Part 7: Complement Sytem

Jules Bordet

Discovered the nature of complement

Liver

Most complement are produced in the _______

Intestine

C1 is found in the _____

Adipose

Factor D is found in the _______

Cell Lysis

End product of Complement System

Antiviral induction and apoptopsis

Not a function of complement system

Ag-Ab complex (+ CRP, mycoplasma, E. coli)

Classical pathway is triggered by________

Anaphylatoxin

Substance that cause release of histamine

C1

Heaviest complement

Calcium and Magnesium

C1 is stabilized by _________

C1q

Involves in the recognition of antibody

CH2

Binding region for IgG

CH3

Binding region for IgM

C4

Second most abundant complement

C5a

Most potent anaphylatoxin (also a chemotaxin)

C4b

1st in activation/ amplification step

C4b2a

C3 convertase

C3

Major constituent of the complement system;

Pivotal point of all 3 pathways

C4b2a3b (C5 convertase)

Last step in the formation of the activation unit

C5b

Beginning of Membrane Attack Complex

C8

Starts pore formation in RBC but not to nucleated cells which requires C9 to accelerate the process.

Alternative pathway

aka properdin

Bacterial cell wall, LPS, fungal cell wall, yeast, virus, virally infected cell, tumor cell lines and parasites

Alternative pathway is triggered by________

Properdin

C3 convertase stabilizer

Factor D

Cleaves Factor B

MBL (lectin)

Triggered by recognition of carbohydrate on microbial cell wall

Factor I

Cleaves C3b and C4b

CR1 or CD35

Found on peripheral blood, has the greatest affinity to C3b, mediate transport of C3b coated immune complexes to the liver and spleen

MCP (Membrane Cofactor Protein) or CD46

Found on all epithelial and endothelial cells except RBC, most effective cofactor for Factor I

DAF (Decay Accelerating Factor) or CD55

Found on endothelial cells, fibroblast, peripheral blood and epithelial cells. It dissociates C3 convertase; its presence protects hos from by-stander lysis.

S protein

Prevents attachment of the C5b67 complex to cell membrane

MIRL (Membrane Inhibitor Reactive Lysis) or CD59

Function is to bind to C8 and prevent insertion of C9 into host cell

C2 deficiency

Most common deficiency characterized by Lupus0like syndrome, recurrent infection, atherosclerosis

C3 deficiency

Most severe deficiency characterized by severe recurrent infection, glumerolunephritis

C1 inhibitor

Deficiency of this complement leads to Hereditary Angiodema

PNH

Deficiency of DAF leads to

Familial Mediterranean Fever

Defect in protease in peritoneal and synovial fluid (chromosome 16)

CH50

Measures the amount of px serum required to lyse 50% of a standardized concentration of Ab-sensitized sheep RBC

ELISA

Best screening for complement abnormalities

56 degC for 30 minutes

In complement fixation test, serum must be heated to ____ for ___

Cytokines

Small soluble proteins that regulate the immune system

Autocrine stimulation

Affecting the same cell that secreted it

Paracrine stimulation

Affecting neighboring cells

Cytokine Storm

Massive production of cytokine

Pleiotropic

Have many different effects to different cells

Redundancy

Many cytokines share receptor subunits

Antagonism

Cytokine may counteract the action of another cytokine

Synergistic

Acts in networks; one cytokine complements and enhances another

Cascade Induction

A cytokine secreted by a specific type of cell can activate target cells to produce additional cytokines