immunology Flashcards
what are the 4 mechanisms used to induce tolerance
deletion
anergize (switch off)
ignore (ignore the trigger)
regulate (contain the problem)
which is more effective, B cell tolerance or T cell tolerance
T cell tolerance (see transient B cell autoantibodies with infections of some kinds all the time)
what are the 3 mechanisms for central B cell tolerance and which is the major type
deletion (apoptosis) - major type
anergy
ignorance
what causes the ignorance mechanism for B cells
low affinity interactions of the antibodies with self antigens - but there is no cross linking and therefore the cell is not triggered = ignorance
what causes the anergy mechanism for B cells
there is some cross linking of the antibodies with self antigen and therefore activation, but because this is a naive B cell the response is to be turned off (unlike mature B cells which would proliferate)
what causes the deletion mechanism for B cells
extensive cross linking of the antibodies with self antigen –> induces apoptosis of the B cell
What is peripheral B cell tolerance
if an autoreactive B cell gets to the periphery… in the absence of T cell help (CD40L and some cytokines) the B cells life span is short
what is a double negative and a double positive thymocyte
double negative - naive T cell that doesnt have CD4 or CD8 yet
double positive - naive T cell that has both CD4 and CD8
what are the two main mechanisms for central T cell tolerance
- positive and negative selection –> deletion
- T regs –> regulation
what is positive and negative selection of T cells
positive selection - thymocytes that express TCRs capable of recognising self-MHC are selected to survive
negative selection - removal of thymocytes that have too strong a reaction to self MHC
what happens if a T cell can not recognise MHC
it dies by neglect
how are T cells shown the self antigens it needs to see before leaving the thymus
specific TF = AIRE - turns on some genes to express particular proteins associated with organs other than the thymus –> facilitating negative selection
which mechanisms are involved in peripheral T cell tolerance
deletion
anergy
ignorance
reguation
explain the ignorance mechanism of tolerance in T cells
the T cell never encounters the antigen (eg. in a place in the body like the eyes that are immunologically privileged)
explain the anergy mechanism of tolerance in T cells
there is presentation of the self antigen by MHC cells but there is no costimulation –> failure to proliferate –> inactivation
what is the main mechanism by which Tregs help T cell toleance (in general)
expression of Foxp3 –> inhibits a whole bunch of T helper cell responses and CD8 cell responses
what are the 2 major types of Tregs
nTreg - derived from the thymus during T cell development (subset of CD4 cells that are committed to Treg)
iTreg - derived following activation of naive CD4 T cell in the presence of TGF-beta
how do iTregs promote T cell tolerance
- secrete immunosuppressive cytokines - IL10 and TGF-beta
- express CTLA4 and inhibit co-stimulation
- release molecules that create a ‘suppressive’ environment
3 key components that lead to autoimmune disease
- genetic susceptibility
- environmental
- loss of self tolerance
autoimmunity results from a
chronic ongoing autoimmune response with ongoing tissue damage
2 classes of autoimmune diseases
organ specific
systemic
what causes APECED (disease of autoimmunity)
defect in the AIRE gene –> decreased central tolerance –> multi-system autoimmunity
what causes IPEX (disease of autoimmunity)
defect in the Foxp3 gene of Treg –> loss of Tregs and peripheral tolerance mechanism
what are 3 diseases with B cell mediated autoimmunity
graves disease (stimulatory Ab) - Type 2 HS myasthenia gravis (inhibitory Ab) - Type 2 HS SLE (immune complex deposition) - Type 3 HS
what are 2 diseases with T cell mediated autoimmunity
insulin dependent diabetes mellitus
multiple sclerosis
is MS associated with CD4 or CD8 T cell autoimmunity
CD4
what Thelper cells are associated with MS
Th1 and Th17 (IFN-gamma and IL17)–> detrimental
Th2 –> remission
what are the two thoughts about the initiation of autoimmune disease
bystander
molecular mimicry
what is the bystander thought of autoimmune initiation
infection can activate DCs to provide co-stimulation of T cells with exposure of self Ag due to dying cells
in which part of the thymus, and by what cells is AIRE expressed
in the medulla by epithelial cells
