Flashcards in Immunology-9 (Kyle) Deck (39)
What is the classical pathway for complement activation?
Antigen : Ab complexes (First to act)
What is the lectin pathway of complement activation?
Lectin binding to pathogen surfaces (Second to act)
What is the alternative pathway of complement activation?
Pathogen surfaces. (Third to Act)
What is the common theme of complement activation?
Clevage of C3 to C3a and C3b. C3b will be covalently bound to surface components of pathogen.
What does the clevage of C3 do to the pathogens?
Recrutes inflammatory cells,
What does the complement cascade do?
Marks pathogens for destruction by phagocytes ( Opsonization )
What are anaphylatoxins?
Inflammatory mediators rpoduced by the complement cascade.
What do anaphylatoxins actually do ?
These small molecules are chemotactic and induce vascular permeability which induces inflammatory responses.
Where are components of the complement cascade produced?
In the liver in their inactive form.
What do anaphylatoxins do?
Recruit fluid and immune cells to sites of antigen deposition.
What is the most important product of the complement cascade?
Deposition of the opsonin C3b
Why is C3b important?
Complement receptors on phagocytes bind to C3b (and fragments of C3b) which facilitates uptake and destruction of the pathogen
What enzyme is C3b a part of that activates the membrane attack complex?
What does C3a do ?
Is the alternative pathway of activation a purely innate mechanism?
What is the race of C3 cleavage?
Very low but in the presence of bacteria the rate will be greatly increased.
What happens after C3b is deposited on the surface of a bacterium?
It becomes a ligand for factor B. When factor B binds to C3b, factor D cleaves factor B.
When factor D cleaves factor B what is the end result?
C3b, Bb, and Ba are produced.
What happens when C3b binds to C3b, Bb ?
C5 convertase is produced.
What binds to C5b?
C6, C7, C8, and tons of C9. This attack complex forms a pore in the bacterial membrane.
What complement component is a main part of the lectin pathway of complement activation?
MBP (mannose- binding proteins)
What does MBP do ?
MBPbinds to the terminal mannose residues on the surface of the bacteria. The glycoproteins and glycolipidsthat hae mannose residues which are unique to the bacteria and not the host.
Once bound to the microbial surface what does MBP have a high affinity for ?
MASP-1 and MASP-2 which activates them.
What happens when MASP-1 and MASP-2 are activated?
They are able to cleave C4 to form C4a and C4b. And cleave C2 to C2a and C2b.
What happens when C2b and C4b bind to the pathogen surface?
Together they for the active C3 convertase which cleaves C3 to C3a and C3b.
**After this step the cascade is identical to the classical pathway
What is the end result of the classical pathway of complement activation?
Implantation of C3b onto the bacterial cell membrane.
What are the components of the classical C3 convertase ? What binds to the classical convertase?
C2a and C4b.
C3, which is ceaved to C3a and C3b. C3b implants in the pathogen surface.
What is the purpose of the C5b, C6, C7, C8 complex do ?
Recrute tols of C9 which physically form the pore
What is the most important end result of complement activation ?
What does C3b deposition do ?
In the Classical and Lectin pathways will still be activated but the alternative pathway will amplify the response. The Pathogen will be opsonized.
For people who cant make an activated membrane complex, what pathogen is a big problem ?
What is the mechanism of innate activation of the classical pathway?
C1 binds to C-reactive protein and IgM. This complex bonds to phosphocholine which is on the surface of the pathogen.
Why is opsonization via complement important?
Look this up
Is deposition of C3b permanent?
Yes, Once compement has been deposited it is there forever and is a permanent marker for destruction.
Is C1q always activated?
There is always some level of activation but it is not always fully activated.
What does C1inhibitor do? (C1INH)
C1INH binds to activated C1r : C1r forcing the dissociation from C1q
What happens when C1INH is deficient?
C1INH deficiency causes a serious illness that is characterized by systemic edema.
What is the systemic edema from in (C1INH) deficiency?
Overproduction of anaphylatoxins. Results in hereditary angioneurotic edema (HANE) which is treated by C1INH replacement therapy.