Regulation of Lymphocyte Responses Flashcards
What is autoimmunity pathogenesis based on?
Genetic predisposition and environmental triggers
How are allergic reactions mediated?
IgE, mast cells and T cells in delayed type hypersensitivity
What happens when mast cells meet their antigen?
Degranulate and release their histamines causing inflammation
What is hypercytokinemia?
Too many cytokines in the blood
What is sepsis?
When bacteria cross from mucosa into blood
What is the relationship between sepsis and hypercytokinemia?
Sepsis can cause hypercytokinemia
What are the failures of the immune system? (3)
Autoimmunity, allergy, and hypercytokinemia
What happens to lymphocytes as pathogens with their antigens run out?
Apoptose or become memory cells, this is a regulatory function
What happens with chronic exposure to antigens?
The immune response downregulates, e.g. in HIV
What is central tolerance? Explain.
Destroying self-reactive B and T cells before they enter the circulation. If an immature B cell encounters an antigen that can crosslink with their IgM apoptosis is triggered.
What is peripheral tolerance?
Destroying self reactive B and T cells that do enter the circulation
What is a tolerogenic T cell?
Induced tolerance by regular exposure
What cells produce antigens to be tested in bone marrow?
Stromal cells
What is the autoimmune regulator (AIRE)?
A specialised transcription factor that allows the expression of genes that are expressed in peripheral tissues so the thymus can express all the proteins in the body. All the proteins are presented on MHC to developing T cells promoting self-tolerance.
Four main mechanisms for peripheral tolerance?
Anergy, ignorance, deletion and regulation
Explain anergy
Presenting an antigen without a costimulatory signal leads to either apoptosis or anergy where the cell increases its unresponsiveness to the antigen
Explain ignorance
There are some immune privileged sites where the risk of inflammation outweighs the risk of infection, and so T cells cannot become activated as there are no APC’s
Explain deletion
Where the antigen induces T cell death, this is usually by expression of the death Fas ligand
What cell and cytokines are involved in regulation of T cells?
Treg and IL-10
What CD (not including CD3) is a Treg cell?
CD4 T helper cell
What is the mechanism of action of Treg cells?
They secrete immunosuppressive cytokines and engage T effector cells and turn them off
What are 3 examples of immunosuppressive cytokines?
TGFb. IL-10 and IL-35
What does IL-10 do specifically?
Has a role in shutting down dendritic cells and is leads to APC’s presenting antigen in anergic or apoptotic forms
What are the two types of Treg and what are the differences?
Natural (nTreg) which develop in the thymus and reside in peripheral tissues, and induced (iTreg) which when exposed to APC’s turn from being Helper to Treg
What is resolution?
No tissue damage and the SOI returns to normal
What is repair?
Healing with scar tissue and regeneration
Where is Treg VITAL?
In pregnancies
What is self limitation?
The immune response eliminates the antigen that initiated the response causing the immune response to shut down
