The Alternative Pathway - The Complement System (Part II) (FL-Immuno/14)

Summary

The video introduces the alternative pathway of complement activation, one of the first responses of the innate immune system to pathogens. The process begins with spontaneous hydrolysis of C3, followed by the binding of Factor B and cleavage by Factor D, resulting in the formation of the C3 H2O BB complex. This complex serves as a C3 convertase, activating more C3 molecules. C3b molecules bind to microbial surfaces in a process called complement fixation, and the alternative C3 convertase is stabilized by the protein properdin. This pathway plays a crucial role in immune defense and leads to the generation of C3 convertases.

Takeaways

• 😀 The alternative pathway of complement activation is one of the first responses of the innate immune system to invading pathogens or infections.
• 😀 C3 is the most abundant protein in the complement system, and its hydrolysis is essential for initiating the alternative pathway.
• 😀 The first step in the alternative pathway involves spontaneous hydrolysis of C3, resulting in C3 H2O, which reveals a binding site for the next proteins.
• 😀 Factor B binds to the C3 H2O molecule, and Factor D cleaves Factor B into larger and smaller fragments, with the larger fragment (BB) remaining bound.
• 😀 The complex formed by C3 H2O and BB is called the C3 H2O BB complex, which has protease activity and rapidly activates more C3 molecules.
• 😀 The C3 H2O BB complex acts as a C3 convertase and is a soluble form of C3 convertase before the infection.
• 😀 During an infection, some of the activated C3b molecules bind covalently to microbial surfaces, a process known as complement fixation.
• 😀 The C3b-bound microbial surface leads to the formation of the C3bbb complex, which has C3 convertase activity and works at the pathogen's surface.
• 😀 The C3bbb complex is unstable, and another protein called properdin (P) binds to stabilize it.
• 😀 All three complement activation pathways lead to the formation of C3 convertase, and the terminal steps of these pathways are the same.

Q & A

What is the alternative pathway of complement activation?

The alternative pathway is one of the first responses of the innate immune system to invading pathogens or infections. It is activated spontaneously and leads to the generation of C3 convertase.

When was the alternative pathway discovered in relation to other complement pathways?

The alternative pathway was discovered after the classical pathway, hence its name 'alternative pathway'.

What is the most abundant protein of the complement system?

C3 is the most abundant protein in the complement system.

What happens in the first step of the alternative pathway?

In the first step, C3 undergoes spontaneous hydrolysis in the blood, forming a molecule called C3 H2O.

How does the C3 H2O molecule facilitate the next steps in the alternative pathway?

The hydrolysis of C3 opens a site on the molecule, allowing the binding of Factor B, which is crucial for further steps in the pathway.

What role does Factor D play in the alternative pathway?

Factor D cleaves Factor B into larger (BB) and smaller (Ba) fragments. The larger fragment, BB, binds to the C3 H2O molecule, forming the C3 H2O BB complex.

What is the function of the C3 H2O BB complex?

The C3 H2O BB complex acts as a C3 convertase with protease activity, rapidly cleaving and activating more C3 molecules into C3b and C3a fragments.

What is meant by 'complement fixation' in the alternative pathway?

Complement fixation refers to the binding of C3b molecules to the microbial surface, making them firmly attached to the pathogen.

What happens after C3b binds to the microbial surface?

After C3b binds to the microbial surface, Factor D cleaves Factor B, generating the C3bbb complex, which acts as the alternative C3 convertase on the pathogen surface.

How is the alternative C3 convertase stabilized?

The alternative C3 convertase (C3bbb) is unstable, but it is stabilized by the binding of a protein called properdin (P).

Do all complement activation pathways lead to the same outcome?

Yes, all three complement activation pathways lead to the generation of C3 convertases, and the terminal steps of all pathways are the same.