T-Cell Mediated Immunity -- Regulation and Termination Flashcards

1
Q

How do antigens get to the lymphatics?

A

Dendritic cells take up bacterial antigens in the skin and move to lymphatic vessels.
DCs with antigen enter the noce and settle in T-cell areas.

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2
Q

Following exposure to antigen, dendritic cells will transition from…

A

phagocytic to antigen presenting.

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3
Q

How are endocytosed bacteria typically presented?

A

MHC Class II

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4
Q

How can viral antigens spread from one dendritic cell to another?

A

Vesicle Fusion

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5
Q

How do antigens that cross present viruses after phagocytic uptake get presented?

A

MHC Class I

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6
Q

How do antigens get to Ts from skin infection?

A

Dendritics pick up, undergo maturation, and migrate to periph. LN

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7
Q

How do antigens get to Ts from the blood?

A

They get trapped by DCs in the spleen

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8
Q

How do antigens get from the mucosal tissues to the Ts?

A

Collected in tonsils, peyer’s patch, appendix, mesenteric LN

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9
Q

How do native T cells get into LNs

A

High Endothelial Venules or Upstream LNs

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10
Q

What lets Naive Ts hold onto HEVs?

A

L-selectin

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11
Q

What happens to naive T cells who enter a node and don’t match anything on?

A

They hit the efferent lymphatic vessel and move on

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12
Q

Four steps in T cell homing process?

A

Rolling
Chemokine
Firm Adhesion
Diapedesis/Extravasation

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13
Q

What bonding occurs in the rolling stage?

A

L-Selectin (tcell) binds onto host Gly-CAM-1 and CD-34

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14
Q

What boding occurs in the chemokine phase?

A

CCR7 + SLC/ELC

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15
Q

What bonding is important in the firm adhesion stage?

A

LFA-1 binds onto integrins (es. ICAM-1)

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16
Q

CD4 T cell LFA-1 binds…

A

ICAM1/2

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17
Q

CD4 T cell CD2 binds…

A

LFA-3

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18
Q

CD4 T cell CD4 binds…

A

MHCII

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19
Q

CD4 T cell TCR/CD3 binds…

A

MHCII/Peptide

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20
Q

CD4 T cell CD28 is required for…

A

B7-1/B7-2

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21
Q

TCR/CD3:MHCI binding activates….

A

T Cell through PIP/DAG/IP3

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22
Q

Value of integrins?

A

TCR/MHC requires its stability

Both directly and indirectly enhances T Cell Reaction

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23
Q

Which integrins are on the T cell?

A

ICAM-3, CD2

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24
Q

Relationship of TCR/MHC and LFA-1 bond?

A
  1. Weak bond btw T’s LFA and DC ICAM-1
  2. Stabilizes TCR MHC bond
  3. Bonding signals LFA-1 conformational change that increases affinity and prolongs contact.
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25
Q

Most important co-receptor bond?

A

T cell CD 28 must bind to DC B7

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26
Q

B7 can bind to what two molecules (with what purpose)

A

CD28 (Initiation)

CTLA4 (Termination)

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27
Q

Who expresses CTLA4?

A

Activated Ts

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28
Q

Three cytokines important for DC maturation.

A

TNF-alpha
IL6
IFN-gamma

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29
Q

What happens when TCR activation happens without CD28?

A

Anergy

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30
Q

Can cells return from anergy?

A

No

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31
Q

Who expresses B7?

A

Only Pro Antigen Presenting cells

DCs, B Cells, Macrophages

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32
Q

Which cells are most important for turning Ts on?

A

DCs

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33
Q

How are antigens picked up by the three types of APCs?

A

DCs - Macropino+Phago
Macro - Phago
B Cells - Ig Receptor

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34
Q

Other than LNs, where can the APCs be found?

A

DC - Connective Tissue + Epithelium
Macro - Connective Tissue+ Body Cavities
B Cells – Peripheral Blood

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35
Q

DCs are good at presenting…

A

Bacterial and Viral Antigens

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36
Q

Macrophages are good at presenting….

A

Extracellular Bacteria

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37
Q

B cells are good at presenting…

A

Soluble Antigen

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38
Q

What induces dendritic cell maturation?

A

Bacterial products such as LPS, Cell Wall, and Cytos like TNF-alpha

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39
Q

Can mature DCs act as phagocytes?

A

No.

40
Q

TCR associated steps in T cell activation.

A
Binding of MHC to TCR
Stabilize by CD4 binding to MHC
LCK Ps ITAM
ZAP70 binds P'd ITAMS
ZAP 70 P'd by Lck
41
Q

Describe the intracellular events of T cell activation.

A

ZAP70 activated phospholipase gamma (PLC-gamma)
PLC cleave PIP2 to DAG and IP3
DAG and IP3 promote NFkB, NFAT, and AP-1 expression
Cell division and differentiation

42
Q

What does DAG do in T cell activation?

A

Activates PK-C -> Activated NfkB

Activates RasGRP -> Turns on MAP kinase cascade that activates Fos, and in turn AP-1

43
Q

What does IP3 do in T cell activation?

A

Increases intracellular Ca
High Ca activates Calcineurin
Calcineurin turns on NFAT

44
Q

T cell activation promotes production of what cytokine?

A

IL-2

45
Q

How do cyclosporin A and FK506 suppress immune response?

A

Blocking NFAT activation, an thus Il-2 production.

46
Q

What does Il-2 do?

A

Inc. T cell prolif.
B cell prolif
NK prolif

47
Q

How do integrins change in activated Ts?

A

VLA4 shows up to bind VCAM 1 (CD49d-C29)

48
Q

Naive or activated: Who displays L selectin?

A

Naive

49
Q

Naive or activated: Who displays VLA-4?

A

Activated

50
Q

Naive or activated: Who displays CD45RA?

A

Naive

51
Q

Naive or activated: Who displays CD45RO?

A

Activated

52
Q

Cytokines produced by TH1?

A

IFN-g, IL-2

53
Q

What do TH1 cells promote?

A

Cell Mediated Immunity

54
Q

Cytokines produced by TH2?

A

IL-4, 5,

also IL-2, 3, 9, 13

55
Q

What do TH2 cells promote?

A

Humoral Immunity

56
Q

What do TH17 cells promote?

A

Inflammation in multiple tissues

57
Q

What cytokines do TH17 cells produce?

A

IL-17, 22

58
Q

Who promotes TH1 polarization?

Inhibits it?

A

IL-12, IFN-g

IL-4, 10

59
Q

Who polarizes TH2 cells? Inhibits?

A

IL4

IFN-g

60
Q

Who polarizes TH17?

Inhibits?

A

IL-1, 6, 23

IL-4, IFN-g

61
Q

What cell type promotes IgE?

A

TH2

62
Q

Prevalent marker for Treg, Th1, and Th2

A

Treg – FoxP3
Th1 – T-bet
Th2 – GATA-3

63
Q

Tregs suppress _____ via _____

A

TH1/TH2

TGF-b and IL-10

64
Q

Who makes the Il4 to induce TH2?

A

Mast Cells

65
Q

Who makes the IL-1 to induce TH1

A

APC

66
Q

Cytotoxins used by CD8

A

Perforin
Granzymes
Granulysin

67
Q

What are T-follicular helper cells

A

T’s specialized in Helping B Cells

Stay in LN producing IL-21

68
Q

What do Th17 cells do?

A

Enhance neutrophil response to fungal and extracellular bacteria

69
Q

What do IFN-g and CD40s do?

A

Activate mac

70
Q

What do TNF-a and LT from TH1 do?

A

Activate endothelium to induce mac adhesion and exit from vessel

71
Q

Two cell types that release CXCL2 to cause macro. acc.

A

TH1 and Th17

72
Q

Five functions of the cell mediated immune response?

A
  1. control intracellular pathogens/tumor
  2. Mediate transplant rejection
  3. Mediate type 4 sens.
  4. Granuloma Formation
  5. Chronic Inflammation
73
Q

Four macrophages surface markers

A

C3b receptor
LFA-1
Fc Receptor
MHC II

74
Q

TH1 Cell: Who activates?
What do they make?
What do they do?

A

DC Il-12
Produce IFN-g
Activate CD8, NK, and Macro

75
Q

How do CD8 T cells kill bad guys? (4)

A

TNF-b
perforin
Granzymes
FAS

76
Q

What turns NKs on?

A

IL-2, 12, IFN-g

77
Q

Macrophages produce what cytokines?

A

IL-2, 10, 1, 6, TNFa, IFNa

78
Q

What turns CD8 Ts on?

A

IL-2, 12, IFN-g

79
Q

When do CD8 T cells need CD28? When don’t they?

A

Need CD28 to become effector cells

Don’t need CD28 to kill target cells, just MHC1

80
Q

TCR activation causes what structural change in CD8?

A

Polarization to target lytic granules

81
Q

Explain two ways in which CD8 activation may occur? What is the key cytokine in this interaction?

A

Strong enough bonding to DC can activate
Bonding of CD4 and 8
IL-2 drives T differentiation and proliferation

82
Q

What do inflamed endothelial cells express to recruit effectors?

A

P- and E- selectins

83
Q

What assay is used to assess cell killing activity of CD8 T cells

A

51Cr Release Assay

84
Q

Cell type that turns up Macrophage microbicidal-ness

A

TH1

85
Q

What is a granuloma?

A

Aggregated infected epithelioid macrophages frequently seen in infection and inflammation

86
Q

Purpose of granuloma formation?

A

Defense mechanism to limit spread of pathogens/foreign substances

87
Q

Common granuloma former?

A

Tuberculosis

88
Q

Four activities promoted by IFN-g

A

Macrophage Activation
Isotype switching to complement-fixers
Th1 Development
Increased MHC Antigen Presentation

89
Q

Role’s of TH2’s –
IL4?
IL5?
IL-4/10?

A

IL4-Induce IgE + neutralizing G
IL-5 - Induce Eosinphil
4/10 - Suppress Macro

90
Q

Two types of leprosy?

A

Tuberculoid and Lepromatous

91
Q

Difference between tuberculoid and lepromatous leprosy?

A

Tub turns on TH1s
Lep turns on TH2

Since 2s don’t turn on macrophages, fatality

92
Q

Other name for Tregs?

A

FoxP3+

93
Q

Tregs express what four things?

A

FoxP3, CD4, CD25, CTLA4

94
Q

What happens if you don’t have Tregs?

A

Autoimmune Diseases in Multiple Organs

95
Q

TH17 -
What induces? Inhibits?
What do they Produce?
Why?

A

Induce – 1, 6, 23
Inhibit – 2, 4, IFN-g
Produce – IL17, 22
Impt. for fighting bac and esp. fungal infections

96
Q

How does stress modulate the immune system?

A

Acts as an immunosuppressant via testosterone/estradiol/progesterone and cortisol