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MSS-IHL Final Exam > Tolerance and Autoimmunity > Flashcards

Tolerance and Autoimmunity Flashcards

1
Q

tolerance

A

unresponsiveness to self antigens

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2
Q

autoimmunity

A

results when immune system recognizes self antigens

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3
Q

anergy

A

functional unresponsiveness

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4
Q

central tolerance

A

takes place in central lymph organs

  • B cells in bone marrow
  • T cells in thymus

ex/ negative selection

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5
Q

peripheral tolerance

A

what mature lymphocytes undergo out in body
-lymph nodes and spleen

ex/ T reg function, anergy, cell death

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6
Q

T cell development?

A

positive and negative selection

ones that recognize MHC - selected for

central tolerance

negative selection if high affinity for MHC and self-antigens

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7
Q

Foxp3

A

transcription factor

signals to become a T reg cell

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8
Q

where are T reg cells formed?

A

thymus

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9
Q

when does selection for T reg cells occur?

A

intermediate affinity

-upregulate Foxp3

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10
Q

function of T reg cell

A

check on immune system to keep it from going out of control

also involved transplantation tolerance

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11
Q

peripheral T cell tolerance?

A

Regulatory T cells in the periphery

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12
Q

what do T reg cells express?

A

Foxp3 and CD25

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13
Q

CD25

A

on T reg cells

is the IL-2 receptor

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14
Q

what do T reg cells secrete?

A

IL-10 and TGF-beta

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15
Q

T reg cells depend on what for survival?

A

IL-2

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16
Q

T reg cells?

A

CD4+

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17
Q

anergy?

A

peripheral T cell tolerance

-occurs when T cells activated without co-stimulation**

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18
Q

what happens without co-stimulation in T cell activation?

A

leads to signaling block

-leads to anergy of T cell

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19
Q

what can lead to anergic T cell?

A

1 signal without co-stimulation

2 engagement of inhibitory receptors (CTLA-4)

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20
Q

co-stimulation in T cells?

A

B7:CD28 interaction

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21
Q

what could break anergy?

A

a very strong danger signal

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22
Q

cell death in T cells?

A

peripheral tolerance

  • normally anti-apoptotic signals are higher
  • absence of co-stimulation has more pro-apoptotic signals
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23
Q

Fas and FasL?

A

upregulated when T cell recognizes self antigen

results in apoptosis

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24
Q

what can mutations in Fas result in?

A

children with autoimmune diseases

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25
tolerogenic antigens?
usually in generative organs high concentrations long-lived exposure (bc its self)
26
immunogenic antigens?
in blood and periphery short lived
27
central B cell tolerance?
in bone marrow if recognizes self antigen (T-independent antigen) -can die (apoptosis) -can undergo receptor editing
28
peripheral B cell tolerance
anergic -if self antigen recognition without T cell help apoptosis -exclusion from the lymphoid follicle
29
immature B lymphocyte?
IgM+ and IgD-
30
tolerance-sensitive cell for T cells?
CD4+ CD8+ (double positive) T cells
31
effector mechanisms of autoimmunity?
circulating autoantibodies and autoreactive T lymphocytes
32
principle factors in development of autoimmunity?
susceptibility genes and environmental triggers
33
Type I diabetes
autoimmune destruction of beta cells in pancreas - genetic predisposition - Dq8 - thought to be an environmental trigger can predict the onset based on autoantibodies goes through phases: - genetic predisposition - insulitis - pre-diabetes (loss of first phase insulin response) - diabetes
34
insulitis
beta cell death (type I diabetes)
35
types of autoimmune disease?
organ-specific and systemic
36
what sex has more autoimmune diseases?
female - much more likely in women - don't know why
37
factors contributing to autoimmunity
genes, infections, and environmental factors
38
HLA-B27
ankylosing spondylitis | autoimmune disorder
39
HLA-DR4
rheumatoid arthritis | autoimmune disorder
40
HLA-DR3/DR4
Type I diabetes mellitus
41
HLA-DR4
pemphigus vulgaris | autoimmune disorder
42
AIRE
gene that if we lose will result in autoimmune polyendocrine syndrome (APS-1) responsible for expressing self antigens in the thymus (no negative selection)
43
Foxp3
defects in this gene lead to deficiency of regulatory T cells can lead to X-linked polyendocrinopathy and enteropathy (IPEX)
44
Fas
defect leads to autoimmune hypoproliferative syndrome (ALPS) defective apoptosis of self-reactive T and B cells in periphery
45
IPEX
from loss of Foxp3 gene
46
what would cue you to think a single gene defect?
multiple autoimmune disease at early age
47
action of IL-10
suppress IgE production
48
action of TGF-beta
inhibit IgE prduction
49
what do T reg cells secrete?
IL-10 and TGF-beta
50
how does IL-4 and IL-13 induce IgE formation?
activate STAT6 to induce isotype switching
51
how does TGF-beta induce IgE formation?
inhibit Id2-repressor of IgE isotype switching
52
treatment of IPEX
bone marrow transplant -to restore Foxp3 expressing cells poor prognosis for IPEX
53
triggers of autoimmunity?
presence of microbe induces co-stimulators on the APC presenting self antigen molecular mimicry - microbe antigen resembles the self tissue
54
streptococcus pyogenes?
rheumatic fever molecular mimicry for protein on heart muscle activated T cells will attack cardiac muscle
55
what is pathogenic in lupus?
antibody
56
what is pathogenic in diabetes?
T cells
57
what is pathogenic in myasthenia gravis?
antibody
58
what is pathogenic in multiple sclerosis?
T cells
59
autoantibodies
can be stimulatory or blocking
60
stimulatory autoantibodies?
ex/ bind the TSH receptor and result in upregulation of thyroid hormones Graves disease
61
inhibitory autoantibodies?
ex/ bind the acetylcholine receptor (without activation) -prevent the muscle activity myasthenia gravis
62
effect of corticosteroids?
immunosuppression
63
cyclophosphamide
immunosuppression
64
multiple sclerosis
Th1 cell response against mylein more likely in women HLA-DR2
65
oligoclonal immunoglobulins in central nervous system for MS?
never been exposed to all these new self antigens!
66
treatment of multiple sclerosis?
corticosteroid, cyclophosphamide, IFN-beta
67
treatment of MS with IFN-gamma not favorable?
because promoting Th1 cytokines (don't want that)
68
why feed MBP (myelin basic protein) to mice to prevent EAE?
because this would place self-antigen in their bodies (induce peripheral tolerance)
69
can you induce EAE in CD28 knockout mice?
no because no co-stimulation CTLA-4 mice would be really terrible EAE

MSS-IHL Final Exam (15 decks)

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