2. Innate Immunity Flashcards
What are collectins and how can they activate complement?
Pattern Recognition Receptors
- Lectin head binds to sugars on bacterial surfaces
- Collagen tail binds to phagocytes
activates complement cascade
Host cells are protected via sialic acid covering mannose
E.g MBL
Ficolins
Trimer molecule that recognises acylated compounds on bacterial cell walls
- opsonisation
- activate complement
What is complement
proteins floating around that cause a series of reactions before immune cells take action
Part of innate immunity
Heriditary Angioedema
C1 inhibitor deficiency
-no inhibition so C1 can’t inhibit C4 and C2
Describe the classical pathway of the complement system
Binding of C1 to Ag-Ab complexes activates classical pathway
C2 and C4 is cleaved off
C3 convertase (C4b2a)
Describe the alternative pathway of the complement system
- Activated by C3b or C3i binding to microbial surfaces
- C3 spontaneously splits into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb (aka C3 convertase) can hydrolyse more C3 creating more C3b which can amplify the signal
- C2bBb and C3b=C3bBbC3b aka C5 convertase
….MAC
Describe the lectin pathway of the complement system
- Antibody independent
- Activated by ficolins with MBL- these bind carbohydrates
- Forms complex with MASP-1 and MASP-2 after binding with MBL
- Active complex cleaves C2 and C4
Lysozyme
Antimicrobial enzyme
- Found in tears, saliva
- Disrupts bacterial cell wall
Most effective against Gram-positive bacteria
Antimicrobial peptides
Amino acid chains secreted by neutrophils, paneth cells (SI)
-cover epithelial surfaces, found in saliva
- Disrupts bacterial membrane
- Attacks fungi and viruses
- Inhibits RNA and DNA synthesis
Collectins, ficolins and pentraxins
What are they?
Actions?
Soluble innate immune molecules
-Act as opsonins
bind to pathogens targeting them for phagocytosis
activate complement through the classical/lectin pathway
Activated by C3b or C3i binding to microbial surfaces . This best describes which complement pathway?
Alternative pathway
MASP1 and MASP2 assembling on MBL best describes which complement pathway?
Lectin pathway
Complement System Pathways and initiators
- Classical: C1q
- Alternative: C3b (“tick over”)
- Lectin: MBL/Ficolins
2 consequences of complement deficiencies
- Heriditary Angioedema
- Recurrent infections
- pts deficient in C8 suceptible to infections with N.meningitis
What can deficiency in C4 lead to?
90% develop SLE
C4 deficiency means less C3b (C4b2a is C3 convertase)