8 - Regulation of Lymphocyte Responses Flashcards
What are the 2 parts of immune regulation?
- stop there from being too much of an immune response
- prevent reactions against self-antigens
NOTE: failure of these mechanisms is the underlying cause of immune-mediated inflammatory diseases
What is autoimmunity?
immune response against self pathogens
What causes autoimmunity?
can be due to genetic predisposition and/or environmental triggers
if the MHC can recognise a broad spectrum of antigens, it could include self antigens
FUNDAMENTAL PROBLEM:
IMBALANCE BETWEEN IMMUNE ACTIVATION AND CONTROL
Define immune-mediated inflammatory diseases
What cells can cause it?
diseases with prominent inflammation, often cause by failure of tolerance or regulation
(can be autoimmune)
can be caused by T-cells and antibodies
Define allergy
a harmful immune response to non-infectious agents that cause damage and disease
What cells mediate allergy?
mast cells and IgE
What cells mediate allergy to bring about delayed type hypersensitivity?
T cells
What happens when mast cells are exposed to their antigens?
they degranulate and release histamine, causing local inflammation
What causes hypercytokinemia and sepsis?
too much immune response
What is the positive feedback mechanism in hypercytokinemia?
by triggering inflammation, you cause damage to local cells, leading to the release of more inflammatory mediators
What happens in hypercytokinemia?
too many cytokines in the blood
What happens in sepsis?
bacteria cross from the mucosa to into the bloodstream (pathogens in the blood)
NOTE: sepsis can cause hypercytokinemia
What is a tolerogen?
A foreign antigen that suppresses immune response, or produces immune tolerance. In comparison with immunogen (that induces an immune response), a tolerogen evokes immune tolerance.
breakdown of self tolerance leads to ___
autoimmunity
What is therapeutic potential (with reference to tolerance)?
can turn T cells from being activated into tolerogenic - inducing tolerance by regular exposure
What is considered when selecting T-cell receptors?
If the T-cell receptors can bind MHC
- if the binding is too weak, then it may not be enough to allow signalling when binding to MHC presenting a foreign antigen
if the binding it too strong, then it may result in signalling irrespective of whether a self antigen or foreign particle can be found in the groove
Why is AIRE necessary?
the is a part of central tolerance
- the cells in the thymus can’t produce all all 250,000 gene products that your body can produce
- AIRE is a specialised TF that allows the thymus expression of genes that are expressed in peripheral tissues
(THE THYMUS CAN EXPRESS ALL THE PROTEINS IN THE HUMAN BODY) - therefore, all the proteins are presented on MHC to the developing T-cells
- you are negatively selecting against the entire peptide library
- PROMOTING SELF-TOLERANCE
(people without AIRE are autoimmune)
What is anergy?
unresponsiveness (impacts the activation energy)
if an antigen is presented in the absence of costimulation, you get apoptosis or anergy
What is ignorance?
in come immunepriveged sites (where the risk of inflammation far outweighs the risk of infection), T cells cannot become activated because there are no APCs
What is deletion (antigen-induced cell death)?
- activation through the TCR can lead to apoptosis of the T-cell
- in peripheral T-cells this can often be caused by the expression of the Fas ligand (death ligand)
What is regulation?
- regulated by Treg cells
- produces cytokines (IL-10) which inhibits other self-reactive T-cells
What gene drive Treg cells?
FoxP3
What CDs do Treg have?
CD4 (a type of T-helper cell)
Give the mechanism of action of regulatory T-cells?
- secrete immunosuppressive cytokines (e.g. TGFb, IL-10)
- they engage with other T cells and turn them off
- IL-10 has a role in shutting down DCs
