Lecture 13-14 - Tcell Mediated Immunity Flashcards

1
Q

What do dendritic cells do after taking up bacterial antigens in the skin?

A

Travel via lymph, enter node and settle in T cell areas to present antigens to Tcells

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2
Q

Dendritic cells increase ________ before presentation to lymphocytes

A

expression of MHC

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3
Q

Dendritic cells present antigens from extracellular bacteria on _____, and viruses on _______

A

Bacterial antigens = MHC2

VIral = MHC1

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4
Q

Wher aer viral antigens processed (during antigen uptake/presentation)

A

ER

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5
Q

Naive T cells can enter a draining lymph node via two routes:

A
  1. In the blood (HEV)
  2. afferent lymphatics coming from an upstream node
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6
Q

How do Naive T cells get themselves into a HEV

A

They express L selectin and other adhesion molecules

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7
Q

Adhesion molecules expression is ____ specific

A

tissue-specific

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8
Q

L selectin binds to

A

GlyCAM-1 + CD34

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9
Q

SLC and ELC (T cell chemokines) bind to ___

(on endothelial cells)

A

CCR7

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10
Q

Activated LFA-1 binds to

A

ICAM-1

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11
Q

Which adhesion molecule allows for the T cell to rol along surface?

A

L-selectin

rolLing

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12
Q

CD2 (on T cell) binds to

A

LFA-3

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13
Q

CD28 binds to

A

B7.1 and B7.2

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14
Q

Function of LFA-3/CD2 and ICAM1/LFA1

A

adhesion of Tcell to APC

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15
Q

MHC binds to

A

TCR and CD4/8

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16
Q

____ is needed for Co-activation of T cell (with TCR)

A

CD28 binding to B7.1/B7.2

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17
Q

All T cell surface molecules that interact with APC (list them)

A
  1. LFA1
  2. CD2
  3. CD4
  4. TCR/CD3
  5. CD28
  6. CTLA4
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18
Q

Function of integrins (During interaction between T cells and APC)

A

They help prolong the activation signal from TCR and CD28 receptors on T cells

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19
Q

ICAM1/LFA1 interaction is ____ when MHC isn’t bound to TCR/CD4

A

low affinity

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20
Q

For full activation, T cells require signals from…

A

TCR + CD28 signals

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21
Q

____ is expressed in all T cells

A

CD28

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22
Q

B7 binds to both ___ and ____

Where are they found and whats the difference?

A

CD28 + CTLA4

CD28 is costimulatory for T cell activation

CTLA4 on activated T cells, and is an inhibitor of T cell activation

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23
Q

B7 is expressed highly by ________ cells

A

Activated dendritic cells

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24
Q

What happens when there is no CD28/B7 interaction?

A

T cell anergy

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25
Q

Professional APC’s: 3 facts

A
  1. DCs, BCs, MQs
  2. Express lots of MHC1 and MHC2
  3. Express costimulatory receptors like B7
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26
Q

Professional APC’s are each good at specializing in presenting a particular type of antigen. Which ones are they?

A

DCs = bact/viral in lymphoid tissues

MQ = Extracellular bacteria (at site)

B cells = soluble antigens

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27
Q

____ and ____ can induce dendritic cell maturation

A

Bacterial products (LPS) and inflammatory cytokines (TNFa)

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28
Q

Mature DC’s express ___, ___, and ____

A

CCR7

MHC1/2

B7

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29
Q

Immature DC’s are good at ________, but lack _________

Mature DC’s have ____and_____ but lack ___________

A

Phagocytosis, co-stimulatory/presenting ability

MHC and B7, but lack phagocytic ability

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30
Q

T cell activation signal transduction pathway (5 steps

A
  1. Antigen binds MHC
  2. ITAMs of T cell receptor complex are phosphorylated
  3. Coreceptor binds MHC
  4. ZAP-70 binds to phosphorylated ς-chain ITAMs
  5. Lck phoshphorylates ZAP-70 and activates it
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31
Q

CD3 ITAMS are phosphorylated by ___ or ____.

What effect does this have

A

Fyn or Lck

Allows zap-70 to bind

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32
Q

What does activated zap-70 do?

A

activates PLC-gamma

which causes…

PIP2-> DAG + IP3

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33
Q

DAG activates ___ and ____. Downstream effects of those?

A

PKC and RasGRP

PKC >> NFkB

RasGRP >> MAPK >> AP-1 (Fos)

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34
Q

IP3 function?

A

increases intracellular Ca++
>> calcineurin activated

>> NFAT activated

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35
Q

NFkB, AP-1, and NFAT all have what effect on the T cell

A

change the pattern of gene expression to favor

  • division
  • proliferation
  • differentiation
36
Q

Effects of cyclosporin A and FK506

A

block NFAT activation, thus blocking IL-2 production

37
Q

A consequence of T cell activation is enhanced production of _______, and induction of ________ expression

A

enhanced IL-2

induction of IL-2Ra

38
Q

Pathway of IL-2 production by activated T cells

A

Nuclear-ly controlled by Phosphorylated STAT

JAK binds cytokines –> JAKs dimerize –> phosphorylation of intracellular part –> phosphorylation of STAT –> goes to nucleus

39
Q

What is the “#1 cytokine” according to Dr. Kim?

What are it’s three major effects?

A

IL-2

  1. T cell proliferation (++IL4, IFNg)
  2. B cell proliferation (++Antibodies)
  3. NK cell proliferation, with increased cytolytic activity
40
Q

B cells and NK cells need _____ for cellular expansion

A

IL-2

41
Q

Naive and effector (activated) T cells express different cell surface molecules. 2 Examples?

A
  1. L-selectin (LFA-1…Naive) vs VLA-4 (active)
  2. CD45RA** (naive) vs CD45RO** (Active)
42
Q

Both TH1 and TH2 can promote…

A

humoral immune response

43
Q

Major Cytokines form active TH1 cell

functions?

A

IL-2, IFNg

MQ and B cell activation, opsonizing antibodies

44
Q

Major cytokines from Th2

Function?

A

IL-4, IL-5

General activation of B cells to make antibodies

45
Q

Cell mediated response is promoted by ____ T cells,

Humoral / Ig response is largely promoted by ________ cells

A

TH1

TH2

46
Q

TH2 cells are functinoally _____ because they stimulate a ____ response

A

antiparasitic

IgE response

47
Q

Major cytokine that induce differentiation into Th1 cells

A

IL-12

48
Q

Major cytokine that promotes differentiation into TH2 cells

A

IL4

49
Q

TH1 pathway major players

A
  1. T bet
  2. IL12
  3. IFNgamma
  4. STAT4
50
Q

TH2 major players

A

GATA-3

IL4

STAT6

51
Q

Cytokines secreted by Th1 cell

A
  • IFN gamma
  • GM-CSF
  • TNFa
  • LT
  • IL-3
52
Q

Cytokines secreted by TH2 cell

A

IL’s 4, 5, 10, 13

53
Q

Tregs are controlled by ___ transcription factor

A

FoxP3

54
Q

Main functions of Th1, Th2, Tfh, Th17, and Treg cells

A

TH1 = helps MQ with intracellular infections

TH2 = helps granulocytes and Bcells with Parasites

Tfh = Help activate Bcells & switch/mature its antibodies

TH17 = Help neutrophils deal with fungal and extracellular infections

Treg = suppress all the other ones

55
Q

Tfh cytokines

A

IL21

IL4

IFNgamma

56
Q

TH17 cells cytokines

A

IL- 17, 21, 22, 26

57
Q

____ induces class switching in antibodies

A

IL-4

58
Q

According to Dr. Kim, what is the unique cytokine for Th1 cells?

A

IFN gamma

59
Q

Treg cytokines

A

TGFbeta

IL-10

IL-35

60
Q

(CORE)

CMI response functions (5)

A
  1. Control intracellular pathogens and tumors
  2. Transplant rejectinon
  3. Type 4 hypersensitivity
  4. Granuloma formation
  5. Chronic inflammation
61
Q

Three “connections” made by TH1 and MQ to activate the latter

A

TCR > MHC

CD40L > CD40

IFNg > IFNg receptor

62
Q

Four cells involved in CMI

A
  1. TH1 cells
  2. CD8+ TC1 & TC2
  3. NK cells
  4. MQ
63
Q

TH1 secretes CXCL2, which is a ..

A

chemokine

for MQ to travel to site of infection

64
Q

CD8 T cells kill virus/tumor cells by these four things:

A

TNFb, perforin, granzymes, FAS ligand

65
Q

Cytolytic activity of CD8’s are promoted by…

A

IL-2, IL-12, IFNgamma

66
Q

CD8+ cells need ___________ from APCs to become effector CD8s

A

CD28 activation signal

67
Q

At the effector stage of CD8+ cells, _____ is NOT needed

A

CD28

Only need to bind to the MHC

68
Q

CD8 cells secrete ____ which induces apoptosis on target cell

A

FAS ligand

69
Q

Role of the endothelium in CMI

A

expresses P and E selectins

70
Q

CD8+ mediated killing of cells can be detected by…

A

51Cr release assay

51Cr enters cells, wash away any extracellular, and cells that get killed by CD8 will release Cr into the medium.

71
Q

Granulomas are made of _________

A

aggregated infected epithelioid MQ

Surrounded by T cell

Common in TB infection, where pathogen can persist in MQ for a long time!

72
Q

IFNg promotes what 4 things?

A
  1. Antigen presentation
  2. Isotype switching
  3. TH1 development
  4. MQ activation
73
Q

TH2 cells suppress…

A

Macrophage activation

Via IL-10

74
Q

Functions of TH2 cells

A

Production of IgG, IgE

Eosinophil activation

MQ suppression

75
Q

____ activates eosinophils

A

IL-5

*from TH2

76
Q

TH2 cells activate B cells via _____and ______

A

cytokines and CD40L

77
Q

Tuberculoid vs lepromatous leprosy

A

TL = Th1 cells produce IFNgamma and activate MQ

LL = TH2 cant activate MQ

78
Q

TH17 are induced by what cytokines

What cytokines do they produce?

A

IL- 1, 6, 23

Make IL-17 and IL-22

79
Q

Cytokines that inhibit the production of TH17 cells

A

IL-2, IL-4, IFNg

80
Q

TH17 function

A

antibacterial and antifungal

role in chronic AI inflammation in skin, joints, CNS

81
Q

Major subset of Tregs are positive for…

A

FOXP3+

CD4+

CD25+

82
Q

Tregs express

A

CD25 and CTLA4

83
Q

Tregs produce

A

TGFb and IL-10

84
Q

Purpose of Treg cells

A

prevent AI diseases

85
Q

Disease from FOXP3 mutation

A

IPEX (XLAAD)

unchecked TH1 and TH2

86
Q

Cortisol/Catecholamines suppress…

A

CD8/TH1 cells