Immune Tolerance Flashcards
Why is immune regulation important?
- to avoid excess lymphocyte activation + tissue damage
- prevent inappropriate reactions against self antigens
What is autoimmunity?
immune response against self-antigens
what are the 3 failures of immune regulation
autoimmunity
allergies
hypercytokinemia
What is the fundamental problem in regulating immune responses?
The imbalance between immune activation and control
How are allergies considered an autoimmune disease?
An allergic response is a harmful immune response to an normally non-harmful antigen which causes tissue damage and disease
What is hypercytokinemia?
A cytokine storm
which group of people are more likely to get autoimmune conditions?
women
what are some underlying causative factors that can lead to autoimmune diseases?
- some have genes that make them more susceptivle
- but only activated when there is an environmental trigger
what are the 2 mechanisms of auto immunity?
- attacks self antigens
- attacks microbial antigens found in our microbiome
what are the 2 ways allergies are mediated?
- IgE and mast cells (type 1 hypersensitivity)
- T cells ( delayed type 4 hypersensitivity)
What is meant by self-limitation?
when the immune response declines after elimination of the antigen that initiated the response
What are the three mechanisms which license a cell to respond?
Antigen recognition
Co-Stimulation
Cytokine release
What are the three possible outcomes of an immune response?
Resolution - no damage
Chronic Inflammation - active inflammation and attempts to repair damage
Repair - healing with scar tissue and regeneration
What is meant by self tolerance? d
Self Antigens will not cause harm to us
Inducing tolerance may be exploited to prevent…
Graft rejection, treat autoimmune conditions and allergic diseases
What is central tolerance?
The destruction of self- reactive T and B cells in the sites of their production / maturation, before they enter circulation
Where does central tolerance occur?
In the bone marrow and the thymus for B and T cells
What is the central tolerance mechanism for B cells?
if immature B cells in the bone marrow encounter any antigen which can cross link their IgM, then death of that cell is triggered via apoptosis
What is the mechanism for central tolerance for T cells?
If the T cells binds MHC too strong = apoptosis (negative selection)
If the T cell doesn’t bind any MHC = apoptosis
If the T cell binds MHC too weakly, kept
How can a T cell developing in the thymus encounter MHC bearing peptides that might be expressed in other parts of the body?
AIRE is a specialised transcription factor which allows for the expression of genes that are normally expressed in peripheral tissues, so these proteins and therefore peptides can be made and presented to T cells
What does an AIRE deficiency lead to ?
Multi-organ autoimmunity
What is peripheral tolerance?
Ensures that self reactive T and B cells which escaped central tolerance do not cause autoimmunity
What are some of the immunosuppresive cytokines that Tregs release?
TGF- B, IL-10, IL-35
What are Tregs?
T Regulatory cells which regulate the activation of other T cells