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Lecture 7

Humoral immunity

QuestionAnswer
Innate humoral immunity -Complement cascase - ~30 serum proteins -core complement components (C1-C9) -Products are cleaved into active split forms (C3 -> C3a and C3b) -all to make C3 convertase
Complement system pathways 1. Classical -binds antibody (innate - adaptive bridge) 2. Lectin -Mannose binding lectin (MLB - innate) -microbial sugars 3. Alternative -just tick over a complement protein C3 -spontaneous C3 activity -pathway always on at low levels
Complement helpers vs regulators Helpers -Factor B, D Regulators -Factor H, Factor I
Classical pathway activation -binding of C1q to antibody-antigen complex -C4b2a (bound C3 convertase) splits C3 -> C3a + C3b -C5 convertase (C4b2a3b) -cleaves C5 -C5a -> anaphylotoxin - C5b -> Membrane attack complex (MAC) -CD59 on host cells
C3a vs C3b -C3a =anaphylatoxin (mast cell degranulation) -inflammation, activate immune cells, vascular permeability -C3b - binds to bacterial membrane (opsonization), binds to the convertase to upgrade to C5 convertase (C4b2a3b)
CD59 CD59 on host cell -inhibids C( polymerization ( 10-18 C9 to make a pore) -prevents damage to self
Lectin activation -MBL binds bacterial sugars -binding exposes serine proteases -> C1s and MLC associated serine protease (MASPs) -both MPs cleave C4 and C2 -C4a binds covalently to nearby surface (anchor to bacteria) -recruits C2b = C3 convertase (C4b2a)
Alternative activation -C3 in blood -spontaneous hydrolysis = C3(H2O) - C3 activated without serine protease -binds factor B - factor D can cleave factor B -> Bb -C3(H2O)Bb= fluid phase C3 convertase -short lived, low efficiency
Pathways similarities/differences -all about getting C3 convertase -major difference is the anchor -classical/lectin = C4b (C4b2a) -alternative = C3b (C3bBb) -downstream is the same
Opsonization -C3b bound to bacterial membrane (opsonization) can change from weaponized to informational (tames the complement cascade -C3b -> bunch of steps involving factor I -> C3d (long lived, covalently bound) -C3d binds to CR2 -flag = complement sees antigen
BCR and CR2 bind -if BCR and CR2 bind same antigen = 10 - 100x the activation -links innate sensing and adaptive decision making
Created by: user-2017899
 

 



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