February 7 Notes

Immunology, February 7, 2008
I. Complement components
Complement Cascade- sequence of events during complement activation
Classical- antibody activation, acquired immunity response
Complement proteins are always around, but inactive— activation by cleavage into fragments (A&B)
A=small, induce inflammatory responses
B=big, catalyze future steps
a. C1, C2, C4
1.Antibody binding to microbe
2.C1 binds to antibody- conformation change to C1 proteins
3.C1 obtains proteolitic properties, cleaves C2 into C2a & C2b
C2b attaches to microbe surface via C1— cleaves C4
4. C2b cleaves C4 into C4a and C4b— attaches to C2b, which is attached to C1, which is attached to microbe (C4bC2b= C3 convertase)
b. C3
i. C3 convertase (C4bC2b) cleaves C3 into C3a and C3b
C3a is an inflammatory activator (increases neutrophils, increases vascular permeability)
1. C2bC4b
ii. C3b- opsonin- formation of MAC or Membrane Attack Complex
c. C5
d. C6, C7, C8, C9 = Membrane attack complex (MAC)
II. Complement pathways
a. Classical pathway
i. antibody binding to a microbe
ii. C1 bind to antibody
iii. C1 binding to ab conformational change in C1 so that it can now cleave C2 into C2a & C2b
1. C2b is attached microbe via C1
iv. C2b cleave C4 into C4a and C4b
1. C4b: attached to microbe via C2b
2. C4bC2b (aka C3 convertase)
v. C3 convertase cleaves C3 into C3a and C3b
1. C3b: opsonin; leads to MAC form; amplifies complement production
2. C3a: inflammation activator: recruit neutrophils

b. Alternative pathway
c. Lectin pathway(mannose binding lectin): MBL: acute-phase protein; secreted by liver in response to inflammatory activators
First: MBL blind to mannose, fucose- containing motifs in microbial cell wall
**Then, MASPs(MBL-associated serine proteases) bind to MBLs
**MASPs then cleave C2 and C4
*
This results in the formation of C4b-C2b= C3 convertasae
Rest of steps same as classical
*
C3 into C3a and C3b
*C5 into C5a and C5b
*
C6, C7, C8, C9 lots) = MAC

III. Avoidance of complement
a. How do our cells avoid complement?Proteins present on membranes to stop complement components from binding.
* Decay accelerating Factor (DAF) and membrane Co-factor Proteolysis (MCP)
b. Pathogen strategies for avoiding complement- they try to mock our defenses, such as having molecules that are similar to DAF and MCP, or they try to be engulfed in order to live in our cells.

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