Complement System Flashcards
The complement system is part of what part of immunity?
innate immunity
Why is complement immunity part of the innate immunity?
NON-SPECIFIC
- more general: respinds to any PAMP (just like TLR reacting to PAMPS)
- while adaptive immunity attacks specific antigens via specific antibodies.
QUICK REACTION
- aaptive immunity takes time to react (long response)
The compliment system is a quick or slow reaction? To what?
quick reaction to an antigen
What is special about the complement system?
it has different activation parts (evolutionary process adapted to newer systems):
- activated very quickly: PAMP recognition
- activated slowly: after the antibodies are produced and bound to the antigens
What does the complement system consist of?
different proteins that interact with each other
- does not include cells.
What proteins is the complement system composed of?
acute phase proteins:
- proteins overproduced in the liver
What happens to the complement system in a healthy individual?
it is inactive
generally circulate the blood stream in an inactive form
What is the complement system activated by?
PAMPs or antigen-bound
antibodies
What are the 3 activation pathways?
- classical
- lectin
- alternative
What acute protein connects all 3 pathways?
C3
What two pathways use C4 and C2?
- classical pathway
- lectin pathway
What is special about C3?
- extremely similar actions to antibodies
- reacts with PAMP like antipodies
- opsonise the pathogen
- recognised by phagocytotic cells
What is the terminal complement complex?
MAC
What is the first immunity pathway that was developed?
alternative pathway (ancient!)
What is the alernative pathway?
an evolutionary ancient pathway
What happens in the alternative pathway of healthy animals?
C3 protein breaks down spontaneously into C3a and C3b, resulting in
protein H binding on C3b, marking it for
destruction by protease called protein I.
What happens when C3b binds to the wall of a bacteria?
- protein H is unable to bind to C3b
- factor B binds to C3b, forming C3bB
complex, which stays bound to the surface of the bacteria and generated more C3b
What does the lectin pathway involve?
lectins in the bloodstream that react to microbial carbohydrates (PAMPs)
Explain the lectin pathway.
- Mannose-binding lectin (MBL) binds to bacteria, which in turn activate MASP-2 protease (MBL- associated serine protease).
- MASP-2 acts on complement component C4, splitting it into C4a and C4b, which binds to the microbial surface
- C2b then binds to C4b, forming C4b2b, which is a protease that generates C3b
What is the classical pathway activated by?
antigen-bound antibodies
Explain the classical pathway.
- Fc regions of antibodies activate C1, which in turn splits C4 into C4a and C4b.
- C2b then binds to C4b, forming C4b2b, which in turn generates C3b.
Explain the generation of MAC.
- generated C3b binds to C5, resulting in C5 being cleaved by C3bBb into C5a and C5b
- C5b then binds C6 and C7, forming C5b67 complex, which can penetrate microbial cell membrane
- C5b67 binds C8 and 12-18 C9
molecules, which results in membrane
attacking complex (MAC) formation
What is MAC?
membrane attacking complex
What is the role of MAC?
MAC= membrane attacking complex
MACs insert themselves into microbial wall and punch holes in it, eliminating the microorganism via osmotic lysis
