2.4 Autoimmune Disorders Part 1 Flashcards
What is central and peripheral tolerance?
Central = occurring in the bone / thymus
Peripheral = Occurring in the periphery
What is the general progression of T cell maturation?
Double positive to single positive
What type of selection is occurring when T cells are double and single positive respectively?
Double = Positive selection (recognize MHC?)
Single = negative selection (bind self antigen?)
What is autoimmune polyendocrine syndrome?
Mutation in the AIRE gene, that inhibits the thymus medullary epithelial cells from expressing self antigens for T cell negative selection, allowing self reactive T cells to escape into the periphery
Where do positive and negative selection occur in the thymus respectively?
Positive = cortex Negative = medulla
What are the cells in the medulla of the thymus that hold self antigen to test maturing T cells?
- Dendritic cells
- Medullary epithelial cell
What is the classic triad of s/sx in Autoimmune polyendocrine syndrome?
- Hypoparathyroidism
- Adrenal gland failure
- Chronic candida infections or oral mucosa
What are the two processes that B cells can undergo if they bind to self MHC molecules presented by bone marrow Dendritic cells?
- Receptor editing (reexpression of RAG genes)
- Apoptosis through the mito pathway
What are the genes that are responsible for the rearrangement of B cell Ig?
RAG
What are the two outcomes of peripheral tolerance?
-anergy or apoptosis
Which is on which cells: CD28 and B7
CD28 = CD4 cells B7 = APCs
What is the mechanism by which T cells undergo anergy in the periphery?
If not costimulatory molecules (e.g. CD28 / B7 interaction), then cell shuts down
What is the mechanism by which B cells undergo apoptosis in the periphery?
B cell continuously binds antigen without receiving costimulatory signal induces apoptosis via the Death receptor (CD95) and FasL
What is autoimmune lymphoproliferative syndrome (ALPS)?
Mutations in the Fas apoptosis pathway, allowing for the survival of self reactive lymphocytes
What are the s/sx of ALPS? (3)
- Autoimmune hemolytic anemia / thrombocytopenia
- LAD / HSM
- Lymphoma
What are Tregs? How do they work?
T cells that suppress immune cell responses via expression of CTLA4, which binds B7 on APCs, and inhibits the costimulatory molecules
What are the cytokines that Tregs can secrete to reduce the immune response? (2)
IL-10
TGF-beta
What is the function of IL-10 in the reduction of immune response?
Lowers the expression of MHC class II
What are the three proteins that identify a T reg?
CD4
CD25
FOXP3
What is the other name for CD25?
IL-2 Receptor
What is FOXP3?
Transcription factor for Tregs that is needed for their development
Why is there an association between CD25 polymorphisms and DM I / MS?
If CD25 (=IL-2 receptor) is defective, then Tregs are not produced properly, and thus cannot calm immune system
What is IPEX syndrome? Defect in this?
Immune dysfunction
Polyendocrinopathy
Enteropathy
X-linked
Defect in FOXP3, leading to defective Tregs
Who is classically affected by autoimmune diseases?
Women of childbearing age
What are the diseases that HLA-B27 are associated with? (4)
Psoriatic arthritis
Ankylosing spondylitis
IBDs
Reactive arthritis
What is the PTPN22 gene mutation?
Y phosphatase mutation that results in cell signalling defect for apoptosis of autoimmune cells
What is the cause of the overlapping features of autoimmune diseases?
Epitope spreading–new antigens exposed as autoimmune cells destroy cells
