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IMMUNOLOGY > Lecture 24: Tolerance and Autoimmunity > Flashcards

Lecture 24: Tolerance and Autoimmunity Flashcards

1
Q

state of specific unresponsiveness to an antigen induced by prior exposure to that antigen

A

immune tolerance
tolerance is an active process

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2
Q

How does the immune system address inevitable reactivity to self

A

Elimination of self-reactive T cells in the thymus: Central tolerance

Failure to provide the signals to induce a T cell response: Peripheral tolerance

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3
Q

what is AIRE (autoimmune regulator)

A

transcription factor that facilitates expression of non-thymic proteins in the thymus to test reactivity

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4
Q

_____ anergy is initiated when T-cells are exposed to antigen in the absence of costimulation

A

Clonal

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5
Q

what is the mechanism of clonal anergy

A

suppression of NFKB and decreased production of cytokines (IL-2)

lasts for several weeks

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6
Q

what is immune paralysis

A

high doses of antigen that bypass APCs, bind TCR directly, lack costimulation and induce paralysis

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7
Q

antigen dose affects ____ of tolerance

A

induction

Very low doses of antigen fail to send a sufficient signal, inadequate co-stimulation occurs

very high doses can overstimulate the cells and initiate peripheral tolerance

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8
Q

where and when does central tolerance of B-cells occur

A

occurs in bone marrow once B-cell can express IgM (immature B cell)

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9
Q

random somatic mutations of B-cells occur in __________ organs, and must be controlled peripherally

A

secondary lymphoid

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10
Q

what things cause mature B cells to undergo peripheral tolerance

A

chronic antigen recognition
absence of costimulation
excessive suppressor cell activity
excessive T-independent antigen

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11
Q

once an antigen is eliminated, tolerance….

A

subsides

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12
Q

bone marrow activity (production of new cells) ______tolerance

A

reduces

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13
Q

immunosuppressive drugs _______ tolerance

A

prolong

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14
Q

______drive the immune response, _______turn it off

A

antigens, antibodies

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15
Q

antibodies have a feedback loop on _____cells to ______further production of antibodies

A

Bcells, inhibit

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16
Q

______antibodies inhibit antibody production in the newborn

A

maternal

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17
Q

Adaptive immune responses are _______Driven

A

antigen

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18
Q

adaptive immune response is initiated only when…? when does it cease?

A

initiated only on exposure to antigen
ceases when antigen eliminated

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19
Q

what happens when self or other antigens don’t reach lymphoid tissue

A

fail to induce immunity to tolerance
self antigens form immune privledged sites

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20
Q

the effect of antigen can be modulated by…?

A

adjuvants

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21
Q

antibodies suppress _____cell responses

A

B

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22
Q

IgM suppresses only..?

A

IgM

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23
Q

IgG suppresses production of _____ and _____

A

IgM and IgG

24
Q

Antibody mechanism of B-cell suppression?

A

inhibitory B-cell receptor CD32b

25
abnormally high Ab concentrations (myeloma) inhibit....
normal Ab synthesis increased susceptibility to infection
26
what is the action of FcRn (neonatal immunoglobulin receptor)
regulates serum half life of IgG and albumin | endothelium, muscle, hepatic sinusoids
27
________receptors inactivate or eliminate pathways that are no longer needed, suppress the activity of the lymphocytes when their mission is completed
inhibitory
28
what does CD32b do
negative feedback that suppresses B-cell activation crosslinking of BCR and Ab bound to CD32 w/ antigen
29
what is the function of Treg cells
homeostasis of peripheral immunity + tolerance induce apoptosis in effector cells
30
what immunosuppressive cytokines do Treg cells produce
* IL-10 * IL-35 * TGF-B | suppression of Tcell and macrophage function
31
Treg deficiency results in...?
multisystemic autoimmunity and massive inflammation
32
what are the Treg cells in cattle
WC1.1, WC1.2, γ/δ and Tcells
33
where do Treg cells originate from, where are they induced
Originate in thymus induced in secondary lymphoid tissues (most important in intestine)
34
what induces cell cycle arrest in effector Tcells
Galectin
35
what does CTLA-4 do
induces apoptosis of effector T cells
36
what are the 3 ways Treg cells suppress immune responses
direct contact suppressive molecules interference w/ antigen presentation
37
what ILs activate M2
IL-4, IL-13
38
effect of Indoleamine 2,3 dioxygenase
tryptophan depletion and cell cycle arrest
39
stress is highly .....
immunosuppressive
40
disease resulting from an attack by an individual's immune system against its own tissues
autoimmune disease
41
Up to what percentage of new B and T cell receptors can bind self antigens?
50%
42
what is cental tolerance
elimination of self-reactive T cells in the thymus
43
what is peripheral tolerance
Failure to provide the signals to induce a T cell response
44
what does it mean for tissues to be immune privileged
Areas of the body where inflammatory immune response does not occur following exposure to an antigen, ex) the eyes
45
Which type of cell does not remain tolerant as readily as the other, and will reactivate if tolerance is not maintained?
B-cell
46
what is functional deletion
The cell is still in the body, but the cell is no longer functioning
47
can self antigens can induce immunity or tolerance.
no
48
what is FoxP3
Transcriptional repressor protein of regulatory T cells
49
What 3 things must be present for an immature Th cell to become a Treg cell?
IL-2, TGF-B, Retinoic Acid
50
Can suppress macrophages, Th1 cells, Th2 cells, dendritic cells, natural killer cells, and Th17 production
IL-10
51
Regulates T-cell activation, macrophages, and B-cell function
TGF-B
52
What is the classically activated regulatory macrophage known as?
M1
53
What regulatory macrophage s activated by IL-4+IL-13 and induces tolerance, suppresses inflammation, and is responsible for tissue repair?
M2
54
IL-22 is produced by..?...and involved in..?....
Produced by Th17, involved in tissue healing
55
IL-17 is produced by_______,stimulates____________ and mobilizes________
Produced by Th17 cells, stimulates growth factors, Th cells, epithelial cells, macrophages. Also mobilizes neutrophils to promote inflammation.

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