Immunology and Immunopathology

GENERAL FEATURES OF THE IMMUNE RESPONSES
Organization and function of the immune system. Characteristics of innate and adaptive immune responses. Organs, tissues, humoral and cellular components of the innate and adaptive immune system. Role of innate immunity in the activation of specific immunity. Clonal organization of the adaptive immune system. Immunological tolerance and memory.

INNATE IMMUNITY
Recognition of molecular patterns
Recognition of pathogens and danger signals by innate immunity cells: molecular patterns associated with pathogens (PAMPs), molecular patterns associated with tissue damage (DAMPs), Toll-like receptors and other pattern recognition receptors (PRR).
Complement
Complement proteins and cascade activation by classical, alternative and lectin pathways. Structure and mechanism of action of the membrane attach complex. Biological functions of the complement: cytolysis, opsonization, anaphylotoxin production, solubilization and elimination of immune complexes. Role of the complement in the inflammatory response. Mechanisms of regulation of complement activation.
Cytokines and chemokines
General characteristics of cytokines and chemokines. Structure and function of these molecules and their receptors.
Natural killer cells (NK)
Characteristics of NK cells and their biological activities. Activator receptors and inhibitory receptors. Cellular targets and cytotoxic mechanisms of NK cells.
Dendritic cells (DC)
Origin and function of DC subpopulations. Activation and maturation of DC. Role of DC in activation, polarization and regulation of the immune response.

ADAPTIVE IMMUNITY
Organization and development of the adaptive immune system.
Central organs: ontogenesis of lymphocytes. Structure of bone marrow and thymus. Function of medullary and thymic micro-environments in the development of lymphocytes, in the generation of the immune repertoire and in the induction of central tolerance.
Peripheral organs: structure of lymph nodes, spleen and lymphatic system associated with mucous membranes. Function of peripheral organs as a site for immune responses. Modality and function of lymphocyte circulation; localization of lymphocytes in lymphatic and non-lymphatic tissues and role of adhesion molecules.
Antigens (Ag)
Definition of Ag, immunogen, antigenic determinant / epitope, carrier-hapten. Physico-chemical characteristics of epitopes for B lymphocytes and for T lymphocytes. Binding of peptides to class I and II MHC molecules; role of the MHC polymorphism in the selection of epitopes. Superantigens.
Immunoglobulins (Ig) and generation of the variability of their repertoire
Ig structure: heavy and light chains; domains of constant and variable regions; hypervariable regions; combinatorial site. Function of the Ig as membrane receptors for the antigen and as effector molecules (antibodies). Antigenic determinants of Ig: isotypes, allotypes and idiotypes. Molecular characteristics and biological properties of immunogobulin classes and subclasses. Molecular basis of the generation of antibody repertoire variability: organization of light and heavy chain genes and their rearrangement. Class switching and affinity maturation.
Antigen-antibody reaction
Physico-chemical basis of the link between antigen and antibody. Precipitation, agglutination and neutralization reactions. Antibody titre. Principles of flow cytometry and diagnostic applications.
Monoclonal antibodies
Hybridoma production techniques. Murine, chimeric, humanized and human antibodies. Use of monoclonal antibodies in diagnostics and therapy.
B lymphocytes: development, selection, activation
Structure of the B lymphocyte receptor complex (B cell receptor, BCR). Maturation and maturation stages of the B lymphocytes. Description of the different subpopulations of B lymphocytes (B-1, follicular and of the marginal zone). Activation, proliferation and differentiation of B lymphocytes. Responses to thymus-independent antigens. Responses to thymus-dependent antigens: collaboration between T helper lymphocytes and B lymphocytes; structure and function of germinative centers; class switching, affinity maturation, immunological memory; kinetics of primary and secondary responses.
Molecules of the Major Histocompatibility Complex (MHC)
Organization of MHC genes and their inheritance. Polygeny and polymorphism. Structure and function of class I and II MHC molecules. Cellular distribution of MHC molecules.
Processing and presentation of antigen to T lymphocytes
Professional and non-professional Ag (APC) cells. Endogenous and exogenous way. Cross-priming.
T lymphocytes: development, selection, activation.
T cell receptor (TCR) structure: alpha, beta, gamma and delta chains; variable and constant region; hypervariable region; combinatorial site. Molecular basis of generation of TCR repertoire variability: organization of alpha, beta, gamma and delta chain genes; rearrangement mechanisms. Structure of the TCR receptor complex. Structure and function of accessory molecules CD4 and CD8. MHC restriction. Biochemical phenomena induced by the link between Ag and TCR. T lymphocyte maturation in the thymus. Positive and negative selection. Subpopulations of T lymphocytes and their activation.
T helper (Th) lymphocytes: cellular interactions, adhesion and costimulatory molecules, and cytokines involved in Th activation. Factors that regulate the differentiation of Th0 towards the different functional subtypes. Immune functions of the functional subtypes and the cytokines they produce.
Cytotoxic T lymphocytes (CTL): cellular interactions, adhesion and costimulation molecules, and cytokines involved in CTL activation. Mechanisms of cytotoxicity and molecules involved.
Regulatory T lymphocytes (Treg): distinctive features of natural Tregs and inducible Tregs. Origin, markers and function of the different Treg subpopulations, and their action mechanisms.
Memory T lymphocytes. Characteristics and function of gamma-delta T lymphocytes. Features and functions of NKT cells.
Immunological tolerance
Definition of tolerance. Inducibility of tolerance towards foreign Ag. Natural tolerance towards autologous Ag. Tolerance of T and B lymphocytes. Mechanisms of central and peripheral tolerance. Role of Tregs and other cells with suppressive activity in the control of peripheral tolerance.
Modulation of the immune response in defense against infections: active and passive immunization. Various types of vaccines. Adjuvants and immunomodulators. Transplacental passage of IgG and intake of IgA with breast milk in the defenses of the newborn.
Transplantation immunology
Molecular and cellular bases of allogeneic recognition. Mechanisms of hyperacute, acute, chronic rejection. Principles of HLA typing techniques. Transplantation reaction to the host (Graft Versus Host Disease, GVHD). Main organ transplants in clinical practice. Leukocyte mixed culture (MLR) reaction and activation of alloreactive T lymphocytes.
Tumor immunology
Antigens and tumor markers. Effector mechanisms of immunity against tumors. Immunosurveillance and immunoediting theory. Mechanisms of avoidance of immune control by tumors. Immunological therapies of tumors.

IMMUNOPATHOLOGY
Hypersensitivity reactions
Molecular mechanisms and classification of allergic reactions based on the type of response and the type of effector mechanism responsible for the damage (IgE, IgM and IgG allergies, immune complexes, T lymphocytes). Principles of allergy diagnostics in vivo and in vitro. Principles of specific immunotherapy.
Autoimmunity and autoimmune diseases
Etiopathogenesis of autoimmune diseases. Autoimmune diseases due to immunological deficits. Humoral and cell-mediated immunopathological mechanisms of the most common autoimmune diseases.
Immunodeficiency syndromes
Congenital and acquired immunodeficiency syndromes. Immunodeficiencies due to Ig deficiency; deficiency of T lymphocytes, combined deficits; phagocyte deficiency; deficit of complement components. Acquired immunodeficiency syndrome (AIDS)