Acute Phase Proteins Flashcards
What is an acute phase response?
A change in composition of the blood during an early stage of an infection since the liver is changing its protein production.
Which interleukins releases cytokines that signals the hepatocytes to change the livers protein production?
IL-6, IL-1, and TNF
What is the function of acute phase protein?
- Combat infections
- Eliminate debris from wounded tissue / aids in healing
- Protect the host from potential dangerous parts of the inflammatory response
Which acute phase protein is involved with coagulation?
Fibrinogen, which is consumed in the tissue damage and builds fibrin networks that creates blood clots
What is the CRP (C-reactive proteins function)?
They bind to bacterial and fungal surfaces and then activates the complement system.
fun fact: It is the clinical biomarker of inflammation
What is the function of MBL (Mannose binding lectin)?
They bind to particular carbohydrate structures (mannose and fucose residues with the right spacing) on microbial structures.
What are the most important complement proteins and why?
C3 and C4. Complement proteins C3 and C4 both have a hidden thioester. When bound to surfaces R-OH this causes a strong thioester bond. A spontaneous “tick-over” temporarily exposes the thioester due to cleavage of the native molecule and it can then bind strongly to microbe surfaces.
The proteins in the complement system are usually proteases
that only become active when cleaved by another protease, what are the effects of the activation?
Local activation gives a strong and rapid amplification in the next
cleavage step, unless inhibited.
What are will occur regardless of the activation pathway?
i) the system is mainly activated by/at biological surfaces
ii) all activation pathways result in formation of C3-convertases
and surface bound C3b
iii) All activation pathways lead to a common “terminal”
pathway, surface bound C3 convertase which forms C5 convertase when bound to C3b. Enzyme-cleaving cascade forms the pore-forming membrane attack complex (MAC) which kills by destorying the membrane integrity of pathogens.
iv) true complement activation is to a large degree a result of
poor inhibition of the cascade; most microbes do not express
complement inhibitors (like host cells do)
The main event of activation is:
Proteolytic cleavage of C3 to C3b and C3a
The protelytic cleavage is achieved by 2 convertases that are assembled by 3 pathways, name the pathways different ways each pathways starts.
Classical : activated by complement protease C1q that binds directly to pathogen surface or indirect to an antigen/antibody complex .
Alternative : The protein C3 is spontanously hydrolyzed into C3a and C3b. When C3b is formed, it can bind to the surface of pathogens, such as bacteria or viruses.
Lectin : activated by MBL or ficolin that has bound to carbohydrate structures on a microbial surface.
Describe the classical pathway in 4 steps
- C1q binds to 2 IgG or 1 IgM via one or more globular head
- The activated C1s cleaves C4. This results with C4a and C4b. C4b will bind to a microbial surface.
- Then C4b binds to C2 which cleaves it. This results with C2a bound to C4b on the surface and C2b leaving.
- C4b2a is a C3 convertase and cleaves C3. C3b binds to microbial surface to be as an opsonin.
Describe the lectin pathway
- Activates by MBL (mannose binding lectin) or ficolins
- MASP-1 and 2 work similarly to C1s, same process as classical after step 2.
Describe the alternative pathway
- C3 undergoes spontanous hydolysis and which binds to a B factor that is cleaved by D factor
- C3(H2O)Bb is a soluable C3 convertase, which will cleave C3 into C3a and C3b
- C3b will then bind to another B factor which will cleave it into Bb and Ba. C3bBb is a C3 convertase.
