Tolerance and Autoimmunity Flashcards
(51 cards)
AutoImmunity results from the Breakdown of?
Self Tolerance
What induces Central tolerance and in what location?
Immature Self reactive Lymphocytes in Primary Lymphoid Organs
What induces Peripheral tolerance and in what location
Induced by mature self reactive lymphocytes in Lymph nodes or peripheral sites such as submucosal tissues
Three mechanisms to deal with recognition of self antigen in the central tolerance
Deletion by Apoptosis
Change of BCR specifitity
development of Treg cells
Three mechanisms induced in peripheral tolerance to deal with Mature self reactive lymphocytes
Inactivated (anergy)
Deleted ( apoptosis)
Suppressed by the Treg cells
Central T cell Tolerance location and Process
In Thymus
Strong binding to self Ags get deleted
No affinity at all undergo apoptosis
binding self antigen under certain threshold the develop into effector T cell
Small percentage develop into Treg Cells
Treg Cells
Develop in the Thymus
Positively selected due to strong TCR interactions with self AG
Not eliminated because can produce Anti Apoptotic molecules to protect them
Express FOXP3 and CD4+ and CD25+
Tregs need what to survive and function
IL-2
Induced Treg Cells
Produced outside of the Thymus and is induced by FOXP3 in Naive CD4+ upon AG recognition in the presence of TGF-B
Ag recognition in the presence of TGF-B and IL-6
Creation of Th17 cells rather than iTreg because IL-6 represses FoxP3 and induces expression of REtinoic acid receptor related orphan nuclear receptor (RORyt) to make Th17
Where are Inducible Treg cells produced
in the periphery especially in GI tract and Lymph nodes
What cytokines do Treg cells release
IL-4, IL-10, TGF-B
3 mechanisms of Peripheral tolerance?
Anergy- functional unresponsiveness
Suppression: Block activation of effector cell
Deletion: Promote APoptosis
what is the mechanism of T cell Anergy
Ag recognition with out adequate CD80:CD28 costimulation binding
What is the mechanism of T cell suppression
T rells may engage inhibitory receptors: CTLA-4 and PD-1
expressed on both CD4 and CD8
Therapeutic application of Anti-CTLA-4 and anti-PD1
Treat patients with cancer to enhance antitumor immune response leading to breakdown of tumor but does ldevelop auto immune reactions
What is the intrinsic pathway of apoptosis
Mitochondrial release of cytochrome C that activates caspase 9 that induces Death pathway
What is the Extrinsic pathway of Apoptosis
Death receptor FasL and Fas or TNF receptor that initiats Caspase 8 to induce apoptosis
3 outcomes of B cell Tolerance
die by apoptosis of high affinity for self
Receptor editing
Low avidity my lead to anergy in the bone marrow
BCR editing
the rearrangement occurs on the k light chain.
All BCR that contain the lambda light chain underwent BCR editing
Peripheral B cell Tolerance and mechanism of?
Mature B cell that recognize self Ag in peripheral tissues in the absence of specific Th cells may be rendered funcutionally unresponsive or die by apoptosis
CD22 inhibitory receptor is phosphorylation by Lyn and recruits SHP-1 tyrosine phosphatase to attenuate the BCR signaling
What are some ways Treg cells mediate the peripheral tolerance
inhibit CD4 T cell activation by APCs
inhibit T cell differentiation into CD8 CTLs
Prevent T cells from providing help to B cells in producing Abs
what is the function of Symbiotic bacteria
inhibit pathogen colonization of the GI tract and skin and have anti inflammatory activities
How do Microflora suppress pathogens
induction of regulatory immune resposes involving Treg cells and IL-10
