Untitled - D Ank Unlimited

equinar sodium (BQR) 114 Bretscher–Cohn theory
F
5 4
6
3 CH3 7
8
N
1
C H 3
C H 3 C H2
α1 - α2 α1 - α2
CO 2 Na
2
brequinar sodium (BQR)
An antineoplastic and immunosuppressive agent. Its
major activity is inhibition of the de novo biosynthesis of
pyrimidine nucleosidases, resulting in inhibition of both
DNA and RNA synthesis. BQR has also been shown to
interfere with immunoglobulin M (IgM) production by
interleukin-6 (IL-6)-stimulated SKW6.4 cells, although in
a manner independent of DNA synthesis. In transplantation
studies, BQR has been shown to inhibit both humoral
and cellular immune responses of the host, thereby significantly
suppressing acute and antibody-mediated graft
rejection.
Bretscher–Cohn theory
A theory that allows self/not-self discrimination to occur at
any stage of lymphoreticular development. The concept is
based on three principles: (1) engagement of the lymphocyte
receptor by antigen, providing signal 1; signal 1 alone is a
tolerogenic signal for the lymphocyte; (2) provision of signal
1 in conjunction with signal 2, a costimulatory signal,
results in lymphocyte induction; and (3) delivery of signal
2 requires associative recognition of two distinct epitopes
on the antigen molecule. The requirement for associative
6'
1'
2'
5'
3'
4'
6''
Structure of brequinar sodium (BQR).
1''
F
5''
2''
3''
4''
α3 α3
C H 2
β 2 m β 2 m
Brambell receptor.
Low IgG
A
High IgG
A
B
B
C
H
recognition blocks the development of autoimmunity in
an immune system where diversity is generated randomly
throughout an individual’s lifetime.
G
C D
H
G
Mechanism of γ-globulin protection from catabolism. IgG (Y) and plasma
proteins (°) (A) are internalized into endosomes of endothelium (B)
without prior binding. In the low pH (H + ) of the endosome (C), binding of
IgG is promoted. (D), (E), (F) IgG retained by receptor recycles to the cell
surface and dissociates in the neutral pH of the extracellular fluid, returning
to circulation. (G), (H) Unbound proteins are shunted to the lysosomes
for degradation. With low IgG, receptor efficiently rescues IgG from
catabolism. With high IgG, receptor is saturated and excess IgG passes to
catabolism for a net acceleration of IgG catabolism.
D
F
E
F
E
H
H