immunological tolerance

Question 1

a state of unresponsiveness for a particular antigen

Answer 1

immunological tolerance

Question 2

immunological tolerance is ____, very ____, and induced by ____

Answer 2

learned; specific; prior exposure to antigen

Question 3

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

Answer 3

self tolerance

Question 4

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

Answer 4

central tolerance

Question 5

in peripheral sites involving mature self-reactive lymphocytes encountering self antigen

Answer 5

peripheral tolerance

Question 6

self-tolerance may be induced in ____ in generative lymphoid organs (central tolerance) or in ____ lymphyocytes in peripheral sites (peripheral tolerance)

Answer 6

immature self-reactive lymphocytes; mature

Question 7

imm. tolerance is an ____ response to a particular ____ and is just as specific as an immune response

Answer 7

active; epitope

Question 8

self-tolerance can be ___ (i.e. self tolerance, oral tolerance) or ____ (e.g. prevent allergies, graft rejection, or autoimmunity)

Answer 8

natural; induced

Question 9

reactivity is prevented by processes that occur during ____ rather than being ____

Answer 9

development; genetically pre-programmed

Question 10

positive selection (low avidity interaction with self-antigen) and ____ takes place in the cortical region of the thymus

Answer 10

lineage commitment

Question 11

negative selection mediated by ____ takes place in the medullary region of the thymus

Answer 11

high avidity interactions with self antigen

Question 12

some self-reactive CD4+ T cells that see self antigens in the thymus are not deleted but instead differentiate into _____

Answer 12

regulatory T cells

Question 13

choice between lymphocyte activation and tolerance is determined by:

Answer 13

• the properties of the antigens
• state of maturation of the antigen-specific lymphocytes
• types of stimuli received when these lymphocytes encounter self antigens

Question 14

3 responses of immature lymphocytes upon recognition of self antigen

Answer 14

1. apoptosis (deletion)
2. change in receptors (receptor editing; B cells)
3. development into regulatory T lymphocytes (CD4+ T cells only)

Question 15

3 responses of mature lymphocytes upon recognition of self antigen

Answer 15

1. anergy
2. apoptosis
3. suppression

Question 16

central tolerance in B cells occurs in ____ in the ____; potentially autoreactive cells can be _____ or ____ by contact with self Ag

Answer 16

immature B cells; bone marrow; eliminated; inactivated

Question 17

___ and ____ of the self Ag determine the fate of B cells

Answer 17

nature; concentration

Question 18

_____ and ____ induce B cell death

Answer 18

multivalent Ag (membrane associated proteins)
high concentrations of Ag

Question 19

___ of small, soluble self Ag induce functional anergy which results in:

Answer 19

lower concentrations

results in 1. decreased membrane Ig and 2. blocked signal transduction by membrane bound Ig

Question 20

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

Answer 20

peripheral tolerance

Question 21

4 mechanisms of peripheral tolerance

Answer 21

1. clonal deletion/apoptosis
2. clonal anergy
3. suppression
4. ignorance

Question 22

T regulatory cells involved with suppression

Answer 22

CD4+/CD25+ regulatory T cells

TGF-beta or IL-10 secreting regulatory T cells

Question 23

factors determining which mechanism(s) of peripheral tolerance are operative:

Answer 23

• concentration of self Ag in generative lymphoid organs
• affinity of Ag receptor for Ag
• nature of Ag
• concentration and availability of co-stimulatory molecules

Question 24

2 signal hypothesis for B cell activation

Answer 24

signal 1 generated thru Ag receptor

signal 2 mediated by Cd40 and CD40L

Question 25

anergic T cells show a block in TCR-induced signal transduction, which could be caused by:

Answer 25

- lack of costimulation by B7/B72 | - costimulation by inhibitory receptors (e.g. CTLA-4)

Question 26

CTLA-4 completes with ___ for B71 and B72 and binds with higher affinity

Answer 26

CD28

Question 27

in a normal ag recognition response, ___ on APC binds with ____ on naive T cell

Answer 27

B7; CD28

Question 28

3 things that can lead to apoptosis in peripheral tolerance of T cells

Answer 28

1. activation in the absence of IL-2 can lead to death 2. persistent Ag 3. activation-induced death

Question 29

suppression in peripheral tolerance causes:

Answer 29

- inhibition of T cell activation | - inhibition of T cell effector functions

Question 30

the state of tolerance may be maintained by ____ through ____ produced by ____

Answer 30

immune regulation; cytokines; regulatory CD4+ T cells

Question 31

protein Ags administered ____ or ____ with adjuvants favor ____

Answer 31

subcutaneously; intradermally; immunity

Question 32

high doses of Ags administered ____ without adjuvants tend to induce ____

Answer 32

systemically; tolerance

Question 33

oral administration of Ag favors ____; a state of immune ____ follows oral administration of an antigen

Answer 33

tolerance induction; hyporesponsiveness

Question 34

principal sites of tolerance induction in T and B lymphocytes

Answer 34

T: thymus (cortex); periphery B: bone marrow; periphery

Question 35

Immune System targets Central Nervous System via myelin specific T cells

Answer 35

multiple sclerosis (MS)

Question 36

A systemic disorder in which a variety of autoantibodies (DNA, nucleoproteins, platelets, lymphocytes) can cause multisystem damage

Answer 36

systemic lupus erythematosus (SLE)

Question 37

2 examples of systemic autoimmune diseases

Answer 37

``` Systemic Lupus Erythematosus (SLE) rheumatoid arthritis (RA) ```

Question 38

2 examples of organ specific autoimmune diseases

Answer 38

1. insulin dependent diabetes mellitus (IDDM) | 2. multiple sclerosis (MS)