Perturbations of the Super System

Question 1

What is the function of Super Ag?

Answer 1

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.

Question 2

How do Super Ag work in the host?

Answer 2

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.

Question 3

What response does the Super Ag elicit?

Answer 3

Polyclonal T cell response

Question 4

What are the problems that can occur with the rapid T cell activation caused by the Super Ag?

Answer 4

It leads to a ‘cytokine storm’ that can cause a variety of effects based on the MHC from mild symptoms up to toxic shock

Question 5

What is toxic shock syndrome?

Answer 5

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.

Question 6

Why is the method leading to toxic shock not preferable for the virus?

Answer 6

Viruses need living host more than bacteria

Question 7

How do virus change TLRs to evade the immune response?

Answer 7

Downregulate TLRs

Question 8

How do viruses interfere with NK cells?

Answer 8

Produce inhibitory signals

Question 9

How can viruses affect DCs?

Answer 9

Suppress DC function

Question 10

How can viruses counteract the effects of cytotoxic cells?

Answer 10

Block apoptosis via increasing BcL display or blocking the CASPASE system

Question 11

What are the main factors that play main role in the acquisition of autoimmune diseases?

Answer 11

• Genetics
• Genders
• Environment

Question 12

What is the central cause of autoimmune diseases?

Answer 12

Loss of tolerance

Question 13

What is central tolerance?

Answer 13

It is dependent on the thymus via positive and negative selection

Question 14

What is is AIRE?

Answer 14

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

Question 15

What is peripheral tolerance?

Answer 15

It is an active tolerance that is Ag specific and mediated by CD4/25 Tregs

Question 16

What is the function of CTLA-4?

Answer 16

It functions as a brake on the immune system by increasing Tregs as it binds B7 and prevents the CD28 costimulation

Question 17

What happens with an increased TGF-beta to IL-6 ratio?

Answer 17

Treg function will be increased

Question 18

What cytokine are Treg dependent upon?

Answer 18

IL-2

Question 19

Are AI Ab required for DM Type I?

Answer 19

NO

Question 20

How can viruses cause DM Type I?

Answer 20

• 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

Question 21

Why is the presence of self reactive B cells no cause for alarm?

Answer 21

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