Flashcards in Immune Regulation- Debiel Deck (19):
When an APC interacts with a CD4+ T-cell what determines if it is activated or undergoes anergy?
T-cell activation: CD28 on T cell + B7 (CD80/86) on APC
T-cell anergy: Lack of B7 (CD80/86) interaction
What are the 4 types of Treg effector mechanisms used to control proliferation?
1. Releasing of immunosuppressive cytokines (IL10, TGFB, IL35)
2. IL-2 consumption
3. Cytolysis (granzyme mediated)
4. Modulation of dendritic maturation and function → CTLA4 binds to CD80/86 on the dendritic cell → converts tryptophan to kyneurenin = growth inhibitory signal
What are the functions of IL-2?
IL-2 → T-cell proliferation. Secretion after CD28/B7 interaction
What are the functions of IL-35?
IL-35 → auto inducer of T-regulatory cells (+ feedback)
Functions of IL-10
IL-10 → suppresses Th1 growth, (+TGF-B can cause proliferation of B-cell and class switch to IgA)
Functions of IL-12
IL-12 → potent initial stimulus for IFN gamma production by T cells or NK cells → promotes TH1 differentiation
Functions of TGF-B?
TGF-β → strong inhibitory signal for many effect T-helper cells
Functions of CD25?
CD25 → high affinity IL-2 receptor
Functions of CCR7?
CCR7 → on dendritic cells, important in trafficking to the lymph node
What are the 4 different types of B-cell tolerance mechanisms?
Clonal deletion- induction of apoptosis via inhibition of survival signal or activation of death receptors
Receptor editing- continued V(D)J recombination to avoid self re-activity
B-cell intrinsic mechanisms:
-Anergy: down regulation of BCR and upregulation of CD5
-Lack of T-cell help or survival factors
Which types of T-cells produces the following key effector cytokines?
IL-2 =T helper
IL-10 = T reg
IL-13 = Th2
IL-17 = Th17
IL-35 = T reg
IFN-γ = Th1
TNF-α/β =dendritic cells, Th1
What are the two mechanisms of antibody dependent B-cell suppression?
Crosslinking: IgG can inhibit B cell differentiation by cross-linking the antigen receptor with the Fc receptor on the same cell (suppressive antibody and the BCR antibody may recognize different epitopes) --> Constant region receptor sends signal to B-cell to stop proliferating
Antibody blocking → IgM and IgG can act to modulate the immune response through an Fc-dependent mechanism and immune complex formation with antigen
(Basically so much soluble antibody is produced that the soluble antibody binds up the antigen, and there is no antigen left to continue the immune response)
IPEX is caused by a mutation in what gene?
FOXP3 - results in absence of Treg cells
What are they symptoms of IPEX?
Rashes on the skin
Hair falling out
Failure to thrive
In a patient with IPEX what would their labs look like?
Normal WBC, HgB, Platelets
High eosinohpils (IL-5 from TH2)
High IgE (IL-5 from TH2)
Autoantibodies to GAD65
What is the treatment for IPEX?
bone marrow transplant
What gene mutation is found in APECED?
Defect in transcription factor AIRE gene
-bascially can't weed out auto reactive t-cells in thymus before sending them out to periphery
-NO NEGATIVE SELECTION : many autoantibodies produced
Symptoms of APECED?
Slow bone growth
Chronic yeast infections of mouth
Dark pigmenting around scrotum and nipples