Lab

Complement C3

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Complement C3, Complement C4, Complement CH50, Complement Pathway, Complement Activation, Alternative Complement Pathway, Classical Complement Pathway, Mannose-Binding Lectin Complement Pathway

  • Physiology
  • General
  1. Complement are components of both Innate Immunity and the humoral Immune System
  2. Multiple triggers including Antigen-Antibody complex as well as direct exposure to pathogen (see activation below)
  3. Results in inflammatory response (Chemoattractant), Phagocytosis (as Opsonin on cell surface) and pathogen lysis
  4. Solubilizes immune complexes to aid in clearance
  • Physiology
  • Complement Pathway
  1. Images
    1. idComplementPathway.jpg
  2. Activation
    1. Classical Pathway (C1, C2, C3, C4)
      1. C1 binds Antigen-Antibody complex
    2. Alternate Pathway (Properdin, Factor B, Factor D, C3)
      1. Activation via microbe cell surface
    3. Lectin Pathway (Mannose Binding Lectin or MBL)
      1. Mannose Binding Lectin (MBL) binds mannose on microbe surface
      2. Mannose Binding Lectin Associated Proteases (MASP-1, MASP-2) are activated
      3. Classical Pathway (above) is stimulated
  3. Enzyme C3 Convertase (C3bBb or C4b2a) Formation
    1. Enzyme C3 Convertase splits C3 into C3a and C3b
    2. C3a stimulates inflammation (attracts Neutrophils, histamine release)
    3. C3b stimulates Phagocytosis, inflammation (as with C3) and lysis (see below)
  4. Opsonization
    1. Microbe coated with an Opsonin such as an Antibody or complement (e.g. C3b)
    2. Surface Opsonins target microbes for Phagocytosis
  5. Phagocytosis
    1. Phagocytes such as Neutrophils (PMNs) and Macrophages attract and engulf targeted organisms
  6. Inflammation (via C3a, C5a)
    1. Chemoattraction of Neutrophils
    2. Anaphylatoxic activation of Mast Cells and Basophils to degranulate, releasing histamines and vasoactives
      1. Inflammation occurs when histamine-induced capillary dilation results in fluid and protein release
  7. Lysis
    1. C3b splits C5 into C5a and C5b
    2. Membrane attack complex or MAC (C5b, C6, C7, C8, C9) binds microbe surface
    3. MAC promotes microbe lysis
  • Labs
  1. Complement C3
    1. Marker for Intrinsic and Extrinsic Pathway Function
    2. Measured by immunochemical assay
  2. Complement C4
    1. Marker for Intrinsic Pathway Function
    2. Measured by immunochemical assay
    3. Deficient in 1% of population
    4. Deficient in 11% with Systemic Lupus Erythematosus
  3. Complement CH50
    1. Marker for function of entire intrinsic cascade
    2. Measured by serum ability to lyse IgG coated RBCs
      1. Most affected by delay in performing assay
  • Low Complement levels indicate depletion
  1. Rheumatic causes
    1. Systemic Lupus Erythematosus
    2. Mixed Connective Tissue Disease (MCTD)
    3. Vasculitis (especially cryoglobulinemia)
  2. Non-Rheumatic Causes
    1. Septic Shock
    2. Liver failure
    3. Severe Malnutrition
    4. Pancreatitis
    5. Severe burns
    6. Atheromatous embolization
  • Indications
  • Follow rheumatic disease activity
  1. Complement fall 20% below baseline signal exacerbation