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Undeleted > Adaptive Immunity: T cells > Flashcards

Adaptive Immunity: T cells Flashcards

1
Q 
MHC class \_\_\_ expressed on all nucleated cells 
Activates \_\_\_ T cells --> eliminate \_\_\_\_ pathogens
A

Class 1
CD8+
Intracellular pathogens

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2
Q

Calnexin

A

Binds to alpha chains of MHC class 1 in ER until Beta 2

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3
Q

Calreticulin, ERp57

A

chaperone proteins that bind to MHC class 1 in ER after calnexin releases it

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4
Q

TAP complex

A 
Translocate peptide to ER for MHC class 1 loading
Binds to MHC by tapasin
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5
Q

US6 and ICP47

A 
Inhibition of MHC class 1 Expression:
block antigen presentation by preventing peptide movement through TAP peptide transporter
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6
Q

E19

A 
Inhibition of MHC class 1 Expression:
compete and inhibit peptide loading onto MHC class 1 proteins
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7
Q

mK3

A 
Inhibition of MHC class 1 Expression:
mark MHC class 1 for degradation through ubiquitin
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8
Q 
MHC class \_\_\_ expressed on APC 
Activates \_\_\_ T cells --> eliminate \_\_\_\_ pathogens
A

Class 2
CD4+
extracellular

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9
Q

HLA-DM

A

Binds to MHC to release CLIP fragment –> antigen peptide binds to MHC

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10
Q

Bare Lymphocyte Disorder Type 2

A 
Defect in one of the transcription factors needed for MHC class II expression --> reduced number of activated CD4 T cells
Death by 10 y/o due to severe infection
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11
Q

Bare Lymphocyte Disorder Type 1

A

Defect in expression of TAP1, TAP2 or Tapasin –> Don’t activate CD8+ T cells
Sensitivity t bacterial and parasitic infections later in life
Can use NK cells to fight viral infection but not efficient

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12
Q

DC licensing

A

dendritic cels need to be activated by CD4 T cells to cross present

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13
Q

Cross presentation

A 
Dendritic cells:
Present extracellular ligands on MHC class I
Present intracellular ligands on MHC class II
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14
Q

MHC class 1 gene loci

A

HLA A, B, C

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15
Q

MHC class 2 gene loci

A

DP, DQ, DR

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16
Q

MHC class 3 gene loci code for ____

A

complement factors, cytokines

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17
Q

What stage does lineage bias occur for T cell development?

A

DN1

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18
Q

What stage does commitment to T cell during development occur?

A

DN2

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19
Q

When does beta chain rearrangement occur in T cell development?

A

DN3

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20
Q

When does alpha chain rearrangement occur in T cell development?

A

Double positive

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21
Q

Notch1

A

Cell surface receptor that determines T cell or B cell fate

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22
Q

TCR alpha chain gene

A

multiple copies of V and J regions + 1 copy of constant region –> V+J+ 1 constant

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23
Q

TCR beta chain gene

A

multiple copies of V, D and J regions + 2 copies of constant region –> V+D+1 constant

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24
Q

Recombination signal sequence (RSS)

A

TCR variable region rearrangment:

Surrounds each V, D and J region

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25
Q

12/23 Rule

A

Spacing of 23 and 12 bp of RSS

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26
Q

RAG1 and RAG2

A

TCR variable region rearrangment:

enzymes that recognize RSS sequence –> catalyze cleavage of RSS –> form closed DNA hairpin loop

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27
Q

Ku70/Ku80 proteins

A

Joining of cleaved DNA during TCR recombination:

Bind coding joint and signal joint

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28
Q

DNA ligase IV:XRCC4

A

Joining of cleaved DNA during TCR recombination:

Recruited by Ku70/Ku80 –> ligate DNA ends

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29
Q

DNA-PK and artemis

A

Joining of cleaved DNA during TCR recombination:

Recruited by Ku70/Ku80 –> open hairpin loop –> then released

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30
Q

TdT

A

Joining of cleaved DNA during TCR recombination:

Recruited by Ku70/Ku80 –> adds random basepairs to coding joint –> then released

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31
Q

Combinatorial diversity

A

V, D and J regions randomly recombined

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32
Q

Junctional diversity

A

V, D and J regions are recombined using random number of nucleotides

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33
Q

Immature T cell leukemia

A

Inappropriate expression of pre-TCR alpha chain

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34
Q

CDR1 and CDR2

A

Complementarity Determining Regions in variable region
Interact w/ MHC –> don’t want too much variation
Genomically encoded by V regions

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35
Q

CDR3

A

Complementarity Determining Regions in variable region
Interact w/ peptide –> needs a lot of variation
Encoded by recombination of V, D and J

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36
Q

CD4 binds _____

CD4 expressed on ____

A

MHC Class II

T helper cells

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37
Q

CD8 binds _____

CD8 expressed on _____

A

MHC Class I

Cytotoxic T cells

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38
Q

CD4 and CD8 interact w/ ______ region on MHC

A

invariant

39
Q

ITAMs

A

Immune-tyrosine based activation motifs

On CD3 gamma, delta, epsilon, TCR zeta chains of TCR

40
Q

Lck

A

Kinase that phosphorylates tyrosine on ITAMs on TCR –> initiates intracellular signaling
Dragged to TCR site of binding by CD4

41
Q

ZAP-70

A

Recruited to phosphorylated ITAMs

Gets phosphorylated by Lck –> activated ZAP-70 phosphorylates adaptor protein LAT

42
Q

PLC-gamma

A

Phospholipase C that cleaves phosphatidyl inositol 4,5 phosphate into DAG and IP3

43
Q

Diacylglycerol (DAG)

A

second messenger that activates PKC –> transcription

44
Q

Inositol 1,4,5 phosphate (IP3)

A

Second messenger –> signal Ca++ influx

45
Q

SLP-76

A

Binds LAT –> recruit tyrosine kinase ITK –> phosphorylates PLC-gamma 1

46
Q

Phosphatidyl inositol 3 kinase (PI3K)

A

phosphorylates PI on 3rd position –> forms PIP3 –> binds to proteins w/ pleckstrin homology domains

47
Q

Akt

A

Serine/threonine kinase activated by PI3K –> regulates T cell survival

48
Q

Guanine nucleotide exchange factor (GEF)

A

Recruited to LAT –> stimulate G proteins –> induce kinase cascade –> –> induced transcription factors

49
Q

Ras/MAP kinase pathway

A

Ex kinase cascade

Activated LAT –> recruit GEF –> stimulate Ras –> induce Raf –> activate MEK –> ErK –> –> transcription factors

50
Q

Calmodulin

A

activated by Ca2+ influx activated by PLC-gamma –> activate phosphatase calcineurin –> dephosphorylates NFAT –> activated NFAT –> translocate to nucleus

51
Q

Calcineurin

A 
target for large class of immunosuppressant
Activates NFAT in T cells --> transcription factor
52
Q

IKK complex

A

Classical pathway: DAG activates PKC –> activates IKK complex –> phosphorylates inhibitory protein I-kB –> degraded by proteasome –> release NF-kB –> translocate to nucleus –> gene transcription

53
Q

p100

A

Alternative pathway: Activation of IKK –> phosphorylation and partial degradation of p100 –> formation of p52 –> facilitate translocation of RelB to nucleus –> gene transcription

54
Q

Vav1

A

Recruited by LAT –> VAV1 –> Rac/CDC42 and WASp –> activates Arp2/3 complex –> regulate actin branching for formation of phyllopodia and lamellipodia in T cells

55
Q

WASp

A

Activates Arp2/3 complex

56
Q

Arp2/3 complex

A

regulate actin branching for formation of phyllopodia and lamellipodia in T cells

57
Q

CD62L

A

High expression of CD62L on HEV epithelial cells causes T cells to go to lymph node

58
Q

Sphingosine 1-Phosphate (S1P) Receptor

A

Expressed on T cells, made consistently on T cells
Activated when high conc. of S1P in blood bind –> cause T cells to move to lymph node –> S1P degraded
High expression when in lymph, low expression when in blood

59
Q

CCR7

A

Drives maturation of DC
Expressed on DC when it recognizes a pathogen –> follows gradient of CCL19 and CCL21 –> migrate to lymphatics to T cells –> becomes mature DC –> activates T-cell

60
Q

CCL19 and CCL21

A

Gradient produced at T cell zone by stromal cells that DC follow to activate T cells

61
Q

B7-1 and B7-2 ( CD80, CD86)

A

Expressed on mature APC. Ligand for CD28 expressed on naive CD4 and CD8 T cells

62
Q

CD28

A

Always expressed on CD4 and CD8 T cells. Receptor for B7-1 and B7-2 on mature APC.
Necessary for activating naive T cells

63
Q

CD40L (CD56)

A

Expressed on T cells when co-activation of TCR and CD28 occurs –> Activate CD40 on APC –> increase ligands for second wave of costimulatory receptors

64
Q

IL-2

A

Principle cytokine that drives differentiation and expansion of T-cells

65
Q

CD69

A

Promotes S1P receptor degradation
Upregulated after T cell activation
Binds to S1P receptor w/o activation –> keep T cell in lymph

66
Q

TNF and IL-1

A

Made by activated tissue macrophages and mast cells –> activate endothelium to express E/P selectins, chemoines, ICAM –> attract T cell to site of infection

67
Q

VLA4

A

Expressed by activated T cells –> adhesion, trasmigration, migration of T cell to site of infection

68
Q

TH1 cell

Produce _____ to activate ____ transcription factor, which produces _____ which activates _____

A 
Respond to intracellular pathogens
IL-12, IFN gamma 
T-bet 
IFN gamma, TNF
macrophage activation, inflammation
69
Q

TH2 cell

Produce _____ to activate ____ transcription factor, which produces _____ which activates _____

A 
Respond to mucosal surface pathogens and big things
IL-4
GATA3
IL4, 5, 13
allergic and helmith response
70
Q

TH17 cell

Produce _____ to activate ____ transcription factor, which produces _____ which activates _____

A 
Respond to extracellular small things (bacteria)
IL-6, TGF-beta
ROR gamma t
IL-17A, IL-17F, IL-22
inflammation, neutrophil activation
71
Q

IL-4

A

Produced by TH2 CD4 T cell
B cells switch to IgG and IgE
Alternative activation of macrophages

72
Q

IL-13

A

Produced by TH2 CD4 T cell

Promotes mucus secretion and peristalsis

73
Q

IL-5

A 
Produced by TH2 CD4 T cell
Activate eosinophiles and B cell class switching to IgA subtypes
74
Q

IL10 + IL-4

A

Produced by TH2 CD4 T cell

Activate macrophage

75
Q

IL-17

A

Produced by TH17 CD4 T cell

Recruits/activates neutrophils, enhances production of epithelial cell to produce anti-microbial peptides

76
Q

IL-22

A

Produced by TH17 CD4 T cell

Induces keratinocytes to produce antimicrobial agents, promote epidermal hyperplasia

77
Q

IL-21

A

stimulate activation of CD8 T cells , B cell class switching, NK and NK T cell differentiation, CXCL8 release from APCs

78
Q

CCL20

A

Produced by TH17 CD4 T cell

regulates recruitment of TH17 cells to inflamed tissues

79
Q

Fas/FasL

A

Mediated cell killing

CD8 T cells express Fas ligand –> activate Fas receptor on target cell –> apoptosis of target cell

80
Q

TNF alpha

A

Enhance target cell killing

Activate macrophages

81
Q

Cytokines released by CD8 T cells

A

IFN gamma, TNF alpha, chemokines

82
Q

Hyper IgE Syndrome (HIES)

A

Caused by mutations in STAT3, DCK8, Tyk2

Without STAT 3 –> tries to use TH2 response –> doesn’t work

83
Q

STAT3

A

Drives TH17 response

84
Q

Autosomal dominant HIES

A

Mutation in STAT3
Facial deformity
Dental problems: don’t lose baby teeth

85
Q

Autosomal recessive HIES

A

Mutation in DOCK8 or Tyk2
Severe viral infections and allergic symptoms
No dental or facial issues

86
Q

Hemophagocytic Lymphohistiocytosis

A

Mutation in perforin or proteins needed for granule release
Can’t clear viral infections –> continuous inflammation –> cytokine storm disease
Similar to Bare Lymphocyte Disease but can’t even use NK cells to clear infection

87
Q

Cortical epithelial cells

A

In cortex of thymus
Produces metabolite factors
Express MHC 1 and 2 –> start of + and - selection

88
Q

Medullary thymic epithelial cells

A

Can express almost every protein made in the body

Source of self peptides that are used in self testing of T cells

89
Q

AIRE

A

transcriptional chromatin regulator
Removes suppressed gene expression –> allows for promiscuous expression of proteins in medullary thymic epithelial cells

90
Q

List the immunologically privileged organs

A

Brain
Eye
Testies
Uterus

91
Q

CTLA-4

A

Inhibit CD28 binding to B7 ligands
Expressed by regulatory T cells when it’s time to contract
Binds to B7 w/ higher affinity that CD28

92
Q

PD-1

A

Phosphotase (dephosphorylates)
Suppress signaling induced by TCR and costimulatory receptors
Upregulated in TCR and CD28-stimulated T cells
Pd-1 ligands expressed on DC and cell types during inflammation

93
Q

FOXP3

A

Expressed in regulatory T cells
Controls differentiation and function of regulatory T cells
Epigenetic regulator

94
Q

CD25

A

On regulatory T cells that binds IL-2 to inhibit T cell differentiation

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