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Immunology > Tolernace > Flashcards

Tolernace Flashcards

1
Q

antigens that elicit the functional Activtion of lypho bearing specific receptors for those antiG

A

Immunogenic antigens

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2
Q

Activation via immunogenic antiG require what 3 things

A
  • co-stim of T cells by activated APCs
  • foreign antiG not present during B/T cell devo
  • acute antiG exposure
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3
Q

elicit functional INACTIVATION of killing of lymphocytes bearing specific receptors for those antiG

A

Tolerogenic antigens

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4
Q

Killing of lymphocytes that bear specific receptors can have what 3 thigs

A
  • present antiG w/out co-stimulation or T cells help
  • delete antiG that recognize self antiG
  • chronic antiG exposure
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5
Q

antigens that are IGNORED by lypphocytes bearing specific recetpors for those antignes

A

Ignorance or Non-immunogenic

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6
Q

the specific UNRESPONSIVENESS of normal adaptive immune sytem to SELF antibengs

A

Immunologic tolerance

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7
Q

T cell tolerance is long/short lived

A

long lived

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8
Q

B cell tolerance is long/short lived

A

short lived and less complete than in T cells and

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9
Q

What three things can induce tolerance

A
  1. immunologic maturity : neonates/elderly are immuno immature and respond poorly to antiG
  2. AntiG structure and dose: respond to a simple molecule at really high or really low dose
  3. Immunosuppresive therapy enhances tolerance
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10
Q

Immunosuppresive therapy enhances

A

tolerance

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11
Q

AntiG structure and dose:

A

respond to a simple molecule at really high or really low dose

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12
Q

abnormal immune responses to self antigens and non-pathogenic antigens lead to

A

autoimmune

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13
Q

loss of tolerance to self antig

A

autoimmunity

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14
Q

immune response to envirom antig

A

allergy

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15
Q

immune respone in transplant

A

transplant rejection of GVHD

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16
Q

immature lymphocytes exposed to self antigen have 4 options

A
  • apoptosis
  • change in receptor (B cells edit)
  • Devo of regulatory T lymphocytes
  • ESCAPE
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17
Q

If lyphocytes escpase Central tolerance and recognizes self antigens in periphery… three options occur

A
  1. Anergy
  2. Apoptosis
  3. Suppressed by Treg
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18
Q

Tolerance obtained by immature cells in generative lymphoid organs (bone marrow for B cells or thymus for T cells) as they encounter self antiG

A

Central tolerance

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19
Q

tolerance obtained by mature cells in peripheral lymp tissue

A

peripheral tolerance

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20
Q

The T cell maturation goes through regular checkpoints:

1st checkpoint is: does the T cell express the proper _____ recomibation on this chain______

A

VDJ recombination on the TCR betta chain

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21
Q

Second checkpoint for T cell: Does immature T cell express this combination ______ on this chain ____

A

VJ comibination on the TCR alpha chain

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22
Q

3rd checkpoint for T cell devo: Does the antiG receptor recgonize self antig?
weak results in
strong results in

A

weak means you get positive selection

strong recognistion of self is negative selection

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23
Q

When pro T cells leave the bone marrow, they head to the Thymus andn are said to be

A

double negative: don’t express CD4 or CD8

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24
Q

Immature T cells called _______ beging to express both TCR betta and TCR alpha and are now _______ for CD4 and CD8

A

thymocytes

double positive for CD4 and CD8

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25
Q

Double positive T cells will undergo this process as our 3rd checkpoing

A

positive and negative selection

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26
Q

First step of maturation of T cells occurs in ______

A

thymic cortex

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27
Q

When T cells are in thymic cortex, they recognize either MHC I (CD8 + ) or MHC II (CD4+) in a process called

A

positive selection

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28
Q

after recognized MHC I or II in cortex, T cells move to ______ to be presented with Self antiG in process called:

A

medulla

negative selection

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29
Q

Defects in negative selection often result in

A

mature T cells that recognize self antiG = autoimmunity

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30
Q

Weak recognition of MHC + self peptide by TCR and co receptor (either CD8 or CD4) results in

A

positive selection

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31
Q

No recognition of MHC + self peptide by TCR and co-receptor results in

A

death by neglect

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32
Q

Strong recognition of MHC + self pep by TCR and co receltpr results in

A

negative selection

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33
Q

Surviving cells of positive selection are not

A

CD8 + or CD4+ naive T cells and exit thymus to enter periphery

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34
Q

T cells under go + selection in the

A

corticoepithelium as cortical epithelial cells present self-peptide to double positive thymocytes

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35
Q

T cells undergo - selection in

A

medullary epithelial cells that express the Aire transcription factor gene

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36
Q

This gene drives expression of numerous tissue specific self-peptides to T cells in medullarly epi of thymus

A

Aire gene

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37
Q

Before undergoing negative selection, T cell thymocyte populations consist of :

A

Self and foriegn antiG specific Single positive T cells

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38
Q

Positive selection results int

A

self and foreign antiG recognizing thymocytes that are either CD4 or CD8 positive

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39
Q

Loss of Aire results in

A

lack of negative selection of self-reactive T cells in thymus

40
Q

these make autoantiBs to immune proteins important in controle of fungal infections

A

Aire helps with IL-17

41
Q

pt devos wide range of auto-antiBs to organ-specific antiG of endocrine organs and liver and skin

A

loss of Aire

42
Q

clinical syndrome associated with autoimmune adrenal and parthyroid disease

A

APCED

43
Q

see autoimmune hypothryoidism, hypogonadism, vitiligo and pernicious anemia with this diesease

A

Autoimmune polyendocrinopathy candidiasis ectoderlal dystrophy = APECED

44
Q

APECD is caused by

A

defect in AIRE thus failure of negative selection thus lots of self reactive T cells

45
Q

These guys are key to stepping in when Central tolerance isn’t complete

A

T reg cells (self-reactive CD4 + cells)

46
Q

What do T reg cells express

A

foxP3

47
Q

T reg cells are positive for what CD’s?

A

CD24, CD25 and Foxp3

48
Q

Activation by MHC+ self peptide stimulates T cell apoptosis by these three methods:

A

Anergy, suppresion, deletion

49
Q

this is induced when mature T cells recognize self peptide in peripheral tissues or in mucosa

A

Periperal T cell tolerance

50
Q

Develeop in thymus once they recognize selfantigen by immature double positive thymocytes

A

T regs

51
Q

T regs are activated in periphery by:

A

self antigen and IL-2

52
Q

APC’s lack co-stim molecules (like B7) thus results in

A

anergy

53
Q

T cells express _______ moleclue to send inhibition signal to T cells upong bindint to the APC B7

A

CTLA-4

54
Q

T cellls express CD28 that bind to _____

and with high levels of B7 the T cells are:

A

ITAM (acitvation)

activated d/t that CD28 + B7 levels

55
Q

T cells express CTLA-4 that bind to _______

and will low levels of B7, the T cells become

A

ITIM( inactivation)

anergic via that CTLA-4 signal

56
Q

What is this?
T regs bind directly to mature T cells to introduce inhibitory signal CTLA-4 (surface bound TGFbetta) and kills the T cell that is regonizing self antigen via performin/granZ

A

Contact Dependent T regulation: Suppresion

57
Q

T regs cells secrete high levels of TGFbetta and IL-10 that inhibit T cell activation (of T cells recognizing self antiG) so it can’t interact with the APC

A

contatct INdependent T regulation: suppresion

58
Q

You can uses CTLA-4 immunotherapy on

inhibits second signal by stopping of the binding of CD28

A

Rheumatoid arthritis
psoriasis
IBD
Type I diabetes

59
Q

Mutation in Foxp3 and we see hyper-inflammatory mucosa

(bowel, skin, pancrease, ) think IBD!!! Think Boys!

A

Immune dysregulation polyednocrionpathy X linked syndrome

IPEX in boys

60
Q

IPEX tx is

A

BMT to reboot immune system

61
Q

Repeated exposure to self-antiG leads to:

A

cell death d/t deficiency of survival signals
cell death by engagement of death receptors
Ultimately… T cell deletion

62
Q

Death receptor ligand is

A

Fas and FasL

63
Q

tolorogenic self antiG located in:

A

generatie organs and will induce negative selection and other mech. of central tolerance

64
Q

Tolerogenic self antiG and acompnying costimulation:

A

lack of co-stimulators can lead to anergy or apoptosis or devo of T regs

65
Q

Tolerogenic self antiG duration of antiG exposure:

A

long lived persistance, so prolongued TCR engagement may induce apop to get T cell deletion in periphery

66
Q

3 factors that contribute to tolerance or breakdown in tolderance

A

location
abundance
persistance

67
Q

1st checkpoint for B cell : does immature B lymp express _____ recombined antiG receptor in the _______chain

A

VDJ

IgHeavy chain

68
Q

2nd checkpoint for B cell: does immature B cells express ____ in this receptor chain

A

VJ

IgLight

69
Q

3rd checkpoint: does antiG receptor recognize ______

A

self
strongly—must die
weakly— can live

70
Q

Where does B cell complete maturatoion

A

w/in bone marrow

71
Q

Central B cell tolerance is based wholly on strength of nascent surface immunoglobin (_____ or ______) to reconize soluble _______

A

IgD or IgM

self-antiGens

72
Q

If a B cell recognizes self antiG with High avididty, what happens?

A
  1. receptor editing of the IgL chain

2. Deletion via apotosis (upregulates pro-apoptosis genes)

73
Q

If B cell recognizes self antiG will low avidity what happens (so NO avidity)

A

Anergy-

74
Q

Where does receptor editing happen in the B cell if there is high avidity to self-antiG

A

in the IgLight

75
Q

How do B cells receptor edit?

A

internalize the BCR, generate new IgL with some new VJ recomination events and try again

76
Q

Where does peripheral B cell tolernace occur

A

germinal centers during immune response

77
Q

How is peripheral B cell tolerance different from naive B cells?

A

short lifespan
defects in BCR
defects in gerinal centerl

78
Q

immune response against self antiG, failure of tolerance

A

autoimmunity

79
Q

What are prinicple factors of autoimmune disease

A
  1. inherit genes which contribute to FAILURE of SELF-TOLERANCE
  2. Envi triggers that activate self reactive lymphocytes
80
Q

What is our perfect storm for developing autoimmunity

A

envirornment + genetically susupecitlbe indivdual

81
Q

Multpile genes will predispose indi to autoimmune disease: for twins this means

A

one devos disease, other very likey if gets same enviroment exposures

82
Q

Many autoimmune disease have been linked to this gene

A

MHC or particular HLA allele

83
Q

Are mutations in HLA genes the cause of autoimmune diesase

A

NO…. some can inherit it and not develope it but it can contribute

84
Q

How does mutation in MHC contribute to autoimmune disease

A
  1. defects in central tolerance bc of ineffecient display of self antigens so we don’t get rid of immunogenic T cells
  2. Defect in peripheral tolerance–> mutant MHC may not trigger Treg cells
85
Q

How do microbes upregulate autoimmunity?

A

assuem you have APC that is presenting a self antiG that then gets infected with a microbe… it will upregulate it’s co-stimulatory signals so it’s like…. hey T cell, help, i’m infected, but T cell that is reactive to self antiG will react to that self antiG it’s displaying and not the microbe that infected the APC

86
Q

A microbe is ingested and displayed by APC… T cell that is kinda retarded regonizes this microbe, but it really is specific for self antigen so it startes to repliate and attack self tissue… this is example of

A

microbe mimicry

87
Q

immune system developed this to suppress autoreactive lymphocytes

A

immune tolerance

88
Q

This occurs when adaptive immune response is directed against self antigens to elicit tissue damage

A

autoimmune disease

89
Q

autoimmune disease are multifactorial and may result from: 3 things

A

immunological abnormalities
susceptibility genes
infections

90
Q

this induces death of immatre lypmp that encounters self antigen in bone marrow or thymus

A

central tolerance

91
Q

this results from recogniztion of self-antiG by mature lymphocytes in periphery

A

peripheral tolerance

92
Q

This is the positive and negative selection 3rd checkpoint in T cell devo

A

Central T cell tolerance

93
Q

Mech of peripheral T cell tolerance include:

A

anergy
suppresion
deletion

94
Q

this is induced when immature cells recognize self antiG in bone marrow

A

Central B lymphocyte tolerance

95
Q

tolerance through anergy when mature B cells recognize self antiG w/out T cel help

A

Peripheral B tolerance

96
Q

Strongest gene that contributes to devo of autoimmunity is

A

HLA for mostly T cell releated autoimmune disesase

97
Q

Infections can predispose to autoimmunity through

A

induce abherrant co-stim moleucle or

molecular mimicry

Immunology (12 decks)

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