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    Complement System Therapeutics

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    murfiqahharizah03
    The document describes the complement system, which is part of the innate immune system. It has three pathways - the classical, lectin, and alternative pathways. The classical pathway is antibody-dependent and is triggered by antigen-antibody complexes. The lectin pathway is also antibody-independent but resembles the classical pathway. The alternative pathway can be initiated directly by bacterial surfaces and does not require antibodies. All three pathways result in the formation of the membrane attack complex that can lyse pathogen cells. The complement system also facilitates opsonization, the inflammatory response, and clearance of immune complexes.

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    Complement System Therapeutics

    Uploaded by

    murfiqahharizah03
    15 views36 pages
    The document describes the complement system, which is part of the innate immune system. It has three pathways - the classical, lectin, and alternative pathways. The classical pathway is antibody-dependent and is triggered by antigen-antibody complexes. The lectin pathway is also antibody-independent but resembles the classical pathway. The alternative pathway can be initiated directly by bacterial surfaces and does not require antibodies. All three pathways result in the formation of the membrane attack complex that can lyse pathogen cells. The complement system also facilitates opsonization, the inflammatory response, and clearance of immune complexes.

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    COMPLEMENT SYSTEM THERAPEUTICS

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    The document describes the complement system, which is part of the innate immune system. It has three pathways - the classical, lectin, and alternative pathways. The classical pathway is antibody-dependent and is triggered by antigen-antibody complexes. The lectin pathway is also antibody-independent but resembles the classical pathway. The alternative pathway can be initiated directly by bacterial surfaces and does not require antibodies. All three pathways result in the formation of the membrane attack complex that can lyse pathogen cells. The complement system also facilitates opsonization, the inflammatory response, and clearance of immune complexes.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    15 views36 pages

    Complement System Therapeutics

    Uploaded by

    murfiqahharizah03
    The document describes the complement system, which is part of the innate immune system. It has three pathways - the classical, lectin, and alternative pathways. The classical pathway is antibody-dependent and is triggered by antigen-antibody complexes. The lectin pathway is also antibody-independent but resembles the classical pathway. The alternative pathway can be initiated directly by bacterial surfaces and does not require antibodies. All three pathways result in the formation of the membrane attack complex that can lyse pathogen cells. The complement system also facilitates opsonization, the inflammatory response, and clearance of immune complexes.

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    2.

    3 complement
    system &
    therapeutics
    MURFIQAH HARIZAH BT M. HISHAM
    (DPMH 0031)
    LEARNING OUTCOME
    DESCRIBE THE FUNCTION OF DESCRIBE THE CLASSICAL
    COMPLEMENT SYSTEM PATHWAY OF THE COMPLEMENT
    SYSTEM

    DESCRIBE THE ROLE OF


    COMPLEMENT SYSTEM IN INNATE
    IMMUNITY
    introduction
    Sistem pelengkap atau Cascade System ialah
    sebahagian daripada sistem imun badan yang
    membersihkan sel-sel yang rosak, membantu badan
    sembuh selepas kecederaan atau jangkitan dan
    memusnahkan organisma mikroskopik seperti bakteria
    yang membuat anda sakit.
    Sistem pelengkap merupakan barisan hadapan
    pertahanan untuk sistem imun.
    WHAT IS THE COMPLEMENT
    SYSTEM?
    Sistem pelengkap
    Sebahagian daripada pertahanan imun semula jadi
    Terdiri daripada lebih daripada 40 protein yang berfungsi bersama
    untuk membantu, atau "melengkapkan,"
    Tindakan antibodi dalam memusnahkan patogen.
    Terdiri daripada pelbagai jenis protein:
    - protein terlarut beberapa pengawal selia dan reseptor pelengkap
    terikat membran
    Mempunyai banyak fungsi yang berbeza.
    COMPONENTS OF COMPLIMENT
    SYSTEM
    These are covered by nine central components of the cascade (C1 to C9),
    Multiple activation products (such as C3a and C3b),
    Regulators and inhibitors (e.g. Factor H and C4BP),
    Proteases and newly assembled enzymes (e.g. C4b2a and Factor B),
    Effector molecule receptors (such as C3aR and C5aR)
    GENERAL PROPERTIES OF
    COMPLIMENT SYSTEM
    These are glycoproteins and are synthesized primarily by liver
    cells and to a very less extent by macrophages and many other
    cell types. The rate of synthesis of the various complement
    glycoproteins increase when complement is activated and
    consumed.
    The complement usually does not bind to the antigen or antibody
    but only to antigen–antibody complex.
    The importance of the complement lies in the fact that it
    contributes to both the acquired and innate immunity of an
    individual.
    BIOLOGICAL EFFECTS OF
    COMPLEMENTARY SYSTEM

    AND
    PHAGOCYTOSIS.
    01 CELL LYSIS
    The membrane-attack complex can lyse a broad
    spectrum of cells: 02 INFLAMMATORY
    RESPONSE
    G(-) bacteria
    parasites
    Various peptides generated during activation of complement play a
    viruses
    decisive role in the development of an effective inflammatory
    erythrocyte
    nucleated cells (tumor cells) response.
    C3a, C4a, C5a (called anaphylatoxin) bind to complement receptors on
    Because the activation of alternative and lectin mast cells and basophils
    pathways is Ab-independent, these pathways serve The anaphylatoxins also induce smooth-muscle contraction,
    as important innate immune defenses against increased vascular permeability,
    infectious microorganisms. and induce degranulation with release of histamine and other
    mediators.
    extravasation, and chemoattraction (induced byC5a, C3a, and C5b67)
    03 OPSONIZATION
    C3b is the major opsonin of the complement
    system,

    although C4b and iC3b also have opsonizing


    activity

    04 CLEARANCE OF
    IMMUNE CELLS
    Removes immune IMMUNE
    CLEARANCE complexes from the
    circulation and
    deposits
    THERE ARE FOUR MAIN
    EFFECTS OF COMPLEMENT:
    TIT CAUSES LYSIS OF CELLS IT GENERATES MEDIATORS THAT
    (SUCH AS BACTERIA, VIRUSES, PARTICIPATE IN TRIGGERING SPECIFIC
    ALLOGRAFTS, AND TUMOR CELL FUNCTIONS, INFLAMMATION, AND
    CELLS). SECRETION OF IMMUNOREGULATORY
    MOLECULES.

    IT FACILITATES OPSONIZATION, THE


    PROCESS BY WHICH BACTERIA ARE IT CAUSES IMMUNE CLEARANCE, IN
    MORE READILY AND MORE WHICH IMMUNE COMPLEXES FROM
    EFFICIENTLY ENGULFED BY THE CIRCULATION ARE REMOVED
    PHAGOCYTES. AND ARE TRANSPORTED TO
    SPLEEN AND LIVER.
    ACTIVATION OF
    COMPLEMENT SYSTEM

    CLASSICAL PATHWAY ALTERNATIVE PATHWAY LECTIN PATHWAY


    Lectin pathway:
    Classical pathway Alternative pathway
    also antibody independent but
    adalah laluan bergantung antibodi dan adalah laluan bergantung
    dicetuskan oleh pembentukan kompleks resembles classical pathway
    antibodi yang dirangsang oleh
    antigen-antibodi larut atau dengan mengikat
    antibodi kepada antigen yang ada pada antigen secara langsung MBL
    permukaan sel sasaran. components include: MASP-1
    MASP-2  MASP -
    • all complement components are labelled ‘C’ Factor B mannanassociated serine
    • numbering of C1 – C9 Factor D protease
    01
    CLASSICAL
    PATHWAY
    CLASSICAL PATHWAY
    •The classical complement pathway is the main pathway by which the
    complement system occurs. ( part of acquired immunity).

    The antibody binds to an antigen on the surface of a pathogen, activating the C1


    complement protein.

    C1 acts a protease and cleaves C2 and C4 to form C4b2b.

    C42b converts C3 into C3a and C3b, which forms a C5 convertase.

    C5 convertase cleaves C5 into C5a and C5b.

    C5b forms a complex with C6, C7, and then C8, and C9, which becomes the membrane
    attack complex that lyses the pathogen.
    COMPONENTS OF CLASSICAL PATHWAY
    COMPONENTS OF CLASSICAL PATHWAY
    03
    LECTIN
    PATHWAY
    LECTIN PATHWAY
    •The lectin pathway is not caused by antibody binding, but by a

    carbohydrate -binding-protein called mannan-binding-lectin (MBL). It is an


    acute phase reactant produced in the liver and binds to the carbohydrates
    on the surfaces of many pathogens. The steps for the lectin pathway are:

    1.MBL binds to the carbohydrates on a pathogen.

    2.Proteases bound on the other side of the MBL cleaves C4 into C4a and C4b.
    3.C4b creates C3 convertase, and the rest of the steps happen identically to

    the classical pathway from the C3 convertase step


    02
    ALTERNATIVE
    PATHWAY
    ALTERNATIVE PATHWAY
    Ab independent pathway

    Contains many unrelated cell surface substances, e.g., bacterial lipopolysaccharides


    (endotoxin), fungal cell walls, and viral envelopes, can initiate the process by binding C3
    and factor B. This complex is cleaved by a protease, factor D, to produce C3bBb. This acts
    as a C3 convertase to generate more C3b. Alternative pathways are more important the
    first time we are infected by a microorganism because usually activated by products of
    micro-organisms like endotoxin.

    Other activators include:


    1. Complexes containing IgA
    2. Some virus-infected cells (e.g. EBV)
    3. Many gram negative and gram positive organisms
    4. Parasites – Trypanosomes, Leishmania
    5. Erythrocytes
    6. Carbohydrates (agarose)
    COMPONENTS OF ALTERNATIVE PATHWAY
    PROJECT SUMMARY
    THANK YOU!

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