The induced response to infection (2) Flashcards
What triggers the lectin pathway of complement activation?
Mannose-binding lectin
What pathway does C-reactive protein trigger?
The classical pathway
What triggers interferon response?
Internal detection of viral infection
What do plasmacytoid dendritic cells do?
They are factories for making large quantities of type I interferons
What are the main lymphocytes involved in innate immunity?
NK cells
Where are NK cells distributed?
2 populations of NK cells are differently distributed in blood and tissues
Where is NK cell cytotoxicity activated?
At sites of virus infection
What happens between NK cells and macrophages at site of infection?
They activate each other
What do CRP and Mannose-binding Lectin do?
They bind do structural features of bacteria and opsonise the bacteria thus activating complement and facilitating phagocytosis and direct lysis of bacteria by terminal complement components.
How does Mannose-binding lectin circulate in plasma?
As a complex of 2 serine protease zymogens - MASP1 and MASP2
What do MBL, MASP1 and MASP2 do?
Together MBL, MASP1, and MASP2 trigger the complement cascade
What is MBL?
Mannose-Binding Lectin which is a C-type lectin and acute phase protein
What does MBL bind?
Mannose-containing carbohydrates of bacteria, fungi, protozoa, and viruses
What does the complex between MBL, MASP1+2 look like?
A bunch of flowers
Each flower has 3 identical polypeptides
Stalks are rigid triple helices like collagen, with a single bend
Each flower comprises 3 carbohydrate binding domains
What are MASPs?
MBL Associated Serine Proteases
How does MBL, MASP1 and MASP2 initiate complement activation?
The complex cleaves C4 into C4a (anaphylatoxin) and C4b can bind to pathogen surface alongside MBL.
C2 gets cleaved by MBL forming C2a which attaches to C4b. The resulting protein is C4b2a.
C4b2a is a C3 convertase which allows C3b opsonisation of pathogen surface.
The C4b2a is called an Classical C3 convertase.
What is C4a like compared to C3a and C5a?
It is much weaker
How does CRP initiate the classical pathway of complement activation?
CRP bound to bacterium can also interact with C1 which is the first component of classical pathway activation.
CRP bound to bacterium interacts with C1 resulting in cleavage of C4 and opsonisation of bacterial surface with C4b.
Also cleaves C2 leading to formation of classical C3 convertase C4bC2a
Which of the 3 pathways for complement activation is fastest?
The alternative pathway
What does C1 complement component look like?
Consists of C1q, C1r, and C1s subunits.
C1q consists of six identical subunits each with a site for binding of Fc region of IgM or IgG. [CRP and antibodies can trigger the classical pathway as a result of this]
Extended amino-terminal stalk regions that interact with each other and with proteases C1r and C1s
How do human cells detect viral infections?
Human cells have sensor proteins in the cytoplasm that can detect viral nucleic acids and initiate defensive response.
What is the key cytokine in viral infections?
Type 1 Interferons
What do interferons do?
They interfere with viral replication
How are viral nucleic acids detected in the cell?
Via RIG-1-like receptors (RLRs)
How do RLRs detect viral presence in the cell?
They have a recognition domain that is similar to RNA helicase
2 CARD domains that interact with MAVS (mitochondrial antiviral signalling) protein