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Immunology PY2 > Lecture 29: Immune Regulation, Foreign vs Self Antigens > Flashcards

Lecture 29: Immune Regulation, Foreign vs Self Antigens Flashcards

1
Q

what is regulation?

A

control of immune responses

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2
Q

what is tolerance?

A

prevention of immune responses

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3
Q

immune responses to foreign antigens diminish as the antigens are eliminated, leading to a return of the immune system to a resting state; how is this mediated?

A

mediated by self-regulation and regulation by other immune celsls

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4
Q

what are the 2 main ways the immune system regulates itself?

A
  1. Passive (default on) systems

2. active regulation

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5
Q

what are 2 passive systems of the immune system to regulate itself?

A
  1. antigen density changes

2. activation-induced cell death (AICD)

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6
Q

what are 3 active methods of immune self regulation

A
  1. cytokine secretion (contact independent)
  2. regulatory co-stimulation (contact dependent)
  3. induction of apoptosis or energy
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7
Q

what cells secrete cytokines in active regulation of the immune system/

A

regulatory T cells and myeloid reg cells

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8
Q

what are 2 examples of co-stimulation in immune regulation?

A
  1. PD-1 & PD-L1

2. CTLA4 & CD80/86

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9
Q

t/f as the antigen concentration decreases, so does the immune response

A

t

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10
Q

continued immune responsiveness requires continuous exposure to ____

A

antigens

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11
Q

foreign antigens promote the survival of activated antigen-reactive lymphocytes through induction of _____, an anti-apoptotic protein

A

Bcl-2

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12
Q

clearance of antigen via _______ eventually results in less antigen being available to activate B and T cells

A

phagocytosis of immune complexes

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13
Q

when Bcl-2 expression drops, this makes the activated lymphocytes more susceptible to ______

A

apoptosis

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14
Q

immune-mediated elimination of foreign antigen deprived immune effector cells of ___ signals, resulting in _____

A

survival signals; causes effector cells that are o longer need to die by apoptosis

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15
Q

memory lymphocytes are ____ and therefore survive

A

quiescent

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16
Q

a high concentration of circulating ____ complexes indicate that there is no need for further B cell activatio

A

antigen-IgG complexex

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17
Q

immune complexes formed by antigen-IgG crosslink ____ and ____ on B cells leading to the phosphorylation of ___on the cytoplasmic tail of ___

A

surface immunoglobulin and FcyRIIb; ITIM; FcyRIIb

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18
Q

negative feedback from antibodies regulates further activation of ___ cells

A

B

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19
Q

in negative feedback to regulate B cell activation, a ____ is recruited to the ITIM of B cells and blocks further signalling through the BCR

A

phosphatase

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20
Q

the BCR is assocoiated with ____ that has an ITIM on its cytoplasic tail

A

CD22

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21
Q

what happens to the ITIM on the cytoplasmic tail of CD22 when B cells are activated?

A

is phosphorylated and recruits SHP-1 tyrosine phosphatase

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22
Q

once antigen levels drop., there will be a decrease in BCR signalling, allowing ____ to remove any residual phosphatases from the ___

A

SHP-1; ITIMS

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23
Q

CD22 knockout mice are prone to ____ as they age

A

autoimmunity

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24
Q

CD___ inhibit B cell activatio

A

CD22

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25
Q

CD5 is expressed on what cell types?

A

T cells and B-1 subset of cells

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26
Q

CD5 promotes ___ of multiple signalling pathways, which can lead to secretion of ___, which downregulates immune responsiveness

A

activation; IL-10

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27
Q

what type of B cells secrete immunoregulatory IL-10 when activated?

A

B10 regulatory cells

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28
Q

sometimes a competing foreign antigen can regulate the immune response to an unrelated foreign antigen, what happens in this case?

A

an immuno-dominant antigen that stimulates a Th1 response with attendant IFN-y synthesis would down-regulate a less potent Th2 response to an unrelated antigen

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29
Q

what is an example of competition between antigens?

A

cytokine cross-regulation

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30
Q

____ is expressed after several days of T cell activation and competes with CD28 for its ligands, CD80/86

A

CTLA-4

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31
Q

CTLA-4 binding to ___ molecules deprives T cells of essential co-stimulatory signalling through CD28

A

B7

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32
Q

CTLA-4 ligation also activates a _____ that further suppresses T cells activation

A

phosphatase

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33
Q

what is the role of programmed cell death-1 (PD-1)in T cell regulation?

A

binds to PD-L1 and PD-L2 on APCs and inhibits T cells activation

34
Q

activation-induce cell death (AICD) is an important mechanisms for maintaining ____

A

T cell homeostasis

35
Q

T cell activation by antigen leads to expression of ___ and ___ on t cell surface

A

Fas and Fas ligand

36
Q

what happens to the Fas and Fas ligand on T cells to cause the T cells to undergo apoptosis?

A

trimerization of Fas by Fas ligand on neighbouring T cells

37
Q

what happens to mice that lack functional Fas or Fas lingands?

A

have excessive numbers of T cells ans spontaneously develop autoimmune dx

38
Q

____ Treg cells that express FoxP3 develop in the periphery after continued stimulation of T cells by foreign antigen

A

CD4+CD25+ (aka inducible Treg cells)

39
Q

CD4+CD25+ Treg cells are ___ dependent and ___ specific

A

IL-2, antigen

40
Q

Treg cells that interact with APC via CTlA-4 induce ______ which creates an inhibitory environment

A

indolamine 2,3-dioxygenase (IDO)

41
Q

how does idolamine 2,3-dioxygenase (IDO) create an inhibitory environment?

A

by converting tryptophan to kynurenine

42
Q

what happens to T cells that are deprived of tryptophan?

A

die by apoptosis

43
Q

T reg cells secrete what inhibitory cytokines>

A

IL-10 and TGF beta

44
Q

T reg cells compete for ____

A

T cell growth-promoting IL-2

45
Q

what is the expected effect of decreased Treg and increased T reg?

A

decreased Treg: limit unwanted immune repsonse (ex: autoimmunity, allograft rejection)
increased Treg: promote desirable immune repsonse (ex: anti-tumour)

46
Q

under some conditions, macrophages produce ____ which inhibit immune responses in a non-specific manner

A

prostaglandins like PGE2

47
Q

PGE2 produced by macrophages promotes _____ accumulation in T cells, which inhibits the synthesis and signalling of what cytokine?

A

cAMP; IL-2

48
Q

Il-2 is needed for ____ and ____

A

clonal expansion and survival

49
Q

what are myeloid-derived suppressor cells?

A

immune myeloid cells that suppress antigen-specific T cell responses

50
Q

how to myeloid-derived suppressor cells suppress antigen-specific T cell responses?

A

by secreting IL-10, TGFB, and or IDO

51
Q

myelod-derived suppressor cells can also express ____

A

PD-L1

52
Q

what is central tolerance?

A

negative selection to remove developing lymphocytes with receptors that might become self reactive

53
Q

what is peripheral tolerance?

A

deletion, induction to anergy or active regulation (i.e. by T regs ) of lymphocytes with self-reactive capacity after development

54
Q

____ refers to an active state of specific immunologic unresponsiveness exhibiting antigen specificity

A

tolerance

55
Q

tolerance may involve the elimination of _____ cells or changing them so they cannot ____-

A

potentially self-reactive; generate an inflammatory immune response

56
Q

failure to develop and maintain tolerance to self antigens lead to ____

A

autoimmunity

57
Q

t/f multiple sclerosis is an autoimmune dx

A

true

58
Q

in central tolerance, lymphocytes express antigen receptors specific for a particular self antigen and they encounter that antigen during ___ and this causes ____

A

development; apoptosis of the lymphocyte

59
Q

many self antigens found in other tissues are also expressed in the ___, so that responsive T cells are also deleted

A

thymus

60
Q

the expression of antigens in central tolerance is controlled by what transcription factor?

A

AIRE

61
Q

some cells with high affinity for self-antigens are intentionally kept to serve what purpose?

A

regulatory functions (hopefully)

62
Q

the T regs that are produced by central tolerance are called ____. Are they the same as the peripheral Treg cells?

A

thymic T reg cells (tTreg cells)

63
Q

CD4+CD25+ tTreg cells are AKA ____

A

natural Treg cells

64
Q

CD4+CD25+ tTreg cells with high affinity for self antigen express ____ and arise in the ___

A

FoxP3; thymus

65
Q

tTreg cells migrate to the periphery where they suppress immune responses to self antigen by secreting ______ and ____ etc.

A

IL-10 and TGF-B

66
Q

do CD8+ tTreg cells express FoxP3?

A

no, but they still inhibit the developmemt of immunity to self antigens

67
Q

peripheral tolerance can happen in what 3 ways?

A
  1. apoptosis
  2. anergy
  3. regulation
68
Q

what 3 things are REQUIRED to activate a T cell response?

A

antigen presentation must be from APC, cytokines, co-stimulation of Cd28 to CD80/86

69
Q

tolerance is more easily induced in ____ lymphocytes

A

immature

70
Q

t/f fetal exposure to self antigens before the immune system is fully developed results in tolerance

A

t

71
Q

_____ promotes and maintains tolerance

A

long term persistence of antigen

72
Q

do high doses of antigen tend to promote tolerance or an immune response?

A

tolerance

73
Q

antigens introduced by what routes tend to promote tolerance?

A

oral and IV

74
Q

___(low/high) levels of costimulation lead to tolerance

A

low

75
Q

exposure to antigen in the absence of adjuvants (ie w/o PRR stimulation) ____ (promotes/inhibits) tolerance

A

promotes

76
Q

antigen presentation by immature or unactivated antigenpresenting cells ____ (promotes or inhibits) tolerance

A

promotes

77
Q

certain self antigens are located in tissues w/ no lymphatic drainage (ex: lens of eye). Exposure of T cells to these autoantigens can result in ____

A

autoimmune dx

78
Q

the absence of ____ on most cells prevents the presentation of antigen to T helper cells

A

MHC2

79
Q

the absence of costimulation of T cells results in ____, since T cells that bind self antigen via TCR w/o costimulation can either undergo ____ or become ___

A

clonal anergy; apoptosis or anergic

80
Q

what does it mean to be anergic?

A

unresponsive

81
Q

t/f CTLA-4, PD-1 and AICD are all involved in marinating peripheral tolerance to self-antigen

A

t

Immunology PY2 (20 decks)

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