immuno tolerance and autoimmunity Flashcards
is tolerance Antigen specific?
yes
Central tolerance is induced in?
Immature self-reactive lymphocytes in generative lymphoid organs
Peripheral tolerance is induced in?
mature self-reactive lymphocytes in peripheral sites
What does Central tolerance ensure?
that mature lymphocytes are NOT reactive to self-antigens. however, it is not perfect and occasionally some self reactive lymphocytes appear.
Why is Peripheral tolerance needed?
to prevent activation of potentially dangerous self-reactive lymphocytes.
Central tolerance is located in the?
Thymus
Recognition of self-antigens by immature T cells in the thymus leads to 2 pathways. They are?
- Apoptotic death by negative selection
2. development of Regulatory T Cells that enter the peripheral tissues.
Cell injury results in T cell deletion by apoptosis via?
Mitochondrial Intrinsic pathways using Cytochrome C, Caspase 9, BH3 proteins, and endonuclease activation. This pathway can be in either Central or Peripheral tolerance.
Receptor-ligand interactions of Fas and TNF-receptor are involved with T cell deletion by Apoptosis in which pathway?
Death Receptor Extrinsic pathways using Caspase 8 initiation and various executioner caspases that activate endonucleases and cytoskeletal breakdown. This is primarily in Peripheral Tolerance.
Cells with T cell receptors with NO affinity for self-peptide and MHC do NOT receive?
a survival signal therefore undergo apoptosis in the Thymus
Cells whose T cell receptors have a high affinity for self peptides and MHC receive?
the death signal and eliminated by apoptsis
Cells with intermediate….
survive and lwave the thymus…..
impaired production of Regulatory T cells express this deficiency
FoxP3 that causes IPEX syndrome.
Decreased clearance and impaired tolerance induction by apoptotic cells are deficient in?
Complement proteins C1q and C4
incomplete induction of tolerance in the thymus leads to?
AIRE deficiency to cause Autoimmune polyendocrine syndrome
Systemic Lupus Erythmatosis is a mutation in gene C4 which is the breakdown of?
Peripheral tolerance.
AIRE is the only mutation thats involved the failure of?
Central Tolerance
AIRE regulated the expression of?
tissue restricted antigens (TRAs)
If a T cell does not have a normal response with costimulators and MHC then it becomes SAD…
Suppression, Anergy, and Deletion by apoptosis
If the T cell recognizes the self-antigen without the costimulators it becomes Anergic. blocking of the signal from the TCR complex may be result of?
1.recruitment of phosphatases to TCR complex
2.
3. ….
CTLA4 belongs to this family?
CD28 family receptor
CTLA4 is not expressed on naive T cells. only on active T cells and compared to CD28, CTLA4 has?
high affinity
CTLA4 is associated with polymorphisms in several AI diseases such as?
Graves disease and Type 1 diabetes.
blocking of CTLA4 with antibodies results in?
enhancement of Autoimmune diseases
low expression of CTLA4 allows DC’s to activate….
…..
APC’s regulate the fate of?
T cells. if they want to express Costimulators or not.
T cell precursors with gamma chain cytokines bind to FoxP3 to stimulate IL-2….
…..
T regulatory cells express FoxP3 transcriptional factor and are
CD4+ and CD25+ positive
Do T reg cells express high levels of CTLA4?
yes
generation of T regulatory cells requires?
TGF-beta
production of anti-apoptotic molecules by T reg cells protect them from?
negative selection in the Thymus
development and survival of Regulatory T cells require?
IL-2 and FoxP3
in peripheral tissues, T reg cells?
suppress activation of self reactive lymphocytes
IL-10 blocks expression of ?
CD40, CD80/86, and IL-12.
TGF-beta regulates the differentiation of?
peripheral FoxP3+ T regulatory cells
TGF-beta stimulates production of?
IgA by inducing B cell isotype switching in mucosal tissue.
defects in Lyn tyrosine kinase, SHP-1 tyrosine phosphatase, and CD22 inhibitory receptor lead to?
autoimmune disease
Rheumatic fever is triggered by Strep infection and mediated by
cross-reactivity between strep antigens and cardiac myosin
estrogens exacerbate SLE by altering?
B-cell repertoire in the absence of inflammation. more common in women than in men.
