Innate Immunity Part II- Lecture 5 Flashcards
What is the definition of a zymogen in immunology and give an example?
Proteases secreted in inactive form then cleaved into an active form
C3 –> C3a and C3b Via C3 convertase
List the 9 stages of the Alternative Complement Pathway
- C3 is spontaneously cleaved to C3b on the cell surface
- Factor B binds to C3b
- Factor D binds to Factor B
- Factor B is cleaved into Bb and Ba
- Bb is bound to C3b, forming C3Bb (C3 convertase)
- C3 convertase cleaves C3 into C3b and C3a
- C3b combines with C3Bb, forming C3bBbC3b (C5 convertase)
- C5 convertase cleaves C5 into C5b and C5a
- Formation of the MAC
What is the function of MAC?
Membrane Attack Complex causes cell lysis and is the same in all complement pathways
What stabilizes the interactions of the alternative pathway?
Properdin
List the 7 steps of the classical complement pathway.
- IgM binds to the surface of the bacterial pathogen
- C1 binds to the “staple formation” of IgM
- C1s cleaves C2 C2a and C2b, C4 C4a and C4b
- C4b combines with C2a to form C4bC2a (C3 convertase)
- C3 convertase cleaves C3 into C3b and C3a
- C3b combines with C4bC2a forming C4bC2aC3b (C5 convertase)
- Formation of the MAC
What are the functions of the following complement proteins? C3b
C3b- Opsonization via CR1 on Macrophages
What are the functions of the following complement proteins? C5b
C5b- Initiates MAC formation
What are the functions of the following complement proteins?
C7
C9
C7- Inserts into the cellular membrane
C9- Polymerizes to form the pore
What are the functions of the following complement proteins? C5a
C5a- Strong chemoattractant and initiates killing via ROS
What are the functions of the following complement proteins? C5a > C3a
C5a > C3a (anaphylatoxin): Inflammation (SM contraction, increase in vascular permeability, degradation of Mast cells)
What complement proteins make up the MAC complex?
MAC complex: C5b, C6, C7, C8, C9
There are 2 other complement proteins that have regulatory functions. What does each do?
DAF and CR1
DAF- Blocks C2:C4 interactions
Both DAF and CR1: Enhances dissociation of C4bC2a OR C3bBb (both pathways)
CR1- dissociates C4bC2a OR C3bBb, with FI cleaves C4b or C3b, phagocytosis when bound to C3b (all pathways)
What are the 4 ways to activate macrophages?
- TLR activation (especially LPS on TLR 4)
- IFN- gamma via NK cells
- Complement Mediated
a) CR1 (Macrophage activating factor) binds to C3b and is phagocytized
b) Phagosome fuses with lysosome
c) IFN- gamma releases trigger killing of pathogen via ROS
- Note: Catalase (+) bacteria can survive phagolysosome –> formation of water and oxygen
4. CD4 TH1 cells (intracellular pathogens ONLY): Macrophage activating factor presents antigen via MHC class II to T cell and T cell releases IFN- gamma via CD40 on Macrophage activating factor, CD40L on T cells)
What are the 3 inflammatory molecules and what does the first 2 cause?
IL-1: Induces fevers
TNF: Increases vascular dilation and permeability
IL-6: Acute Phase Proteins (CRP, SAP)*
What are the two types of interferons?
Type 1: INF alpha and beta
Type 2: INF-gamma
Describe Type 1 interferons: INF alpha and beta
Intracellular TLR (which are ??), in particular viral RNA
Response: On healthy cells, create antiviral replication proteins, on infected cells enhanced killing via CTL (CD8 cells)
Describe Type 2 interferons: INF-gamma
Response: Enhanced macrophage killing and production of IgG antibodies