- Inactivated by heat

- couples the recognition of antigen by antibodies to a desired biological event

- series of over 30 different serum and membrane proteins (usually inactive)

- do not increase upon immunization

Complement

- made up of a "cascade" --> activation of one component leads to activation of the next component

- rapid amplification, yet relatively unstable

- synthesized in MHC and Hepatocytes

Complement

- complement reactions all occur on cell surface

- initial components attach to cell, which activates it

Fixation

- the inactive form of complement components that circulate in blood

Proenzymes

- abbreviation of complement

C'

- usually the smaller fragment of complement

- usually associated with inflammation

- can be anaphylotoxins (stimulate inflammation)

- when bound, release histamine

'a' complement fragment

- ions required to activate complement

Ca & Mg

- the bond by which C3b attaches to the pathogen cell surface

high-energy thioester bond

- product of all three complement activation pathways

- results in C3b complement fixation to pathogen surface

C3 Convertase

- first complement pathway to act

- does not require the presence of pre-existing antibodies

- starts in solution and moves to pathogen surface

- produces active C3b

Alternative Pathway

- in Alternative Pathway this complex functions as a C3 Convertase

- created from binding of Factor B

iC3Bb

- breaks the thioester bond of C3 to form iC3

water

- a protease that cleaves B into Ba and Bb while it is bound to iC3

Factor D

- feedback from C3b being created by C3bBb in a cycle that proceeds on the pathogen surface that amplifies the response

Positive Feedback Process

- when a pathogen is well-coated by C3b

opsinin

- activated when C3bBb combines with another C3b to form C3b2Bb

C5 Convertase

- stabilizes C3bBb on microbial surface

- works against Factors H and I

Properdin (Factor P)

- makes C3b susceptible to cleavage by Factor I

Factor H, MCP

- a lack of this factor depletes the level of C3 in blood, extracellular fluid and lymph --> clearance of infection less effective

Factor I

- after binding to C3b part of convertase --> causes dissociation and inactivation

DAF

- DAF, MCP, Factor H make up this family

RCA (regulators of complement activation)

- activated after the alternative pathway

- triggered by inflammation--> production of acute-phase proteins

Lectin Pathway

- proteins that bind carbohydrates

- MBL is one example that binds Mannose

Lectin

-protein that is responsible for triggering the classical pathway (without antibody binding)

C-reactive protein

- binds to mannose residues of glycoproteins or carbohydrates on the surface of microorganisms

- MASP then binds it

- looks like a bunch of flowers with stems

MBL

- number of molecules of MASP-1 and MASP-2 that bind MBL after it binds to microorganisms

two

- cleaves C4 into its 'a' and 'b' fragments in Lectin Pathway

MASP-2

- binds to C4b and is then cleaved by MASP-2

- the 'a' fragment stays bound

C2

- the C Convertase complex in the Lectin pathway

- can cleave C3 to create a C5 Convertase

C4bC2a

- the antibodies that activate complement

IgM and IgG

- due to pentameric structure, the most efficient antibody for complement activation

- only one molecule required to do so

IgM

- starts when an antibody directed against a protein binds to the surface of that cell or with CRP

- last pathway to respond

Classical Pathway

- first component of complement to bind in classical pathway

C1q

- functions similarily to MASP-2 in the classical pathway

- looks like an S when free, like a figure 8 when bound to C1q

Cr2s2

- binding of C1q to the antibody molecules activates this complement

C1r

- activated by C1r by cleavage

- cleaves C4 to allow C4b to bind to target surface

C1s

- inhibits activation of C1

- an insufficiency leads to inappropriate release of C2b which can produce leaky vessels and hereditary angioedema

C1-Inh

- binds C4bC2a and increases the sensitivity of C4b to Factor I

C4bp

- functions similar to C4bp on the surface of cells

CR1 & MCP (membrane cofactor protein)

- dissociates C4bC2a

DAF (decay accelerating factor)

- the two C3 Convertases that C3b can bind to

C3bBb & C4bC2a

At what number C complex does the MAC undergo a conformational shift and insert itself into the membrane?

7

- several of tis complement create a pore in the membrane after C5b678 bores deeper into the membrane

C9

- prevent C5b67 from associating with cell membranes

S Protein

Clusterin

Factor J

- prevent recruitment of C9

HRF (homologous restriction factor)

CD59 (protectin)

-components of complement system are extremely labile

- previous substrate midification

- specific regulatory proteins act on the 3 pathways

Regulators of the Complement System

- important effector of humoral immune response

- particularly can target gram negative bacteria (w/ lysozyme)

Cell Lysis

- macrophages and neutrophils recognize the complement coat which enhances phagocytosis and degradation

opsonization

- vasoactive and allows fluid to move from the blood vessels into the tissues

C2b

- have receptors for C3b

- carry immune complexes to spleen where they can be phagocytosed and degraded

Erythrocytes

- comes from a lack of necessary comlement components that leads to high levels of immune complexes that can lead to tissue damage

- defects in C1, C4 or C2

Lupus (SLE)

- comes from a defect in the anchoring proteins for DAF, HRF and CD59

- host's blood cells become more sensitive to complement which leads to lysing

Paroxysmal Nocturnal Hemoglobinurea (PNH)