Lecture 18 Flashcards
(11 cards)
What is immune tolerance?
the prevention of an immune response against a particular antigen
1) tolerance to self-antigens (thymus)
2) tolerance to innocuous food and microbial antigens (periphery)
How does the thymus promote tolerance to self antigens?
AIRE allows expression of tissue specific proteins that occur outside thymus
strong recognition of self antigens presented by cortical or medullary epithelial cells = apoptosis
What happens in type I diabetes?
effector T cell recognizes peptides from β cell specific proteins, kills β cell –> no insulin made
Where could the autoreactive CD8+ T cells come from in T1 diabetes?
1) dysfunctional/aberrant negative selection
2) neoantigens key drivers of aberrant immune, self peptide presented in thymus is mutated/altered when presented in periphery
How do barriers help peripheral tolerance?
limit availability to antigens (mucus)
How are antigens delivered across the intestinal epithelium?
via M cells (specialized epithelial cells)
some might reach across luminal space using dendrites
How do Treg cells promote tolerance to innocuous antigens
production of IL-10 –> immune suppression, maintenance of mucosal homeostasis
How do Tregs constrain pro-inflammatory responses?
inhibit activation of macrophages through IL-10, inhibit Th1 cytokine production
How do members of the microbiome promote colitis development?
harbor proteases that allow destruction of mucosa –> breach of barrier –> unrestrained influx of antigens –> immune response
bacteria present in mouse facilities that are not specific pathogen free (SPF)
How do NOD-like receptor proteins (NLRPs) promote activation of inflammasomes?
NLRP3 senses cellular stress –> cleaves pro-caspase 1 –> releases proinflammatory cytokines like IL-18 (Th1) and IL-1B (neutrophil/macrophage)
What antigens induce Treg development? What antigens induce anergy and apoptosis?
microbial = Treg
food = a&a
