202 • External Disease and Cornea
Tolerance
of
a corneal graft
is
now recognized
as
an active process based on several
features:
• absence of blood and lymphatic channels in
the
graft and its bed
• absence
of
MHC class II+ APCs in the graft
• reduced expression ofMHC-encoded alloantigens on graft
cells
replaced with minor
peptides (nonclassical MHC-Ib molecules) to avoid lysis
by
natural killer cells
• expression
ofT
-c
ell
-deleting CD95 ligand (Fas ligand, or
FasL)
on endothelium,
which can induce apoptosis in killer T cells
Pooyan
6696
1
526-7
• immunosuppressive microenvironment of
the
aqueous humor, including trans-
forming growth factor
~
2
,
a-melanocyte-stimulating hormone, vasoactive intesti-
nal peptide, and calcitonin gene-related peptide
• anterior chamber-associated immune deviation (ACAID) involving the develop-
ment
of
suppressor T cells (ACAID
is
a downregulation of delayed-type cellular im-
munity. Antigens released into the aqueous
humor
are, presumably, recognized by
dendritic cells of the iris and ciliary body. These APCs can then enter venous circu-
lation and induce regulatory T cells in the spleen, bypassing the lymphatic system.)
For an immune response to occur, an antigenic substance
is
introduced and "recog-
nized" (afferent limb), producing the synthesis of specific antibody molecules and the
appearance
of
effector lymphocytes that react specifically with the immunizing antigen
(efferent limb). Although antibodies to foreign tissues are formed during graft rejection,
they are not believed
to
be important in the usual type of allograft rejection. Rather, exten-
sive evidence indicates that allograft rejection
is
associated with cellular immune mech-
anisms. The term delayed hypersensitivity, or type
TV,
reaction
is
used to describe such
T-lymphocyte-mediated responses. Other mechanisms are also probably involved. For
the endothelial cells to be rejected, they must express MHC class II antigens. Streilein sug-
gests that in the presence of inflammatory stress (including mediators
TNF-a
and IFN-y),
the endothelial cells' endogenous minor H antigens, which are recognized by the CD4+
T cells,
le
ad to delayed hypersensitivity and graft rejection.
See
also the discussion
of
clinical signs
of
corneal transplant rejection in Chapter
15
of
this
vo
lume.
BCSC
Section 9, Intraocu lar Inflammation and Uveitis, discusses and
il
-
lustrates the principles of immunology in greater detail.
Bachmann
B,
Taylor
RS,
Cursiefen
C.
Corneal neovasculari
za
tion
as
a risk factor for graft
failure
and
rejection
af
ter keratoplasty: an evidence-based meta-analysis. Ophthalmology.
2010;
11
7(7):1300-l305.e7.
Niederkorn
JY.
Cornea: window to ocular immunology. Curr
lm
mun
ol
Rev.
2011;7(3):
328-335.
Immune-M
ediated
Diseases
of
the
Epi
sc
lera
and
Sclera
Episcleritis
PATHOGENESIS Episcleritis
is
a self-limited,
ge
nerally benign inflammation
of
the episcleral
tissues. An underlying systemic cause
is
found in only a minority of patients.
