Antibodies

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Antibodies:

Varun C N Antibodies

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Antibodies are gamma globulin proteins that can specifically react with an immunogen © Varun C N- Antibodies 2

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Fab- Antigen binding site Fc- Complement binding site Text Book of Immunology- Kuby; 5e © Varun C N- Antibodies 3

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© Varun C N- Antibodies 4 Alain Beck, Thierry Wurch, Christian Bailly & Nathalie Corvaia Nature Reviews Immunology 10 , 345-352 (May 2010)

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Fc fragment Fab fragment Antigen Epitope An antibody (shown in green) latches onto a HIV molecule (shown in red) at its site of vulnerability (shown in yellow). http://evolution.berkeley.edu/evolibrary/news/070301_hiv © Varun C N- Antibodies 5

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© Varun C N- Antibodies Keith Elkon & Paolo Casali Nature and functions of autoantibodies doi:10.1038/ncprheum0895 6

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© Varun C N- Antibodies Izumi Kumagai Antigen–Antibody Binding DOI: 10.1002/9780470015902.a0001117.pub2 7

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© Varun C N- Antibodies 8

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© Varun C N- Antibodies 9 Function of antibodies Opsonization Neutralization Complement activation Immunomodulation

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© Varun C N- Antibodies 10 Types of antibodies IgA IgG IgD IgE IgM

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© Varun C N- Antibodies 11 IgG IgM IgA IgD IgE Type Monomer Pentamer Monomer/Dimer Monomer Monomer Heavy chain γ µ α δ ε Activate complement Yes Yes No No No Half life 23 5 6 3 2.5 Cross placenta Yes No No No No Induce mast cell degranulation No No No No Yes Function Chronic immunity Acute immunity Mucosal immunity Receptor Parasitic immunity/ Allergy

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© Varun C N- Antibodies 12 Text Book of Immunology- Kuby; 5e

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© Varun C N- Antibodies 13 Antibody affinity It represents the strength of the reaction between a single epitope and a single paratope. Antibody avidity It is a measure of the overall strength of binding of an antigen with many antigenic determinants and multivalent antibodies. http://pathmicro.med.sc.edu/mayer/ab-ag-rx.htm

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© Varun C N- Antibodies 14 Immunoglobulin G Highest concentration Long half life 4 subclasses- IgG1 to IgG4 Importance Major immunoglobulin in Humoral defense High affinity but low avidity High capacity to activate complement Only Ab that can cross the placenta (Except subtype IgG2) Presence signifies chronic infection or immunity

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© Varun C N- Antibodies 15 Immunoglobulin M Largest of all antibodies The five monomer subunits are arranged with their Fc regions in the center of the pentamer and the ten antigen-binding sites on the periphery of the molecule. The polymer is held together by a J chain Low affinity, High avidity Most efficient binding Importance Best complement fixation (30 times better than IgG ) Indicates acute immunity (First Ab to appear) Can be selectively removed by treating with mercaptoethanol

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© Varun C N- Antibodies 16 Immunoglobulin A Most predominant Immunoglobulin in mucosal surfaces Can be present in 2 form Monomeric Dimeric Dimeric form has J chain Before secretion pick up additional structure called “secretory piece” Importance: Mucosal immunity Secretory IgA ( SIgA ) represents the most abundant immunoglobulin of body secretions such as saliva, tears, colostrum and gastrointestinal secretions Human colostrum

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© Varun C N- Antibodies 17 Immunoglobulin A Review http://www.invivogen.com/review-iga Schematic drawing of lacrimal gland acinar cell showing the classic mechanism for androgen (indicated here by testosterone) regulation of secretory immunoglobulin A. Dartt etal; (2005) Advances in Organ Biology Vol 10: 21–82

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© Varun C N- Antibodies 18 Immunoglobulin E Most potent immunoglobulin Also known as “ Reaginic antibody” Involved in Parasitic immunity, P-K reaction ( Prausnitz and Kustner ) Implicated in Type 1 Hypersensitivity Text Book of Immunology- Kuby; 5e

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© Varun C N- Antibodies 19 Immunoglobulin D Major membrane bound immunoglobulin expressed by mature B cells

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© Varun C N- Antibodies 20 The Clonal selection theory of antibody formation Gustav J. V. Nossal Nature 421 , 440-444 (23 January 2003) doi:10.1038/nature01409

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© Varun C N- Antibodies 21 This presentation made available at www.microboids.net

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