Lecture 3 - Complement

Question 1

Complement: what is it, how many proteins are present, what does its activation do, and what does it do?

Answer 1

The major system of first-line, highly regulated humoral innate defence

> 50 proteins (soluble and membrane bound)

Triggers an amplifying cascade of sequential interactions - proteolytic cleavage and/or induced conformational changes causing enzyme activation, or a change in binding properties enabling progression to the next step

Products generated cause a range of effector functions and interface with both innate and adaptive immune responses

Question 2

Complement components: where are they mainly sourced from, where else are they sourced from, and how do they react to cytokines?

Answer 2

The main source of serum complement components is the liver (several are acute phase proteins)

Components are also made locally by other cells;
eg monocytes, macrophages, DC, neutrophils, fibroblasts, epithelial cells (found in barrier secretions), B and T cells, adipocytes

First-line defence, and also production is responsive to inflammatory cytokines

Question 3

Complement components nomenclature

Answer 3

C = complement (numbered in the order they were discovered)

Alternative pathway (letters);
Factor B, Factor D, Properdin (Factor P)

Following Cleavage the
Smaller fragment = a (soluble), bigger fragment = b (binding)
EXCEPT C2, where C2a is bigger and C2b is smaller

Question 4

Alternative, lectin, and classical pathways

Answer 5

Triggering of both the classical and lectin pathways is targeted to non-self surfaces, such as microbes, or potentially noxious self surfaces (immune complexes and apoptotic cells), by specialised sensor molecules recognising PAMPs/DAMPs, or, in the case of C1q, targeting linker molecules, such as antibodies or pentraxins.

Triggering of activation leads to formation of the classical pathway C3 convertase (C4bC2a) covalently tethered on the target surface resulting in local generation of C3b

The high reactivity of the thioester bond exposed on the generated C3b ensures that it in turn will be deposited locally on the target surface

Question 6

properdin

Answer 6

Positive regulator

Question 7

Rwgulators

Answer 7

Dissociation of C3 convertase
Co-factor activity to enhance degradation by Factor I