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Antigen recognition in adaptive immunity
Mechanism of diversity of antigen receptors Maturation and selection of B lymphocytes Maturation and selection of T lymphocytes
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Cells display several types of receptor and each of them is specific for a certain ligand
Cells within one clone display only one type of receptor specific for a certain ligand
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Antigen receptors on lymphocytes
B cell T cell Antigens: proteins, polysaccharides, lipids, nucleic acids, small molecules Conformational and linear epitops Complex of peptide-MHC molecule on an APC Linear epitops
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N N N N C C C C
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k l a (a1 a2) g (g1 g2 g3 g4) d e m IgA(1,2) IgG(1,2,3,4) IgD IgE IgM
VH VH VL VL CDR1 CDR2 CDR3 k l CL CL Isotype a (a1 a2) g (g1 g2 g3 g4) d e m IgA(1,2) IgG(1,2,3,4) V (variable) region VL i VH IgD CH CH C (constant) region CL i CH IgE IgM
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Antibodies structure function
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T-cell receptor for antigen (TCR)
structure
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Lymphocyte maturation
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The Nobel Prize in Physiology or Medicine
1987 "for his discovery of the genetic principle for generation of antibody diversity" Susumu Tonegawa
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Inherited configuration of gene loci for antigen receptors
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Inherited configuration of gene loci for antigen receptors
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Recombination and expression of immunoglobulin genes
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Mechanisms of creation of antigen receptor diversity
~100 54 67 27 Mechanisms of creation of antigen receptor diversity 61 4
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Every day 109 lymphocytes with 107 various specificities are generated (young)
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Phases of B-cell maturation and selection
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Phases of B-cell maturation and selection
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Phases of B-cell maturation and selection
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Phases of B-cell maturation and selection
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Phases of B-cell maturation and selection
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T-cell maturation in thymus
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T-cell maturation in thymus
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Faze u sazrevanju i selekciji T-limfocita
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1. TCR gene recombination a. eliminates auto-reactive lymphocytes 2. Negative selection b. proteins, polysaccharides, lipids 3. TCR recognizes c. a and b, or g and d chains 4. Immunoglobulin gene recombination d. peptides within MHC molecule 5. TCR consists of e. constant region of heavy chains 6. Antibody has f. variable regions of heavy and light chains 7. Different isotypes have the same g. occurs only in thymus 8. Positive selection h. provides antibody diversity 9. Antibody can recognize i. two identical heavy and two identical light chains 10. Receptors of different clones of B cells have different j. enables survival of useful lymphocytes 1.____ g 2.____ a 3.____ d 4.____ h 5.____ c 6.____ i 7.____ e 8.____ j 9.____ b 10.____ f
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