Lesson 4.4 Complement Deficiencies and Assays

Complement Deficiencies and Complement Assays Notes

Learning Objectives

  • On completion of this session, students should be able to:

    • Understand how deficiencies in specific complement components disrupt immune responses and contribute to disease.

    • Learn the methods for diagnosing complement deficiencies, including laboratory tests.

Complement Deficiencies

  1. Deficiencies in Classical Pathway Proteins

    • Involves proteins C1, C2, C4.

    • Leads to increased susceptibility to immune complex diseases.

  2. Severity of Deficiencies

    • Varies according to the affected complement component.

  3. C3 Deficiency

    • Associated with increased susceptibility to bacterial infections.

  4. Terminal Pathway Protein Deficiencies

    • Involves proteins C5-C9.

    • Associated with increased susceptibility to Neisseria infections, specifically Neisseria meningitidis.

  5. Deficiencies of Alternative Factor Proteins

    • These deficiencies are rare.

Complement Assays

  1. Activity Assays

    • Measures complement hemolytic activity.

      • Classical Pathway CH50

      • Measures serum concentration required to lyse 50% of a red cell suspension.

      • Alternative Pathway CH50 (AH50)

      • Similar in principle to the classical pathway assay.

    • Variation in Methodology and Reference Ranges

      • It is essential to note that different laboratories may have varied methodologies leading to different reference ranges.

  2. Measurement of Individual Components

    • C3, C4

      • Measured by nephelometry or turbidimetry.

      • Nephelometry Diagram:

        • Components include a light source, lens, scattering detector, and sample container.

    • C1, C2, C5-C9

      • Measured by radial immunodiffusion.

      • Diameter of the precipitate ring correlates with antigen concentration.

Summary of Complement Proteins

  1. Antibody Binding:

    • C1q

  2. Activating Enzymes:

    • C1r, C1s, C2b, Bb, D

  3. Membrane Binding & Opsonins:

    • C4b, C3b

  4. Peptide Mediators of Inflammation:

    • C3a, C4a, C5a

  5. Membrane Attack Proteins:

    • C5b, C6, C7, C8, C9

  6. Complement Receptors:

    • CR1, CR2, CR3, CR4

  7. Regulatory Proteins:

    • C1 INH, C4bp, MCP, DAF, H I

Implications of Complement Deficiencies

  • Deficiencies in specific complement components can impair the immune system's ability to fight infections and regulate inflammation.

  • This can lead to an increased susceptibility to infections and autoimmune diseases.

  • Activity assays are crucial for measuring complement activation, which aids in identifying and managing these conditions effectively.