EX1 Tolerance/Autoimmune Disease - Powell

Question 1

physiological state in which the immune system does not react destructively against self tissues; it is LEARNED

Answer 1

self-tolerance

Question 2

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

Answer 2

central tolerance

Question 3

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

Answer 3

peripheral tolerance

Question 4

True or False

Tolerance is simply a failure to recognize an antigen

Answer 4

False; tolerance is an active response and is just as specific as an immune response

Question 5

Tolerance can be _______ or _______

Answer 5

natural

induced

Question 6

The most important aspect of tolerance is _____ ______; which prevents the body from mounting an immune attach against its _____ ______

Answer 6

self tolerance

self tissues

Question 7

Immature T cells that recognize antigens with _____ _____ are deleted and some some reactive _____ T cells that see self antigens in the thymus are not deleted but instead differentiate into ________ ___ ____

Answer 7

high avidity
CD4
regulatory T cells

Question 8

The choice between lymphocyte activation and tolerance is determined by;
the properties of the ________
state of ______ of the antigen-specific lymphocytes
types of _______ received when these lymphocytes encounter _____ _____

Answer 8

antigen
maturation
stimuli
self antigens

Question 9

Central tolerance of B cells occurs the ___ _____; potentially auto reactive cells can be ______ or ______ by contact with _____ antigens

Answer 9

bone marrow
eliminated
inactivated
self

Question 10

Central tolerance of B cells is achieved via _______ editing

Answer 10

receptor

VDJ rearrangement

Question 11

______ and ________ of the self antigens determine the fate of B cells

Answer 11

nature and concentration

Question 12

True or False

multivalent and high concentrations of antigens induce B cell death

Answer 12

True; lower concentrations induce functional anergy

Question 13

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

Answer 13

peripheral tolerance (PT)

Question 14

Mechanism of PT; actual elimination from the cellular repertoire by activation induced cell death

Answer 14

clonal deletion/apoptosis

Question 15

Mechanism of PT; mature cell is present but its functionally inactivated (can be reserved)

Answer 15

clonal anergy

Question 16

Mechanism of PT; inhibition of cellular activity through interaction with other cell (T-regs, etc.)

Answer 16

suppression

Question 17

Mechanism of PT; coexistence of self-reactive clones and antigen; cells do not respond to antigen

Answer 17

ignorance

Question 18

Factors determining which mechanisms are operative;
________ of self antigen in lymphoid organs
________ of antigen receptor for antigen
______ of the antigen
concentration and availability of _____ molecules

Answer 18

concentration
affinity
nature
co-stimulatory

Question 19

True or False
Peripheral tolerance in B cells; NOT all potentially reactive cells are eliminated or inactivated and enter peripheral circulation

Answer 19

True

Question 20

T cells affect the outcome of B cell activation in the periphery via the ____ _____ ____

Answer 20

two signal hypothesis

Question 21

What are the two signals of the two signal hypothesis

Answer 21

1. generated through the antigen receptor

2. mediated by CD40 and CD40L

Question 22

If one of the signals from the two signal hypothesis is missing B cell ______ occurs

Answer 22

anergy (lack of reaction to the antigen)

Question 23

Anergic cells show a block in _____ ____ signal induction; via lack of co-stimulation by _______ and co-stimulation by ____ _____

Answer 23

TCR-induced
B7/B72
inhibitory receptors

Question 24

________ competes with CD28 for B7 and B72; it helps to keep the T cells in check

Answer 24

CTLA-4 (is an inhibitory receptor on T cells)

Question 25

Knockout mice lacking CTLA-4 develop ______ lymphocyte activation, ______ lymph nodes and spleen, and ______ multi organ lymphocytic infiltrates

Answer 25

uncontrolled enlarged fatal

Question 26

Self-reactive cells may be "deleted" from the repertoire via __________; activation in the absence of _____ can lead to death

Answer 26

apoptosis | IL-2

Question 27

The state of tolerance may be maintained by ____ _____

Answer 27

immune regulation

Question 28

How does ignorance happen; antigen is expressed in a ______ _____ T cells cannot get to the antigen across an ______ _______ perhaps the antigen is not expressed in the context of ______ _____

Answer 28

immuno-privileged site epithelial barrier MHC molecules

Question 29

Foreign antigens may be administered in ways that preferentially _____ _____ rather than immune responses

Answer 29

induce tolerance

Question 30

True or False Oral administration of antigen favors tolerance induction; a state of immune hypo responsiveness follows oral administration of an antigen

Answer 30

True

Question 31

Five factors that lead to immunogeneicity or tolerogenicity of protein antigens include...

Answer 31

``` amount persistance portal of entry/location persistence of adjuvants properties of APCs ```

Question 32

True or False | Mechanisms that lead to autoimmunity remain unclear

Answer 32

True

Question 33

Seven factors can predispose an individual to various autoimmune diseases….

Answer 33

``` MHC associateions familial concordance (occurs in families) gender (women more likely than men) climate (equatorial less likely) chemical agents infectious agents immune dysregulation ```

Question 34

What 3 things involving self-reactive cells initiates an autoimmune response

Answer 34

incomplete deletion aberrant stimulation altered regulation

Question 35

True or False | Autoimmune disease can be systemic or organ specific

Answer 35

True

Question 36

"Bystander activation" involves the induction of co-stimulators on ________ via up regulation of ________ resulting in autoimmunity

Answer 36

APCs | B7

Question 37

_______ _______ results in a microbial antigen imitating a self tissue causing autoimmunity; this is more likely the case

Answer 37

molecular mimicry

Question 38

An example of a systemic autoimmune disease is _____ and an example of organ specific autoimmune disease is _____

Answer 38

``` systemic lupus erythematosus (SLE) - kidney, heart, lungs, CNS multiple sclerosis (MS) - CNS ```

Question 39

SLE produces _________ against self antigens such as DNA, nucleoproteins, lymphocytes, etc

Answer 39

autoantibodies

Question 40

In MS, T cells are specific for components of the _____ ______

Answer 40

myelin sheath