Autoimmunity Flashcards
tolerogens
antigens that induce self tolerance
immunogens
antigens that induce immune response
central tolerance of T cells location and mechanisms
thymus
deletion or become regulatory T cells
central tolerance of B cells location and mechanisms
bone marrow
receptor editing
deletion and anergy
peripheral tolerance of T cells location and mechanisms
spleen, nodes
anergy, suppression and deletion
peripheral tolerance of B cells location and mechanisms
spleen/lymph nodes
anergy, suppression and deletion
development of regulatory T cells in thymus
during negative selection if the T cells recognize self they can be deleted or become regulatory T cells
autoimmune regulator protein
is a transcription factor that is in thymus and helps with presentation of the peripheral tissue self antigens…critical role in self tolerance and negative selection
APECED (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)
recessive inheritance of mutation for AIRE gene leading to autoantibodies
presents with recurrent candidiasis, adrenal insufficiency and hypoparathyroidism
common autoantibodies in APECED for candidiasis
IL-17 and IL-22
master sign of the regulatory T cells
additional signs
FoxP3+
CD3, CD4, CD25
two routes leading to T cell anergy with costimulation
- dendritic cells need microbe to upregulate B7 expression so if T cell binds to dendritic that does not have the microbe antigen the T cell is anergized through inhibitory signals
- if T cell binds to dendritic with a microbial antigen but does nto work costimulation then will be anergized
CTLA-4 receptor on T cells
Inhibitory molecule
this is the receptor involved with negative regulation of immune response and self tolerance
Ipilimumab
monoclonal antibody that bind CTLA4 enhancing T cell activation
Abatecept
CTLA4 molecule and Fc region IgG1 in drug form to bind CD80 on T cells and interrupt co stimulation…anergy
cancer drug
cytokine tht induces FoxP3 in regulatory T cells
TGF-beta
regulatory T cells mechanisms of suppression
expresses cytokines
expressed CTLA4
express IL2 receptor and will capture IL-2
IPEX (immune dysregulation polyendocrinopathy enteropathy X linked syndrome)
X linked recessive
mutations in FoxP3 on T reg cells
triad is dermatitis, endocrine issue, and chronic diarrhea
FasL and Fas
FasL is the death receptor on the T cell and Fas is the ligand that binds to signal apoptosis in the periphery
ALPS (autoimmune lymphoproliferation syndrome)
dominant disorder of apoptosis with Fas and FasL problems leading to accumilation of the lymphoid cells
splenomegaly, lymphadenopathy, hepatomegaly
ALPS risks
autoimmune disorders of the blood and lymphomas
molecular mimicry in autoimmunity
microbe antigen very similar to self antigen that a self lymphocyte can recognize and will lead to activation of the self reactive T cell
Systemic Lupus Erythematosus B and T cell problem
defective B and T cell tolerance
Lupus genetic linkages
complement 1,2,4 issues
TREX1
HLA DR2,3
lupus environmental factors
UV radiation, viral infection, drugs and chemicals
lupus hormone problems
mainly women in childbearing years
estrogen induced flares
SLE mechanism
mainly antinuclear antibodies leading to B and T cell defective tolerance
SLE symptoms
malar rash discoid lupus rash photosensitivity oral/nasal ulcerations arthritis nephritis encephalopathy (seizures) pericarditis cytopenias
Testing for SLE
positive antinuclear antibodies
Antibodies to smith nuclear antigen and dsDNA
two good signs for SLE
