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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
What triggers DC maturation?
Uptake of pathogen or its complex antigens
26
What does mature CD do?
1. Moves to lymph 2. Down regulates phagocytosis 3. Upregulates MHCII presentation 4. IL 12/18 upregulatinoin
27
What does IL 18 do?
Leads to TMMI | Amplifies IL12 properties
28
Critical cytokine for Th1?
IL12
29
How do we identify Th1 resposne?
TF: T-BET
30
What does Tbet signify?
Th1
31
What does Th1 upregulate in presence of its antigen and ILs?
CD28 & 40L
32
What costimulatory signal necessary for T & Bcell mediated repsonse?
CD40/40L | CD28/B7
33
What does commited TH1 produce?
INFgamma
34
What does commited TH1 produce?
INFgamma
35
What can produce INFgamma?
TH1 NK CD8
36
What is pivotal step for amplifying T cell mediated mac activation?
INFgamma
37
What does INFgamma do?
- 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
38
What do activated Th1s do?
Upregulate IL2 production and IL2 receptors
39
What does IL2 do?
Critical growth cytokine in Th1 supporting rapid proliferation stimulated T cells
40
Where do IL12/18 come from?
DC
41
Where does IL2 come from?
Activated TH1s
42
What does INFgamma down regulate?
Th2 | Th17
43
What is IL21?
- Potent activator of CD8 | - Activated Th1 releases
44
What releases IL21?
Activated TH1
45
Where does TH1 activation usually occur?
Lymph node or spleen
46
What are the proinflammatory cytokines?
IL1 IL6 IL8 TNF alpha
47
What produces proinflamatory cytokines?
Activated macrophages
48
Which cytokines can elevate body temp?
IL1 in concert with IL6
49
What cytokines facilitates T cell responsiveness to IL2?
IL1
50
Agonist of IL1?
IL1-Ra
51
How doe IL 6 differ from IL1?
Growth and differentiation effect on B cells | Effects Bone Ca resorption
52
Which inflamatory IL is a chemokine?
IL8
53
What does IL 8 do?
Major stimulus for proliferation, mobilization and recruitment of neurophils
54
What IL is main inducer or neutrophils?
IL8
55
What IL is main inducer or neutrophils?
IL8
56
What produces IL8?
Macs Neuts Many others
57
What is delayed hypersensitivity?
TMMI
58
What is positive TB skin test example of?
TMMI
59
How does quantiferon gold work?
- Lymphocutes from blood incubated with TB antigens | - If patient has had TB, INFgamma is released
60
Do NK cells have CD3?
No
61
How does INFgamma relate to NK?
Produces and highly effected by
62
Are NKs antigen specific?
No, no MHC
63
Most important role of NK?
Frontline defense while adaptive ramps up
64
How can NK activity be repressed?
- KIR - Killer cell inhibitory receptor - Found on surface - Respond to self MHC
65
How does KIR work?
In absence of self MHC, KIR will be turned off only if target cell has NK activating receptor
66
How can NK cells kill?
Direct cytotoxicity | Can mediate antidbody dependent killing via Fc receptor that recognize antibody bound antigen
67
What can CD8s do?
Directly kill foreign, infected, or mutated cells
68
What do CD8s defend against?
Virus & tumor
69
What is different betweeen what NK and CD8 recognize?
CD8 recognizes antigen in MHC | NK recognizes altered MHC1
70
Critical CD8 constimulatory signal?
Produced by NK cells in area: INF gamma IL2
71
Most important influence of CD8 development?
- Concurrent CD4 development | - Activated Th produce IL2 and INF gamma
72
What does HIV virus do?
Destroy CD4 cells
73
What does IL21 do?
Potent proliferative stimulus to CD8
74
Do CD8 cells need costimulation once activated?
- No | - Makes sense as most infected cell are somatic and do not have B7
75
How do APCs recognize virus?
- TLR, display in MHCII | - Also displays some in MHCI which will lead to its death
76
Can most APCs be infected by virus?
No but they will display some antigen in MHC i to prime CD8 whiich will funfortunately lead to their death
77
4 ways CD8 can be activated?
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
First step in CD8?
NK reacting to altered MHCI or CD8 recognition of MHCI with antigen
79
Killing steps of CD8/NK?
- Pore formation vira perforin making cell osmotically unstable - Injection of granzymes - Can also induce apoptosis
80
How do NK/CD8 induce apoptosis?
Fas/FASL system or CASPASE
81
What are Fas/FASL system or CASPASE?
How NK and CD8 induce apoptosis
82
What turns off cytotoxicity?
- Elimination of target | - In absence of target cell will kill itself via FAS/FASL
83
What turns off cytotoxicity?
- Elimination of target - In absence of target cell will kill itself via FAS/FASL - 10% will remain as memory cells
84
What does IL4 cause?/
THO - CD4TH2
85
What signifies TH2?
GATA-3 TF
86
What does GATA3 TG signify
TH2
87
What produces IL4?
- DCs | - Committed TH2
88
What type of infection activates TH2?
Extracellular antigen
89
What type of infection activates TH1?
Intracellular
90
What can stimulate TH2 movement?
IL4 from DC IL4 from TH2 B cell antigen presentation
91
What does IL4 inhibit?
Th1 | Th17
92
What type of response does IL4 drive
B cell growth
93
What is the major source of IL4
TH2 cell
94
What does TH2 produce other than IL4
- IL21, 5, 6, 10 | - Promote B cell growth and antigen switching
95
What promotes B cell growth and antigen switching?
- IL21, 5, 6, 10
96
What does IL21, 5, 6, 10 do?
Promotes B cell growth and antigen switching
97
When is IL21 most effective?
Presence of IL4 | Absence of INF gamma
98
When is IL21 most effective?
Presence of IL4 | Absence of INF gamma
99
What is required for IgE reponse?
IL4 & IL13 & allergy promoting genes
100
Function of TH2 response?
Enhance B cell function and antibody production
101
What activates TH17
IL 23 TGF beta IL6
102
What does IL23 activate?
TH17
103
Th17 TF?
ROR
104
What is ROR
Th17 TF
105
What is TGF beta?
IL for Treg
106
What activates Treg?
TGFbeta
107
What activates TH17?
Extracellular bacteria fungi
108
What does TH17 produce?
IL17
109
What produces IL17?
Th17
110
What does IL17 do?
Recruits neuts
111
Is IL4, IL 23, or INFgamma dominant?
INFgamma and IL4 strongly suprress Th17
112
What does mature CD do?
1. Moves to lymph 2. Down regulates phagocytosis 3. Upregulates MHCII presentation 4. IL 12/18 upregulatinoin
113
Is IL4, IL 23, or INFgamma dominant?
INFgamma and IL4 strongly suprress Th17
114
TF for Treg?
FoxP3
115
What is FoxP3 do?
TF for treg
116
Where can Tregs be created?
1. Thymus with help of AIRE | 2. Periphery with help of IL10 and TGFbeta
117
What CDs are Treg?
4/25
118
What are Tregs dependent on for survival and proliferation?
IL2
119
What does TCR reaction with peptide in MHCI promote?
Activation of CD8
120
What does TCR reaction with peptide in MHCI promote?
Activation of CD8
121
What do TLRs do?
TLR instruct antigen presenting cells to set up cytokine profile appropriate to infection
122
What does TFH do ?
T-FH - promotes optimal high affinity antibody production in germinal center of lymph node “T follicular helper”
123
What makes up CD4 family?
HO, TH1, TH2, TH17, Treg, and THFH
124
What does TH1 encourage along with macs?
CD8
125
What does trigger for TMMI always involve?
The trigger for a TMMI always involves a TLR on a dendritic cell (DC)
126
What response need, and require TH2
- 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
What cytokine is used for host response to stress?
IL1
128
Difference between IL1 & 6?
IL 6 shows strong growth and differentiation effects on B cells in presence of other by cytokines
129
What is known as THE proinflammatory cytokine?
TNF alpha
130
What is angiogenesis?
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
What is angiogenesis?
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
What can cause angioneogenesis?
TNF Alpha
133
What is most effective at recruiting neutrophils?
IL8
134
What do you suspect if there are tons of neutrolphils?
IL8
135
What do you suspect if there are tons of neutrolphils?
IL8
136
What do activated macrophages do?
Activated macrophage will release tons of IL 1, 6, 8 and TNF alpha activating all the macrophages around it to kill the organism
137
What is LCI?
Lymphocyte cytotoxic immunity
138
What mediates LCI?
NK
139
What is on the surface of NK?
No CD3 of alpha beta or gamma delta chains, no antigen receptors
140
Why does NK not kill RBC?
RBCs are not killed as they have neither inhibitory or activating ligand so NK cell does not know they exist
141
How does NK cell activation work?
- 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
Two manners of LCI?
Non specific - NK | Specific - CD8
143
What leads to optimal CD8 activation?
Parallel activation of NK cells, Heler T , and presence of memory cells
144
What activates Th1
IL 12/18
145
What activates Th1
IL 12/18
146
Signals needed for CD8 activation?
Antigen specific is first and INF is second signal
147
What is CD8 powerless without?
CD4
148
What promotes TH2?
Soluble antigens and extracellular pathogens promote TH2
149
Major source of IL4?
Major source of IL4 is the TH2 cell itself
150
What can suppress TH1 in TH2 reaction?
IL4, IL10, IL13
151
How do B cells present antigen?
B cells present in MHCII, not in antibodies on surface
152
What is IGG?
Bind viral antigen in serum marking it for destruction by macs and neutrophils who will phagocytose IGG/antigen complex for destruction
153
What releases IGG?
Plasma cells
154
Trio of cytokines in Th17 response?
IL6, IL23, TGFbeta
155
Trio of cytokines in Th17 response?
IL6, IL23, TGFbeta
156
What is unique to Treg?
CD25

Host Defense (12 decks)

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