5 Immunological Tolerance

Question 1

A state of unresponsiveness for a particular antigen. Learned, specific, induced by prior exposure.

Answer 1

Immunological Tolerance

Question 2

Physiological state in which the immune system does not react destructively against self tissue

Answer 2

Self Tolerance

Question 3

Tolerance that occurs in generative lymphoid organs (bone marrow/thymus) involving immature self-reactive lymphocytes recognizing self antigen

Answer 3

Central Tolerance

Question 4

Tolerance in peripheral sites involving mature self-reactive lymphocytes encountering self antigen. The mechanism by which mature T cells that recognize self antigens in peripheral tissue become incapable of responding to these antigens.

Answer 4

Peripheral Tolerance

Question 5

T/F Immunological tolerance is an active response to a particular epitope and is just as specific as an immune response

Answer 5

True

Question 6

Reactivity is prevented by processes that occurs during ____ rather than being genetically pre-programmed.

Answer 6

Development

Question 7

Those lymphocytes that do not bind MHC through their TCR are destined to _____.

Answer 7

Die by apoptosis

Question 8

This takes place in the ____ region of the thymus: Positive selection and lineage commitment; low avidity interaction with self antigen

This takes place in the ____ region of the thymus: negative selection mediated by high-avidity interactions with self antigen

Answer 8

Cortical

Medullary

Question 9

During maturation in the thymus, most immature T cells that recognize antigens with high avidity are ____. Some self-reactive CD4 T cells that see self antigens in the thymus are ___.

Answer 9

Deleted

Differentiated into regulatory T cells

Question 10

Choice between lymphocyte activation and tolerance is determined by these properties:

Answer 10

1. Properties of antigens
2. State of maturation of antigen-specific lymphocytes
3. Types of stimuli received when these lymphocytes encounter self antigens

Question 11

B cell central tolerance occurs in ____ B cells in the ____. Potentially autoreactive cells can be eliminated or inactivated by contact with self Ag

Answer 11

Immature

Bone Marrow

Question 12

The _____ and _____ of the self Ag determine the fate of B cells.
Multivalent Ag or High concentrations of Ag induce ____.
Lower concentrations of small, soluble self Ag induce ____.

Answer 12

Nature
Concentration

Cell Death

Functional anergy

Question 13

A peripheral tolerance mechanism. Actual elimination from the cellular repertoire by activation induced cell death

Answer 13

Clonal Deletion/apoptosis

Question 14

A peripheral tolerance mechanism. Mature cell is present but is functionally inactivated (can be reversed)

Answer 14

Clonal Anergy

Question 15

A peripheral tolerance mechanism. Inhibition of cellular activity thru interaction with other cells (T regs)

Answer 15

Suppression

Question 16

A peripheral tolerance mechanism. Co-existence of self-reactive clones and antigen; cells do not respond to antigen

Answer 16

Ignorance

Question 17

Factors determining which mechanisms are operative:

Answer 17

1. Concentration of self antigen in lymphoid organs
2. Affinity of antigen receptors for antigen
3. Nature of antigen
4. Concentration and availability of co-stimulators molecules

Question 18

T cells affect the outcome of B cell activation in the periphery by two signal hypothesis:
Signal one- generate thru ___ receptor
Signal two- mediated by ___ and ___

____ results if one of the signals is missing

Answer 18

Ag

CD40
CD40L

B cell anergy

Question 19

Lack of costimulation by B7/B72 OR costimulation by competitive inhibitory receptors (such as ____) results in ____.

Answer 19

CTLA-4

Anergy

Question 20

Apoptosis is caused by three main mechanisms:

Answer 20

1. Activation in absence of IL-2 -> death
2. Persistent Ag
3. Activation-induced cell death

Question 21

Suppression (T cell-mediated) happens by 4 main mechanisms:

Answer 21

1. IL-10 inhibits functions of APCs (IL-12 secretion, B7 expression)
2. TGF-beta inhibits T cell proliferation
3. IL-4 inhibits IFN-gamma
4. IL-10, TGF-beta inhibit macrophage activation

Question 22

Self-reactive T cells may ignore self antigens (passive). Ignorance happens in 3 main ways:

Answer 22

1. Antigen is expressed in a privileged site/sequestered
2. T cells can’t get to antigen across endothelial barrier
3. Antigen is not expressed in context of MHC molecules

Question 23

Foreign antigens may be administered in ways that preferentially induce ____ rather than immune responses.

• Protein antigens administered subcutaneously with adjuvants favor ____
• High doses of antigens administered systemically w/out adjuvated induces ____

Answer 23

Tolerance

Immunity

Tolerance

Question 24

Oral administration of Ag favors ____ induction. A state of immune ____ follows oral administration of an antigen.

Answer 24

Tolerance

Hyporesonsiveness

Question 25

Group of more than 80 serious chronic illnesses/syndromes that can involve almost every organ system. Occurs when the immune system becomes dysregulated and attacks the organs it was designated to protect. Affects 5% of US population. 2% of world.

Answer 25

Autoimmune Disease

Question 26

List factors that predispose an individual to autoimmune disease:

Answer 26

1. MHC associations
2. Gender- women more common
3. Climate
4. Chemical Agents
5. Infectious Agents
6. Immune Dysregulation
7. Genetics

Question 27

What initiates an autoimmune response?

Answer 27

1. Incomplete deletion of self reactive cells
2. Aberrant stimulation of normally anergy self reactive cells
3. Altered regulation of anergy self reactive cells

Question 28

Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are both \_\_\_\_ autoimmune diseases.
Insulin Dependent Diabetes Mellitus (IDDM) and Multiple Sclerosis (MS) are both \_\_\_\_ autoimmune diseases.

Answer 28

Systemic

Organ Specific

Question 29

This is a multi system disease where large amounts of autoantibodies are produced against self antigens.

Answer 29

SLE (Systemic Lupus Erythematosus)

Question 30

This is the most common inflammatory disorder of the central nervous system. Pathological hallmark is the CNS plaque with loss of myelin and depletion of oligodendrocytes with or without axon loss. T cell mediated. Impairs nerve conduction.

Answer 30

MS