3. •Immune privilage mechanisms
include :
• Poor supply of lymphatics
• Low expression of MHC molecules.
• The presence of immunosuppressive
molecules such as TGF-β and Fas-Ligand.
4. • The ocular immune response involves :
• Local :
• Conjunctiva
• Cornea and sclera
• Anterior chamber, anterior uvea and
vitreous
• Retina, retinal pigment epithelium ,
choriocapillaries and choroid
6. Conjunctiva
• The conjunctiva is a complex element of
mucosal immune defense system and
actively participates in the ocular immune
response against the foreign agents.
• Composed of 2 layers :
• 1. epithelial layer
• 2. connective tissue layer – substantia
propria.
9. • Immunological features of MALT :
• Rich investment of Antigen presenting
cells (APC)
• Specialized structures for localized antigen
processing
• Unique effector cells ( eg: intraepithelial T
lymphocytes and abundant mast cells)
• Predominant leucocyte in conjunctiva – T
cells 90%
• 76% CD 8 and 14% CD 4
10. • Lymphocyte distribution :
• Suppressor T cells outnumber helper T
cells
• Most of them are in epithelium
• Lymphocytes are more concentrated in
substantia propria.
11. • The high endothelial venules
characteristic of MALT has been
demonstrated in conjunctiva.
• Most immunoregulatory cells of the ocular
surface are the APC
• Langerhans cells are the principal APC of
the ocular surface.
• Substantia propria is richly infiltrated
with mast cells.
• Mast cells have been associated with
allergic conditions like vernal
keratoconjunctivitis or giant papillary
conjunctivitis.
12. • Antigen presenting cells in the ocular
tissue are of 2 types :
• 1. Bone marrow derived dendritic cells
expressing MHC class II molecules.
• 2. Tissue macrophages.
• APC – found in ciliary epithelium and iris
epithelium.
• Also present in the ciliary muscle, ciliary
processes and trabecular meshwork.
• Posterior segment – dendritic cells are
found in neural retina near ora serrata
and choriocapillaries.
13. Immune responses of cornea :
• Normal eyes – only limbus is vascularized and has
langerhans cells.
• Paracentral and central cornea – devoid of APC and
avascular.
• Various stimuli such as mild trauma, certain cytikines
(IL-1) can recruit APC to the central cornea.
• Peripheral cornea – complement, IgM and IgG
• Central cornea – IgM
• Neutrophils, monocytes and lymphocytes can readily
migrate through the stroma if chemotactic stimuli is
activated.
• Can adhere to endothelial surface during
inflammation – keratic precipitates.
14. • Afferent pathway of immune recognition
in normal and inflamed eyes :
• Normal cornea lacks lymphatic drainage.
• Afferent pathways from the anterior
chamber follow the aqueous outflow to the
venous system and the spleen.
• Vascularized corneal lymphatic beds,
possess lymphatic channels that drain
corneal foreign body antigen or APC
through conjunctival lymphatics to the
regional lymph nodes.
15. • Immunosuppressive properties of aqueous
humor :
• Aqueous inhibits T cell proliferation and
lymphokine production.
• Exposure of APC prevents stimulation of
delayed hypersensitivity response.
• TGF-β – immunosuppressive cytokine
found in aqueous.
• Suppressor of T cell proliferation and γ-
interferon production.
16. • Anterior chamber :
• Anterior chamber is a fluid filled cavity
• Circulating aqueous humor provides a unique
medium for intercellular communication
among cytokines, immune cells and resident
tissue cells of the iris, ciliary body and corneal
endothelium.
• A partial blood ocular barrier is present
• Fenestrated capillaries in the ciliary body
allow a size dependent concentration gradient
of plasma macromolecules to permeate the
interstitial tissue.
17. • The tight junction between the pigmented
and non pigmented epithelium provides a
more exclusive barrier
• Prevents interstitial molecules permeating
directly through the ciliary body into the
aqueous humor.
18. Anterior chamber associated
immune deviation (ACAID)
• The specific features of ACAID :
• Suppresses delayed hypersensitivity.
• Preserves humoral immunity.
• Primed cytotoxic T cell responses.
19. • Following injection of antigen into anterior
chamber
The afferent phase begins
• Specialized macrophages in the iris
recognise and takes up antigen
20. • These macrophages leave by the
trabecular meshwork and schlemms canal
• Enters the venous circulation
• Preferentially migrates to spleen
• Antigen signal is processed
21. • CD8 regulatory cells
• Alters CD4 helper T lymphocyte response
• Downregulation of CD4 T lymphocyte
delayed hypersensitivity responses
• Selective suppression of antigen specific DH
&
• Selectively diminished production of
complement fixing isotype of antibodies.
22. • Effector blockade includes production
of the following :
• Immunomodulatory cytokine, produced by
the ocular tissues
• Immunomodulatory neuropeptides,
produced by the ocular nerves
• Functionally unique APC
• Complement inhibitors in aqueous humor.
23. • Most important mechanism of effector
blockade – Fas Ligand.
• FasL – expressed on the iris and corneal
endothelium
• Potent trigger of apoptosis
• If an immune response develops to an
ocular antigen, the inflammation can be
downregulated by this mechanism of
effector blockade.
24. • Jerry et al studied that anterior chamber priming
with alloantigens promotes corneal allograft
survival in non immune and preimmune hosts.
• Loss of immunoregulatory systems in anterior
chamber can influence corneal allograft immunity.
• FasL expression on corneal endothelium has been
observed to be essential for allograft protection.
