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Flashcards in Adaptive Immunity: T cells Deck (94):
1

MHC class ___ expressed on all nucleated cells
Activates ___ T cells --> eliminate ____ pathogens

Class 1
CD8+
Intracellular pathogens

2

Calnexin

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

3

Calreticulin, ERp57

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

4

TAP complex

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

5

US6 and ICP47

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

6

E19

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

7

mK3

Inhibition of MHC class 1 Expression:
mark MHC class 1 for degradation through ubiquitin

8

MHC class ___ expressed on APC
Activates ___ T cells --> eliminate ____ pathogens

Class 2
CD4+
extracellular

9

HLA-DM

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

10

Bare Lymphocyte Disorder Type 2

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

11

Bare Lymphocyte Disorder Type 1

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

12

DC licensing

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

13

Cross presentation

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

14

MHC class 1 gene loci

HLA A, B, C

15

MHC class 2 gene loci

DP, DQ, DR

16

MHC class 3 gene loci code for ____

complement factors, cytokines

17

What stage does lineage bias occur for T cell development?

DN1

18

What stage does commitment to T cell during development occur?

DN2

19

When does beta chain rearrangement occur in T cell development?

DN3

20

When does alpha chain rearrangement occur in T cell development?

Double positive

21

Notch1

Cell surface receptor that determines T cell or B cell fate

22

TCR alpha chain gene

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

23

TCR beta chain gene

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

24

Recombination signal sequence (RSS)

TCR variable region rearrangment:
Surrounds each V, D and J region

25

12/23 Rule

Spacing of 23 and 12 bp of RSS

26

RAG1 and RAG2

TCR variable region rearrangment:
enzymes that recognize RSS sequence --> catalyze cleavage of RSS --> form closed DNA hairpin loop

27

Ku70/Ku80 proteins

Joining of cleaved DNA during TCR recombination:
Bind coding joint and signal joint

28

DNA ligase IV:XRCC4

Joining of cleaved DNA during TCR recombination:
Recruited by Ku70/Ku80 --> ligate DNA ends

29

DNA-PK and artemis

Joining of cleaved DNA during TCR recombination:
Recruited by Ku70/Ku80 --> open hairpin loop --> then released

30

TdT

Joining of cleaved DNA during TCR recombination:
Recruited by Ku70/Ku80 --> adds random basepairs to coding joint --> then released

31

Combinatorial diversity

V, D and J regions randomly recombined

32

Junctional diversity

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

33

Immature T cell leukemia

Inappropriate expression of pre-TCR alpha chain

34

CDR1 and CDR2

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

35

CDR3

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

36

CD4 binds _____
CD4 expressed on ____

MHC Class II
T helper cells

37

CD8 binds _____
CD8 expressed on _____

MHC Class I
Cytotoxic T cells

38

CD4 and CD8 interact w/ ______ region on MHC

invariant

39

ITAMs

Immune-tyrosine based activation motifs
On CD3 gamma, delta, epsilon, TCR zeta chains of TCR

40

Lck

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

41

ZAP-70

Recruited to phosphorylated ITAMs
Gets phosphorylated by Lck --> activated ZAP-70 phosphorylates adaptor protein LAT

42

PLC-gamma

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

43

Diacylglycerol (DAG)

second messenger that activates PKC --> transcription

44

Inositol 1,4,5 phosphate (IP3)

Second messenger --> signal Ca++ influx

45

SLP-76

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

46

Phosphatidyl inositol 3 kinase (PI3K)

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

47

Akt

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

48

Guanine nucleotide exchange factor (GEF)

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

49

Ras/MAP kinase pathway

Ex kinase cascade
Activated LAT --> recruit GEF --> stimulate Ras --> induce Raf --> activate MEK --> ErK --> --> transcription factors

50

Calmodulin

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

51

Calcineurin

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

52

IKK complex

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

p100

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

54

Vav1

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

WASp

Activates Arp2/3 complex

56

Arp2/3 complex

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

57

CD62L

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

58

Sphingosine 1-Phosphate (S1P) Receptor

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

CCR7

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

CCL19 and CCL21

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

61

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

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

62

CD28

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

CD40L (CD56)

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

IL-2

Principle cytokine that drives differentiation and expansion of T-cells

65

CD69

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

66

TNF and IL-1

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

VLA4

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

68

TH1 cell
Produce _____ to activate ____ transcription factor, which produces _____ which activates _____

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

69

TH2 cell
Produce _____ to activate ____ transcription factor, which produces _____ which activates _____

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

70

TH17 cell
Produce _____ to activate ____ transcription factor, which produces _____ which activates _____

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

71

IL-4

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

72

IL-13

Produced by TH2 CD4 T cell
Promotes mucus secretion and peristalsis

73

IL-5

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

74

IL10 + IL-4

Produced by TH2 CD4 T cell
Activate macrophage

75

IL-17

Produced by TH17 CD4 T cell
Recruits/activates neutrophils, enhances production of epithelial cell to produce anti-microbial peptides

76

IL-22

Produced by TH17 CD4 T cell
Induces keratinocytes to produce antimicrobial agents, promote epidermal hyperplasia

77

IL-21

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

78

CCL20

Produced by TH17 CD4 T cell
regulates recruitment of TH17 cells to inflamed tissues

79

Fas/FasL

Mediated cell killing
CD8 T cells express Fas ligand --> activate Fas receptor on target cell --> apoptosis of target cell

80

TNF alpha

Enhance target cell killing
Activate macrophages

81

Cytokines released by CD8 T cells

IFN gamma, TNF alpha, chemokines

82

Hyper IgE Syndrome (HIES)

Caused by mutations in STAT3, DCK8, Tyk2
Without STAT 3 --> tries to use TH2 response --> doesn't work

83

STAT3

Drives TH17 response

84

Autosomal dominant HIES

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

85

Autosomal recessive HIES

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

86

Hemophagocytic Lymphohistiocytosis

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

Cortical epithelial cells

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

88

Medullary thymic epithelial cells

Can express almost every protein made in the body
Source of self peptides that are used in self testing of T cells

89

AIRE

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

90

List the immunologically privileged organs

Brain
Eye
Testies
Uterus

91

CTLA-4

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

PD-1

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

FOXP3

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

94

CD25

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