Immunological Tolerance - Powell

Question 1

What is the difference between peripheral and central tolerance?

Answer 1

Central Tolerance = occurs in generative lymphoid organs involving immature self reactive lymphocytes recognizing self antigen.

Peripheral Tolerance = in peripheral sites involving mature self- reactive lymphocytes encountering self antigen.

Question 2

How is tolerance achieved?

Answer 2

Tolerance can be natural or induced

• Natural = self tolerance or oral tolerance.
• Induced = graft rejection, prevent allergies, or autoimmunity.

Question 3

What is Tolerance?

Answer 3

a state of unresponsiveness for particular antigen

Question 4

What is self tolerance?

Answer 4

Immune system does not react destructively against self tissue. IMPORTANT

Question 5

What is Anergy?

Answer 5

Programmed “ignorance” to ignore certain cells…

Question 6

Tolerance is an active response that is just as specific as an immune response, True or false?

Answer 6

True

Question 7

The most important aspect of tolerance is ______.

Answer 7

Self tolerance

Question 8

Central Tolerance in B cells occurs in the ______.

Answer 8

Bone Marrow

Question 9

____ & ____ of the self Ag determine the fate of B cells in Central tolerance.

Answer 9

Nature & Concentration

• High concentration of and Multivalent Ag induce Cell death
• Low concentrations of small, soluble Ag induce functional Anergy

Question 10

What is Peripheral Tolerance?

Answer 10

Is the mechanism by which mature T cells that recognize self antigens in peripheral tissues become incapable of responding to this antigens.

Question 11

What are the 4 mechanisms of Peripheral Tolerance?

Answer 11

1. Clonal deletion/apoptosis
2. Clonal Anergy
3. Supression
4. Ignorance

Question 12

What is Clonal deletion/apoptosis?

Answer 12

Actual elimination from the cellular repertoire by activation induced cell death.

Question 13

What is Clonal Anergy?

Answer 13

Mature cell is present but its functionally inactivated (but can be reversed)

Question 14

What is Suppression?

Answer 14

inhibition of cellular activity through interaction with other cells.

Question 15

What is Ignorance?

Answer 15

Co-existing of self reactive clones and antigen; do not respond to antigen.

Question 16

In regards in peripheral tolerance, What factors determine which mechanisms are operative?

Answer 16

• Concentration of Self antigen in generative lymphoid organs.
• Affinity of antigen receptor fro antigen.
• Nature of antigen.
• Concentration and availability of con-stimulatory molecules.

Question 17

True or False? In peripheral tolerance in B cells, all potentially reactive cells are eliminated or inactivated and enter peripheral circulation.

Answer 17

False, not all potentially reactive cells are eliminated or inactivated.

Question 18

How do T cells Affect the outcome of B cell activation in the periphery?

Answer 18

TWO SINGAL HYPOTHESIS
Signal 1 = Generated through the Ag receptor.
Signal 2 = mediated by CD40 and CD40L

Question 19

What is B cell Receptor editing? (Central tolerance)

Answer 19

Is the attempt to modify receptor on B cell to be more “friendly”. If he cannot be reformed he undergoes apoptosis.
*receptor editing in B cells (Central tolerance) is a one shot deal.

Question 20

How does peripheral tolerance: Anergy work?

Answer 20

Anorexic cells show a block in TCR-induced signal transduction.

• Lack of costimulation by B7/B72
• costimulation by inhibitory receptors

Question 21

In Peripheral Tolerance (Anergy) , CTLA-4 does what?

Answer 21

• Competes with CD28 fro B71 and B72

- Keeps T cells in check

Question 22

Mice lacking CTLA-4 will develop what?

Answer 22

• uncontrolled lymphocyte activation
• Massively enlarged lymph nodes and spleen
• Fatal multiorgan lymphocytic inflitrates

Question 23

How does Peripheral tolerance: Apoptosis work?

Answer 23

Self reactive cells may be deleted from the repertoire.

• Activation in the absence of IL-2 can lead to death.
• Persistent Ag
• Activation-induced cell death

Question 24

How does Peripheral tolerance: Suppression work?

Answer 24

T cell mediated suppression

- Supressive T cells inhibit T cell activation, T cell proliferation or T cell differentiation

Question 25

The state of tolerance may be maintained by _______.

Answer 25

Immune regulation

Question 26

_____ inhibits T cell proliferation. (Suppression)

Answer 26

TGF-beta

Question 27

_______ & ______ inhibit macrophage activation. (Suppression)

Answer 27

IL-10 & TGF-beta

Question 28

_______ inhibits actions of IFN-gamma. (suppression)

Answer 28

IL-4

Question 29

How does Peripheral tolerance: Ignorance occur?

Answer 29

1. Antigen is expressed in a privileged site/sequestered.
2. T cells cannot get to the antigen across an endothelial barrier.
3. Perhaps the antigen is not expressed in the context of MHC molecules.
   * Ignorance is not typical a method the immune system uses.

Question 30

Protein antigens administered subcutaneously or intradermally with adjuvants favor ________.

Answer 30

Immunity

Question 31

High doses of antigens administered systemically without adjuvants tend to induce ______.

Answer 31

Tolerance

Question 32

Oral administration of Ag favors ________ induction.

Answer 32

Tolerance

Question 33

A state of ________ follows oral administration of antigen.

Answer 33

hypo-responsiveness