Perturbations of the Super System Flashcards
What is the function of Super Ag?
They are used by bacteria and viruses to circumvent conventional immune regulation.
It is a primitive and is one of the least effective methods of immune circumvention.
How do Super Ag work in the host?
Super Ag is often a toxin that bridges CD4 to MHC class II. They do not bind to the conventional antigen binding site. They do so in unprocessed form and can activate up to 20% of available CD4 cells.
What response does the Super Ag elicit?
Polyclonal T cell response
What are the problems that can occur with the rapid T cell activation caused by the Super Ag?
It leads to a ‘cytokine storm’ that can cause a variety of effects based on the MHC from mild symptoms up to toxic shock
What is toxic shock syndrome?
Massive macrophage activation via T cells leads to large amounts of TNF-alpha which can cause a loss of endothelial integrity and decreased vascular resistance which becomes SHOCK.
Why is the method leading to toxic shock not preferable for the virus?
Viruses need living host more than bacteria
How do virus change TLRs to evade the immune response?
Downregulate TLRs
How do viruses interfere with NK cells?
Produce inhibitory signals
How can viruses affect DCs?
Suppress DC function
How can viruses counteract the effects of cytotoxic cells?
Block apoptosis via increasing BcL display or blocking the CASPASE system
What are the main factors that play main role in the acquisition of autoimmune diseases?
- Genetics
- Genders
- Environment
What is the central cause of autoimmune diseases?
Loss of tolerance
What is central tolerance?
It is dependent on the thymus via positive and negative selection
What is is AIRE?
It is near the portico-medullary junction where it expresses self-Ag that are found in the body and any self reactive T cells will be converted into Tregs
What is peripheral tolerance?
It is an active tolerance that is Ag specific and mediated by CD4/25 Tregs
What is the function of CTLA-4?
It functions as a brake on the immune system by increasing Tregs as it binds B7 and prevents the CD28 costimulation
What happens with an increased TGF-beta to IL-6 ratio?
Treg function will be increased
What cytokine are Treg dependent upon?
IL-2
Are AI Ab required for DM Type I?
NO
How can viruses cause DM Type I?
- They can directly infect pancreatic beta cells and initiate CD8 attack against them
- Exhibit antigens that mimic Beta cell antigens which causes CD8 cells to mistakenly attack Beta cells
- Infect non beta cell sites in the pancreas and incite collateral damage to beta cells
- Viruses may attack the Tregs for the beta cells
- Partial autoimmune regulator (AIRE) defect that allowed beta cell reactive T cells to emigrate from the thymus during development and that these cells were activated by the viral infection
Why is the presence of self reactive B cells no cause for alarm?
In most cases, a parallel auto-reactive T cell will not be there and a T reg will be there- so there is no T cell help and very little autoantibody formation
