BLG 307 Lecture Notes - Cd19, Cowpox, Monocyte

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28 Jan 2013
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IMMUNOLOGY
COMPLEMENT SYSTEM
I. Overview
-proteins necessary for humoral and cellular immjunity in a highly regulated cascade of proteolytic events
-activated directly by exposure to foreign cell surfaces -indierectly through interactions with
Ab
-split products mediate cell migration, activation/adhesion- interact with CR on other cells
(leuk/plat/endo/SM/epi)
-terminal proteins (C5b-C9) = pore forming structure that can activate or lyse cells
Complement initiates
1. Attracting/Activating granulocytes and macs
2. Opsonizing bacteria/cells to target for phag
3. Pore Formation in c ell membranesrupture
4. Activation of antigen-specific B and T cells
Complement Actiavation (All converge in the activation of C3)
A. Classical Pathway
1. C1 binds Fc portion of ANTIBODY via Q domain (C1Q)
-C1 is a multiprotein complex: C1Q has six ubunits with collagen like tails and globular head
-Ab can be with antigen or on cell surface
-must bind MULTIPLE antibodies Fc’s for protease activity
-(IgM bound to antigen for steric change 2 IgG’s aggregagte by binding antigenic surace)
-C1q critical physical link between the Ab and complement arms of immunity
2. C1S (ser protease) cleaves C4 into A and B C4B (thioester group) attaches to bacterial surface.
attracts C2
-note C4B stron nucleophile and will be deactivated by water
-C1S cleafves many C4s
3. C1S cleaves C2 into A and B C4B + C2A = CLASSICAL C3 CONVERTASE (C3-directed
protease)
B. MBL (mannose-binding lectin) Pathway
-lectin and alternative pathway are key in immediate defense and natural immunity
-don’t have memory but can differentiate self (evolved before classical pathway)
1. same process except MBL substitutes C1 complex (by passes Ab)
binds mannose via its lectin heads
MBL MASPS cleaves C4 and C2 to make Classical C3 Convertase (C4B + C2A)
**no antibody recognition necessary; bacteria is directly recognized**
C. Alternative Pathway
-simplest, most primitive way (relies on C3 tickover) NO SPECIFICITY binds any nucleophile
-amplification pathway b/c always making C3b which could form anathor C3 convertase
(1) C3 binds bacterial surface spontaneously
Microenvironment of binding determine activation of factor b or inactivation of C3b by H
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