Regulation of Lymphocyte Responses Flashcards
define autoimmunity
immune response against self antigens, pathological
What are the general principles of autoimmunity?
pathogenesis - susceptibility genes and environmental triggers
systemic or organ specific
What are the features of autoimmunity?
chronic and self perpetuating
inflammation
T cell of antibody driven
imbalance beween immune activation and control
define allergy
immune response to non-infectious agents
What are the types of allergy?
anaphylaxis - mediated by IgE and mast cell
DTH - mediated by T cells
define hypercytokinemia and sepsis
too much immune response due to positive feedback
How do hypercytokinemia and sepsis differ?
sepsis = when pathogens enter wrong compartment such as blood hypercytokinemia = failure to regulate response level
What is self limitation? How is it done?
decline in immune response by eliminating antigen to decrease stimulation for T cell activation
What is tolerance?
active control mechanisms function to limit responses to persistent pathogens
define immunological tolerance
specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen
How is immunological tolerance significant?
individuals are tolerant to their own antigens
can be used therapeutically to prevent rejection
What is central tolerance?
destroy self reactive T/B cells before they enter the circulation
Summarise the process of central tolerance
lymphocytes that recognise self antigens before maturation are apoptosed or changed
change:
-B cells change specificity
-T cells develop into Treg
apoptosis:
-B cells apoptosis triggered if IgM crosslinks with self antigen
-TCR and MHC binding can’t be too weak/not at all as no signal produced if peptide bound
-TCR and MHC binding can be too strong as signalling may happen without foreign peptide
define peripheral tolerance
destroy self reactive T/B cells that enter circulation
What is autoimmune regulator (AIRE)? Why is is important?
transcription factors allow transcription of proteins normally just expressed in peripheral tissues to be expressed in thymus to T cells encounter all self proteins
What are the 4 mechanisms of peripheral tolerance?
anergy, ignorance, deletion, regulation
What is anergy?
naive T cells need costimulatory signals to be activated
most cells lack costume. proteins and MHCII
naive T cell sees MHC?peptide without costim.
tells T cell to shut down and become anergia
less likely to be activated in future even if co stimulation present
What is ignorance?
no antigen or costimulation so no activation
compartmentalisation means T cells and APC never in same tissue
What is deletion?
APC drives apoptosis of T cell via TCR activation
What is regulation?
block activation using Treg cells to inhibit T cells
What is an immunologically privileged site? give examples
no APC so no reaction as risk of immune response damage greater than infection damage
e.g. brain, eye
Give characteristics touristic of Treg cells
high IL-2 receptor levels
low IL-7 receptor levels
FoxP3 TF
secretes immunosuppressive cytokines to inactivate lymphocytes
Why are Treg essential for pregnancy?
50% of MHC isn’t self
What are the flavours of Treg?
natural Treg
inducible Treg
What happens post infection?
resolution - no tissue damage, returns to norma phagocytosis of debris
repair - healing with scar tissue and regeneration with fibroblasts and collagen synthesis
chronic inflammation -active inflammation and attempts to repair damage ongoing
Summarise cross regulation by T cell cytokines
Th cells produce cytokines which cross-regulate with each other
cytokines has diverse action on a wide range of cells
and influence outcome of immune response
focuses response of single subset and regulates macrophages
Give characteristic of IL-10
master regulator multifunctional anti inflammatory cytokine shuts down IR acts on may cells down regulates macrophages
Explain T-B cell collaboration
T cell recognises MHC:peptide
T cell expressed CD40L to activate B cell and CD28 to be activated
B cell expressed CD40 to be activated and B7 to activate T
T cell produces IL-4, IL-21, IFN-gamma
