Brainscape's Knowledge GenomeTM

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


See full index

MIMM 314 > Protecting thyself: mechanism of self tolerance > Flashcards

Protecting thyself: mechanism of self tolerance Flashcards

1
Q

why control immune pathologt

A

-don’t want healthy cells
-cause autoimmune disease

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

high immune reactivity=

A

autoimmune disease
chronic disease
pregnancy failure

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

high tolerance=

A

-immunosupperssion
persistent/overwhelming infectopm

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

what is a classic case of immune tolerance

A

fetal igs

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

what are the 4 outcomes for peripheral self tolerance: t cell intrinsic

A

-ignorance
-anergy
-phenotypic skewing
-apoptosis

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

what is ignorance in immyune cells

A

-never encouinter its own antigen
-ex: in the BBB
-anatomical and cellular locations (where buried may be released by infection, leading to autoimmune diseases)

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

what causes anergy

A

no costimulation via CTLA-4 or PD-1

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

what is phenotypic skewing:

A

-activated T cells devlop a non-pathogenetic pehnoitype
-incomplete differentiation or immune deviation

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

what is involved in apoptosis

A

-cells are deleted by AICD involving fas-fasl interactions

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

what are the 2 things for peripheral self tolerance: t cell intrinsic

A

-Tolerogenic dendritic cells:
-Regulatory T cells:

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

what are tolerogenic DCs

A

-self proteins are continously sampled by these cells or immature DCs
-low expression of costimulatory ligands on these dcs lead to T cell tolerance
-possibly maintain T cell tolerance indirectly by the induction of Tregs

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

what is the Tregs in perioheral self tolerance

A

-maintain the balance of activation and supression

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

what are suppressor T cells ideotypes

A

T cells that recognize another T cell by bits of TCR that are dedicated to recognise antigens

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

what are the regulatory T cells

A

-nkt cells
-cd8
tr1
th3
foxp2+ and-

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

what do Tr1 secrete

A

il-10

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

consequence of lost balance:

A

-immune diseases; involving auto reactive t and B cells
c=vaccines
allergens and tumours
pathogens and commensals
transplant
auto immunity
-auto inflammatory diseases

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

what are some examples of auto inflammatory diseases

A

-involves a hyperactive innate immunity
-alzeimers
-atherosclerosis
-type 2 diabetes

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

true or false anti dc5 and C KO most cd4 expression

A

true

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

what happens when you transfer a lot of depleted spleen cells back into immunodeficient individuals

A

more incidences of autoimmune disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what happens when you transfer depleted spleen cells back into immunodeficient individuals

A

autoimmunuity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what happens if you KO completely CD4

A

no autoimmune diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

true or false: CD4 os essential for disease

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

CD4 expressing … at the same time can regulate disease

A

cd25

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

true or false; if you KO a pop of cd4 cd25 is still expressed

A

true
the remaning pop will contribute to the onset of the autoimmune disease

25
Q

what did sakaguchi et al discovered

A

A population of CD4 and CD25 t cells that appeared to be immune-suppressive

26
Q

what sakaguchi et al concluded

A

these t cellls
-of the conventional (canonical) hemoiesis process
-but they are a unique subset defined by their constitutive expression of cd25
-recall cd25 is usually expressed ion T cells that are activated
-tolerogenic; their presence may explain why certain individuals have auto-reactive t cells but not have an autoimmune disorder

27
Q

what is the TF for tregs

A

foxp3

28
Q

mice that lack a functional foxp3 will develop…

A

severe, multi organ autoimmunity

29
Q

what is scurfin

A

-a known mutation of the foxp3 gene that makes it defective
-mice with the mutation are called scurfy models

30
Q

what is a thymectomy

A

removal of the thymus
-the development of T cells is greatly inhibited
-that have that thing are very susceptib;le to infections

31
Q

performing the thymectomy; days 1 and 2

A

no t or b cells

32
Q

performing the thymectomy; days 3

A

severe autoimmune disease

33
Q

performing the thymectomy; days4-7

A

severe autoimmune disease

34
Q

performing the thymectomy; AFTER DAY 7

A

no effec5t on ones populatopn og T ce3lls since periofery T cells had already establ;iched themselves in tissues outside of the thymius

35
Q

true or false: Tregs are responseble for cleaning up after T effector cells

A

true and they also suppress autoreactive cells

36
Q

positive roles of t regs

A

-suppression of autoimmunity
-limit allergic immune response
-prevent tissue damage due to immune response yo pathogens

37
Q

negative roles of Tregs

A

-suppression of anti-tumor immunity
-limits the clearance of chronic imfections

38
Q

can T cells experience fatigue?

A

they can
Tregs during chrionic infections and will fatigue easily; their effectiveness will diminish greatly

39
Q

what is functional plasticity

A

functional plasticity =fluid phenotypes

40
Q

true or false; Thelper cells have functional plasticity

A

false: Tregs have functional plasticity

41
Q

what are pros and cons of functional plasticity in Tregs

A

-pro: promoting the appropriate activity of the immune system , suppressing when required and promoting tissue repair
-cons: Tregs choose to back off on immunosuppression altogether-> resulting in over active inflammation
-in the context of vaccination you would want to Tregs to be inhibited for a brief nperiod such that Teffector cells can be trained-> but we also want to ensure that we do not permanent “disable” our Tregs
-the Tregs still need to be in order to ensure that the system does not mount an overreaction

42
Q

would adjuvants have an affect on the activation of T regs

A

yea
there are adjuvants that can stimulate the production of cytokine such as ccl22 and cl17 that can transiently inhibit Tregs

43
Q

what are some inborn errors that may lead to a dysfunctional immune system

A

congenital errors

44
Q

true or false: inborn error \s may influence disease

A

true
this leads to a pre clinical situationm to develop into full blown clinical pathology

45
Q

what is IPEX

A

-immunodysregulation, polyendocrinopathy and Enteropathy and X linked syndrome
-it is an x linked genetic disease

46
Q

true or false: IPEX is polygenic

A

it is monogenic
-it mostly affect younger men
-individuals suffer from catastrophic, multi organ failure and autoimmunity from birth

47
Q

IPEX is caused by a germline mutation in the

A

….Foxp3-hence it is known as a Treg-opathy
-they represent a whole cluster of disease

48
Q

a majority of these germline mutations fall within the… domain of Foxp3

A
49
Q

what is the role of the forkhead

A

it is responsible for binding directly to the dna
-hence without the ability to bind to dna, foxp3 can’t behave as a TF

50
Q

true or false; the impact of each mutation of foxp3 expression/function are still unknown

A

facts
tho we know some mutations

51
Q

a384T mutation

A

-ala residue has been substituted for a Thr residue
-the FHD structure is unaltered->still possesses capability to bind to DNA
-the cases of IPEX are typically mild to severe
-these mutations represent 10-15% of all mutations

52
Q

people that have that mutation have???

A

-donot have lowered levels of Tregs as compared to other individuals of the same sex or age
-it appears that the expressions of foxp3 is womewhat decreased but not totally

53
Q

what is the r397 mutation

A

-fatal mutation
-results in severe IPEX each time

54
Q

true or false ifoxp3 is a DNA binding transcriptional activator

A

false it is a repressor

55
Q

what does foxp3 bind to

A

il2 gene, inf-y gene ans suppress their transcription

56
Q

true or false t regs are anergic

A

true

57
Q

true or false; the intracellular activity of foxp3 drives the genetic programming required for Treg cell lineage commitment and identity`

A

true
-it will directly target more than 700 genes
-but the product of these genes may go up to induce further transcriptionak effecrs
-this is known as the transcriptional and receptor signalling network
-the 700 genes directly targeted bu foxp3 technically only represent a small fraction of the T reg programming

58
Q

true or false; mutations inm foxp3 can resulting into organ specific autoimmunity

A

false
‘multi-organ, catastrophic autoimmunity

MIMM 314 (11 decks)

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