Tolerance & Autoimmunity Flashcards
Tolerance does what?
protect us from self-reactive lymphocytes
Central tolerance happens where for Ts and Bs?
T-Cells: Thymus
B-Cells: Bone Marrow
Peripheral tolerance happens where?
Via Tregs
4 ways to induce tolerance:
- delete
- anergize
- ignore
- regulate
Compare B-cell vs. T-cell tolerance very generally
B-cell tolerance is less efficient than T-cell tolerance
What happens to B-cells that:
- multivalent self reactive
- soluble self
- low affinity non-cross linking?
- apoptosis
- anergic
- ignorance
peripheral B-cell tolerance happens how? when?
- don’t get CD4 co-stim and they die off
- occurs also via post-somatic hypermutation
T-cell in thymus: what are DN? DP?
- DN = double negative: not CD4 or CD8
2. DP = double positive: both CD4 & 8 then differentiate and commit
what is positive selection?
T-cells kept for recognizing self MHC but not too strongly
what is negative selection?
T-cells that react too strongly to self are removed
what happens to T-cells that don’t recognize MHC at all?
death by neglect
What is autoimmune regulator of expression (AIRE) transcription factor?
It turns on certain genes in thymic epithelial cells that looks like organ tissues to make the T-cells tolerant to all body structures
what happens if you have defects in AIRE?
get autoimmunity because AIRE not there to negative select reactive T-cells that react to organ tissues
T-cells in central tolerance happens how?
deletion
selection of T-regs
T-cells in peripheral tolerance happens how?
deletion
anergy
ignorance
regulation
How do T-cells become anergic?
They don’t get the costim (signal 2), and inactivate
Tregs suppress ? via which cytokines? 3
all types of T-cells
TGFB
CD25, IL-10
nTregs from where?
thymus during T-cell development
iTregs from where?
from naive CD4 in presence of TGF-B
3 components of autoimmunity:
- genetic
- environmental
- loss of self-tolerance
what is it called when antigen is not availble to T-cell?
ignorance
How do you control an autoreactive B-cell?
let it die out, no CD4 T-cell co-stim = no maturation = short lived.
autoimmune response always with autoimmune disease?
Yes
autoimmune disease automatically if you have autoimmune response?
Nope. Response does not equal disease
autoimmunity is defined as?
chronic ongoing autoimmune response with ongoing tissue damage
B-cells in autoimmunity do what?
make autoantibodies: TypeII Grave’s, Type III immune complexes (lupus)
T-cells in autoimmunity do what? 3 things, which diseases
- help b-cells
- release cytokines
- CTL killing of stromal cells (DM1, MS)
2 classifications of autoimmune disease
- Organ specific: eg. DM1, MS, myasthenia gravis
2. systemic: Lupus, RA
What does Foxp3 gene do?
makes naive CD4s into T-regs to allow for peripheral tolerance
central loss of tolerance happens how?
defect in AIRE gene
Multiple sclerosis happens how immunologically?
polygenic
CD4 Tcells degrade myelin via Th1-Th17
dysregulation of Tregs
what is associated with MS remission?
Th2 responses
How do autoimmune diseases bystander effect begin?
- recognition of self-antigen in presence of inflammation
2. activate DCs/co-stim with self antigens
How do autoimmune diseases molecular mimicry effect begin?
pathogen antigens similar to tissues, cross react with autoreactive T/B cells. eg. rheumatic fever
