Tolerance To Self And Other Antigens

Front 1

What is immunological tolerance?

Back 1

The absence of autoreactive clones

Front 2

Tolerance is primarily regulated at what level?

Back 2

At the Th-cell level, since most auto-antigens are dependent on activation by the Th-cell.

Front 3

At what stage of immunological development does tolerance occur?

Back 3

At the early stage in lymphoid cell development.

Front 4

What does Negative selection remove?

Back 4

T cells which express T cell receptors that have more than low affinity for the MHC complex.

Front 5

What percent of T-cells are negatively selected?

Back 5

95%

Front 6

What is central tolerance? Where does it occur?

Back 6

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!

Front 7

When T cells do have T cell receptors which recognize less than low affinity, they are said to be ?

Back 7

The T cells are said to be clonally ignorant.

Front 8

At what stage do the T-cells get deleted? (95%)

Back 8

At the double positive small resting, CD3+ TCR +, CD4+, 8+.

Front 9

What could trigger an autoimmune response in an MHCb mouse?

Back 9

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.

Front 10

T cells that cannot recognize self-peptides (in the context of MHC) undergoes what event?

Back 10

Death by apoptosis since it does not receive positive selection signal.

Front 11

Can anergized cells be reactivated?

Back 11

No.

Front 12

What occurs to the T cell when the co-stimulator binds to a T cell surface receptor?

Back 12

No effect on the T cell.

Front 13

Peripheral tolerance involves:

Back 13

Inactivation of T cells through anergy.

Front 14

Induction of anergy can occur through:

Back 14

Binding of T cell receptor onto an antigen specific signal without other signals such as CD28-B7. LACK OF co-stimulatory signal 2.

Front 15

After T cell activation, the cell requires co-stimulatory signals in order to kill target cells. True or false, why?

Back 15

It has already received the secondary signal to become activated. False.

Front 16

Most of the B cell tolerance occurs where? Where else?

Back 16

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.

Front 17

Induction of tolerance is easier in which type of B-cell?

Back 17

In immature B cells. Mature B-cells are much harder to toleize.

Front 18

What occurs when polymeric antigens crosslink IgM on the surface of B-cell?

Back 18

Clonal deletion.

Front 19

Peripheral B-cell anergy consists of? (3)

Back 19

B-cell recognizes a soluble self antigen.
Forced to migrate to the periphery.
Induction of Anergy by low affinity IgD receptors.

Front 20

Details about B-cell stage and induction of tolerance.
Amount of antigen required to cause deletion.

Back 20

(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.

Front 21

In the absence of stromal or cytokine signals, what occurs to high affinity B-cells?

Back 21

They will undergo Clonal exhaustion. They are constantly activated.

Front 22

Lack of T-cell help will impair what events in B-cell development?

Back 22

Isotype Switching, affinity maturation, and somatic mutation.

Front 23

B cell central deletion occurs at what B-cell stage? (What cell surface molecules are present)

Back 23

Sm IgM+/IgD-

Front 24

What is the difference in self-recognition in the central tolerance of B-cells and T-cells?

Back 24

Clonal deletion of B-cells require the recognition of intact self antigens whereas T-cells recognize soluble self antigens.

Front 25

What dose of antigen is required to induce peripheral tolerance in B cells? in T cells?

Back 25

Low dose in T cells
High dose in B-cells.

Both require costimulatory signals.

Front 26

Development of tolerance occurs during what stage of development?

Back 26

During embryonic stage, but can still occur throughout life.

Front 27

Injection of modest levels of antigen during what stage of development can induce tolerance?

Back 27

Injection of modest amounts of antigen into the fetal or neonatal stage.

Front 28

Can tolerance occur after embryoni development?

Back 28

Yes.

Front 29

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?

Back 29

Yes, since the bone marrow and Thymus still produce new cells which can create a new cell against the antigen.

Front 30

State different cases of immune tolerance vs B-cell response when injecting mice with certain doses. Secondary injections

Back 30

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.

Front 31

Once the antigen (which induced tolerance) is degraded, which cells are the first to be reactivated ?

Back 31

Mature B cells (2 months)-->Immature B cells--> T-cells (150+ days)

Front 32

Tolerance can be targetted to a specific branch of the immune system. Explain this.

Back 32

Tolerance can be induced in specific areas of the human body. In mucosal tissues, tolerance can be induced in IgE B-cells.

Front 33

What is the optimal immunogenic dose?

Back 33

100 micrograms.

Front 34

What is the low dose Zone?

Back 34

10-1000 nanograms will cause T-cells to become anergic and B-cells will remain normal.

Front 35

High Dose Zone:

Back 35

1-100 mg will cause both B and T cells to become anergic.

Front 36

Form of tolerance in adults can be obtained using what type of antigen?

Back 36

Purified protein with naturally low immunogenicity.

Front 37

Activation of the Th2 cells lead to? (3 cascade)

Back 37

The production of IgA that may block the activation of Th1 cells or activate T-regulatory cells.

Front 38

What reduces the severity of autoimmune diseases?

Back 38

Immunization via mucosal tissues.

Front 39

Interferon gamma is secreted by what cell? and inhibits what cell?

Back 39

Secreted by Th1 and suppresses Th2 proliferation.

Front 40

IL-10 is secreted by which cell? and inhibits what activity?

Back 40

Secreted by Th2 and inhibits INF gamma production.

Front 41

How is tolerance broken? (6 methods)

Back 41

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

Front 42

How do Th-cell regulate tolerance?

Back 42

Only when Th2 cell recognize self-antigen does it release cytokines for B cells to mature and mount an immune response.

Front 43

Breaking Tc-Cell tolerance and B-cell tolerance requires what two types of cells? What do these cells accomplish?

Back 43

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.

Front 44

Type 1 diabetes versus type 2 diabetes.

Back 44

Type 1: Adult onset diabetes, less production in the pancreas, and insulin resistnace.

Type 2: Juvenile diabetes, virus targets pancreatic cells producing insulin.

Front 45

Local production of Th1 cytokines.

Which cytokine is produced? How is it produced?
Where is it produced?
What does it affect?

Back 45

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.

Front 46

INF-gamma causes what type of local reponse?

Back 46

Inflammatory rsponse.