1. The document discusses Anterior Chamber Associated Immune Deviation (ACAID), where antigens injected into the anterior chamber lead to a suppression of delayed hypersensitivity responses but preservation of humoral immunity. 2. Specialized macrophages in the iris take up antigens and migrate to the spleen, where they alter CD4 T cell responses to downregulate delayed hypersensitivity to the antigen. 3. The major mechanism of ACAID is expression of Fas Ligand on iris and corneal endothelium tissues, which can trigger apoptosis and downregulate inflammation to ocular antigens.

1. ANTERIOR CHAMBER
ASSOCIATED IMMUNE
DEVIATION (ACAID)
Moderators : Dr. K.N.Jha (professor)
Dr. A.R.Rajalakshmi (assoc. prof.)

2. OCULAR IMMUNE RESPONSE
•Eye is more sensitive than most
tissues to the consequences of
injury and repair.

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

5. • Regional :
• Lacrimal gland
• Lymph nodes
• Systemic :
• Anterior chamber associated immune
deviation (ACAID)
• Spleen
• Thymus
• Mucosa associated lymphoid tissue
(MALT)

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.

7. Mucosa associated lymphoid
tissue (MALT)
MALT
Ocular
surface and
adnexa
Respiratory
tract
GIT and
GUT

8. OcularMALT Lacrimal gland,
tear film
conjunctiva
cornea

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.