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
2
Q
Calnexin
A
Binds to alpha chains of MHC class 1 in ER until Beta 2
3
Q
Calreticulin, ERp57
A
chaperone proteins that bind to MHC class 1 in ER after calnexin releases it
4
Q
TAP complex
A
Translocate peptide to ER for MHC class 1 loading Binds to MHC by tapasin
5
Q
US6 and ICP47
A
Inhibition of MHC class 1 Expression: block antigen presentation by preventing peptide movement through TAP peptide transporter
6
Q
E19
A
Inhibition of MHC class 1 Expression: compete and inhibit peptide loading onto MHC class 1 proteins
7
Q
mK3
A
Inhibition of MHC class 1 Expression: mark MHC class 1 for degradation through ubiquitin
8
Q
MHC class \_\_\_ expressed on APC Activates \_\_\_ T cells --> eliminate \_\_\_\_ pathogens
A
Class 2
CD4+
extracellular
9
Q
HLA-DM
A
Binds to MHC to release CLIP fragment –> antigen peptide binds to MHC
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
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
12
Q
DC licensing
A
dendritic cels need to be activated by CD4 T cells to cross present
13
Q
Cross presentation
A
Dendritic cells: Present extracellular ligands on MHC class I Present intracellular ligands on MHC class II
14
Q
MHC class 1 gene loci
A
HLA A, B, C
15
Q
MHC class 2 gene loci
A
DP, DQ, DR
16
Q
MHC class 3 gene loci code for ____
A
complement factors, cytokines
17
Q
What stage does lineage bias occur for T cell development?
A
DN1
18
Q
What stage does commitment to T cell during development occur?
A
DN2
19
Q
When does beta chain rearrangement occur in T cell development?
A
DN3
20
Q
When does alpha chain rearrangement occur in T cell development?
A
Double positive
21
Q
Notch1
A
Cell surface receptor that determines T cell or B cell fate
22
Q
TCR alpha chain gene
A
multiple copies of V and J regions + 1 copy of constant region –> V+J+ 1 constant
23
Q
TCR beta chain gene
A
multiple copies of V, D and J regions + 2 copies of constant region –> V+D+1 constant
24
Q
Recombination signal sequence (RSS)
A
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
