In
Graves
disease
,
B
and
T
lymphocyte
-
mediated
autoimmunity
____________________
known
to
be
directed
at
4
well
-
known
thyroid
antigens
:
thyroglobulin
,
thyroid
peroxidase
,
sodium
-
iodide
symporter
and
the
thyrotropin
receptor
.
____________________
,
the
thyrotropin
receptor
itself
____________________
the
primary
autoantigen
of
Graves
disease
and
is
responsible
for
the
manifestation
of
hyperthyroidism
.
In
this
disease
,
the
antibody
and
cell
-
mediated
thyroid
antigen
-
specific
immune
responses
are
well
____________________
.
Direct
proof
of
an
autoimmune
disorder
that
is
mediated
____________________
autoantibodies
is
the
development
of
hyperthyroidism
in
healthy
subjects
by
transferring
thyrotropin
receptor
antibodies
in
serum
from
patients
with
Graves
disease
and
the
passive
transfer
of
thyrotropin
receptor
antibodies
to
the
fetus
in
pregnant
women
.
The
thyroid
gland
is
____________________
continuous
stimulation
by
circulating
autoantibodies
against
the
thyrotropin
receptor
,
and
pituitary
thyrotropin
secretion
is
____________________
because
of
the
increased
production
of
thyroid
hormones
.
The
stimulating
activity
of
thyrotropin
receptor
antibodies
is
____________________
mostly
in
the
immunoglobulin
G1
subclass
.
____________________
thyroid
-
stimulating
antibodies
cause
release
of
thyroid
hormone
and
thyroglobulin
that
is
mediated
by
3
,
'5'
-
cyclic
adenosine
monophosphate
(
cyclic
AMP
)
,
and
they
also
stimulate
iodine
uptake
,
protein
synthesis
,
and
thyroid
gland
growth
.
