Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

immuno med wk 2 > Central/Peripheral Tolerance > Flashcards

Central/Peripheral Tolerance Flashcards

1
Q

Where does central tolerance occur

A

in the lymphoid generative organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

where does peripheral tolerance occur?

A

in the peripheral lymphoid tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how does central tolerance for T cells work?

A

thymic epithelial cells present self-Ags to immature T lymphocytes

if they do not recognize sellf-Ag —> they receive no survival signal, undergo apoptosis

if they recognize self-Ag too strongly —> they receive a death signal undergo apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what happens after central tolerance?

A

they mature and then migrate to the periphery where they can be activated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

destruction of endocrine organs by antibodies

A

AutoImmune REgulator: failure of central tolerance

AIRE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

AIRE

What is it, where is located etc

A

autoimmune regulator protein is suspected to be the mutation associated with failure of central tolerance to select viable lymphocytes

its located in medullary thymic epithelial cells
its associated with decreased expression of self-Ag
proposed as a transcription factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the role of medullary thymic epithelial cells?

A

they present self-Ags to developing lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

AIRE’s regulate

A

tissue restricted antigens (TRAs)

these peptides are displayed by medullary thymic epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

who recognizes TRAs?

A

immature Ag-specific TCRs recognize tissue restricted antigens in the medulla

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the central outcome of AIRE?

A

self-reactive lymphocytes fail to be eliminated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Strong recognition of self-Ags by immature T cells leads to

A

developing of either T(reg) cells that enter the peripheral tissues or apoptosis (negative selection)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

T(reg) cell production

A

They are generated after strong interactions with self Ag in the thymus. After stimulation they produce strong anti-apoptotic molecules (in the thymus).

Their major cytokine requirement is TGF-beta.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Surface molecules expressed by T(reg) (both unique and common) + transcription factor + survival signal

A

CD4+, CD25+ (unique), FOXP3, IL-2 is the survival signal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the role of T(reg)?

A

Long lived endogenous cells that prevent autoimmune reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Natural/Inducible T(reg) cells

A

“natural” have been present in the absence of the non-immunized; generated by self-Ag recognition in the thymus

inducible T(Reg) are produced by Ag recognition in the LNs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is their role in peripheral tissue?

A

they protect against self-reactive lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What cells do T(reg) inhibit?

A

inhibit T cell responses, inhibit other cells like B cells and NK cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What cytokine do the iT(regs) produce

A

IL-10, anti-inflammatory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

T(reg) Immunosuppressive “acts”

contact inhibition

A

reduces APC expression of:

IL-12 (can not influence Th1 or activate phagocytes)
CD80/86

but T(reg) upregulates expression of:

IL-10

20
Q

T(reg) Immunosuppressive “acts”

Immunosuppressive Cytokines

A

IL-4, IL-10, TGF-beta inhibit

CD40 expression on APC

21
Q

TGF-beta: effects on T cells

A

inhibits proliferation of T cells

inhibits differentiation of Th1 and Th2 effector cells in cooperation with IL-6 and IL-1

22
Q

TGF-beta: effects on phagocytes

A

inhibits macrophage activation

23
Q

TFG-beta: effects on T(reg)

A

regulates differentiation of FOXP3 T(reg)s

24
Q

TGF- beta on Abs

A

stimulates IgA by inducing isotype switching

25
Q

TGF-beta effects on tissues

A

promotes tissue repairs by stimulating collagen synthesis by macrophagea and fibroblasts

26
Q

Breaking peripheral tolerance

A

impaired production of T(regs)

27
Q

FOXP3 deficiency —>

A

IPEX, impaired production of FOXP3

28
Q

Impaired tolerance induction of apoptotic cells =

A

complement impairment of C1q and C4

29
Q

Altered immune signaling

A

CTLA-4 polymorphisms

30
Q

CTLA-4 polymorphisms produce what two effects

A

failure of T cells to undergo anargy: lymphoproliferation of T cells in multiple organs, especially the heart

lethal by 4-5 wks

31
Q

IPEX

A

FOX03 deficiency: failure of T(reg) to develop

32
Q

SLE

A

deficiency of C4. defective clearance of immune complexes

33
Q

ALPS

A

autoimmune lympho-proliferative syndrome (ALPS)

problem with Fas/FasL

defection deletion of anergic self-reactive B cells

nephritis, arthritis, etc

34
Q

problems with IL-2

A

inflammatory bowel disease

anti-erythrocyte and anti-DNA autoantibodies

defective development, survival or function of regulatory T cells

35
Q

What do CTLA-4s do?

A

during self-Ag recognition, CTLA-4 inhibits CD28/B7 interactions by replacing CD28

terminate T cell response

THEY TERMINATE IMMUNE RESPONSE AND MAINTAIN SELF TOLERANCE

36
Q

CLTA-4 KO would lead to

A

uncontrolled lymphocyte proliferation

37
Q

CTLA-4 deficiency leads to

A

autoimmune illness such as type I diabetes (autoreactive T lymphocytes attacking pancreas?), Graves disease, etc.

38
Q

Two important actions of CTLA-4 cells

A

1) expressed on low/resting T cells until Ag activation
2) once expressed, they terminate T cell activation

CTLA-4 is expressed on T(reg) and mediates suppressive function of these cells by inhibiting the activation of naive T cells

39
Q

How CTLA-4 works on APCs

A

CTLA-4 can either directly prevent APCs from activating other cells by inhibiting CD80/86 expression (Cell intrinsic function of CTLA-4)

or

CTLA-4 can reduce B7 expression by binding to APC while it interacts with T cells, and in this way “blocking and removing” of B7’s costimulatory effects on T cells
(apparently cell extrinsic ctla-4)

40
Q

Central B CELL tolerance

A

immature B cells that recognize Ag in bone marrow with high avidity die by apoptosis OR undergo receptor editing and change the specificity of their BCRs

weak recognition of self-Ags in the bone marrow may lead to anergy of the B cells

41
Q

There are 3 outcomes for self-Ag recognition in B cell central tolerance

A

1) strong avidity —> apoptosis –> dead B cell
2) strong avidity —> receptor editing –> non-self reactive B cell
3) no avidity –> anergic B cells

42
Q

Peripheral B cell tolerance

A

non-T cell assisted recognition of self-Ags may lead to apoptosis or anergy

43
Q

defects in CD22 –>

A

no inhibitory signals, autoimmunity

44
Q

defects in Lck phosphorylation

A

no inhibitory signals, autoimmunity

45
Q

defects in SHP-1 tyrosine phosphatase

A

no inhibitory signals, autoimmunity

immuno med wk 2 (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions