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Antigen Recognition By T Lymphocytes > Chaper 8 > Flashcards

Chaper 8 Flashcards

1
Q

Which anatomical sites do naive TC encounter antigen

A

At the start of the primary immune response

In a secondar lymphoid node

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2
Q

Why are dendritic cells more efficient than macrophages?

A

DC are migratory and transport antigen to neighboring secondary lymphoid tissue

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3
Q

Which selectin has a role in circulation of TC b/w blood and lymphoid tissues

A

L-selectin binds to carbs in hEV

3 types :

GLYCSM-1
CD34

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4
Q

3 classes of effector TC

A

Cytotoxic TC
Th1
TH2

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5
Q

TC activation= TCA is what?

A

Referred to as the priming an is the first stage of a primary adaptive immune response

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6
Q

What are the events of T-lymphocyte Imm?

A

Priming of naive TC
Activation of TC
Response of activated T helper and T cytotoxic

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7
Q

Printing of naive TC is analogous to?

A

what of BC activation by FDC

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8
Q

What does dendritic cells link?

A

Innate and adaptive imm sys.

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9
Q

What is priming most often initiated by?

A

Dendritic cells

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10
Q

Where do dendritic cells reside?

A

In the epithelial cells

Langerhand cells - spec in the skin

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11
Q

Where for priming occur at?

A

Lymph node the nearest one

2nd tissue

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12
Q

How does the dendritic cell work?

A

Engulfs -bac,virus,proteins etc

Does antigen capture

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13
Q

What is antigen capture?

A

AC is what dendritic cells do they

  1. phagocytosis
  2. recept mediated endocytosis
  3. macro-pintocytosis
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14
Q

What is the major function of DC?

A

Trigger TC response

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15
Q

What mcH does DC express?

A

Both!

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16
Q

What receptors do DC have?

A

Mannose

TLR

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17
Q

What does AC lead to?

A

Maturation into APC

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18
Q

Activation of DC means what additional?

A

Pro inflam cytokines

  • TNF
  • IL-1
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19
Q

DC activation causes….

A

No longer able I further engulf more antigens

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20
Q

Activation of DC does…

A

Increase mHc II

Migration of lymph node expresses ccr7
Cytokines receptor

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21
Q

Activation of DC summary

A

Pro inflamm cytokines
-TNF, IL-1

No longer engulf role has changed to priming

Increase MHC II

Migration of LN

  • expression of CCR7
  • cytokines receptor for CCL21 made in 2LN
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22
Q

How does the naive TC enter LN?

A

Via afferent lymph vessel

From bv pass through HEV

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23
Q

What chemokine attracts naive TC into LN?

A

CCL18- secreted by DC

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24
Q

Function of CCL18

A

Gets naive to the right place

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25
Q

What does CCL19&21 function?

A

Cause the DC leave the draining lymph and enter draining lymph

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26
Q

What chemokine a are secreted by stromal cells and DC?

A

CCL21&19

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27
Q

What is the receptor that binds to CCL21&19?

A

CCR7

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28
Q

CCL21& 19 are bound to what?

A

HEV where they establish a concentration grad along the endothelial surface

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29
Q

What are the Homing cytokines in the LN ?

A

CCL21&19

In the LN cortex

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30
Q

Homing of TC to LN adhesion molecules are what?

A

TC =L-selectin

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31
Q

HEV adhesion molecules

A

CD34 & GlyCAM-1

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32
Q

Adhesion molecules cause what to happen to the TC?

A

Causes the naive TC to slow down & attach to the HEV

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33
Q

What is apart of the afferent lymphatics?

A

Mature DC can’t home through blood

Up regulated CCR7 in response to inflammation

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34
Q

Who does LFA-1 strength hold to?

A

ICAM

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35
Q

What are the steps of homing TC to LN?

A
  1. The binding of L-selectin to slow naive TC down
  2. The binding of CCR7: CCR19 or 21
  3. Tight adhesion between LFA-1 and ICAM-1
  4. Diapedesis- lymphocytes leaves blood and enters LN
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36
Q

What is on the DC?

A

lFA-1 & ICAM-1

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37
Q

What happens if the TC encounters matching antigen?

A

Intracellular signaling
Weak binding - strong binding lFA-1 binds tightly to ICAm-1
Then the TC remains in LN attached to DC to becomes primed”

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38
Q

What type of change does the TCR send to LFA-1?

A

Conformational change to increase the affinity and prolongs the cell-cell contact

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39
Q

What happens then of TC does not meet antigen

A

TC dissociates from DC - no strong binding

It leaves via efferent vessel to keep searching

Because naive TC can. Survive for years

Will still undergo occasional replication

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40
Q

What are the two signals that are needed for priming events?

A

TCR-peptide/ CD-MHC

Co stimu by B7 (only on DC )

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41
Q

What does B7 express and bind to?

A

Expressed by only APC
Initiation by infection

B7 binds to CD28 on naive TC

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42
Q

What do the two activations signals for priming to occur do?

A

TC prolifer and activation

Need both to happen at the same time on same cell

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43
Q

Recap of receptors

What’s on CD4 helper T ?

A 
CD4
TCR
CD3
Zeta
CD28
LFA-1
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44
Q

What is CD 4?

A

Signal transduction

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45
Q

What Is TCR ?

A

Antigen recognition

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46
Q

What are the signal transduction molecules?

A

CD3
Zeta
CD28

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47
Q

What is the adhesion molecule on CD4?

A

LFA-1

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48
Q

What’s is expressed on MHC II?

A

B7

ICAM-1

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49
Q

What binds to what?

CD4 helper T lymphocytes binds to ligand in mHc expressing APC

A

TCR-MHC II
CD28-B7
LFA-1 to iCAM-1

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50
Q

Name the 3 types of APC

A

DC
Macrophages
BC

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51
Q

Where are macrophages located?

A

Cortex and medulla
They hang out where they are
They prevent systemic infection
Can present to TC in the peripheral tissue only in the LN

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52
Q

What types of cells do macrophages present peptides to ?

A

Already primed TC

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53
Q

What do macrophages present in the presence of infecTion?

A

They induce B7 a co stimulation needed for TC proliferation

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54
Q

If the macrophage is outside the 2nd lymph will it activate TC?

A

No! Only in LN it will

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55
Q

Where is DC found?

A

Only in cortical TC area

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56
Q

macro an DC come from what?

A

The same lineage

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57
Q

BC is what type of effectiveness of an APC?

A

The least !
Does not express co-stim
Needs to be activated by TC
Present via mHc II

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58
Q

Order of APC

A

DC>Macro>BC

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59
Q

What initiates TC synapse ?

A

Clustering

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60
Q

Where is the signal transmitted for the TC synapse?

A

Interior

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61
Q

What is associated with TC -S?

A

ITAMs - ass with CD3

ZAP-70 : ass with protein kinase

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62
Q

What is the sequence of the signaling in TC?

A 
Bindin of mhC-TCr
Phosphor of ITAMs
Co Recp binds 
Binding of zap 70 to zeta CD3
Zap70 phosphor by LCK
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63
Q

Wht is LCK ?

A

A signal transduction molecule

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64
Q

If a def in zap70?

A

Normal TC #
Unresponsive TC
SCID

We lose transcription factor

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65
Q

Def in zap70

A

Unable to develop intracellular signals in engagement of their antigen receptor

66
Q

What are the ultimate TF of downstream signaling pathways?

A

NF-kb
NFAT
AP-1

67
Q

Downstream signaling pathway means what ?

A

TF
TC proliferation
IL-2 production

68
Q

What is IL-2 ?

A

Secreted by activated TV

69
Q

What does IL-2 bind to?

A

IL-2 receptor in TC autocrine

That drives clonal expanison

70
Q

Why does IL-2 drive ?

A

Clonal expanison

71
Q

What does IL 2 require ?

A

Signals via TCR complex - activation of NFAT

Co-stim signals
- TF to increase transcription of IL2 gene

72
Q

IL 2 receptor have?

A

B and gamma

73
Q

What does IL 2 receptor synthesis ?

A

Alpha chain

High affinity of Il-2 receptor

74
Q

Hat does the IL2 receptor stimulate?

A

TC to enter cell cycle =proliferation

75
Q

What is the important result of priming?

A

Expression of IL-2 receptor on surface

Secretion if IL-2
=activation

76
Q

What happens when IL-2 binds to the IL-2 receptor?

A

TC stimulates itself
TC rep expansion of primed TC
Now ready to respond to re MHC peptide

77
Q

What happens is there is no co stim for TC proliferation?

A

The cell because anergy= floats around can’t respond

Can’t make IL-2

78
Q

After the TC is primed why doesn’t the TC respond immediately?

A

B/c don’t want the DC to be destroyed by the t-cytoxic cell

79
Q

Why after priming is CTLA-4 expressed?

A

It dampens down activation and limits cell proliferation= down regulation

80
Q

What is CTLA4 structurally similar to?

A

CD28

81
Q

What does CTLA 4 bind to?

A

Any remaining B7

82
Q

Again what is the purpose of CTLA after priming?

A

Inhibits co-stimulation

Not letting the TC get too strong

83
Q

What does CTLA4 stand for?

A

Cytotoxic T lymphocyte antigen 4

84
Q

What is CTLA 4 an alternative ligand for?

A

B7 because CTLA has a higher affinity

85
Q

Why is priming important?

A

Because if unprimed TC encounters MHC peptide wo co-stimulation

86
Q

Why is priming necessary?

A

No priming can occur if TC binds to self peptide wo B7

If primed wo B7 =anergic

Autoimmunity may be inhibited

87
Q

What does l-selec bind to ?

A

GlyCAM-1

Slows down rolling

88
Q

What does CCL21 bind to?

A

CCR7

Chemo attractant drawing into the homing

89
Q

LFA-1 on the TC binds to what?

A

ICAM-1 on APC

Tight adhesion stops the rolling

90
Q

CD28 is on what binds to what on what…?

A

Cd28 on TC

Binds to B7 on APC

91
Q

If a cell has the b7 and CD28 but is present on other self cell what which this cell have?

A

No effect

92
Q

If a cell complex has cd28 but no b7 what effect will this have?

A

No co stim =anergy

93
Q

What are CD4 Called?

A

Helper TC

Reg TC

94
Q

What types of helper TC are there ?

A

1= cell mediated
2= humoral
And Th17

95
Q

What is TH1 function ?

A

Type II INTERFERON
TNF
Cytotoxic TC, macrophages

96
Q

Why are Th2 cells?

A

IL4
IL6
BC activation

97
Q

What does IL4 do?

A

A type of Th2

And function to isotype switching to IgE

98
Q

What creates Treg cell?

A

TGF-B

99
Q

What secreted TH1?

A

IL-12

IFN-gamma

100
Q

What cytokines induced TH2?

A

IL-4

101
Q

What is does a Treg cell express?

A

Foxp3
TGF-B
IL-10

102
Q

What does TH1 have?

A

TBET
IL-2
INF-gamma

103
Q

What does TH2 cell have?

A

GATA- 3
IL4
IL5

104
Q

What does the most adaptive imm respon contrib?

A

From both TH 1&2

105
Q

Leprosy if bias to TH1 ….?

A

Macro suppresses bacterial growth
Slow disease progression
Pt survival

106
Q

Leprosy bias towards TH2?

A

Inaccessible to antibody
Widespread
Fatal

107
Q

Th1 has what type of clinical sig?

A

Type 1 diabetes
Specific for peptides in pancreas
Overstim macro

108
Q

Other helper TC ?

A

Th17

109
Q

What does Th17 secret ?

A

Il-17

110
Q

What is Th17 important with?

A

Inflammation

  • recruit of neutrophils
  • secretion of defensins
  • implicated for autoimmune disorders
111
Q

Where is Th17 found at?

A

Interfaces of external environment and internal enir

112
Q

Where else is Th17 found at?

A

Bacterial and fungal infections

113
Q

What is the naive cd8 cell activated by?

A

On DC

114
Q

Which has the stronger co stim activity ?

A

CD8

115
Q

How is naive cd8 activated?

A

3 ways

Virus infec DC
Two ways that APC offer co stim

  • Help from cd4 cytokines induce B7
  • cd4 cytokines ex IL-2 act directly in CD8
116
Q

Summary of activation of CD

A

Virus DC express B7

CD4 activates APC expressing B7

CD4 secretes IL-2 then binds to CD8

117
Q

What effector cells leave the 2 lymphoid?

A

CD8
CD4
TH1

118
Q

What effector cells remain in secondary lymphoid?

A

CD4

TH2- bcuz import for BC and BC are found in 2 lymph

119
Q

Why is relaxation good for maturation into effector cells?

A

Host cells son have B7 want relaxed the cd8 cell can respond to antigen wo co stim

120
Q

Alternation of cell surface marker is what?

A

LFA-1

121
Q

LFA -1 does what?

A

Mediates cell migration and interaction with Apc

122
Q

What is Cd2

A

Cell adhesion molecule
Binds to Cd2R
Mature TC

No BC

123
Q

CD2 receptor is what?

A

LFA-3

124
Q

What does CD2 bind to?

What is the function of CD2?

A

To LFA 3 on APC
Enables TC to response to lower concentrations of antigens
Mediated adhesion between TC and APC
Induces TC cytokines produc

125
Q

What is VLA -4?

A

An integrin that allows effector TC to move into inflamed tissue

126
Q

Effector TC excludes what?

A

LN = no L-selectin

127
Q

What does the alt of cel surface marker do ?

A

Decrease L-selec

128
Q

Effector TC function is Carried out by what?

A

Cytokines

Cytotoxins

129
Q

What do cytokines do ?

A

Alter behavior of targets cells

Autocrine paracrine agents

130
Q

Why do cytotoxins do?

A

Used to kill infected cells

CTL

131
Q

CTL

A

Belong to CD8
A:b TCR
Recog MHC I

Most dies or become memory

132
Q

What MHC does cTL belong to ?

A

MHC I

133
Q

CTL effector response?

A

Sacrifice host cell to prevent infection

134
Q

CTL effector Resp

A

Path inaccessible to antibodies an soluble proteins

135
Q

What does CTL contain ?

A

Lyric granules

136
Q

Types of CTL lytic granules?

A

Mod lysosomes

Contain cytotoxins!!!

137
Q

What are cd8?

A

Selective killers of target cells

138
Q

What is the process of killing for CD8?

A

Need TCR

  • MTOC center
  • GA=Golgi

Release cytotoxins
CTL makes new granules

139
Q

Cytotoxic TC kill TC by what?

A

Apop

140
Q

How does apop occur from cytotoxic TC

A

Release cytoxins

Fas ligand

141
Q

More in cytotoxins they contain what?

A

Granzymes

Perforins

142
Q

Wht are granzymes?

A

Act apop

Create ROS

143
Q

Perforin does what?

A

Creates pores for delievery

144
Q

What does fas -L expressed by

A

CTL express death activator

145
Q

What does Fas do?

A

Activates caspases

Apop

146
Q

Other func of CtL

A

InF- gamma activates macrophages

147
Q

Lymphotoxins are what ?

A

Induces adhesion on endothelial cell allowing phagocytic cell to bind

148
Q

If pathogens live in macrophages then it is not presented by what mHC?

A

No MHC I

Therefore infect is fought by TH1 and CD4

149
Q

What is macrophage activation?

A

Alternation that enables the activated macro to perform function that can be performed by resting macro

150
Q

What are the two signals for macrophage activation?

A

Interferon gamma

Binding of CD40

151
Q

What is interferon gamma express?

A

CD40

152
Q

What is IFN- gamma produced by?

A

CD8 and TH1

153
Q

What does CD8 not produced ?

A

CD40

154
Q

What else has IFN-gamma?

A

NK cells

155
Q

TH2 activated BC cytokines?

A

IL4
5
6

156
Q

Where is the follicular B helper TC func ?

A

Germinal center

157
Q

What does CD40 & CD40L help?

A

Interaction between TC & BC

158
Q

What is diff between TFH and TH2?

A

TFH distinct homing in 2nd Lymph

159
Q

NK cells

A 
TC 
A:b TCR
Glycolipid antigens
Secrete cytokines
IFN-gamma
IL-4
160
Q

NK is a link bw what?

A

Adaptive and innate imm

Antigen Recognition By T Lymphocytes (4 decks)

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