Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

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
what did sakaguchi et al discovered
A population of CD4 and CD25 t cells that appeared to be immune-suppressive
26
what sakaguchi et al concluded
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
what is the TF for tregs
foxp3
28
mice that lack a functional foxp3 will develop...
severe, multi organ autoimmunity
29
what is scurfin
-a known mutation of the foxp3 gene that makes it defective -mice with the mutation are called scurfy models
30
what is a thymectomy
removal of the thymus -the development of T cells is greatly inhibited -that have that thing are very susceptib;le to infections
31
performing the thymectomy; days 1 and 2
no t or b cells
32
performing the thymectomy; days 3
severe autoimmune disease
33
performing the thymectomy; days4-7
severe autoimmune disease
34
performing the thymectomy; AFTER DAY 7
no effec5t on ones populatopn og T ce3lls since periofery T cells had already establ;iched themselves in tissues outside of the thymius
35
true or false: Tregs are responseble for cleaning up after T effector cells
true and they also suppress autoreactive cells
36
positive roles of t regs
-suppression of autoimmunity -limit allergic immune response -prevent tissue damage due to immune response yo pathogens
37
negative roles of Tregs
-suppression of anti-tumor immunity -limits the clearance of chronic imfections
38
can T cells experience fatigue?
they can Tregs during chrionic infections and will fatigue easily; their effectiveness will diminish greatly
39
what is functional plasticity
functional plasticity =fluid phenotypes
40
true or false; Thelper cells have functional plasticity
false: Tregs have functional plasticity
41
what are pros and cons of functional plasticity in Tregs
-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
would adjuvants have an affect on the activation of T regs
yea there are adjuvants that can stimulate the production of cytokine such as ccl22 and cl17 that can transiently inhibit Tregs
43
what are some inborn errors that may lead to a dysfunctional immune system
congenital errors
44
true or false: inborn error \s may influence disease
true this leads to a pre clinical situationm to develop into full blown clinical pathology
45
what is IPEX
-immunodysregulation, polyendocrinopathy and Enteropathy and X linked syndrome -it is an x linked genetic disease
46
true or false: IPEX is polygenic
it is monogenic -it mostly affect younger men -individuals suffer from catastrophic, multi organ failure and autoimmunity from birth
47
IPEX is caused by a germline mutation in the
....Foxp3\-hence it is known as a Treg-opathy -they represent a whole cluster of disease
48
a majority of these germline mutations fall within the... domain of Foxp3
Forkhead domain -
49
what is the role of the forkhead
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
true or false; the impact of each mutation of foxp3 expression/function are still unknown
facts tho we know some mutations
51
a384T mutation
-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
people that have that mutation have???
-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
what is the r397 mutation
-fatal mutation -results in severe IPEX each time
54
true or false ifoxp3 is a DNA binding transcriptional activator
false it is a repressor
55
what does foxp3 bind to
il2 gene, inf-y gene ans suppress their transcription
56
true or false t regs are anergic
true
57
true or false; the intracellular activity of foxp3 drives the genetic programming required for Treg cell lineage commitment and identity`
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
true or false; mutations inm foxp3 can resulting into organ specific autoimmunity
false 'multi-organ, catastrophic autoimmunity

MIMM 314 (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions