Lecture 12 Flashcards
(16 cards)
immunological tolerance
unresponsiveness to self antigens
What are the outcomes for T cell central tolerance?
- Apoptosis
- development of regulatory T cells (T regs)
- receptor editing (B cells)
What components help distinguish CD4+ T cells?
-CD25 and Foxp3
AIRE (autoimmune regulator)
-expressed on EC of thymus and allow for negative selection of thymocytes that recognize peripherally expressed tissue-specific antigens
What are the outcomes for T cell peripheral tolerance?
-self-reactive T cells undergo apoptosis, anergy, or suppressed by Tregs
Which 2 signals are required for T cell activation?
- MHC:peptide recognition (TCR complex and coreceptor)
- engagement of T cell activating receptor CD28 by costimulatory B7 on APC
When is B7 expression on APC upregulated?
when PRR engaged by PAMPS or DAMPS
When can T cells become anergic?
- receive signal 1 but not signal 2
- inhibitory receptors (CTLA-4 or PD-1) engage co-stimulatory B7 on APC to prevent CD28 binding
Which cytokines suppress autoreactive T cells?
-IL-10 and TGF-Beta
Which two ways can apoptosis be induced?
-mictochondrial or death receptor pathway
What is unique about central B cell tolerance?
-receptor editing of self-reactive BCR
What are the outcomes of peripheral B cell tolerance?
- auto-reactive B cells become anergic
- suppressed by Tregs
- undergo apoptosis by death receptor Fas with FasL on neighboring T cell
autoimmunity
reaction to self antigens and require genetic susceptibility and environmental trigger
Genetic susceptibility for autoimmunity occurs from which 3 groups of genes?
- MHC genes (largest association with autoimmunity)
- Non-MHC polymorphic genes
- defective genes
Examples of polymorphism (variants) in genes for autoimmunity
- PTPN22- activation of B and T cells
- NOD2-for PRRs
- IL23R-IL23 cytokine for Th17
- CTLA4-T cell inhibitory receptors
- CD25-alpha chain of IL-2
How do defective genes contribute to autoimmunity?
- release brakes on immune system (defect in CTLA-4, FOXP3) and FAS
- lack of expression of tissue-specific proteins on thymic EC (defect in AIRE)
