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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
Q

True or False: If a patient cannot generate IL-12, he or she cannot generate a TMMI response

A

TRUE

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26
Q

What do antigen-activated Th1 cells in the presence of IL-12 and 18 upregulate?

A

CD28 and CD154 (40L)

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27
Q

What cytokines propagate the TMMI response and where are they produced?

A

IL-2 and INF-y (produced by Th1 cell)

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28
Q

IL-___ and IL-___ start the TMMI response but _____ and _____ propagate it

A

12; 18 and 2; INFy

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29
Q

What 3 cells can produce INF-y?

A

1) activated Th1 (CD4)
2) NK
3) CD8

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30
Q

What does INFy do?

A
  • 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)
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31
Q

In the absence of INFy, what does IL-21 do?

A

promotes B cell growth and development

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32
Q

What does IL-2 do and where is it produced?

A

promotes growth; produced by activated Th1 cells

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33
Q

What is the main objective of the TMMI response?

A

to recruit massive amounts of macrophages

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34
Q

What is the end result of the TMMI?

A

the activated macrophage

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35
Q

What is the classic tetrad of macrophage produced pro-inflammatory cytokines?

A

1) IL-1
2) IL-6
3) IL-8
4) TNFa

36
Q

What kind of cytokine is IL-1?

A

PRO-inflammatory

37
Q

What does IL-1 do?

A

acts with IL-6 to cause fever, depression

promotes neutrophil growth and emigration from marrow
Stimulates APCs to increase Ag presentation

38
Q

What 2 cytokines cause fever?

A

IL-1 and IL-6

39
Q

What does IL-6 do?

A
  • 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
Q

How is IL-6 distinguished from IL-1?

A

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
Q

What does TNFa do?

A
  • recruits macrophages
  • activates endothelial homing and adhesion molecules
  • upregulates MHC/cytokines
  • induces apoptosis
  • has systemic effects like flu-like symptoms
42
Q

What is the most potent cytokine for mobilizing/recruiting neutrophils to the site of infection?

43
Q

What is the difference between a cytokine and chemokine?

A

cytokine –> activates to kill

chemokine –> recruits other things

44
Q

What produces IL-8?

A

macs, neutrophils

45
Q

What 3 cytokines are produced by activated macrophages in a TMMI response?

A

IL-6
IL-8
TNFa

46
Q

What is delayed hypersensitivity?

A

archaic term for TMMI

47
Q

Why might some patients present with a positive skin TB test even thought they do not have the disease?

A

they have been in contact with the pathogen before and have TB specific CD4 Th1 cells

48
Q

What is the process that makes infections visible?

A

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
Q

Once a TMMI is evoked, what percentage of cells at the site are macrophages vs lymphocytes?

A

95% macs

5% lymphocytes

50
Q

When are natural killer cells activated?

A

when altered MHC-Is and activating ligands on the target cell are present

NOT ANTIGEN SPECIFIC

51
Q

Why aren’t RBCs attacked by natural killer cells because they do not express MHC-I?

A

I DONT KNOW

52
Q

What cytokine is produced by Natural Killer cells?

53
Q

Do natural killer cells express and CDs or TCRs?

A

NO

no CD3, no ab, no yd

54
Q

How can NK cells tell when an MHC-I has been altered?

A

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
Q

What happens first, NK killing or T-cell killing of infected cells?

56
Q

Aside from detecting defunct MHC-I molecules, when else do NK cells kill?

A

when pathogen complexed with antibody binds to their Fc receptors

57
Q

How do CD8 cells recognize and kill foreign cells?

A

via display of endogenously produced antigen in an MHC-I determinant

58
Q

What does OPTIMAL activation of CD8 require?

A

parallel activation of

1) NK cells
2) antigen specific CD4 helpers
3) present of memory cells

59
Q

What are the CRITICAL INITIAL cytokine signals that are provided by activated NK cells?

A

IL21
IL2
IFNy

60
Q

Aside from activated NK cells, what other cells can produce the critical cytokines to sustain the CD8 response?

61
Q

What are 2 mechanisms that initiate and enhance CD8 toxicity?

A

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
Q

Can CD8 cells kill repeatedly in the absence of co-stimulatory signals?

63
Q

What turns off cytotoxicity in CD8s?

A

absence of specific targets (CD8 activate their own death genes by Fas and FasL)

64
Q

A Th2 reaction is any infection or antigenic stimulus that causes ______ to be the dominant cytokine

65
Q

When do Th2 responses occur?

A
  • 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
Q

What type of antigens do B cells bind?

A

extracellular or soluble

67
Q

What type of antigens promote Th2 responses?

A

soluble and extracellular

68
Q

What 4 cell types can drive Th0 to Th2?

A

1) committed Th2 cells
2) B cell presentation of antigen
3) Mast cells
4) DC and TLR under specific gene influences

69
Q

Which cytokine is an ABSOLUTE requirement for Th2 reaction?

70
Q

Once activated by IL-4, what does the Th2 cell produce?

A

IL-21 (B cell stimulator in the absence of IFNy)

71
Q

What are the major drivers of B cell differentiation/isotype switching and where are they produced?

A

IL-5, IL-6, IL-10 (produced in Th2 cell)

72
Q

Which cytokines suppress the development of a Th1 reaction?

A

IL-4, IL-10, IL-13

73
Q

Which cytokine has a similar ancestry to IL-4 and is important in IgE responses?

74
Q

What is the function of the Th2 response?

A

enhance B cell function and ultimately antibody production

  • make pathogens more attractive to macs
  • bind toxins
  • target mutant/viral infected cells for killing
75
Q

What are the 2 important cytokines driving Th2 response?

A

IL-4

IL-21

76
Q

What determines the dominant T helper response?

A

1) type of infection
2) type of TLR activated
3) dominant cytokines present

77
Q

IL-12 activates _____
IL-23 activates _____
IL-4 activates _____

A

Th1
Th17
Th2

78
Q

What induces a Th17 response?

A

bacteria and fungi that live outside of the host cell

79
Q

What is the trio of cytokines behind Th17 response?

A

IL-6
IL-23
TGFb

80
Q

What is the transcription factor behind Th17?

81
Q

If either _____ or ______ are the dominant cytokines, Th17 reactions are strongly inhibited

82
Q

What are the 6 cardinal characteristics of the CD4-Th17 subset?

A

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
Q

What 2 sites do Tregs arise?

A

1) Thymus (natural regs)

2) Inducible (peripheral lymphoid tissue)

84
Q

Tregs are dependent on which cytokine for survival?

85
Q

What CDs are expressed on Tregs?

A

CD3
CD4
CD25

86
Q

Th-FH transcription factor?

Host Defense (21 decks)

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