Flashcards in Immuno Tolerance Deck (25):
How are non thymic self-antigen reactions cells eliminated?
AIRE-TF that is mainly expressed in the medulla of the thymus
-induces expression of genes expressed by other organs
-negative selection of thymocytes reactive to these antigens
What is the disease associated with failure of central tolerance gene AIRE?
Autoimmune polyendocrine syndrome (APS)
-endocrine organs are destructed by antibodies and lymphocytes
What is dominant suppression?
imposed by professional regulators
-Regulatory T cells stop the other guys
What is cell intrinisic inactivation?
Change of the state of the T cells-become unresponsive to stimulation
What diseases is tolerance prevent?
autoimmune disorders such as IBD(inflammation of the colon) or hyperimmune disorders (allergy)
What type of T cells do FoxP3- come from?
What are myeloid derived suppressor cells?
become potent immunological regulators when exposed to inflammation (IFN gamma) and blocks T cell responses
-often tumor associated
What is clonal anergy?
When T cells are stimulated in a manner that is incomplete- cells become non-response to further stimulation
What do mature nTregs express?
CD25, Il2R alpha chain
What happens when there is a mutation in the FoxP3 gene?
-multiple tissue damages caused by self reactive T cells
What are nTregs against vs. iTregs?
nTregs:Self-antigens(make sure the tcells dont attack self)
iTregs: foreign antigens (make sure the Tcells dont attack things that should be there like babies)
Most cells that are reactive against self antigens are going to die (central tolerance)but there are regulatory cells that can stop the immune response against self antigens, where is the generation of these T cells?
What is TSLP?
In the hassall's corpuscles and helps differentiation of FOXP3_ regulatory T cells via activation of a subset of dendritic cells
What are iTregs induced by?
antigen presenting cells that are present in the mucosal environment such as the intestine
What cofators needed to induce iTregs?
Tr1 cells produce what?
Il 10-potnet immuno-suppressive cytokine
Are Tr1 cells foxp3 negative ?
What do Tr1 cells develop in response to?
antigenic stimulation when TGF beta and IL27 are present
-vitamin D upregulates IL10 -linked to generation of Tr1 cells
What do Tregs develop in response to?
TGF beta and IL2
Is direct cell-cell essential for Tregs?
CTLA-4 plays a significant role
-they do use soluble factors such as TGF beta and IL10 but that only to enhance where as Tr1 mainly uses IL10
-adenosine is another effector molecule generated by Tregs to suppress other lymphocytes
When is anergy induced?
When antigen is presented in absence of costimulatory signal CD28 (binds to B7-which is only expressed on APCs)
Does CTLA have a higher affinity for B7?
What does CTLA do?
competes with CD28 for B7
-and recruits signaling molecules that suppress TCR signaling and blocks antigen activation
Can CTL4 be used to improve the frequency of graft vs host disease?
yes, there is a man made CTLA-4IG, which is soluble and can block autoimmune disorders