Dr David McGrath

Spine Physician

MB BS (Hons) FAFOM, RACP, FAFMM
Master of Pain Medicine

Chemical Messengers (Plasma Proteins)

Defensive Complement System

1. Approximate 30 liver glycoproteins in the serum or on Membranes as Receptors.

2. Inactive UNTIL activated by components from one of three pathways. A proteolytic cascade occurs until a complex is formed which engages the cellular immune system. Intermediate proteins are also biologically active.
3. The cleavage of the protein gives an a,b part. (the b part is active in the cascade)(the "a" component is often active as a cytokine or local hormone)
4. The C1 component has three sub-components.
5. Partial activation of the cascade can occur.
Complement Cascade

CLASSICAL PATHWAY (Immune Complexes)	LECTIN PATHWAY (Carbohydrates, Collectins)	ALTERNATE PATHWAY (Activating Surfaces like bacteria)	BIOLOGICAL ACTIVITY
C1q	MBP (mannan binding protein)		The main opsonin in the body,for destroying bacteria
C1r	C1r MBP	C3b
C1s	C1s OR MASP (associated serine protease)	P factor
C4	C4 C4	D factor
C2	C2 C2	B factor
C3	C3	C3
C3b	C3b	C3b
C5b678(9) Membrane Activating Complex (MAC)	MAC	MAC	Cytotoxic Cytolytic (damaged cells or bacteria )

Individual component Activities

Component	Physiological Role
C3b,C4b,MBP	Opsonins Bacterial lysis Antibody Binding
MAC	Cell Lysis
C5a,C3a,C4a (Anaphyla/toxins	Vascular Permaeability Smooth muscle Contraction Degranulation of Mast Cells and Basophils

Protein Protection Mechanisms Anti-Proteolytic Proteins

1.A major physiological process, is proteolysis. A segment or amino-acid is split off from the protein. This can activate enzymes or damage their function (bacteria). This activity is up-regulated during stress and immunological activity. White cells can release a number of proteases, as part of our defence. The proteolytic enzymes are increased and more active. There is spill over into the plasma and circulation.Collateral damage to healthy tissue can result. The liver under the influence of hormones, increases its output of anti-proteolytic enzymes, in order to keep this in check.

ProteinEffect	Effect
Anti-Trypsin	Protease Inhibitor Restricts proteolytic action to localised sites
alpha2-Macroglobulin	Protease Inhibitor
Anti-Chymotrypsin	Protease Inhibitor

Clotting system

Fibrinolytic System (anti-clotting or plasmin system)

Kinin System

(to be continued)