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    Complement System

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    El Fatih
    The complement system is a group of proteins that mediate various functions including opsonization, membrane attack, and inflammation. It consists of three activation pathways - classical, lectin, and alternative - that are tightly regulated to prevent damage to host cells. Laboratory tests are used to identify deficiencies in the complement system that may underlie recurrent or severe infections.

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    Complement System

    Uploaded by

    El Fatih
    110 views21 pages
    The complement system is a group of proteins that mediate various functions including opsonization, membrane attack, and inflammation. It consists of three activation pathways - classical, lectin, and alternative - that are tightly regulated to prevent damage to host cells. Laboratory tests are used to identify deficiencies in the complement system that may underlie recurrent or severe infections.

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    Complement System

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    The complement system is a group of proteins that mediate various functions including opsonization, membrane attack, and inflammation. It consists of three activation pathways - classical, lectin, and alternative - that are tightly regulated to prevent damage to host cells. Laboratory tests are used to identify deficiencies in the complement system that may underlie recurrent or severe infections.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    110 views21 pages

    Complement System

    Uploaded by

    El Fatih
    The complement system is a group of proteins that mediate various functions including opsonization, membrane attack, and inflammation. It consists of three activation pathways - classical, lectin, and alternative - that are tightly regulated to prevent damage to host cells. Laboratory tests are used to identify deficiencies in the complement system that may underlie recurrent or severe infections.

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    © All Rights Reserved
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    Download as pptx, pdf, or txt
    of 21

    COMPLEMENT SYSTEM

    DEWI WULANDARI
    Clinical Pathology Departement
    Faculty of Medicine, University of Indonesia
    Cipto Mangunkusumo Hospital
    Jakarta
    Complement system
    • First described in the 1880s as a system
    capable of inducing lysis of bacteria and red
    cells.
    • In 1919, the Nobel Prize:
    the Belgian microbiologist Bordet for his description
    of the complement system.
    • The term complement was given to
    – the unnamed protein in serum from guinea pigs
    – that complemented the antibody fraction in a lytic
    assay.
    • Today, the complement system is understood
    as:
    – a group of 14 proteins (C1-9, Factor B, D, H, I,
    properdin)
    – comprising the complement cascade
    – more than 10 regulatory proteins
    – at least seven receptors
    – mediate the biologic functions
    – a variety of proteins are capable of activating the
    cascade.
    Synthesis & Function
    • Normal: 5% of serum protein
    • In inflammation states: 7%
    • Synthesis :
    – Hepatocytes
    – C1q, properdin, C7 : by myeloid cells
    – Factor D : by adipocytes

    • Main Biologic functions:


    – Opsonization
    – Membrane pertubation including lysis
    – Proinflammatory mediator
    Activations
    • Classical pathway
    • Alternative pathway
    • Lectin activation
    pathways
    Classical Pathway
    • The first pathway to be described
    & was thought as the only
    complement activation
    mechanism.
    • Activated primarily by immune
    complexes
    • Only IgG and IgM can activate
    complement.
    IgM > IgG3 > IgG1 and IgG2
    • Other activators:
    C-reactive protein, serum amyloid
    P, B-amyloid, DNA/chromatin,
    cytoskeletal filaments, some
    pathogens (mechanisms remain
    unclear)
    Alternative Pathway
    • The basis for this pathway
    is a spontaneous hydrolysis
    of C3, which occurs in the
    serum at a rate of 0.2% to
    0.4% per hour.

    • the alternative pathway is


    generally activated through
    the recognition of
    oligosaccharide and charge
    differences common to
    pathogens.
    The Lectin Activation Pathway
    • The MBL (mannose-binding lectin)
    protein is structurally related to C1q
    • Part of the family, which includes
    surfactant proteins and conglutin. H-
    ficolin, L-ficolin, and M-ficolin
    • MBL and ficolins all activate MBL-
    associated serine proteases (MASPs)
    to initiate the cascade.
    The Lectin Activation Pathway

    • Mammalian glycoproteins generally


    are decorated with galactose and
    sialic acid. that are not recognized by
    MBL.
    • MBL binds to oligosaccharides
    associated with bacteria, yeast, and
    parasites such as mannose, N-acetyl-
    glucosamine, fucose, and glucose.
    Membrane Attack Complex
    • The cleavage of C5 followed
    the bind of C6, C7, and C8
    • can insert firmly into a lipid
    membrane.
    • The addition of C9 leads to the
    formation of a true pore
    • They are most efficient at
    lysing gram-negative bacteria
    and red blood cells., which
    have no capability of repairing
    membrane damage.
    Complement in Inflammation
    • Anaphylatoxin: C3a, C4a, C5a
    • The receptors are expressed
    on mast cells, basophils,
    eosinophils, neutrophils,
    platelets, endothelial cells,
    and smooth muscle cells
    • Activation may result as:
    – Vasodilatation
    – smooth muscle contraction
    – Recruitment of neutrophils
    – Aggregation of platelets
    – Mucus release
    – Macophages activation
    Complement Receptors
    Regulators
    Regulators of the
    classical pathway
    Regulators of the
    alternative pathway
    Regulators of the MBL
    activation pathway
    Complement Deficiencies
    Laboratory Tests
    • Indications: Patient with
    – recurrent sinopulmonary infections
    – recurrent sepsis or systemic infetions
    – Sepsis on a background of autoimmune disease
    • Laboratory analysis:
    – Quantitative: level of C1q, C3, C4 & other
    components
    – Qualitative: CH50, AH50

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