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What is the body's first line of defence against invading pathogens?

The innate immune system. 

Physical barriers first, then chemical and biological barriers.


Why are the complement proteins found in the bloodstream?

Because they are soluble proteins


What is the overall aim of complement proteins?

To destroy invading pathogens


What is opsonisation?

The process of the complement proteins coating the outer surface of the pathogen which allows phagocytes and macrophages to engulf the pathogen. 


Why does opsonisation make it easier for macrophages to engulf pathogens?

Because macrophages have special receptors for specific complement proteins.


What is the process of making a membrane attack complex?

A group of complement proteins makes a hole in a pathogen, which causes inrushing fluids, creating an imbalance in osmolarity and causes the pathogen to lyse and be destroyed. 


What are the 3 main functions of complement proteins?

  1. Opsonisation
  2. Making a membrane attack complex
  3. Enhancing inflammation


Where are complement proteins produced?

Produced in the liver, then travel through the bloodstream. 


Which form do the circulating complement proteins take and when and why does this change?

Complement proteins circulate in an inactive form and therefore they don't attack self. 

When they discover a pathogen, they become activated. 


What are the 3 complement pathways?

  1. Classical pathway
  2. Alternative pathway
  3. Lectin pathway


Which complement proteins are involved in the classical pathway?

  • C1q
  • C1r
  • C1s
  • C4
  • C2


Which complement proteins are involved in the alternative pathway?

  • Factor D
  • Factor B
  • Properdin
  • C3


Which complement proteins are involved in the lectin pathway?

  • MBL
  • Ficolin
  • MASP-2
  • C4
  • C2


What is the main purpose of all the proteins involved in the classical, alternative and lectin pathways?

To help in splitting / activating complement protein 3 to make C3a and C3b.


What is the main function of C3a?

C3a, together with other proteins enhances inflammation


What is the main function of C3b?

C3b initiates opsonisation, and lysis of the cell to create a membrane attack complex.


How does the classical pathway activate C3 (by cleaving it into C3a and C3b)?

  • The classical pathway gets initiated / activated when antibodies bind to the antigen of a pathogen. 
  • When this happens, some complement proteins composed of C1q, C1s and C1r bind to the antibodies. 
  • What the C1q-C1s-C1r complex does is form another complement protein complex known as C4b2a complex. Another name for this is C3 convertase (because it is also an enzyme). 


How does the classical pathway activate C3 (by cleaving it into C3a and C3b)?

  • The lectin pathway is initiated by proteins binding to carbohydrates on te pathogen. 
  • For example, a protein called ficolin binds to the oligosaccharides on a pathogen.
    • Ficolin also has other proteins bound to it - MASP1 and MASP2. 
  • Mannose-binding-lectin (MBL) binds to mannose parts of the pathogen. 
    • MBL also has other proteins bound to it - MASP1 and MASP2. 
  • Ficolin and MBL, together with the MASPs, form a complement protein complex, exactly the same as the classical one: C4b2a complex (C3 convertase). 


How does the alternative pathway activate C3 (by cleaving it into C3a and C3b)?

  • The alternative pathway becomes activated when the classical pathway and lectin pathway forms C4b2a complex. 
  • C4b2a complex splits C3 into C3a and C3b. The alternative pathway is initiated with the C4b2a complex activates C3b.

  • This C3b then binds to the surface of the pathogen.

  • The alternative pathway then forms another type of C3 convertase, different to the one formed by the classical and lectin pathways. 

  • This C3 convertase is called C3bBb complex (C3 convertase).

  • The alternative pathway can also form another type of C3 convertase with a protein called properin. It is known by the same name (C3bBb complex which is a C3 convertase).


What is the function of C4b2a?

It splits C3 into active forms: C3a and C3b.


What does C3a do?

C3a, along with other complement proteins (such as C5a, which is one of the most important complement proteins) enhances inflammation. 


What does C3b do?

C3b initiates opsonisation and initiates the formation of the membrane attack complex.


What is the joint action of C3a and C5a?

Stimulation of mast cells to create histamine. 


What does histamine do?

It enhances inflammation. It increases vascular permeability which allows leukocytes to pass through more easily. Histamine also attracts leukocytes.


Which kind of bond is formed between C3b and a pathogen?

Thioester bond


What is the name of the process where many C3bs form thioester bonds with the pathogen surface, coating the pathogen?



Which complement protein is enlisted to help C3b engulf pathogens?



Why is C5a needed for C3b to phagocytose a pathogen?

  • When C5a binds to the C5a receptor of a macrophage, this allows the macrophage to bind to the C3b protein through the CR1 receptors.
  • Through this, the macrophage can phagocytose the pathogen.


C3b can opsonise and form the membrane attack complex. What is its alternative function?

C3b can alternatively bind to the C4b2a complex. When it binds it forms the C4b2a3b complex. This is also known as C3/C5 convertase. 


What are the 2 functions of C3/C5 convertase?

  • Cleave and activate C3 to form C3a and C3b
  • Cleave and activate C5 to form C5a and C5b