Levings Content Flashcards
immune tolerance
- state of unresponsiveness to an antigen
antigens that should not become targets of effector cells (2)
- self-antigens
- non-harmful foreign antigens
self-antigens (3)
- systemic (eg. RBC)
- tissue specific
- developmental stage specific
non-harmful foreign antigens examples (4)
- allogeneic fetus
- commensal bacteria
- food
- inhaled antigens
how are TCRs and BCRs made
- somatic recombination to make random receptors
what occurs when tolerance goes wrong (3)
- autoimmunity
- allergy (to non-harmful antigens)
- auto-inflammation
what occurs when tolerance works too well (2)
- cancer
- persistent infections
what are some clinical uses for tolerance
- induce tolerance to transplanted cells and organs/foreign tissues
two layers of tolerance (2)
- central
- peripheral
central tolerance (3)
- bone marrow (B cells)
- thymus (T cells)
- regulates tolerance to self by removing potentially self-reactive immature lymphocytes
peripheral tolerance (2)
- tolerance in places other than BM and thymus
- regulates tolerance to self and non-harmful foreign antigens
central T cell tolerance (2)
- T cells that bind antigens too loosely do not pass
- T cells that bind antigens too strongly do not pass
AIRE (2)
- thymic epithelial cells express this TF
- allows expression of as many genes as possible in thymus
AIRE genetic mutation
- results in severe autoimmune disease as process if negative selection is defective
how does AIRE work
- as a TF, it worked by controlling transcription
thymic “mimetic” cells (3)
- express peripheral tissue antigens
- mirror extra-thymic cell types but maintain thymic epithelial cell identity
- allows for negative selection of all cell types in the thymus
AIRE and Treg development
- AIRE-deficiency results in T cell escape from negative selection AND defective Treg cell development
thymic development of FOXP3+ Tregs (2)
- immature CD4+ T cells that have medium-high affinity for self-antigens take on FOXP3-CD25+ Treg cell precursor phenotype in a TCR dependent manner
- FOXP3+ Treg cell develops in a TCR independent manner, but relies on IL-2 and IL-15
how accurate is central T cell tolerance (2)
- not perfect; some self-reactive T cells escape negative selection
- to handle this, peripheral tolerance is employed as a second level of control
T cell activation signals (3)
signal 1: antigen (presence, absence, affinity)
signal 2: co-stimulation vs co-inhibition
signal 3: cytokines
what is peripheral T cell tolerance controlled by
- quality of T cell activation
major mechanisms of peripheral tolerance (3)
- deletion
- anergy
- suppression
peripheral tolerance: deletion (2)
- activation induced cell death
- Fas/FasL pathway critical for deletion of T cells that have been stimulated repeatedly in periphery by antigen
result of mutations of Fas/FasL
- lymphadenopathy (swelling lymph nodes) and autoimmunity