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What is tolerance?

The lack of response to a specific antigen.


Is tolerance innate or acquired?



What are the 2 major mechanisms of tolerance? What are the other 3

1 Deletion of reactive cells.
2 Inactivation of reactive cell: ANERGY
3 Functional Deletion
4 Generation of Suppressor or Regulatory Tcells (Treg)
5 Blocking of presentation or Activation


Is anergy reversible?



What is the major difference in the way T-reg cells interact with APC compared to other T-cells

It interacts with B7 via CTLA-4 instead of CD28 and then they send suppression signals to the T-cell


How are T-Cells turned off after an immune response?

They start up-regulating CTLA-4 after a certain period of time and down-regulate CD28. CTLA-4 binds B7 with higher affinity and sends a suppressing signal to the cell.


What are the mechanisms of tolerance in B cells?

1 Clonal Deletion
2 Clonal abortion/clonal Anergy
3 Functional Deletion


Where does clonal deletion take place for B-Cells?
Is the level of deletion at this site higher or lower than what you see in the thymus with T-cells?

The Bone Marrow. Less deletion than in thymus with T-Cells


If an immature B-cell in the bone marrow reacts with multivalent self antigen what happens? what it if reacts with solubilized self antigen?

Multivalent - apoptosis
Solubilized - Anergic B-cell in periphery (IgD predominately expressed)


Describe which physical forms of an antigen favor an immune response and which favor tolerance

Immune- Large, aggregated, complex molecule
Tolerance- Soluble, aggregate-free, relatively smaller, less complex molecules not processed by APC


Describe the routes of antigen administration that favor immune response and those that favor tolerance

Immune- SQ or IM
Tolerance- Oral or sometimes IV


Describe the dose of an antigen that favors immune response versus tolerance

Immune- optimal dose
Tolerance- Very large or sometimes very small dose


Describe the age of responding animal that favors an immune response versus tolerance

Immune- Older and immunologically mature
Tolerance- Newborn, immunologically immature


Describe the differentiation state of cells that favor immune response versus tolerance

Immune- Fully differentiated cells; memory T and memory B
Tolerance- Relatively undifferentiated: B cells with only IgM, thymocytes


What surface markers do Regulatory T-Cells Have?

FoxP3, CD25, CD4


Why are immune responses to lipids and polysaccharides short lived?

Because you need protein immunogens to activate T-cells which cause B-cells to class switch to memory cells and give capability of secondary responses. T-Cells can only see protein.


What is one way to try and limit responses to allergies?

Repeated small dose exposure


What do adjuvants do?

They help keep antigen around for longer period of time, they also cause more of an inflammatory response. They can also help antigen be ingested and presented on cell surface. Creates more of a "DANGER" signal to the body.


What type of immune response is necessary to fight off leprosy?



What cytokines do Tregs secrete that actively turn off auto reactive T-cells?

IL-10 and TGF Beta


What is the most important thing that must happen for something to be immunogenic?

It must be pagocytosed and presented such that a TCR can recognize it. Recognition by B-cells alone is not enough.


How does a direct combs test work?

Washed fetal red blood cells coated with maternal antibody, add rabbit anti human and look for agglutination


How does an indirect combs test work?

Maternal serum is added to Rh+ RBCs, wash, add rabbit anti human and look for agglutination


What drug is given to mothers to prevent Rh antibodies from attacking th fetus?

Rhogam, works by hiding Rh antigen from mothers B-cells