Mechanisms_of_diseases

A.Y. 2024/2025
14
Max ECTS
184
Overall hours
SSD
MED/04
Language
English
Learning objectives
The course focuses on the causes of cell, tissue, and organ injury (general pathology), on the principal mechanisms of responses to injury and defense (inflammation and immunity), and on the general processes of the most relevant causes of human diseases (cardiovascular pathology, oncology, immunopathology). Integrating contributions from different disciplines (i.e. general pathology, immunology and oncology), the course offers a comprehensive description of the main different mechanisms of disease organized in 6 modules: A. Cellular pathology B. Inflammation and innate immunity C. Adaptive immunity D. Immunopathology E. Oncology F. Vascular pathology
Expected learning outcomes
At the end of the course, students will gain understanding of:
· general pathological mechanisms leading to cell injury and Death
· how the body reacts to physical, chemical and biological agents to recover homeostasis
· molecular and cellular basis for inflammatory disease states
· normal and abnormal functions of the innate and adaptive immune system
· molecular basis of neoplastic diseases
· molecular basis of vascular alterations
Single course

This course cannot be attended as a single course. Please check our list of single courses to find the ones available for enrolment.

Course syllabus and organization

Single session

Responsible
Course syllabus
MECHANISMS OF DISEASES - 1ST SEMESTER Legend: A = asynchronous learning
LEARNING OBJECTIVES BLOCK A: CELLULAR PATHOLOGY 1. Introduction to MOD and its organization 2. Mechanisms of cellular adaptation, injury and death 3. Oxidative stress in human health and diseases 4. Intra- and extracellular accumulations leading to human diseases 5. The stem cell 6. Cellular senescence and aging BLOCK B: INFLAMMATION AND INNATE IMMUNITY 1. Origin of innate immune cells: hematopoiesis (A) 2. The acute inflammatory response 3. Cell mediators of acute inflammation 4. Soluble mediators of acute inflammation 5. Leukocyte recruitment (A) 6. Pathogen recognition in innate immunity I 7. Pathogen recognition in innate immunity II (A) 8. The complement system 9. Pathogen killing 10. Immunometabolism (A) 11. Resolution of the inflammatory response 12. Tissue repair and fibrosis 13. Chronic inflammation 14. Acute phase reaction and systemic inflammation BLOCK C: ADAPTIVE IMMUNITY 1. From innate to adaptive immunity: basic concepts 2. Antigen processing and presentation 3. Antigen presenting cells 4. T cells development 5. Tolerance (A) 6. T cells functions 7. B cells development 8. Antibodies 9. Immune response polarization 10. Immune circuits in chronic inflammation 11. Negative regulators of the immune response (A) 12. Immunometabolism in adaptive immunity ( A) 13. Immune response memory (A)
MECHANISMS OF DISEASES - 2ND SEMESTER BLOCK D: IMMUNOPATHOLOGY 1. Immune responses to viruses 2. Immune responses to intracellular bacteria 3. Immune responses to extracellular bacteria and fungi 4. The immune system at the epithelial barriers 5. The interaction between microbiome and the immune system (A) 6. Hypersensitivity reactions - part I 7. Hypersensitivity reactions - part II 8. Autoimmunity 9. Primary immunodeficiencies (A) 10. Acquired immunodeficiencies 11. Transplantation immunology 12. Systemic metabolism and immune response in complex diseases (A) 13. Immunosenescence BLOCK 5: ONCOLOGY 1. Introduction to tumors 2. Distinctive features of benign, precancerous and malignant growth 3. Molecular basis of cancer 4. Carcinogenesis: physical and chemical agents 5. Health impacts of air pollution (A) 6. Carcinogenesis: infectious agents (A) 7. Immune responses to tumors 8. CAR T cells in cancer immunotherapy (A) 9. Inflammation and cancer 10. Metabolic changes in patients with tumors (A) 11. Angiogenesis 12. Tumor angiogenesis BLOCK 6: VASCULAR PATHOLOGY 1. Hemostasis and coagulation 2. Atherosclerosis (A) 3. Thrombotic disease (A) 4. Shock 5. Anemias (A) BLOCK 7: BIOTECHNOLOGY APPROACHES IN TRANSLATIONAL MEDICINE 1. From somatic cells to stem cells 2. New technologies for the diagnosis and the therapies of immunologic diseases 3. From genetics to immunology: the auto-inflammatory diseases case 4. Regulation and ethics of modern technology in modern medicine 5. Flow cytometry applications in immunopathology
EXPECTED LEARNING OUTCOMES BLOCK A Adaptation of cellular growth and differentiation Mechanisms of cellular injury and cell death (necrosis, apoptosis, autophagy, pyroptosis, necroptosis) Reactive oxygen species (ROS): types, source, effects Balance between ROS and antioxidants in human health and unbalance in human disease Intracellular accumulations of endogenous and exogenous substances Molecular and cellular aspects of protein misfolding and mechanisms of protein-folding diseases The stem cell and the concept of pluripotency Main properties of embryonic and adult stem cells The hematopoietic stem cell as a paradigm of adult stem cells Reprogrammed cells and induced pluripotency Somatic cell reprogramming by nuclear transfer ("therapeutic cloning") Hallmarks of aging BLOCK B The hematopoietic niche and hematopoietic stem cells Hematopoietic lineages and cytokines The normal and altered blood counts Biological and physical barriers of innate immunity Cardinal signs of acute inflammation Blood flow alterations and vascular permeability The endothelium as a reactive biological structure Mast cells, phagocytes and NK cells Molecular mediators active on vessels Molecular mediators active on leukocytes Primary inflammatory cytokines Eicosanoids Cell adhesion: adhesion molecules and cell migration, the chemokine system Pathogen-Associated Molecular Patterns (PAMPs) and Pathogen Recognition Receptors (PRRs) Danger-Associated Molecular Patterns (DAMPs) and their receptors The TLR system Intracellular PRR Opsonic receptors Genetic defects in pathogen recognition Complement system: Activation pathways, functions, regulatory mechanisms, genetic defects in the complement system Mechanisms of cell-mediated cytotoxicity: phagocytosis and degranulation Oxygen-dependent mechanisms, oxygen independent mechanisms, opsonic agents Genetic defects in pathogen killing mechanisms Energy for immunity Metabolic signatures and profiles of key immune cells Metabolic control of immune responses Neutrophils metabolism and bioenergetics of anti-microbial action Metabolism of macrophages Metabolic shifts in macrophage activation and polarization Negative regulators of the inflammatory response The hypothalamic-pituitary-adrenal axis Anti-inflammatory cytokines and eicosanoids Stem cells and growth factors in tissue renewal Multistep process of tissue repair, fibrosis, anomalies in wound healing Distinct types of chronic inflammation Cellular and molecular effectors of chronic inflammation Macrophage polarization in chronic inflammatory responses Systemic inflammation: Fever, leukocytosis, acute phase proteins BLOCK C Key features of acquired immunity: specificity, memory, tolerance The lymphoid system Primary and secondary lymphoid tissues, lymphatic vessels The antigen: source, structure, processing Thymus-dependent and thymus-independent antigens Structure and function of Major Histocompatibility Complex I and II MHC-I and MHC-II loci organization Superantigens Professional and non-professional antigen presenting cells Dendritic cells origin and subsets Dendritic cells maturation and migration Costimulatory molecules Intrathymic development Positive and negative selection of T lymphocytes TCR structure and repertoire generation Central and peripheral tolerance The TCR/CD3 signalling complex and transduction pathways Helper and cytotoxic T lymphocytes BCR signalling and B cell activation Antibody classes: structure and functions Isotype switch Antibody classes in primary and secondary immune responses Affinity maturation T helper subsets and polarized immune responses Differentiation and signalling in T helper cells Immune response polarization in pathology T cell / macrophage crosstalk in chronic inflammatory responses Impact on effector cells Immune granulomata: an immune perspective Regulatory T cells Myeloid regulatory cells Metabolic differences between innate and adaptive immunity Metabolism of specific T cell lineages T cell metabolism changes during immune response Vaccines and their development BLOCK D Recognition of viral infection by the immune system Effector mechanisms against viral infections Viral strategies for evading antiviral immune responses Recognition of intracellular infection by the immune system Microbial strategies for evading immune responses The mucosal immune system Mucosal immunity and commensal microorganisms Mucosal immunity to pathogenic microbes General issues on hypersensitivity reactions Type I hypersensitivity Type II hypersensitivity Type III hypersensitivity Type IV hypersensitivity The multifactorial pathogenesis of autoimmune diseases Failure mechanisms of the central and peripheral tolerance Effector mechanisms of autoimmune reactions Immune mechanisms of the most common autoimmune diseases Differential features of autoimmune vs autoinflammatory diseases Immune deficiency caused by defects in innate immunity Immune deficiency caused by defects in B and T maturation Iatrogenic immunodeficiencies HIV infection and immune response Acquired immune deficiency syndrome (AIDS) pathogenesis Immunological basis of allograft rejection Major and minor histocompatibility antigens Molecular basis of direct and indirect allorecognition Mechanisms of hyperacute, acute and chronic rejection graft-versus-host disease Age-related changes in the innate immune system Age-related changes in the adaptive immune system Impact of immunosenescence on diseases and vaccination Obesity as a multifactorial disease Immunological implications of obesity BLOCK E Definition of cancer and epidemiology Tumor nomenclature, TNM classification Differentiation and cell grading, rate of growth Local invasion Metastasis, pathways of spread Oncogenic signaling and tumor microenvironment as drivers of cancer metabolism Tumor sensing and metabolic adaptations to hypoxia and nutrient deprivation Signals and targets of metabolic reprogramming in cancer cells Advantages and liabilities of tumor cell metabolism Genes in which mutations cause cancer: oncogenes, tumor suppressor genes (gatekeepers and caretakers genes) Type of genetic alterations responsible for initiating cancer Activating or gain of function mutations Ectopic or heterochronic mutations Chromosome translocations Loss of function mutations Genomic instability and tumor progression The hallmarks of cancer The cancer-associated genes involved in the hallmarks of cancer Genomic instability and multistep carcinogenesis Cancer stem cells UV and ionizing radiations Chemical carcinogenesis: initiation, promotion and progression Metabolic activation of chemical compounds in vivo Factors that control chemical carcinogenesis Genotoxic and non-genotoxic effects of carcinogens Oncogenic DNA and RNA viruses Genetic mechanisms underlying the oncogenic process Host interaction with oncogenic viruses Pathogenic role of viruses into the oncogenic process Role of bacteria into the oncogenic process: the H. pylori case The immunosurveillance hypothesis Determinants of tumor antigenicity Defensive mechanisms against tumors Mechanisms of cancer immune evasion Cancer immunoediting Principles of cancer immunotherapy Epidemiologic evidence Myeloid-derived suppressor cells Tumor-associated macrophages and neutrophils Mechanisms of angiogenesis and vasculogenesis Endothelial progenitors and other pro-angiogenetic bone marrow-derived cells Angiogenetic cytokines and their receptors Common and distinctive features of blood and lymphatic vessels Role of angiogenesis to tumor survival and growth The role of the tumor microenvironment Cancer-related anorexia and cachexia Metabolic mechanisms of neoplastic cachexia Molecular mediators of neoplastic cachexia Tumor factors contributing to cancer cachexia Clinical characteristics of neoplastic cachexia Paraneoplastic syndromes BLOCK F Platelets Primary and secondary hemostasis and coagulation cascade Fibrinolytic system Mechanisms of atherosclerotic plaque generation: risk factors, clinical manifestations and complications Thrombus formation and evolution Thromboembolism and immunothrombosis Pathogenesis and stages of shock Disseminated intravascular coagulopathy Biology of the red blood cell and classification of anemias
Prerequisites for admission
To understand the contents of MOD course, students must have the background knowledge acquired in: Anatomy, Biochemistry, Genetics
Teaching methods
Synchronous learning: classroom lectures.
Asynchronous learning: The teaching staff will provide audio-video based (pre-recoreded, multimedia platforms), text-based (e-mail, electronic documents) and e-learning material.
Practical activities: · PBL (problem-based learning) sessions. 4 PBLs will be 6 hours each PBL, scheduled during the second semester. Students will work on a clinical problem that will be the starting point for the acquisition and consolidation of topics related to the course program. · Journal club. Organized during the second semester (16 hours). Students will acquire confidence with different sources of scientific information and develop a critical approach based on a constant confrontation with peers and the teacher. In both PBL and journal club activities, each working group will independently organize its individual and collegial activities and may have regular meetings with the teacher to define the key points to be discussed and identify appropriate information sources. At the end of the activity, each group will deliver a seminar to the whole class, presenting results in a one-day PBL or journal club session. · Labster virtual laboratory: each student will have access to the Labster platform, to follow virtual laboratory activities related to the program.
Teaching Resources
AK Abbas, AH Lichtman, S Pillai. CELLULAR AND MOLECULAR IMMUNOLOGY. 10th ed. Elsevier 2021
SUPPLEMENTAL LEARNING MATERIAL:
On specific topics of the program, not discussed during synchronous lessons, additional material will be made available during the course.
V Kumar, AK Abbas, JC Aster. ROBBINS AND COTRAN, BASIC PATHOLOGY. 11th ed. Elsevier 2022 SUPPLEMENTAL LEARNING MATERIAL: On specific topics of the program, not discussed during synchronous lessons, additional material will be made available during the course.
Assessment methods and Criteria
The exam will be based on one written part and two oral parts:
· The WRITTEN TEST 1 will be based on 30 multiple choice questions of general pathology and immunology. This test has a threshold of 23/30 and will not contribute to the final mark, but it will be preparatory for the ORAL EXAMINATION 1&2.· The ORAL EXAMINATION 1 will evaluate general pathology and will result in a mark from 18 to 30L.
· The ORAL EXAMINATION 2 will evaluate immunology and will result in a mark from 18 to 30L.

The grades collected in the two oral examination tests will be averaged and contribute to the final mark.
The final score will be implemented with the score obtained in the journal club session (from 0 to 1 point).

Written test and the oral test can be taken independently from each other in different dates. The oral examination sessions 1&2 have to be taken in a single session.
The mark obtained in the written test will be considered valid indefinitely.

ATTENDANCE: Attendance is required to be allowed to take the exam. Unexcused absence is tolerated up to 34% of the course activities. University policy regarding excused illness is followed. In the PBL sessions, the attendance is considered only if the student attends the whole activity (6 hours). In the journal club session, attendance is required both during the collegial activities (8 hours) and during the one-day journal club session (8 hours).
Registration through SIFA is mandatory.
MED/04 - EXPERIMENTAL MEDICINE AND PATHOPHYSIOLOGY - University credits: 14
Practicals: 64 hours
Lessons: 86 hours
: 34 hours