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Lecture 10/11 Flashcards

1
Q

What receptors do ancestral T cells have?

A
  • Gamma delta

- Modern have alpha beta

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2
Q

What type of antigens did ancestral T cells recognize?

A

Lipid rich

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3
Q

Where are primitive T cells important?

A
  • Host environment interface

- Gut, lungs, skin, etc

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4
Q

What cytokines do ancestral T cells secrete?

A

Inflammatory cytokines
IL6
IL7
IL 17

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5
Q

What is the CD3/4 T cell?

A

Helper T cell

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6
Q

What is Th?

A

Helper T cell

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7
Q

What is orchestrator of adaptive response?

A

T cell

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8
Q

What are T lymphocytes required for?

A

Cell mediated immunity

Antibody immunity by B cells

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9
Q

What regulates T cell repsonse?

A

Treg

Cytokines

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10
Q

What do antibodies recognize?

A

3d form of antigen?

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11
Q

What do T cells recognize?

A

Antigens in context of self MHC

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12
Q

What happens when APC presents antigen to naive T cell??

A 
One of the following will develop:
TH1
TH2
TH17 
Treg
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13
Q

What does subset commitment depend on?

A

Host genetics
Infection type
TLR profile
Cytokine profile

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14
Q

What does Th1 do?

A

Enhances and amplifies cellular mediated immunity by activating macs or CD8s

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15
Q

What does TH2 do?

A

Promotes antibody production

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16
Q

What does Treg do?

A

Modulates or supresses immune response

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17
Q

What does TH17 do?

A

Promotes chronic inflamatoin

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18
Q

What does T follicular do?

A

Promotes optimal antibody formation in germinal centers

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19
Q

Another name for TH1?

A

TMMI - Tcell mediated Macrophage immunity

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20
Q

What is TMMI?

A

TH1 direction

Tcell mediated Macrophage immunity

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21
Q

What cytokine initiates TMMI?

A

IL 12

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22
Q

What does IL12 do?

A

Initiate TMMI

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23
Q

What type of infection causes TMMI?

A

Uptake of complex antigen by DC

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24
Q

TMMI MHC?

A

MHCII

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25
Q

What triggers DC maturation?

A

Uptake of pathogen or its complex antigens

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26
Q

What does mature CD do?

A
  1. Moves to lymph
  2. Down regulates phagocytosis
  3. Upregulates MHCII presentation
  4. IL 12/18 upregulatinoin
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27
Q

What does IL 18 do?

A

Leads to TMMI

Amplifies IL12 properties

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28
Q

Critical cytokine for Th1?

A

IL12

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29
Q

How do we identify Th1 resposne?

A

TF: T-BET

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30
Q

What does Tbet signify?

A

Th1

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31
Q

What does Th1 upregulate in presence of its antigen and ILs?

A

CD28 & 40L

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32
Q

What costimulatory signal necessary for T & Bcell mediated repsonse?

A

CD40/40L

CD28/B7

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33
Q

What does commited TH1 produce?

A

INFgamma

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34
Q

What does commited TH1 produce?

A

INFgamma

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35
Q

What can produce INFgamma?

A

TH1
NK
CD8

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36
Q

What is pivotal step for amplifying T cell mediated mac activation?

A

INFgamma

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37
Q

What does INFgamma do?

A
  • Pivotal step for amplifying T cell mediated mac activation
  • Signature cytokine of ongoing TH1
  • Attracts effector cells to area
  • Controls MHC display by APCs
  • Stimulates killer cells
  • Increases proinflamatory molecules
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38
Q

What do activated Th1s do?

A

Upregulate IL2 production and IL2 receptors

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39
Q

What does IL2 do?

A

Critical growth cytokine in Th1 supporting rapid proliferation stimulated T cells

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40
Q

Where do IL12/18 come from?

A

DC

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41
Q

Where does IL2 come from?

A

Activated TH1s

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42
Q

What does INFgamma down regulate?

A

Th2

Th17

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43
Q

What is IL21?

A
  • Potent activator of CD8

- Activated Th1 releases

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44
Q

What releases IL21?

A

Activated TH1

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45
Q

Where does TH1 activation usually occur?

A

Lymph node or spleen

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46
Q

What are the proinflammatory cytokines?

A

IL1
IL6
IL8
TNF alpha

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47
Q

What produces proinflamatory cytokines?

A

Activated macrophages

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48
Q

Which cytokines can elevate body temp?

A

IL1 in concert with IL6

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49
Q

What cytokines facilitates T cell responsiveness to IL2?

A

IL1

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50
Q

Agonist of IL1?

A

IL1-Ra

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51
Q

How doe IL 6 differ from IL1?

A

Growth and differentiation effect on B cells

Effects Bone Ca resorption

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52
Q

Which inflamatory IL is a chemokine?

A

IL8

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53
Q

What does IL 8 do?

A

Major stimulus for proliferation, mobilization and recruitment of neurophils

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54
Q

What IL is main inducer or neutrophils?

A

IL8

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55
Q

What IL is main inducer or neutrophils?

A

IL8

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56
Q

What produces IL8?

A

Macs
Neuts
Many others

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57
Q

What is delayed hypersensitivity?

A

TMMI

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58
Q

What is positive TB skin test example of?

A

TMMI

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59
Q

How does quantiferon gold work?

A
  • Lymphocutes from blood incubated with TB antigens

- If patient has had TB, INFgamma is released

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60
Q

Do NK cells have CD3?

A

No

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61
Q

How does INFgamma relate to NK?

A

Produces and highly effected by

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62
Q

Are NKs antigen specific?

A

No, no MHC

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63
Q

Most important role of NK?

A

Frontline defense while adaptive ramps up

64
Q

How can NK activity be repressed?

A
  • KIR - Killer cell inhibitory receptor
  • Found on surface
  • Respond to self MHC
65
Q

How does KIR work?

A

In absence of self MHC, KIR will be turned off only if target cell has NK activating receptor

66
Q

How can NK cells kill?

A

Direct cytotoxicity

Can mediate antidbody dependent killing via Fc receptor that recognize antibody bound antigen

67
Q

What can CD8s do?

A

Directly kill foreign, infected, or mutated cells

68
Q

What do CD8s defend against?

A

Virus & tumor

69
Q

What is different betweeen what NK and CD8 recognize?

A

CD8 recognizes antigen in MHC

NK recognizes altered MHC1

70
Q

Critical CD8 constimulatory signal?

A

Produced by NK cells in area:
INF gamma
IL2

71
Q

Most important influence of CD8 development?

A
  • Concurrent CD4 development

- Activated Th produce IL2 and INF gamma

72
Q

What does HIV virus do?

A

Destroy CD4 cells

73
Q

What does IL21 do?

A

Potent proliferative stimulus to CD8

74
Q

Do CD8 cells need costimulation once activated?

A
  • No

- Makes sense as most infected cell are somatic and do not have B7

75
Q

How do APCs recognize virus?

A
  • TLR, display in MHCII

- Also displays some in MHCI which will lead to its death

76
Q

Can most APCs be infected by virus?

A

No but they will display some antigen in MHC i to prime CD8 whiich will funfortunately lead to their death

77
Q

4 ways CD8 can be activated?

A
  1. INFgamma from NK
  2. 40/40L, CD28/B7 presentation by APC
  3. CD4 IL2/21 activation
  4. MHC I /II cross presentation by APC
78
Q

First step in CD8?

A

NK reacting to altered MHCI or CD8 recognition of MHCI with antigen

79
Q

Killing steps of CD8/NK?

A
  • Pore formation vira perforin making cell osmotically unstable
  • Injection of granzymes
  • Can also induce apoptosis
80
Q

How do NK/CD8 induce apoptosis?

A

Fas/FASL system or CASPASE

81
Q

What are Fas/FASL system or CASPASE?

A

How NK and CD8 induce apoptosis

82
Q

What turns off cytotoxicity?

A
  • Elimination of target

- In absence of target cell will kill itself via FAS/FASL

83
Q

What turns off cytotoxicity?

A
  • Elimination of target
  • In absence of target cell will kill itself via FAS/FASL
  • 10% will remain as memory cells
84
Q

What does IL4 cause?/

A

THO - CD4TH2

85
Q

What signifies TH2?

86
Q

What does GATA3 TG signify

87
Q

What produces IL4?

A
  • DCs

- Committed TH2

88
Q

What type of infection activates TH2?

A

Extracellular antigen

89
Q

What type of infection activates TH1?

A

Intracellular

90
Q

What can stimulate TH2 movement?

A

IL4 from DC
IL4 from TH2
B cell antigen presentation

91
Q

What does IL4 inhibit?

92
Q

What type of response does IL4 drive

A

B cell growth

93
Q

What is the major source of IL4

94
Q

What does TH2 produce other than IL4

A
  • IL21, 5, 6, 10

- Promote B cell growth and antigen switching

95
Q

What promotes B cell growth and antigen switching?

A
  • IL21, 5, 6, 10
96
Q

What does IL21, 5, 6, 10 do?

A

Promotes B cell growth and antigen switching

97
Q

When is IL21 most effective?

A

Presence of IL4

Absence of INF gamma

98
Q

When is IL21 most effective?

A

Presence of IL4

Absence of INF gamma

99
Q

What is required for IgE reponse?

A

IL4 & IL13 & allergy promoting genes

100
Q

Function of TH2 response?

A

Enhance B cell function and antibody production

101
Q

What activates TH17

A

IL 23
TGF beta
IL6

102
Q

What does IL23 activate?

103
Q

Th17 TF?

104
Q

What is ROR

105
Q

What is TGF beta?

A

IL for Treg

106
Q

What activates Treg?

107
Q

What activates TH17?

A

Extracellular bacteria fungi

108
Q

What does TH17 produce?

109
Q

What produces IL17?

110
Q

What does IL17 do?

A

Recruits neuts

111
Q

Is IL4, IL 23, or INFgamma dominant?

A

INFgamma and IL4 strongly suprress Th17

112
Q

What does mature CD do?

A
  1. Moves to lymph
  2. Down regulates phagocytosis
  3. Upregulates MHCII presentation
  4. IL 12/18 upregulatinoin
113
Q

Is IL4, IL 23, or INFgamma dominant?

A

INFgamma and IL4 strongly suprress Th17

114
Q

TF for Treg?

115
Q

What is FoxP3 do?

A

TF for treg

116
Q

Where can Tregs be created?

A
  1. Thymus with help of AIRE

2. Periphery with help of IL10 and TGFbeta

117
Q

What CDs are Treg?

118
Q

What are Tregs dependent on for survival and proliferation?

119
Q

What does TCR reaction with peptide in MHCI promote?

A

Activation of CD8

120
Q

What does TCR reaction with peptide in MHCI promote?

A

Activation of CD8

121
Q

What do TLRs do?

A

TLR instruct antigen presenting cells to set up cytokine profile appropriate to infection

122
Q

What does TFH do ?

A

T-FH - promotes optimal high affinity antibody production in germinal center of lymph node
“T follicular helper”

123
Q

What makes up CD4 family?

A

HO, TH1, TH2, TH17, Treg, and THFH

124
Q

What does TH1 encourage along with macs?

125
Q

What does trigger for TMMI always involve?

A

The trigger for a TMMI always involves a TLR on a dendritic cell (DC)

126
Q

What response need, and require TH2

A
  • TH1 & 2 both like IL2 as it helps them grow, however, survival is not dependent on it
  • Treg cells ABSOLUTELY need IL2 for survival
127
Q

What cytokine is used for host response to stress?

128
Q

Difference between IL1 & 6?

A

IL 6 shows strong growth and differentiation effects on B cells in presence of other by cytokines

129
Q

What is known as THE proinflammatory cytokine?

130
Q

What is angiogenesis?

A

Making more blood vessels to make inflammation even more potent by allowing delivery of more cells to site of inflammation
Can be caused by TNF alpha

131
Q

What is angiogenesis?

A

Making more blood vessels to make inflammation even more potent by allowing delivery of more cells to site of inflammation
Can be caused by TNF alpha

132
Q

What can cause angioneogenesis?

133
Q

What is most effective at recruiting neutrophils?

134
Q

What do you suspect if there are tons of neutrolphils?

135
Q

What do you suspect if there are tons of neutrolphils?

136
Q

What do activated macrophages do?

A

Activated macrophage will release tons of IL 1, 6, 8 and TNF alpha activating all the macrophages around it to kill the organism

137
Q

What is LCI?

A

Lymphocyte cytotoxic immunity

138
Q

What mediates LCI?

139
Q

What is on the surface of NK?

A

No CD3 of alpha beta or gamma delta chains, no antigen receptors

140
Q

Why does NK not kill RBC?

A

RBCs are not killed as they have neither inhibitory or activating ligand so NK cell does not know they exist

141
Q

How does NK cell activation work?

A
  • MHCI cellshave both inhibitory/activating ligand for NK
  • When NK cell binds both, it leaves cell alone
  • Altered, or absent MHC I cannot stimulated negative signal telling NK cell to not kill things
  • In such cases NK cell releases granules killing target cell
142
Q

Two manners of LCI?

A

Non specific - NK

Specific - CD8

143
Q

What leads to optimal CD8 activation?

A

Parallel activation of NK cells, Heler T , and presence of memory cells

144
Q

What activates Th1

145
Q

What activates Th1

146
Q

Signals needed for CD8 activation?

A

Antigen specific is first and INF is second signal

147
Q

What is CD8 powerless without?

148
Q

What promotes TH2?

A

Soluble antigens and extracellular pathogens promote TH2

149
Q

Major source of IL4?

A

Major source of IL4 is the TH2 cell itself

150
Q

What can suppress TH1 in TH2 reaction?

A

IL4, IL10, IL13

151
Q

How do B cells present antigen?

A

B cells present in MHCII, not in antibodies on surface

152
Q

What is IGG?

A

Bind viral antigen in serum marking it for destruction by macs and neutrophils who will phagocytose IGG/antigen complex for destruction

153
Q

What releases IGG?

A

Plasma cells

154
Q

Trio of cytokines in Th17 response?

A

IL6, IL23, TGFbeta

155
Q

Trio of cytokines in Th17 response?

A

IL6, IL23, TGFbeta

156
Q

What is unique to Treg?

Host Defense (12 decks)

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