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Materials for the lectures and seminars can be downloaded: Web: www.immunology.unideb.hu Downloads Login: student Password: download List of books: For the first test: Gogolak P., Koncz G. Short textbook of Basic Immunology (uploaded to our website) Parham, P. The Immune System, Fourth Edition Abbul K. Abbas Basic Immunology, Fourth Edition Raif Geha, Luigi Notarangelo: Case Studies in immunology Requirements for Medicine Students Changing of the seminar group – week 1-3 with permission from the Department Absences from the seminars: • More than two absences from the seminars – Department will refuse to sign the student’s Lecture book • Possibility for make up (on the same week of the seminar, should be communicated to both seminar teachers) Syllabus of the practices: (you can find in the curriculum) SCTs: week 5, 11, 15: • 14th of October 2016. (Friday) 06:30 pm – • 24th of November 2016. (Thursday) 06:30 pm – • 21st of December 2016. (Wednesday) 5 pm - Tresholds: • 1st SCT above 70% • 2nd and 3rd SCT above 50% (average) 170 – 204: pass (2) 205 – 239: satisfactory (3) 240 – 269: good (4) 270 – 300: excellent (5) Requirements for MSc in Molecular Biology Molecular Immunology Lecture from week 1-10 Seminars: no absences are allowed • Time: week 4, 7, 9, 11 Wednesdays 8:00-10:00 • Place: LSB 2.209 SCTs: week 5, 11: • 14th of October 2016. (Friday) 06:30 pm – • 24th of November 2016. (Thursday) 06:30 pm – Tresholds: • 1st SCT above 70% • 2nd SCT above 50% 120 – 139: pass (2) 140 – 159: satisfactory (3) 160 – 179: good (4) 180 – 200: excellent (5) Education Office Gabor Koncz, MSc., Ph.D (academic advisor) Official hours: • Tuesday: 2 – 4 pm • Thursday: 10 – 12 pm Place: LSB 2.209 (LifeScience Building 2nd wing 2nd floor) Andrea Dajkane Racz (administrative manager) Official hours: • Monday - Friday: 9 – 12 am Place: LSB 2.207 (LifeScience Building 2nd wing 2nd floor) FcR Affinity for Immunoglobulin Cell Distribution Function High (Kd < 10-9 M); binds IgG1 and IgG3, can bind monomeric IgG Macrophages, neutrophils; also eosinophils Phagocytosis; activation of phagocytes FcγRIIA (CD32) Low (Kd > 10-7 M) Macrophages, neutrophils; eosinophils, platelets Phagocytosis; cell activation (inefficient) FcγRIIB (CD32) Low (Kd > 10-7 M) B lymphocytes Feedback inhibition of B cells FcγRIIC (CD32) Low (Kd > 10-7 M) Macrophages, neutrophils, NK cells Phagocytosis, cell activation FcγRIIIA (CD16) Low (Kd > 10-6 M) NK cells Antibody-dependent cell-mediated cytotoxicity FcγRIIIB (CD16) Low (Kd > 10-6 M); GPI-linked protein Neutrophils Phagocytosis (inefficient) FcΕRI High (Kd > 10-10 M); binds monomeric IgE Mast cells, basophils, eosinophils Cell activation (degranulation) FcΕRII (CD23) Low (Kd > 10-7 M) B lymphocytes, eosinophils, Langerhans cells Unknown FcγRI (CD64) You do not have to know any data presented in the red boxes doi:10.1038/nri3650 Ectopic expression of FOXP3 in naive mouse CD4+ T-cells confers suppressive activity and induces the expression of Treg-associated signature molecules such as CD25, CTLA4 and GITR. Expression of these receptors also correlates with FOXP3 expression in human CD4+ T-cells. FOXP3 has a key role in maintenance of self tolerance. Exams: Based on the slideshows of the lectures Only data presented in the slides will be asked. (Notes are part of the sildes!) Gábor Koncz [email protected] In this lecture: 1. Administration 2. Why do we need immune system 3. Simple schema of the immune system 4. Definition of antigen, lexical data (5) Do we need immune system? GENERATION TIME OF PATHOGENS PATHOGENS Bacteria Virus 3 hrs Viruses 3 hrs Diversity Fast development In the active phase of the HIV 10billion viruses develop/day parasites Bacteria may divide in every 20 minutes The human microbiome HIV Streptococus. Lysteria Andida albicans S. aureus Flu Salmonella Mycobacterium tuberculosis Pneumocystis carnii Trypanosoma brucei Schistosoma mansoni We live in a potentially hostile world filled with infectious agents of diverse size, shape, and composition which would very happily use us as „petri dishes”… How can we survive???? 1. The interest of microbes The human microbiome Normal bacterial flora can be different in each person Transplantation of bacteria? Tightly regulated balance between commensal flora and the immune system 2. The immune system THE TWO ARMS OF THE IMMUNE SYSTEM Differentiation between harmless and harmful impacts DETECTION OF STRESS AND DANGER SIGNALS INNATE IMMUNITY Differentiation between self and non-self structures Antigen-specific recognition ADAPTIVE IMMUNITY INNATE IMMUNITY - immediate reaction - not antigen-specific - no memory ADAPTIVE IMMUNITY - developes in several days - specific - has memory Neutralization and elimination of foreign and harmful structures COORDINATED AND REGULATED ACTIONS Both the innate and adaptive arms of immunity are required for elimination of pathogens THE TWO ARMS OF THE IMMUNE SYSTEM Monocytes, Macrophages, Monocytes, Macrophages, Dendritic cells, Granulocytes, NK Dendritic cells, Granulocytes, NK cells and Complement components cells and Complement components B and T cells OVERVIEW OF THE IMMUNE SYSTEM Monocytes/Macrophages Dendritic cells Granulocytes Immune system The simplest Schema of the immune system Innate immunity Intracellular pathogens Extracellular pathogens Adaptive Immunity T cells B cells The main functions of the immune system: Recognition Communication Elimination (effector functions) The simplest Schema of the immune system Innate immunity Recognition Intracellular pathogens Communication Elimination Extracellular pathogens Adaptive Immunity T cells B cells What can be recognised by the immune system? RECOGNITION OF THE IMMUNE SYSTEM INNATE IMMUNITY ADAPTIVE IMMUNITY Structures shared by classes of microbes Structural details of specific microbial molecules WHAT CAN (Pathogen-associated molecular (Antigen) patterns (PAMP)) CELLS DIFFERENT MICROBES – BUT IDENTICALRECOGNIZE? DIFFERENT MICROBES – DISTINCT MOLECULES!!! STUCTURES!!! Complex antigen: Bacteri a Lipoproteins Flagelli n „Carrier” (no direct interaction with the antigenbinding site) Peptidoglycans LPS Pattern Recognition Receptors (PRR) (non-antigen specific) Epitope s RECEPTORS TCR (on T cells) and BCR (on B cells) (antigen specific) THE ANTIGEN Definition and properties Antigenic determinant (epitope) Antigen recognition by B and T cells DEFINITIONS • ANTIGEN (Ag) - any substance, which is specifically recognized by the mature immune system of a given organism Any chemical structure Soluble or corpuscle Simple or complex Originated from the body or comes from outside Genetically self or non-self Natural or artificial DEFINITIONS • ANTIGENICITY– capability of an antigen to bind specifically with certain product of the adaptive immunity: TCR or BCR/antibody, – immunogenicity - capability of an antigen to induce an (adaptive) immune response, – tolerogenicity - capability to induce immunological tolerance, specific immune non-responsiveness FACTORS INFLUENCING IMMUNOGENICITY I. From the aspect of our body: • Genetics (self/non-self) – species (evolutionarily nonconserved molecules) – individual differences (e.g. MHC polymorphism – see later) • Age – newborn – less reactive immune system – elderly – no new naive lymphocytes • Physiological condition (e.g. immunodeficiencies, starvation) FACTORS INFLUENCING IMMUNOGENICITY II. From the aspect of the antigen: • Physical-chemical properties of the Ag – – – – size/complexity (bigger more epitopes, role of carrier) corpuscular (cell, colloid) or soluble denatured or native (different epitopes!) degradability (by APCs) • Availability (crystalline proteins of the eye are not presented to lymphocytes) FACTORS INFLUENCING IMMUNOGENICITY III. From the aspect of vaccination: • Dose • Route – intradermal/subcutan > intravenous > oral > intranasal (oral vaccine against polio virus!) ANTIGENIC DETERMINANT (=EPITOPE) Part of the antigen which directly interacts with the antigen-binding site of a defined immunoglobulin (BCR / antibody) or TCR B cell epitope T cell epitope recognized by B cells recognized by T cells • proteins polysaccharides lipids DNA steroids etc. (many artificial molecules) • proteins (8-23 amino acids) • cell or matrix associated or soluble • requires processing by APC Communication in the immune system Cell-cell interaction Soluble mediators Soluble mediators: Cytokines „hormons” of the immune system citokinek monokinek interleukinek kemokinek limfokinek interferonok Elnevezés általában a termelő sejttípus alapján Summary of lexical data: 1. balance between commensal flora and the immune system 2. balance between immunogenicity and tolerogenicity 3. Innate and adaptive immune response 4. Antigen 5. Epitope immundef