells (Tc): Differentiation in the thymus b. Thymic selection of T-cell repertoire c. Mature T-cell populations 2. Lymphocyte receptors and accesory molecules. a. B cell and T cell antigen receptors. b. CD molecules. c. Major histocompatibility molecules (MHC) Literature: 1. Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch. 9, pp. 223-228, 235-241; ch.10, pp. 245-254. 5 Subject 6: The Adaptive Immune response. Antigen proccessing and presentation: Cells, receptors and signaling molecules Lecturer: Dr. Michal Besser Type of presentation: Lecture Duration: 3 hours Summary: A. Antigen presenting cells a. Mononuclear phagocytes: macrophages, dendritic cells b. B lymphocytes B. Antigen processing a. Membranal molecules and receptors b. Intracellular components and organelles C. Antigen presentation a. Role of MHC class 1 and 2 in antigen presentation b. Costimulatory molecules c. Adhesion molecules d. Role of Toll Like Receptors (TLR) D. Recognition: Recognition of antigenic determinants by: a. T helper lymphocytes b. T cytotoxic lymphocytes c. B lymphocytes Literature: 1. Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. Ch. 8, pp. 206-222; Ch. 9, pp. 235-241; Ch. 10, pp. 254-268. 6 Subject 7. Regulation of the adaptive Immune response: Role of Cytokines and T regulatory cells. Lecturer: Prof. Yona Keisari Type of presentation: Lecture. Duration: 2 hours Siummary: A. Definitions a. Cytokines, interleukins, chemokines, T helper cells, T regulatory cells. B. General properties of cytokines a. Regulatory cytokines b. Hematopoietic growth factors c. Chemokines. C. Structure and function of cytokines 1. Source of cytokines:T helper 1 and T helper 2. 2. Cytokine receptors D. Regulation of the adaptive immune response 1. Humoral Immunity 2. T cytotoxic cells. 3. Delayed type hypersensititvity 4. T regulatory cells Literature: 1. Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. Ch. 11, pp. 285-287; Ch. 12, pp. 302-326; Ch. 15, 393-400. 7 Subject 8: Structure and function of immunoglobulins (Ig) Lecturer: Dr. Ariel Munitz Type of Presentation: Lecture Duration: 4 hours Summary: A. Introduction 1. B cells, antibodies and receptors B. Antibody structure 1. Heavy and light chains 2. 3D structure 3. Enzymatic treatments C. Antibody subclasses 1. Overview 2. Structure 3. Effector functions D. Antibody: antigen interactions 1. Affinity vs. Avidity E. Fc Receptors 1. Fc Receptor types 1.1 Expression 1.2 Function 2. Ig-superfamily receptors 2.1 Expression 2.2 Function F. Humoral response G. Antibodies in clinical use 1. Introduction 2. Antibodies in diagnostics 3. Antibodies in treatment 4. Future avenues Summary: 1. Antibodies are immunoglobulins (Ig) electrophoretically belonging to and 2 globulins 2. Abnormal Ig concentrations in diseases. 3. Ig are heterogenous except in multiple myeloma. 4. Ig are built of 2 heavy chains and 2 light chains and can be split into fragments. 5. Each chain consists of a constant and a variable part. 8 6. The structure and function of the different Ig classes (IgM, IgG, IgA, IgD and IgE) 7. Ig functions as antigen receptors on lymphocytes. Membrane and secreted Ig's. 8. Amino acid sequences of heavy and light chains: The hypervariable regions, the domains. Evolution of the Ig structure. 9. Structure of the antigen combining sites of antibodies. 10. The 3-dimensional structure of Ig; electron microscopy and x-ray difraction studies. 11. Antigenic determinants. 12. Antigenic determinants of the Ig molecule: Isotypic, allotypic and idiotypic. 13. Ig synthesis, assembly, membrane deposition and secretion. Literature: Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. Ch. 4, pp. 76-110; Ch. 11, pp. 289-301. 9 Subject 9: Immunological Laboratory Tests - Principles and applications Lecturer: Dr. Ariel Munitz Type of Presentation: Lecture Duration: 2 hours Summary: Methods for detection of antigens and antibodies: a. Immunodiffusion. b. Electrophoresis and immunoelectrophoresis. c. Agglutination assays. d. Radioimmunoassays (RIA). e. Enzyme-linked immunosorbent assays (ELISA). f. Nephelometry g. Immunofluorescence. h. Western blotting. Literature: Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch. 6, pp. 145-167. 10 Subject 10: The Complement System Lecturer: Dr. Ariel Munitz Type of Presentation: Lecture Duration: 2 hours Summary: 1. Components of the complement system 2. The sequence of complement activation 3. The classical, alternative and lectin complement pathways 4. Functions of complement 5. Complement receptors 6. Complement and inflammation 7. Complement deficiencies. Literature: Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. Ch. 7, pp. 168-188 11 Subject 11: Organization and expression of T cell receptor, B cell receptor and immunoglobulin genes Lecturer: Prof. Joseph Haimovich Type of Presentation: Lecture Duration: 2 hours Summary: A. Structural genes coding for the immunoglobulin and the T cell receptor. Variable and constant regions. B. The genetic basis for the antibody diversity: Rearrangements and Somatic mutations C. Allelic Exclusion D. Class switch E. Clinical significance Literature: Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch. 5, pp. 111-136; ch. 9, pp. 228-235. Subject 12: B cell activation and differentiation Lecturer: Prof. Joseph Haimovich Type of Presentation: Lecture Duration: 2 hours Summary: Differentiation stages: a. b. c. d. Stem cell – ProB – PreB – B – Plasma cell Cell surface markers in B cell differentiation Signal transductions in B cell differentiation The germinal center reaction Literature: Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch. 11, pp. 271-299. 12 Subject 13 : Effector lymphocytes in the adaptive immune system. Lecturers: Dr. Gal Markel Type of Presentation: Lecture Duration: 3 hours Summary: A. Heterogeneity of effector cells: a. Cytotoxic T cells (CTL). b. Natural killer (NK) cells and NKT cells. c. Cells mediating antibody-dependent cell-mediated cytotoxicity (ADCC). B. Receptors of cytotoxic cells (activating and inhibitory receptors) C. Mechanisms of cytotoxicity: soluble effector molecules (perforin and granzymes) and membrane-bound effector molecules (Fas and Fas ligand) Literature: Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch. 14, pp. 351-370; ch. 10, pp. 264-267; ch. 9, pp. 226-228. 13 Subject 14: Anti microbial and anti parasitic protective immune mechanisms Lecturer: Prof. Yona Keisari Type of Presentation: Lecture Duration: 2 hours Summary: A. Sequence of immunological events following infection by microbial agents B. Collaboration between immune mechanisms for the eradication of microbial pathogens C. Examples of anti viral anti bacterial immunity Literature: 2. Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch. 18, pp. 447-460. 14 Subject 15: Immunological laboratory tests Lecturer: Ms. Irit Altboim Type of presentation: Laboratory Duration: A laboratory session of 3 hours Objectives: Demonstration and exercise of laboratory techniques for assessment of immunological parameters. Summary: A. Determination of antibody concentration in an unknown serum sample by ELISA B. Hemagglutination: Blood group typing Literature: Kuby Immunology (6th ed., 2007) Kindt, Goldsby, and Osborne, eds., Freeman & Co. ch. 6, pp. 145-167. 15