Test 2: lecture 2 immune provilege Flashcards
immunologic ingnorance
can transplant eyes with little immune response
There is a profound antigen-specific suppression of cell- mediated immunity, especially T-cell–mediated inflammation, such as delayed hypersensitivity and a concomitant induction of antibody responses.
Injection of antigens in the anterior chamber of the eye, vitreous or subretinal space induce ____________.
tolerance → will not have a big response (will not attack self)
The prolonged survival of incompatible ocular grafts is what defines immune privilege. This is achieved through ___ to alloantigens and local suppression of inflammatory responses.
induction of systemic tolerance
These mechanisms establish a strong blockade in activating graft ___ immune responses.
destructive
-Immune responses are not completely suppressed, and the mechanisms behind such suppression are in large part due to the regulation of ___ to activate Treg function.
APC activity
No lymphatic vessels drain the ____, vitreous cavity or subretinal space, although lymph drainage for the conjunctiva, ___ and choriocapillaris exists
anterior chamber
sclera
Aqueous humor from the anterior chamber drains through the ____ to enter directly into the ___circulation that serves the conjunctiva, iris, ciliary body, sclera and choriocapillaris
trabecular meshwork
venous
what are some cell surface molecules that promote ocular immune privilege
in the eye what are some soluble factors that promote immune privilege
IL-10, TGF beta
T-cell effector functions are neutralized when crossing the pigment epithelium layer of the eye as this process induces a ___phenotype.
Treg
T cells entering the aqueous humor encounter transforming ____ and neuropeptides such as___- which also favor conversion of T effector into Tregs.
growth factor-β (TGF-β)
α-melanocyte stimulating hormone (α-MSH)
Antigenic material placed in the anterior chamber elicits induces ___ to the antigen (initial experiments using MHC-mismatched skin). Same response in vitreous and sub-retinal space.
systemic tolerance
Antigens released into the aqueous humor are recognized by dendritic cells of the iris and ciliary body. These APCs can then enter the ___ circulation and induce regulatory T cells in the spleen, bypassing the ___ system.
venous
lymphatic
ACAID
anterior chamber–associated immune deviation (ACAID).
ACAID is a down-regulation of delayed-type cellular immunity.
the body will have a decreases immune response (tolerance) to antigens presented in the anterior chamber
The tolerance induced in ACAID is ___ mediated by tolerogenic T cells. It is ___ specific, and it suppresses the activation of ____ responding to the same source of antigen.
efferent suppression
antigen
effector T cells
explain how ACAID works in the eye
antigen from the anterior chamber gets eaten by APC, these go right into venous circulation (skip lymphatics) and go to the spleen
the APC will be seen by NKT cells that produce anti immune cytokines (TGFB, IL-10 and CCL5 that recruits T cells)
The antigen on the APC is seen by T cells, but those cells are tuned into tolerant cells by the cytokines produced by the NKT cell
these suppression cells will then travel back to the eye and decrease immune response
→ tolerance
- The ___ is vulnerable to damage by inflammation and neovascularization.
visual axis
The corneal endothelium and the neuronal retina have limited ___properties.
regenerative
Innate (NK cells, neutrophils, macrophages) and adaptive immune effector cells (Th and Tc cells) and molecules threaten vision by triggering ___ inflammation and angiogenesis, and by destroying irreplaceable cells.
intraocular
-Immune elements posing a major threat to eye health are the main targets of immunoregulatory and___ mechanisms in the eye.
anti-inflammatory
what happens to the efferent and afferent arm of the immune response in the brain
decreases, mildly in the efferent arm
greatly decreases in the afferent arm (cellular route DCs)
drainage of the CNS through the ___ is required to preserve proper nervous function and tissue homeostasis
cribriform plate to the nasal mucosa lymphatics
blood vessels in the parenchyma of the brain have more or less CAMs than blood vessels in the meninges meaning?
less CAMs in the parenchyma → less adhesion and pulling of immune cells into parenchyma then when in the meninges
CNS endothelial cells (___) represent a heterogeneous cell population able to interact and modulate the function of immune cells.
BBB/BMB
GME
similar to MS
lesions in meningeal areas that eat away at cells
(there are a lot of B cells and T cells that attack the brain cells)
astrocytes produce ___ that trigger endothelial cells ___
Shh
immune tolerance→ increase barrier integrity, decrease CAM expression, decrease cytokine release
Astrocytes enhance endothelial barrier properties through the maintenance of ____.
junctional proteins
___ derived factors (e.g: Shh) promotes immune privilege by decreasing the expression of CAMs, chemokines as well as by reducing the adhesion and migration of CD4 T cells across the BBB.
Astrocyte
Astrocyte-derived factors provide a ___ effect and an endogenous anti-inflammatory balance to CNS-directed immune attack.
barrier-promoting
