EX1 Tolerance/Autoimmune Disease - Powell Flashcards Preview

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Flashcards in EX1 Tolerance/Autoimmune Disease - Powell Deck (40):
1

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

self-tolerance

2

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

central tolerance

3

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

peripheral tolerance

4

True or False
Tolerance is simply a failure to recognize an antigen

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

5

Tolerance can be _______ or _______

natural
induced

6

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

self tolerance
self tissues

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 ________ ___ ____

high avidity
CD4
regulatory T cells

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 _____ _____

antigen
maturation
stimuli
self antigens

9

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

bone marrow
eliminated
inactivated
self

10

Central tolerance of B cells is achieved via _______ editing

receptor
(VDJ rearrangement)

11

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

nature and concentration

12

True or False
multivalent and high concentrations of antigens induce B cell death

True; lower concentrations induce functional anergy

13

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

peripheral tolerance (PT)

14

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

clonal deletion/apoptosis

15

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

clonal anergy

16

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

suppression

17

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

ignorance

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

concentration
affinity
nature
co-stimulatory

19

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

True

20

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

two signal hypothesis

21

What are the two signals of the two signal hypothesis

1. generated through the antigen receptor
2. mediated by CD40 and CD40L

22

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

anergy (lack of reaction to the antigen)

23

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

TCR-induced
B7/B72
inhibitory receptors

24

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

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

25

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

uncontrolled
enlarged
fatal

26

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

apoptosis
IL-2

27

The state of tolerance may be maintained by ____ _____

immune regulation

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 ______ _____

immuno-privileged site
epithelial barrier
MHC molecules

29

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

induce tolerance

30

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

True

31

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

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

32

True or False
Mechanisms that lead to autoimmunity remain unclear

True

33

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

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

34

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

incomplete deletion
aberrant stimulation
altered regulation

35

True or False
Autoimmune disease can be systemic or organ specific

True

36

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

APCs
B7

37

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

molecular mimicry

38

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

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

39

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

autoantibodies

40

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

myelin sheath