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Immunology > Tolerance > Flashcards

Tolerance Flashcards

1
Q

T-cells must be tolerant to _____. How is this accomplished?

A

self-antigens; through central tolerance or peripheral tolerance

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2
Q

What is central tolerance?

A

self-reactive T cells are killed

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3
Q

What is peripheral tolerance?

A

these T cells are “turned off” by inappropriate signaling

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4
Q

What causes tolerance?

A

very low or very high antigen doses

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5
Q

How do antibodies regulate antibody production?

A

through negative feedback mechanisms

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6
Q

How does antibody regulation affect newborn animals?

A

Hinder successful vaccination of newborn animals as a result of maternal immunity

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7
Q

How do Treg cells control immune responses?

A

secretion of cytokines such as IL-10 and TGF-b

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8
Q

How do Th17 cell regulate inflammation?

A

by secreting IL-17

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9
Q

Immune system and the CNS system are closely interconnected and influence each other. True or false?

A

True

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10
Q

What percentage of TCR and BCRs are self reactive?

A

20-50%

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11
Q

Where does negative selection occur?

A

in primary lymphoid tissue

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12
Q

Where are self-reactive lymphocytes “turned off”?

A

secondary lymphoid organs

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13
Q

What is the definition of tolerance?

A

unresponsive to an antigen

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14
Q

What is the definition of autoimmunity?

A

reactivity against self

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15
Q

When can tolerance occur?

A

If immature lymphocytes are exposed to antigen early in life and lymphocytes remain tolerant even when exposed later in life

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16
Q

What characterizes autoimmunity?

A

a condition characterized by specific antibody or cell-mediatd immune response (activated T cells) against the constituents of the bodys own tissues

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17
Q

Severe autoimmunity results on _____________.

A

autoimmune disease

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18
Q

What are autoantigens?

A

the bodys own tissues

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19
Q

What are dizygotic twins?

A

non-identical twins; different genetic makeup

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20
Q

Do dizygotic twins share a placenta?

A

yes

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21
Q

Why do CTLs not reject skin grafts from dizygotic twins?

A

Bone marrow cells colonize each other in chimeric calves. Each chimera is tolerance to its twin cells and will accept its twin despite the genetic difference.

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22
Q

What is the result of a BVDV intrauterine infection in a pregnant cow?

A

non-cytopathic BVDCV infects fetus and cows become persistently infected (PI) and remains a carrier for life

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23
Q

What are the consequences of PI calves?

A

they are seronegative and tolerant to BVDV virus and they are a carrier

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24
Q

What are the types of tolerance?

A

central and peripheral

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25
Q

How does central tolerance work?

A

developing lymphocytes react to self antigens and induce negative selection

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26
Q

Which cells remain in a tolerant state longer? T or B cells?

A

T cells

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27
Q

Which cells are more easily made tolerant? T or B cells?

A

T cells

28
Q

How does peripheral tolerance work?

A

mature lymphocytes recognize self antigens in the peripheral lymphoid tissues leading to mechanisms of removal or inactivation

29
Q

What signals a T cell for destruction in peripheral tolerance?

A

low doses of antigen OR lack of costimulation

30
Q

Thymic epithelial cells express ______ that promotes expression of ______.

A

aire transcription factor; self antigens

31
Q

What are the exceptions to central tolerance?

A

brain, eye, testis

32
Q

Negative selection is regulated by the _____.

A

air gene

33
Q

The aire gene is an autoimmune regulator. True or false?

A

true

34
Q

T cells with TcRs that bind with ____ affinity to many self antigens are programmed to ____. What is this called?

A

high; die

negative selection

35
Q

Gene defects lead to ___________ and _________.

A

ineffective central tolerance; autoimmunity

36
Q

What is fas?

A

CD95: death receptor pathway (apoptosis)

37
Q

What are the consequences of mutations of the fas gene?

A

self reactive lymphocytes do not undergo apoptosis

negative selection of T cells can not occur

38
Q

What are the mechanisms of B-cell tolerance?

A

negative selection (Apoptosis)

receptor editing of variable region genes

39
Q

What is receptor editing?

A

Immunoglobulin genes recombine so that a new light chain is splices with a heavy chain

40
Q

What is the product of receptor editing?

A

a B-cell receptor that is no longer specific to self antigen

41
Q

What three mechanisms can suppress mature self-reactive T-cells that?

A

anergy or fucntional inactivation

deletion (activation induced apoptosis)

suppression

42
Q

When does anergy occur?

A

when cells recognize self-antigens/ TcR binds to antigen without adequate levels of costimulatory signals or inhibition of co-stimulatory pathway

43
Q

What is happening when deletion occurs?

A

activation of induced apoptosis

activation of cell self-antigen stimulates T cell clones that kill each other by FasL/Fas pathways

44
Q

What pathway is used in deletion for T cell clones to kill each other?

A

FasL/Fas pathways

45
Q

Suppression by _____, produce ____ or ____.

A

Tregs; TGF-b; IL-10

46
Q

What provides inflammory signals?

A

PRR-PAMP, cytokines

47
Q

What are the inhibitory receptors for co-stimulation?

A

CTLA-4; PDI

48
Q

What is the normal response to antigen recognition?

A

T-cell proliferation and differentiation. Explained more below.

Antigens recognized in the presence of strong co-stimulation/growth factors (IL-2) stimulate production of anti-apoptotic proteins

49
Q

What happens to cause cell death in activation-induced apoptosis?

A

Engagement of death receptors

Recognition of self antigens may trigger apoptosis that results in deletion of the self reactive T-cells though expression of fas/fas ligand

50
Q

How are regulatory T cells generated?

A

By combined actions of IL-2 and TGF-b as well as the presence of retinoic acid

51
Q

How do Tregs suppress mature self reactive lymphocytes?

A

they produce the suppressive cytokines, TGF-b, IL-10, IL-35

suppresses T cell and macrophage function

52
Q

Tregs mediate suppression by secreting ____ and ____.

A

TGF-b; IL-10

53
Q

How is antibody diversity generated?

A

VDJ recombination in primary organs

Random somatic mutation in germinal centers of lymph nodes or spleen

54
Q

What percentage of immature B cells have self-reactive receptors?

A

55-75%

55
Q

What are the induction mechanisms of peripheral B-cell tolerance?

A

clonal exhaustion

immune complexes bind B-cell inhibitory receptors

T-cells induce B-cell apoptosis

idiotypic networks

56
Q

Clonal exhaustion by repeated antigenic challenge results in what?

A

results in plasma cells but no memory B-cells

57
Q

What induces anergy in B-cell peripheral tolerance?

A

CD32 (FcyRII)

58
Q

What is rhogam?

A

antibody to Rh factor prevents the Rh- mother from responding to Rh+ cells

peripheral B-cell tolerance

59
Q

What are some examples of immune complexes binding to B-cell inhibitory receptors?

A

myeloma patients, maternal antibody in neonates (rhogam)

60
Q

T-cells induce B-cell apoptosis via ________.

A

Fas expression

61
Q

Idiotypes networks dampen ________.

A

antibody response

62
Q

What are idiotypic networks?

A

antibodies against antibodies

63
Q

How does presence of maternal antibody in newborn delay the onset of immunoglobulin synthesis?

A

through negative feedback

64
Q

What feedback loops lowers the production of IgG by B-cells when there is a surplus?

A

CD32 (FcyRIIB) has a low affinity for IgGs and down-regulates antibody production in the presence of IgG-Antigen complexes. This shuts off the ability of BCR to become regulated.

65
Q

PSNS and SNS nerves secrete _____ that regulate cytokines - __/__ balance.

A

neurotransmitters; Th1; Th2

Immunology (11 decks)

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