Lecture 14 T Cell Immunity

Front 1

T H 17 are activated in and by

Back 1

secondary lymphoid tissues by DCs

IL-6 and IL-23

Front 2

T H 17 are activated in response to and when

Back 2

extracellular bacteria and fungi

early

Front 3

T H 17 secrete ___, ____ , ____, which ______.

Back 3

IL-17, TNF-alpha, CSCL1

recruit neutrophils to infected sites

Front 4

IL-17 stimulates (3)

Back 4

fibroblasts, epithelial cells, keratinocytes

Front 5

Fibroblasts, epithelial cells, keratinocytes secrete

Back 5

IL-6, CXCL8, CXCL2, G-CSF, GM-CSF which allow for neutrophil and macrophage development and recruitment

Front 6

IL-22 is secreted by and do?

Back 6

T H 17

keratinocytes induced to produce Beta-defensins

Front 7

T FH are found in and do

Back 7

follicles of lymph nodes; help B cells and secrete cytokines that other T cell subsets may also produce

Front 8

IFN-gamma and IL-4

Back 8

both produced by T FH; IFN-gamma --> opsonizing IgG isotype production; IL-4 --> IgE production

Front 9

T regs do?

Back 9

suppress T cell responses

Front 10

T regs are committed in

Back 10

thymus

Front 11

T regs differentiate from naive T cells in

Back 11

periphery

Front 12

T regs express ____ (3) which _____

Back 12

FoxP3; interferes with AP-1 and NFAT-1 binding to IL-2 promoter

CD25 (can sequester IL-2)

CTLA-4 (inhibits B7 binding)

Front 13

T regs produce (2)

Back 13

TGF-beta and IL-10; suppress inflammation and maintain tolerance

Front 14

IL-10

Back 14

inhibits DC IL-12 secretion, reduces co-stimulatory molecule expression, suppresses T cell IL-2, TNF-alpha, IL-5 production

Front 15

T H 2 secretes __ which suppresses ____and T H 1 secretes ___ which suppresses

Back 15

IL-10, IFN-gamma (suppress each other)

Front 16

Skin-homing lymphocytes bind

Back 16

CCL17 and E-selectin and epithelium

Front 17

Keratinocytes express _____ which bind _____ on effector T cell

Back 17

CCL27; CCR10

Front 18

Memory T cells require (2) for survival

Back 18

IL-7 and IL-15

Front 19

IL-IBeta

Back 19

produced by activated DCs and Macrophages

activates endothelium and induces fever

Front 20

IL-6

Back 20

produced by activated DCs/Macrophages

activates lymphocytes and induces acute phase response

Front 21

IL-12

Back 21

produced by activated DCs/Macrophages

activates NKs and TH1

Front 22

TNF-alpha

Back 22

produced by activated DCs and macrophages

activates endothelium, induces fever, activates macrophages to produce NO

Front 23

CXCL8/IL-8

Back 23

produced by activated DCs and macrophages

recruits neutrophils and naive T cells

Front 24

IL-2

Back 24

produced by naive T cells, TH1 and CD8

T and NK growth factor

Front 25

IFN alpha/beta

Back 25

produced by pDCs

activates NKs and induces antiviral state

Front 26

IFN-gamma

Back 26

produced by TH1, CD8 and NKs

increases MHC expression and activates macrophages

Front 27

IL-4

Back 27

produced by TH2

inhibits macrophage activation and favors IgE production

Front 28

IL-10

Back 28

produced by TH2 and Tregs

inhibits TH1 and macrophage function

Front 29

TGF-beta

Back 29

produced by T regs

inhibits B and T cells and macrophage function

Front 30

IL-17

Back 30

produced by TH17 and macrophages

stimulates neutrophil recruitment and epithelial/fibroblast/keratinocyte cytokine secretion

Front 31

hematopoietin family associate with _____ family of tyrosine kinases

Back 31

Jak family

Front 32

Jaks phosphorylate after

Back 32

dimerization

Front 33

STATs are

Back 33

signal transducers and activators of transcription that have SH2 domains that translocate to nucleus and cause gene expression

Front 34

Cytokine signaling is regulated by

Back 34

dephosphorylation by SHP, CD45, T cell phosphatase

Front 35

SOCS proteins

Back 35

suppressors of cytokine signaling

bind Jaks and compete for receptor or direct Jaks degradation

Front 36

PIAS protein

Back 36

protein inhibitors of activated STATS

promote degradation of signaling components

Front 37

Apoptosis is induced by (3)

Back 37

1. cytotoxic T lymphocites release cytotoxic granules
2. TNF family (Fas Fas ligand, TNF-alpha, lymphotoxins) (extrinsic)
3. noxious stimuli or withdrawal of survival factors (intrinsic)

Front 38

Extrinsic and intrinsic both use

Back 38

caspases

aspartic acid-specific cysteine proteases
exist as inactve pro-caspases
activate each other in caspase cascade

Front 39

initiator caspases

Back 39

cleave and activate downstream caspases

extrinsic: 8 and 10
intrinsic: 9

Front 40

effector caspases

Back 40

initiate cellular changes by cleaving proteins used for cellular integrity and by activating endonucleases that degrade chromosomal DNA

extrinsic: 3,6,7
intrinsic: 3,6,7

Front 41

extrinsic pathway

Back 41

death receptor activation; effector T cells express TNF (TNF alpha, lymphotoxins, Fas ligand, CD40 ligand)

Front 42

Intrinsic pathway

Back 42

mitochondrial pathway; noxious stimuli, lack of survival factors, starvation

Front 43

Extrinsic pathway Fas

Back 43

TNF have death domain which trimerize

DD bound by DD of FADD

Death effector domain (DED) of FADD bound by DED of pro-caspases which cut themselves

Front 44

Extrinsic pathway TNFR-I

Back 44

TRADD DED bound to pro-caspase DED

or

TRADD DED binds TRAF-2, which ubiquinates RIP, attracts TAK1 and results in NFkB activation and gene expression

Front 45

intrinsic pathway activated by

Back 45

cellular stress (UV irradiation, withdrawal of survival signals, damage, hypoxia)

Front 46

intrinsic pathway initiated by

Back 46

mitochondrial cytochrome c which binds Apaf-1 which makes apoptosome

apoptosome activates pro-caspase 9

Front 47

Intrinsic pathway Bcl-2 family has pro and anti apoptotic proeins

pro are (3)

anti are (3)

Back 47

pro: Bax Bak Bok ( induce cytochrome release by binding to mito membrane)
anti: Bcl-2, Bcl-XL, Bcl-W (bind mito membrane and inhibit cytochrome c release)

Front 48

apoptotic stimuli activate ___

Back 48

sentinels