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LECTURE 1 INTRODUCTION TO IMMUNOLOGY Jan Zeromski 20010

5 student groupsSubjects:12 lectures approach to basic and clinical immunology5 classes approach to essentials of diagnostic immunology 8 seminars clinical immunologyEvaluation:Midterm testBasic imm. test Final examination Final testDetailed schedule on the website: immuno.ump.e

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LECTURE 1 INTRODUCTION TO IMMUNOLOGY Jan Zeromski 20010

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    1. LECTURE 1 INTRODUCTION TO IMMUNOLOGY Jan Zeromski 20010/2011

    2. 5 student groups Subjects: 12 lectures approach to basic and clinical immunology 5 classes approach to essentials of diagnostic immunology 8 seminars clinical immunology Evaluation: Midterm test Basic imm. test Final examination Final test Detailed schedule on the website: immuno.ump.edu.pl Immunology Course Outline

    3. Recommended books: Introduction to Clinical Immunology Medical University Press, 2009. Abbas, Lichtman, Pillay: Cellular and Molecular Immunology Saunders. Chapel: Essentials of Clinical Immunology Blackwell.

    4. INTRODUCTION TO IMMUNOLOGY

    5. INTRODUCTION TO IMMUNOLOGY Immune system (IS): innate and adaptive immunity Development of IS Cells and tissues of IS Soluble mediators of immunity Antigens Immunopathology Modern approaches to study immunology

    6. Immunologic concept of self Recognizing self whether an encountered molecule is a part of the body Recognizing of absence of self loss of some surface molecules such as MHC in cancer Recognizing nonself - such as pathogens or foreign grafts Recognition possible by: - via pattern recognition receptors - via somatically generated receptors

    8. Major differences between innate and acquired immunity (acc. to U. Koedel & W Pfister 2005) Innate immune system Immediate maximal response No immunological memory Not antigen specific Receptors: germ line encoded, In almost all multicellular organisms, Recognition of conserved molecular patterns, Perfect self/non-self discrimination Only hundreds of different receptors Acquired immune system Lag time (3-4 days) between exposure and max. response Immunological memory Antigen specific Receptors: generated somatically, Only in vertebrates, Recognition of details of molecular structure, Imperfect self/non-self discrimination, Over 100 000 000 000 different receptors

    9. INNATE IMMUNITY

    10. Components of Innate Immunity Barriers (epithelia, defensins) Circulating effector cells (neutrophils, eosinophils, basophils, mast cells, NK cells, monocytes/macrophages) Circulating effector proteins (complement, mannose-binding lectin, c-reactive protein) Cytokines (TNF, IL-1- 25)

    11. Receptors of innate immunity Pattern recognition receptors (TLRs, NLRs, Rig-1), NK cells: killer activated R.(KAR) and killer inhibitor R. (KIR), Complement receptors (on phagocytic cells) Fc receptors for Fc fragment of Igs Scavenger receptors

    12. Complement system

    13. COMPLEMENT SYSTEM MAIN STRUCTURAL FEATURES Consists of about 30 serum proteins marked by C and arabic number (C1q, C2, C3 etc.) Many C proteins are zymogens proenzymes requiring proteolytic cleavage Enzymes are often formed from several C molecules eg. C4B2a cleaves C3 Activation of C is controlled by regulatory proteins eg. DAF

    14. Complement bound and Complement associated biologically active molecules C3a i C5a (anafilatoxins) mediators of inflammation, Membrane attack complex (non-enzymatic assembly of C5b-C9) responsible for cell lysis Complement inhibitory molecules; DAF, CD59 Complement receptors (CR) on various cells (B cells monocytes, neutrophils, some epithelial cells etc):

    15. EFFECTS OF ACTIVATION OF COMPLEMENT SYSTEM Chemotaxis (attraction of cells to sites of infection Opsonization (facilitation of phagocytosis) Increased blood flow Increased blood vessel permeability Damage to plasma membranes Release of inflammatory mediators from mast cells

    16. BIOLOGICAL EFFECTS OF COMPLEMENT Promotion of killing of bacteria Clearing of immune complexes The induction and enhancement of antibody responses Detrimental if activated on a large scale, e.g. in Gram negative septicaemia, in tissue necrosis, in autoimmunity

    17. COLLECTINS (COLLAGEN LECTINS) CALCIUM BINDING LECTINS Lectins: proteins binding shugars in non-enzymatic way. Collectin family includes: mannan binding lectin (MBL), Conglutinin (bovine globulin able to react with bound C3) lung surfactant proteins A and D and also C1q MBL binds mannose groups in the bacteria,yeast fungi, viruses cell walls and then activates serine proteinases (MASP), able to cleave C4 and C2 analogous to C1q interaction with C1r and C1s. Effect: C activation

    18. Cytokines

    19. CYTOKINES SIGNAL TRANSDUCING MOLECULES Interleukins directing other cells to divide and differentiate Interferons type I (alpha/beta), type 2-gamma Colony stimulating factors (CSF) directing bone marrow stem cells Chemokines directing cell movement Other TNF?, TNF?, TGF? involved in inflammation, cytotoxicity and immunosuppression respectively

    20. CELLULAR MECHANISMS OF INNATE IMMUNITY - NEUTROPHIL ACTIVATORS Bacterially derived N-formylated peptides (FMLP) Defensins (natural antibiotics) Products of complement (iC3b) Leukotrienes (products od arachidonic acid metabolism) Cytokines ((TNF, IL-8, GM-CSF)

    21. RECEPTORS OF INNATE IMMUNITY-PATTERN RECOGNITION RECEPTORS Expressed on cells of innate immunity Encoded in the germline and not by somatic recombination of genes Recognize structures of microbes essential for the survival and infectivity Recognize less than a thousand microbial patterns (LPS, double stranded RNA, unme-thylated CpG nucleotides, glycolipids etc.)

    22. TOLL-LIKE RECEPTORS (TLRs) Strongly conserved in evolution Initially detected in fruit fly Drosophila melanogaster Recognize Pathogen-Associated Molecular Patterns (PAMPs), absent in mammals In extracellular portion contain multiple leucine-rich repeats (LRRs),In intracellular portion show high homology to IL-1R (TIR domain) Exist in families (TLR1-TLR-11)

    23. FUNCTIONAL FEATURES OF TLRs Their stimulation leads to: Augmented inflammatory reaction via activation of NF-kappa B transcription factor and increased synthesis of proinflammatory cytokines (IL-1,TNF-alpha, IL-12) Increased expression of MHC antigens Enhancement of maturation of dendritic cells Induction of apoptosis

    24. FEATURES OF ANTIGEN-PRESENTING CELLS Capacity for antigen uptake and partial degradation Expression of MHC molecules (class I and class II Expression of accesory cell interaction molecules Cytokine secretion (IL-12 and others)

    25. ADAPTIVE IMMUNITY

    26. ANTIGENS Thymus dependent (T-dependent) Thymus independent (TI) TI-1 polyclonal B cell activators (LPS, dextran) TI-2 multivalent, partly thymus independent (ficoll, pneumoccocal polysaccharide and other )

    27. ANTIGEN-ANTIBODY BINDING Non-covalent (hydrogen bonding, electrostatic, Van der Waals, hydrophobic) Antibody affinity the strength of a single Ag-Ab bond Ab avidity the sum of strength of all bonds Epitope antigenic determinant able to bind antibody determinant (paratope)

    28. ANTIGEN-BINDING MOLECULES Cell membrane Ig (Ab) Free Ab in body fluids T-cell receptors (TCR) HLA (MHC) class I HLA (MHC) class II Molecules of innate immunity (lectins and others)

    29. MAJOR HISTOCOMPATIBILITY ANTIGENS Histocompatibility antigens are cell surface expressed on all cells (class I) exception: red blood cells and on APC, B cells, monocytes/macrophages (class II) They are targets for rejection They are inherited from both parents as MHC haplotypes and are co-dominantly expressed

    30. MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) Is located on short arm of chromosome 6 It includes 3 regions: class Ia (loci A, B, C) class Ib (loci E, F, G, H), class II (loci DR, DQ, DP) and class III Genes of class Ia and class II are highly polymorphic, while those of class Ib and class III are not Polymorphism means occurence of several allelles ie.genes encoding various qualitatively distinct MHC antigens located at the same locus

    31. MAJOR FUNCTIONS OF CELLS PARTICIPATING IN IMMUNE RESPONSES B cells - recognize antigens and produce antibodies Plasma cells - produce antibodies Th cells - help in immune response, produce cytokines Treg cells - inhibit immune response, produce cytokines Tc cells - kill target cells NK cells - able to to kill virally infected and transformed cells Dendritic cells- present antigens to Th cells

    32. IMMUNOPATHOLOGY Hypersensitivity overactive immune response (IR) Immunodeficiency ineffective IR Autoimmunity reactivity to self antigens Graft rejection Malignancies of the immune system

    33. EFFECTIVENESS OF VACCINES

    34. MODERN APPROACHES IN STUDYING IMMUNOLOGY Immunology is a rapidly developing science, but the novel knowledge is quickly exploited in clinical practice, The load of information is greater in periodicals than in textbooks Problem-based learning (PBL) and Research based learning (RBL) are preferable ways of study today Navigation in the website is the only means to be well informed in this complex field

    35. THANK YOU FOR YOUR ATTENTION ! GOOD LUCK IN STUDYING IMMUNOLOGY!

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