Chapter 3 Information in Test 1 Final

Chapter Overview

  • Chapter 3: All information except slide 8 is from this chapter.

  • Slide 8: Contains information from Chapter 9.

C-reactive Protein (CRP)

  • Structure: Pentamer of identical subunits (part of the pentraxin family).

  • Binding:

    • Binds to phosphorylcholine component of LPS in bacterial and fungal cell walls.

    • Does not bind to phosphorylcholine in human cells.

  • Functions:

    • Acts as an opsonin (enhances phagocytosis).

    • Can bind C1q to initiate classical pathway of complement fixation in the absence of antibodies.

  • Interaction with C1q:

    • CRP binds with C1q via stalks, while antibodies bind through globular heads.

    • Similar complement reaction sequence occurs whether CRP or antibodies interact with the pathogen.

Mannose-binding Lectin (MBL)

  • Structure: Binds mannose-containing carbohydrates; calcium-dependent lectin.

  • Similarity: Similar in structure to C1q with 15-18 potential binding sites for attachment to pathogens.

  • Function: Weak individual interactions can be strong due to multipoint attachments.

  • Binding Characteristics: MBL does not bind to human cells due to geometry preventing multipoint binding.

Acute-phase Response

  • Significance: Increases recognition molecules in innate immunity; demonstrates opsonization by MBL and CRP.

MBL Activation and Functions

  • Proteolytic Enzyme Complex:

    • Known as MBL-associated serine protease (MASP), specifically MASP-2.

    • Cleaves C4 and C2, initiating complement activation via the lectin pathway.

    • Facilitates bacterial uptake by monocytes that do not express the macrophage mannose receptor.

Plasma Levels and Complement Activation

  • Presence: Both CRP and MBL are present at low levels in plasma, but increase during the acute-phase response.

  • Function: Bind structures common to pathogens but absent on human cells, initiating complement activation through pathways similar to those used by antibodies (Abs).

  • Comparison: Complement components in classical and lectin pathways share structural and functional similarities with the alternative pathway.

C3 and C4 Components

  • Similarities: C4 and C3 similar in function and structure.

  • C3 Convertases:

    • Alternative pathway: C3bBb.

    • Classical pathway: C4b2a.

Classical Pathway Initiation

  • Components: Initiated by antibodies (IgM or IgG) binding to C1q, activating the complement cascade.

  • Mechanism:

    • C1r activation leads to cleavage of C1s, which cleaves C4 and C2, similarly to MASP2 in the lectin pathway.

    • C3 convertase formed is C4b2a.

C-reactive Protein and Classical Pathway

  • Interaction: C1 binding to CRP triggers the classical pathway of complement fixation.

  • Pathogen Surface Binding: C-reactive protein binds to phosphorylcholine on the pathogen surface.

Structural Relationships of Pathway Components

  • Comparison:

    • Alternative, lectin-mediated, and classical pathways demonstrate close structural relationships.

    • Proteins involved serve similar functions with homologous components:

      • Initiation: D = MBL-associated C1s serine protease.

      • Control of Activation: Identical regulatory components (CR1).

      • Opsonization and Membrane-attack: C3b and C5b function identically.

Figures Reference

  • Multiple figures referenced (3.27, 3.28, 9.28, 3.39) illustrate complement pathways and structural relationships.