828

chapter

35

Molecular Immunology

F I G U R E 3 5 -2 1

(Also see color figure.) Structures for the immunosuppressant, FK506 (tacrolimus). Tacrolimus is a macrolide isolated

from

S trep to m yces tsu ku b a en sis.

Shown from left to right in approximately the same orientation are the simple line

structure, a stick- structure, and a space-filling structure. The stick and space-filling structures are based on the

3-dimensional structure of the molecule bound to the immunophilin FKBP. Protein data bank designation 1FKF.

T A B L E 3 5 - 3

Proteins o f the Complement System: Alternative, Classical, Lectin, and Membrane Attack Pathways and Complement

Regulating Proteins

ALTERNATIVE

PATHWAY

Initiated by attack of nucleophilic cell surface molecules on thioester in C3

and/or spontaneous hydrolysis by H20 of thioester in C3

Protein /Subunit(s)

Serum Cone.

Molecular

Weight

Description and Role of the

Active Form

(mg/L)

(chains)

Active Forms in These Pathways

D

2

24,000

Cleaves B to Ba and Bb

B

200

93,000

Contains serine protease active site of C3bBb

Ba

Bb

P (properdin)

20-30

-46,000

Chemotactic peptide

Active site-containing chain of C3bBb, the C5

convertase

Stabilizer of C3bBb

C3 Convertase (C3b,Bb)

C3 (see classical pathway also)

1,110-1,710

185,000

Alternative pathway C3 convertase

Precursor to C3a and C3b

C3a

C3b

C3d, C3d,g,

C3e, C3d-K

Anaphylatoxin, increases vascular permeability and

causes mast cell degranulation

C3b contains a thioester bond that can attach C3b

covalently to target cells. Forms complex with

factor B, allowing D to cleave B. C3bBb forms

complex with C5, allowing C3bBb to cleave C5.

C3bBb stabilized by binding P to form C3BbP.

Opsonin

Fragments that interact with complement receptor, CR2

Involved in leukocytosis

( continued)