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46 Cards in this Set

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What is immunological tolerance?
The absence of autoreactive clones
Tolerance is primarily regulated at what level?
At the Th-cell level, since most auto-antigens are dependent on activation by the Th-cell.
At what stage of immunological development does tolerance occur?
At the early stage in lymphoid cell development.
What does Negative selection remove?
T cells which express T cell receptors that have more than low affinity for the MHC complex.
What percent of T-cells are negatively selected?
95%
What is central tolerance? Where does it occur?
Immature T cells that recognize self MHC receive signals for survival. Those that interact strongly with self antigen are removed from the repertoire. Occurs in the thymus!
When T cells do have T cell receptors which recognize less than low affinity, they are said to be ?
The T cells are said to be clonally ignorant.
At what stage do the T-cells get deleted? (95%)
At the double positive small resting, CD3+ TCR +, CD4+, 8+.
What could trigger an autoimmune response in an MHCb mouse?
If their T-cells are not tolerant to self, then any deviation in peptide density could activate mature T-cells and initiate an autoimmune response.
T cells that cannot recognize self-peptides (in the context of MHC) undergoes what event?
Death by apoptosis since it does not receive positive selection signal.
Can anergized cells be reactivated?
No.
What occurs to the T cell when the co-stimulator binds to a T cell surface receptor?
No effect on the T cell.
Peripheral tolerance involves:
Inactivation of T cells through anergy.
Induction of anergy can occur through:
Binding of T cell receptor onto an antigen specific signal without other signals such as CD28-B7. LACK OF co-stimulatory signal 2.
After T cell activation, the cell requires co-stimulatory signals in order to kill target cells. True or false, why?
It has already received the secondary signal to become activated. False.
Most of the B cell tolerance occurs where? Where else?
Central B cell tolerance occurs in the Bone marrow.
Peripheral B cell tolerance occurs because there is improper co-stimulation by Th-cells and the B-cell receptors are low affinity and cannot crosslink enough.
Induction of tolerance is easier in which type of B-cell?
In immature B cells. Mature B-cells are much harder to toleize.
What occurs when polymeric antigens crosslink IgM on the surface of B-cell?
Clonal deletion.
Peripheral B-cell anergy consists of? (3)
B-cell recognizes a soluble self antigen.
Forced to migrate to the periphery.
Induction of Anergy by low affinity IgD receptors.
Details about B-cell stage and induction of tolerance.
Amount of antigen required to cause deletion.
(1) Immature B-cells (IgM) heavy crosslinking causes deletion in the bone marrow.

(2)Mature B cells (IgD and IgM) is present. Require moderate amount of antigen in order to induce anergy.

(3) Memory B cells are impossible to anergize and require high levels of antigen in order to induce anergy.
In the absence of stromal or cytokine signals, what occurs to high affinity B-cells?
They will undergo Clonal exhaustion. They are constantly activated.
Lack of T-cell help will impair what events in B-cell development?
Isotype Switching, affinity maturation, and somatic mutation.
B cell central deletion occurs at what B-cell stage? (What cell surface molecules are present)
Sm IgM+/IgD-
What is the difference in self-recognition in the central tolerance of B-cells and T-cells?
Clonal deletion of B-cells require the recognition of intact self antigens whereas T-cells recognize soluble self antigens.
What dose of antigen is required to induce peripheral tolerance in B cells? in T cells?
Low dose in T cells
High dose in B-cells.

Both require costimulatory signals.
Development of tolerance occurs during what stage of development?
During embryonic stage, but can still occur throughout life.
Injection of modest levels of antigen during what stage of development can induce tolerance?
Injection of modest amounts of antigen into the fetal or neonatal stage.
Can tolerance occur after embryoni development?
Yes.
If the antigen is removed after the primary deletion of B-cells and T-cells, can there still be an immune response to the antigen?
Yes, since the bone marrow and Thymus still produce new cells which can create a new cell against the antigen.
State different cases of immune tolerance vs B-cell response when injecting mice with certain doses. Secondary injections
Low dose: T-cell tolerance
High dose: B-cell tolerance

Secondary injection of antigen causes immune tolerance in B and T cells.
Wheras low dose and secondary injection causes solely tolerance in T cells. B cells can still be activated.
Once the antigen (which induced tolerance) is degraded, which cells are the first to be reactivated ?
Mature B cells (2 months)-->Immature B cells--> T-cells (150+ days)
Tolerance can be targetted to a specific branch of the immune system. Explain this.
Tolerance can be induced in specific areas of the human body. In mucosal tissues, tolerance can be induced in IgE B-cells.
What is the optimal immunogenic dose?
100 micrograms.
What is the low dose Zone?
10-1000 nanograms will cause T-cells to become anergic and B-cells will remain normal.
High Dose Zone:
1-100 mg will cause both B and T cells to become anergic.
Form of tolerance in adults can be obtained using what type of antigen?
Purified protein with naturally low immunogenicity.
Activation of the Th2 cells lead to? (3 cascade)
The production of IgA that may block the activation of Th1 cells or activate T-regulatory cells.
What reduces the severity of autoimmune diseases?
Immunization via mucosal tissues.
Interferon gamma is secreted by what cell? and inhibits what cell?
Secreted by Th1 and suppresses Th2 proliferation.
IL-10 is secreted by which cell? and inhibits what activity?
Secreted by Th2 and inhibits INF gamma production.
How is tolerance broken? (6 methods)
1)- Activation of autoimmunity
2)- Cytokine dysregultion
3)- Thymic escape of forbidden T cell clones
4)- T cell activation to cross-reactive bacteria
5)- Failure of normal or negative feedback
6)- Autoreactive B cell activation to cytokines
How do Th-cell regulate tolerance?
Only when Th2 cell recognize self-antigen does it release cytokines for B cells to mature and mount an immune response.
Breaking Tc-Cell tolerance and B-cell tolerance requires what two types of cells? What do these cells accomplish?
The Tc-cell requires activation of Th-1 cells through crossreactive antigens being presented by APCs.

B-cell requires Th-2 cells to be similarly primed.
Type 1 diabetes versus type 2 diabetes.
Type 1: Adult onset diabetes, less production in the pancreas, and insulin resistnace.

Type 2: Juvenile diabetes, virus targets pancreatic cells producing insulin.
Local production of Th1 cytokines.

Which cytokine is produced? How is it produced?
Where is it produced?
What does it affect?
INF-gamma is secreted by pancreas since the INF gamma gene is attached to Insulin promoter.

Causes activation of Th1 and thus an autoimmune cell-mediated response.
INF-gamma causes what type of local reponse?
Inflammatory rsponse.