8) Immunoregulation Flashcards
Which two surface markers are expressed by Treg cells?
CD4 and CD25
Which transcription factor is present in Treg cells?
FoxP3
Which cytokine is an important growth factor for Treg cells?
IL-2
Treg cells expresses high levels of this molecule that helps to inhibit T cell activation
CTLA-4
What cytokine is required for Treg development?
TGF-beta
What two things do Treg cells prevent?
they prevent:
1) excessive foreign antigens
2) immune response to self antigens missed by tolerization process
this autoimmune disease is characterized by absence of Treg cells
IPEX syndrome
What are the three mechanisms of actions for Treg cells?
1) cytokines IL-10 and TGF-beta
2) CTLA-4/B7 interaction
3) consumes IL-2
How does CTLA-4/B7 interaction down regulate activation of T cells?
CTLA binds to B7 with greater affinity (B7 normally binds to CD28 of T cells). this interaction prevents an important co-stimulatory signal required for T cell activation
How does consuming IL-2 down regulate immune response?
IL-2 is a growth factor for Treg cells, however, it is also a stimulatory cytokine for activated T cells. By consuming available IL-2, this helps down regulate the activity of activated T cells
What are the two mechanisms for Ab feedback?
1) Ab helps eliminate Ag –> no further stimulation
2) immune complex (Ab bound to Ag) binds to Fc receptors on B cells thus inactivating them
What is the term used to describe unresponsive to antigens?
tolerance
What happens when tolerance to self is lost?
autoimmue disease
This type of tolerance occurs in primary lymphoid tissues (thymus or BM) and majority of self-reactive lymphocytes are destroyed here.
central tolerance
This type of tolerance occurs in the periphery and catches self-reactive lymphocytes that have leaked out of primary lymphoid tissues
periphery tolerance
True or False. ALL MHC molecules will present self antigens (both class I and class II).
TRUE. this is why tolerance is important
What are three characteristics of tolerance?
1) antigen-specific
2) acquired
3) each of us has the capacity to develop autoimmunity
True or False. Mature lymphocytes are easier to tolerize than immature lymphocytes.
FALSE. IMMATURE are easier to tolerize than mature (doesn’t mean mature lymphocytes can’t be tolerized)
functional inactivation of viable lymphocytes
clonal anergy
death of antigen-specific lymphocytes
clonal deletion
What happens when T cells interact with APCs without co-stimulatory signals?
T cell is unresponsive (anergic)
True or False. B cells can see non-peptides such as lipids and polysaccharides.
TRUE. these are called thymus-independent antigens
What are the two ways B cells are tolerized?
1) clonal deletion
2) receptor editing
What is receptor editing?
B cell is given a second chance to rearrange its light chain genes to a different antigen specificity (the first time it recognized self-antigens)
Do thymocytes contain TCR?
NO, they do no contain TCR, thus they cannot recognize or respond to antigens
What are the four types of populations of T cells found in the thymus?
1) double negative (CD4- CD8-)
2) double positive (CD4+ CD8+)
3) single positive (CD4+)
4) single positive (CD8+)
What is eliminated in positive selection?
it eliminates thymocytes that bind to foreign MHC proteins
What is eliminated in negative selection?
it eliminates thymocytes that bind to self antigens AND self MHC
Positive selection is mediated by…
cortical epithelial cells
Negative selection is mediated by…
DCs at corticomedullary junction
After the completion of both positive and negative selection, what kind of thymocytes are left?
only ones that recognize to foreign antigens and self MHC
What is the importance of autoimmune regulator (AIRE) gene?
allows for negative selection for self-reactive T cells to “tissue-specific” self antigens e.g. insulin expressed by thymic DCs
What happens when there’s a mutation in the AIRE gene?
widespread autoimmune disease
tissue-specific proteins are under the regulation of…
AIRE
