immunological tolerance and autoimmunity Flashcards
tolerogens
- antigens that induce tolerance
- prolonged exposure
- presence in generative organs
immunogens
- antigens that induce an immune response
- short exposure
- presence in blood and peripheral tissues
self-antigen
an individuals own antigens
immunologic tolerance
unresponsiveness to self-antigens
central tolerance
- immature B (bone marrow) and T lymphocytes (thymus)
peripheral tolerance
- spleen and lymph nodes
- anergy, deletion, suppression
central T lymphocyte tolerance
- negative selection= deletion
- regulatory
during development in the thymus the positive selection of t lymphocytes occur in the medulla/cortex by which cells
CORTEX
cortical epithelium
during development in the thymus the NEGATIVE selection of t lymphocytes occur in the medulla/cortex by which cells
MEDULLA
medullary epithelium
double positive thymocytes
located in the cortex
positive selection
weak recognition of class II MHC –> CD4 t cell ; weak recognition of class I MHC –> CD8
negative selection
- encounters self antigen and those that do are apoptosis, negative selection or deleted
central T lymphocyte tolerance takes ____ months
3
autoimmune regulator protein
transcription factor that reside in the and controls expression of peripheral tissue self-antigens –> critical role in negative selection and self-tolerance = protective immunity
absent of autoimmune (AIRE) regulator protein
leads to autoimmunity
APECED
autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
- autosomal recessive inheritance
- mutations in AIRE chromosome 21
- autoantibodies
regulatory T cell development
- some reactive CD4+ t cells will not be deleted but instead will differentiate into regulatory T cells
- CD3+CD+CD25 high and FOX P3+
- produce anti-inflammatory cytokine IL-10 and TGF-beta
peripheral T lymphocyte tolerance
- anergy, suppression, deletion
CD 19 and CD 20
b cells
B7
APC
CD28
T cells
when B7 and CD28 do not bind or when TCR does not bind correctly
t cell anergy
CTLA-4
- exists on T cells
- inhibitory
- regulatory
- engage CD80/86 on APC
iplilmuman
- blocks CTLA-4 , boost t cell response
- can be autoimmune
abatacept
- recombinant CTLA-4
- used for arthritis
- engage CD80/86 and induce inhibition
regulatory t lymphocytes require which cytokine
IL-2
IPEX
- immune dysregulation polyendocrinopathy enteropathy
- x-linked
- mutations in FoxP3
FasL
death receptors
ALPS
- disorders of apoptosis
- heterozygous dominant
- lymphoproliferation
foxp3
IPEX
