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Host Defense > Lecture 9: T-Cell Immunity 1 and 2 > Flashcards

Lecture 9: T-Cell Immunity 1 and 2 Flashcards

1
Q

What is considered the ancestral or primitive T cell?

A

yd (especially important at host/environmental interfaces like gut, urethra, skin, endometrium, etc)

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2
Q

What early cytokines to yd T cells produce?

A

IL1, 6 and 17

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3
Q

What are considered the orchestrators of the immune response?

A

T cells

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4
Q

What regulates T cell responses?

A

cytokines and Tregs

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5
Q

Antibodies recognize the 3D conformation of antigens while T cells recognize _____________________

A

peptides in the contect of MHc

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6
Q

If an antigen is processed and presented by MHC Class II by an APC to a naive CD4 Th0 cell, one of 5 responses can occur. What are they?

A

1) Th1
2) Th2
3) Th17
4) Treg
5) Th-FH

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7
Q

What determines the response?

A

host genetics, type of infection, which TLR/cytokine profile dominates the early phase of T cell activation

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8
Q

What does the Th1 subset do?

A

enhance and amplify cellular mediated immunity by activated macrophages and/or promoting cytotoxic responses by CD8 cells

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9
Q

What does the Th2 subset do?

A

promote optimal antibody production

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10
Q

What does Th17 do?

A

promotes chronic inflammation

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11
Q

What does the Treg subset do?

A

modulates/suppresses immune response

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12
Q

What do T follicular cells do?

A

promote optimal high affinity antibody production in the germinal center of a lymph node

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13
Q

Where do these T cell responses occur?

A

in secondary lymphoid tissue

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14
Q

What transcription factors are the tell-tale sign that certain immune responses have been triggered?

A 
Th1 --> T-Bet
Th2 --> GATA-3
Th17 --> ROR
Treg --> FoxP3
Th-FH --> Bcl6
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15
Q

True or False: almost all cytokines exhibit pleiotropism and redundancy

A

TRUE (labeled to do one thing but may be able to do something else depending on the context)

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16
Q

What response is activated in the TMMI response?

A

Th1

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17
Q

Define TMMI response

A

T cell Mediated Macrophage Immunity (TMMI)

elicited during infections by organisms that require phagocytosis (uptake of a complex antigen) and intracellular killing

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18
Q

The trigger for TMMI always involves a _____ on a ___

A

TLR on a DC

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19
Q

After complex antigen is phagocytosed by DCs, it is presented by __________

A

MHC Class II

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20
Q

What determines the type and intensity of TLR activation?

A

genetic background of host

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21
Q

When do immature DCs become mature?

A

when they uptake a complex antigen

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22
Q

What happens when immature DC become mature?

A
  • no longer can phagocytize
  • processes antigen to peptides
  • upregulates its MHC-II
  • upregulates co-stimulatory molecules
  • migrates to lymphoid tissue
  • upregulates production IL12 and IL18
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23
Q

What 2 cytokines are critical in TMMI?

A

IL12 and IL18

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24
Q

What cytokine is the obligatory Th1 helper initiator?

A

IL-12

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25
True or False: If a patient cannot generate IL-12, he or she cannot generate a TMMI response
TRUE
26
What do antigen-activated Th1 cells in the presence of IL-12 and 18 upregulate?
CD28 and CD154 (40L)
27
What cytokines propagate the TMMI response and where are they produced?
IL-2 and INF-y (produced by Th1 cell)
28
IL-___ and IL-___ start the TMMI response but _____ and _____ propagate it
12; 18 and 2; INFy
29
What 3 cells can produce INF-y?
1) activated Th1 (CD4) 2) NK 3) CD8
30
What does INFy do?
- turn on all macrophages in sight - upregulates MHC II (to see more antigen) - suppresses Th2 and Th17 - works with IL-21 (a potent promoter of CD8 killing)
31
In the absence of INFy, what does IL-21 do?
promotes B cell growth and development
32
What does IL-2 do and where is it produced?
promotes growth; produced by activated Th1 cells
33
What is the main objective of the TMMI response?
to recruit massive amounts of macrophages
34
What is the end result of the TMMI?
the activated macrophage
35
What is the classic tetrad of macrophage produced pro-inflammatory cytokines?
1) IL-1 2) IL-6 3) IL-8 4) TNFa
36
What kind of cytokine is IL-1?
PRO-inflammatory
37
What does IL-1 do?
acts with IL-6 to cause fever, depression promotes neutrophil growth and emigration from marrow Stimulates APCs to increase Ag presentation
38
What 2 cytokines cause fever?
IL-1 and IL-6
39
What does IL-6 do?
- causes fever - promotes responsiveness to IL-2, accelerating antigen activation - strong growth and differentiation effects on B cells in the presence of other "B" cell cytokines
40
How is IL-6 distinguished from IL-1?
Strong growth/differentiation effects on B cells in the presence of other B cell cytokines and effects on bone mineral metabolism where it ACTIVATES osteoclasts
41
What does TNFa do?
- recruits macrophages - activates endothelial homing and adhesion molecules - upregulates MHC/cytokines - induces apoptosis - has systemic effects like flu-like symptoms
42
What is the most potent cytokine for mobilizing/recruiting neutrophils to the site of infection?
IL-8
43
What is the difference between a cytokine and chemokine?
cytokine --> activates to kill | chemokine --> recruits other things
44
What produces IL-8?
macs, neutrophils
45
What 3 cytokines are produced by activated macrophages in a TMMI response?
IL-6 IL-8 TNFa
46
What is delayed hypersensitivity?
archaic term for TMMI
47
Why might some patients present with a positive skin TB test even thought they do not have the disease?
they have been in contact with the pathogen before and have TB specific CD4 Th1 cells
48
What is the process that makes infections visible?
1) antigen comes in thru the skin and is processed by local APCS 2) Th1 effector cell recognizes antigen and releases cytokines which act on vasculature 3) T cells, phagocytes, fluid, and protein are recruited to site --> making visible bump
49
Once a TMMI is evoked, what percentage of cells at the site are macrophages vs lymphocytes?
95% macs | 5% lymphocytes
50
When are natural killer cells activated?
when altered MHC-Is and activating ligands on the target cell are present NOT ANTIGEN SPECIFIC
51
Why aren't RBCs attacked by natural killer cells because they do not express MHC-I?
I DONT KNOW
52
What cytokine is produced by Natural Killer cells?
INFy
53
Do natural killer cells express and CDs or TCRs?
NO no CD3, no ab, no yd
54
How can NK cells tell when an MHC-I has been altered?
via KIRs (killer cell immunoglobulin like receptors) or lectin0like CD94-NKG2 (MHC-I molecules send negative signal to tell NKs not to kill - if they can't do that, they die)
55
What happens first, NK killing or T-cell killing of infected cells?
NK
56
Aside from detecting defunct MHC-I molecules, when else do NK cells kill?
when pathogen complexed with antibody binds to their Fc receptors
57
How do CD8 cells recognize and kill foreign cells?
via display of endogenously produced antigen in an MHC-I determinant
58
What does OPTIMAL activation of CD8 require?
parallel activation of 1) NK cells 2) antigen specific CD4 helpers 3) present of memory cells
59
What are the CRITICAL INITIAL cytokine signals that are provided by activated NK cells?
IL21 IL2 IFNy
60
Aside from activated NK cells, what other cells can produce the critical cytokines to sustain the CD8 response?
CD4 cells
61
What are 2 mechanisms that initiate and enhance CD8 toxicity?
1) binding of/presenting viral particles to TLRs on DCs ------> recruits CD4 -----> activates CD8 via IL-2, IL-21, and INFy 2) NK response to altered MHC-I (again via IL-21 and INFy)
62
Can CD8 cells kill repeatedly in the absence of co-stimulatory signals?
yes
63
What turns off cytotoxicity in CD8s?
absence of specific targets (CD8 activate their own death genes by Fas and FasL)
64
A Th2 reaction is any infection or antigenic stimulus that causes ______ to be the dominant cytokine
IL-4
65
When do Th2 responses occur?
- when Th1 TLR is not engaged and IL-12 not produced - when TLRs induce DCs to produce IL-4 instead of IL-12 - When B cells present antigen
66
What type of antigens do B cells bind?
extracellular or soluble
67
What type of antigens promote Th2 responses?
soluble and extracellular
68
What 4 cell types can drive Th0 to Th2?
1) committed Th2 cells 2) B cell presentation of antigen 3) Mast cells 4) DC and TLR under specific gene influences
69
Which cytokine is an ABSOLUTE requirement for Th2 reaction?
IL-4
70
Once activated by IL-4, what does the Th2 cell produce?
IL-21 (B cell stimulator in the absence of IFNy)
71
What are the major drivers of B cell differentiation/isotype switching and where are they produced?
IL-5, IL-6, IL-10 (produced in Th2 cell)
72
Which cytokines suppress the development of a Th1 reaction?
IL-4, IL-10, IL-13
73
Which cytokine has a similar ancestry to IL-4 and is important in IgE responses?
IL-13
74
What is the function of the Th2 response?
enhance B cell function and ultimately antibody production - make pathogens more attractive to macs - bind toxins - target mutant/viral infected cells for killing
75
What are the 2 important cytokines driving Th2 response?
IL-4 | IL-21
76
What determines the dominant T helper response?
1) type of infection 2) type of TLR activated 3) dominant cytokines present
77
IL-12 activates _____ IL-23 activates _____ IL-4 activates _____
Th1 Th17 Th2
78
What induces a Th17 response?
bacteria and fungi that live outside of the host cell
79
What is the trio of cytokines behind Th17 response?
IL-6 IL-23 TGFb
80
What is the transcription factor behind Th17?
ROR
81
If either _____ or ______ are the dominant cytokines, Th17 reactions are strongly inhibited
IL-4 | IFNy
82
What are the 6 cardinal characteristics of the CD4-Th17 subset?
1) produce IL-17 - an inflammatory cytokine 2) Induce DC production of IL-23 3) unique nuclear receptor is ROR 4) Suppresed by IL-4 or IFNy 5) Have innate defense role 6) Central role in autoimmune disease
83
What 2 sites do Tregs arise?
1) Thymus (natural regs) | 2) Inducible (peripheral lymphoid tissue)
84
Tregs are dependent on which cytokine for survival?
IL-2
85
What CDs are expressed on Tregs?
CD3 CD4 CD25
86
Th-FH transcription factor?
Bcl6

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