Complement Cascade Flashcards
What is the complement system?
A group of proteins in blood that helps the immune system fight infections
Why is it called a complement cascade?
It is a step by step process which works alongside the immune system
What are the two ways complement proteins can be activated?
- Activated by microbes in the absence of antibodies
- Activated my antibodies attached to microbes
What does amplification refer to in the compliment cascade?
Molecules produced early in the cascade may generate a large number of effector molecules
What are the three main purposes of the complement system?
- Opsonisation
- Chemoattraction
- Membrane attack complex
What is opsonisation?
Marking invaders for destruction so phagocytes can find them and engulf them
What is chemoattraction?
Recruiting immune cells by releasing small protein fragments that cause inflammation
What is membrane attack complex?
Destroy microbes directly by punching holes in their membranes
What are the two different pathways to complement activation that occurs in absence of antibodies?
- Alternative pathway
- Lectin pathway
What is the pathway to complement activation that occurs when antibodies are present?
Classical pathway
How does alternative pathway activation occur?
- Protein C3 is always slowly breaking apart into C3b
- If bacteria or virus present C3b will stick to their surface and start complement cascade
- The complement protein C5 is broken down to initiate the later steps
What happens to C3b if no bacteria or virus is present?
C3b is quickly deactivated to prevent unnecessary damage to our own cells
What does C3 tick over refer to?
The continuous breaking down of C3 into C3b
How does classical complement pathway activation occur?
- Requires an antibody bound to antigens to allow C1 to bind to it
- C1 binding triggers a cascade that leads to C3 cleavage into C3b which bind to antigenic surface
- The complement protein C5 is broken down to initiate the later steps
How does lectin pathway activation occur?
- Triggered by a plasma protein called mannose-binding lectin
- Recognises mannose residues on microbe and bind activating MASP enzymes
- Triggers cascade which leads to C3 cleavage into C3b
- The complement protein C5 is broken down to initiate the later steps
What is the role of C3b and C3a?
C3b - sticks to microbes making them easy to identify
C3a - triggers inflammation attracting immune cells
What is the late steps of complement activation?
- C5b binds to C6, C7 and C8 complement protein and form a hydrophobic complex
- The complex inserts into the membrane of the bacteria
- C9 then joins forming a membrane attack complex pore
- Water ruches in causing the cell to lyse
What is the role of C5a?
Triggers inflammation attracting immune cells
What are the three way complement activation is regulated?
- Decay accelerating factor
- Membrane cofactor protein
- C1 inhibitor
What does decay accelerating factor do?
Stops the formation of C3 convertases
What does membrane cofactor protein do?
Helps break down C3b when no microbe present to prevent damage to host cells
What does C1 inhibitor do?
Prevents the classical pathway from activating when there’s no infection
What does C3 deficiency lead to?
Frequent bacterial infections as opsonisation does not work properly
What does C1 inhibitor deficiency lead to?
Causes uncontrolled complement activation leading to swelling in the face, throat and gut
