Immunological Tolerance

Question 1

What is immunological tolerance?

Answer 1

A learned and very specific unresponsiveness to a particular antigen

Question 2

What is the difference between central tolerance and peripheral tolerance?

Answer 2

Central: occurs in lymphoid organs (bone marrow/thymus) with immature lymphocytes recognizing self antigen

Peripheral: in the periphery involving mature lymphocytes encountering self antigen

Question 3

T/F: Immunological tolerance is the failure to recognize an antigen.

Answer 3

FALSE

Active and specific response

Question 4

T/F: Tolerance is genetically pre-programmed into our bodies.

Answer 4

FALSE

Develops in early development

Question 5

During lymphoid development, what two events wind up in apoptosis?

Answer 5

1. No binding to MHC

2. Strong interaction with self-antigen

Question 6

Where do regulatory T cells come from?

Answer 6

Self-reactive CD4+ T cells that do not get killed in the thymus

Question 7

If an immature lymphocyte results recognizes self antigen what are the three possible outcomes and what type of tolerance do they make up?

Answer 7

1. Apoptosis
2. Change in receptors (B cells)
3. Develop regulatory T cells (CD4+)

CENTRAL TOLERANCE

Question 8

Once lymphocytes mature, what are the three possible results when it recognizes self antigen and what tolerance is this?

Answer 8

1. Anergy
2. Apoptosis
3. Suppression

PERIPHERAL TOLERANCE

Question 9

What determines the fate of B cells in the bone marrow (central tolerance)?

Answer 9

The nature and concentration of self Ag

Question 10

What nature and concentration of self Ag would not result in cell death of a B cell?

Answer 10

Lower concentrations of small, soluble self Ag induce anergy

Question 11

What are the four mechanisms of peripheral tolerance?

Answer 11

1. Clonal deletion/apoptosis
2. Clonal anergy: nonfunctional
3. Suppression: inhibited activity
4. Ignorance: cells do not respond to antigen (both are present)

Question 12

T/F: All B cells that are found to be self-reactive are eliminated in the bone marrow.

Answer 12

FALSE

Question 13

What is the result if one of the signals, either Ag or CD40, is missing during B cell activation?

Answer 13

B cell anergy

Question 14

Which receptor is responsible for competing with CD28 causing anergy in T cells?

Answer 14

CTLA-4

Question 15

T/F: T cells with many CTLA-4 receptors will respond normally to antigens.

Answer 15

FALSE

They will be anergic

Question 16

What three things can lead to T cell death in the periphery?

Answer 16

1. Absence of IL-2 during activation

2. Persistent Ag

Question 17

How do regulatory CD4+ cells inhibit the immune system?

Answer 17

1. IL-10 inhibits APC function
2. TGF-beta inhibits T cell proliferation
3. IL-4 inhibits IFN-gamma actions
4. IL-10 and TGF-beta inhibit macrophage activation

Question 18

How can tolerance be induced?

Answer 18

1. Protein antigens given subcutaneously with adjuvants

2. High doses of antigens systemically without adjuvants

Question 19

T/F: Oral administration of Ag favors tolerance induction.

Answer 19

TRUE

Question 20

T/F: High amounts of protein antigens typically favor tolerance.

Answer 20

TRUE

Question 21

T/F: Short lived presence of protein antigens typically results in tolerance.

Answer 21

FALSE

Prolonged presence

Question 22

What ports of antigen entry typically lead to tolerance?

Answer 22

1. Intravenous
2. Oral
3. Presence in generative organs

Question 23

T/F: If APCs have low levels of costimulators and cytokines tolerance can be favored.

Answer 23

TRUE