Immune Tolerance Flashcards
What are the three things your immune system could do wrong?
Auto-immunity
Allergy
Hypercytokinemia and sepsis ( too much response )
What is the three signal model?
Antigen recognition
Co-stimulation
Cytokine release
All three signals required to allow a response
What are the three possible outcomes of immune response?
- Resolution : no tissue damage, phagocytosis of debris
- Repair : healing and scar tissue, fibroblast and collagen synthesis
- Chronic inflammation : attempts to repair ongoing damage
What are the two types of Tolerance?
Central Tolerance : Before Lymphocytes enter circulation
Peripheral Tolerance : Once in circulation
What is Peripheral Tolerance?
Destroy or control any self reactive lymphocytes which do enter circulation
- or B cells that can change
What Changes occurring in B cells after antigen exposure can cause auto-immunity issues?
Although BCR is made in bone marrow before B cells are released
A process called Affinity Maturation occurs after antibody production that can cause changes
How can a T cell become anergic?
If a naive T cells sees a MHC/peptide without a co-stimulatory signal is is unresponsive and will be less likely to be stimulated in the future by that peptide
How can a T cell response be classified as ‘ignorant’?
Antigen in too low concentrations to reach the threshold for receptor triggering
What is antigen induced cell death?
Activation through T cell receptor can result in apoptosis
Often caused by the induction of expression of the death ligand, Fas ligand ( CD95 ligand, FasL )
What is Central tolerance?
Destroy self-reactive Lymphocytes before they enter circulation as part of their maturation in the generative organs
B cell selection in central tolerance?
If immature B cell in bone marrow encounters an antigen in a form which can cross-link their IgM - apoptosis is triggered
T cell selection in central tolerance?
In the thymus:
- If T cell is useless ( doesn’t bind to any self MHC at all) = apoptosis
- If T cell is dangerous ( binds to MHC too strongly ) = negative selection apoptosis
- If T cell is useful ( Binds to MHC weakly ) = positive selection and signal to survive
How can a T cell developing in the thymus encounter MHC bearing peptides?
A specialised transcription factor allows thymic expression of genes hat are expressed in peripheral tissues otherwise
AIRE ( autoimmune regulator ) promoted self tolerance by allowing thymic expression of genes from other tissues
What do mutations in AIRE result in?
Multi-organ autoimmunity :
autoimmune polyendocrinopathy syndrome type 1
What to T regulatory cells do?
They are a subset of helper T cells
Inhibit other T cells and other cells ( DCs, macrophages, etc)
What do CD4 T reg cells do?
They have a IL-2 receptor on them
FoxP3 transcription factor in them
They secrete immune suppressive cytokines : TGF, IL-10, IL-35
/What do mutations in FoxP3 lead to?
Severe and fatal autoimmune disorder :
Immune dysregulation, Polyendocrinopathy, Enteropathy X -linked ( IPEX ) syndrome
What is special about IL-10?
- KEY anti-inflammatory cytokine
- Multi-functional
- Acts on a range of cells
- Blocks pro-inflammatory cytokine synthesis including TNF, IL-6, IL-8, IFN Gamma
- Downregulates macrophage function
- Viral mimics
Why does T regulation cells exist in only mammals?
Regulation critical during pregnancy
Exposure to new antigens through MHC I through feotus should be tolerated
What are nTregs?
Natural Regulatory T cells:
Reside in peripheral tissues to prevent harmful reactions against self
What are iTregs?
Inducible regulatory T cells:
Develop from mature CD4 T cells that are exposed to antigen in periphery
Used to limit collateral damage
How do t helper cells shape the immune response?
Through Cytokines:
Tfh : Pro-antibody
Th1 : Boost cellular immune response
Th2 : Anti-multicellular organisms
Treg (Th0) : Anti-inflammatory
Th17 : Control bacterial and fungal infection
What are the differences between chemokines and cytokines?
Chemokines drive movement around the body to the right places
Chemokine receptor profiles change with activation state of the cells
Cytokines program immune response
Focus on the right response, to increase or decrease it
Can also include interleukins
