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Flashcards in T cell effector mechanism Deck (97):
1

naïve T cells require two activation stimuli. name them

1) binding of TCR to specific peptide antigen:MHC complex

2) co-stimulatory signal supplied by interaction between CD28 (on the T cell) with B7 molecules (expressed by antigen-presenting cells)

2

What is the only cell that expresses B7 molecules?

professional APCs

3

When is B7 expression upregulated in APCs?

 in response to potential infection

4

T/F armed effector T cells require only a single activation stimulus

true

5

What is the only activation stimulus needed by armed effector T cells? what is the result?

Stimuli => binding of TCR to specific peptide antigen:MHC complex

 

  • when armed effector T cells recognize their specific antigen, they are quickly activated to perform their effector function

6

naïve T cells and effector T cells express a different array of what?

adhesion molecules

7

What reflects and defines the roles of adhesion molecules in immune response?

expression by naive T cells and by effector T cells

8

naïve T cells must enter the secondary lymphoid tissues via process? Describe this process

HEV

mediated by surface adhesion molecules (L-selectin) to have a chance to become stimulated by an antigen presenting cell

9

What keeps naive T cells from entering into inflammatory sites? 

they do not express the adhesion molecules (VLA-4) required for entry into inflammatory sites

 

10

Why does it not make sense for naive T cells to be in inflammatory sites?

they have no effector functions and no role in the environment

11

What allows armed effector T cells to perform their effector functions?

expression of a different array of adhesion molecules

12

Why can effector CD8 T cells not enter secondary lymphoid tissue?

effector CD8+ T cells (CTLs) down-regulate expression of L-selectin

13

What allows CTLs to bind to vascular endothelium at sites of inflammation?

upregulate expression of VLA-4

14

Why is it important for CD8 T cells not to enter secondary lymphoid tissues?

1) they have no role there

2) if they entered secondary lymphoid tissues, they could attack antigen-presenting cells that present their specific peptide antigen

15

What allows CD8 T cells to enter inflammatory sites so they can "target" cells?

down-regulation expression of L-selectin

upregulation expression of VLA-4

16

How does effector CD8 T cells  initiate interactions between the effector T cells with their potential “target” cells?

upregulate expression of cell adhesion molecules (LFA-1 and CD2)

17

Which is not an effector molecule produced by helper T cells?

granzymes

18

T/F Both CD4 and CD8 effectors can initiate apoptotic deal of host cells

true

19

What promotes differentiation of CD4 Tcell into Th1 type cell?

high Ag concentration; IL-12 + IFN-y

20

the effector molecules produced by T cells fall into 2 broad classifications. Describe each of them

1. cytotoxins- perforin, granzymes, Fas ligand

  • cytotoxins are the principal effector molecules of CTLs

2. cytokines - IFN-y, GM-CSF, TNF-a, LT, IL-3, IL-4, IL-5, IL-10, IL-13, TGF-B;

  • cytokines are the primary effector molecules for CD4 T cells; 

21

What defines the Th1 and Th2 cells?

defined by the cytokine profiles they produce

22

Th1 cells produce what type of cytokines?

cytokines that upregulate macrophage functions and generally promote cell-mediated immunity

23

Th2 cells produce what type of cytokines?

generally promote humoral immune responses

24

Define cytokine and their effects

small soluble proteins that can act on the secreting cell, or on a different cell

the effects many cytokines have on cells have been determined

25

What is the primary cytokine produced by CD8 cells? Name its function/role

IFN-y

anti-viral properties and inhibits TH2 cell development

26

TH1 CD4 cells produce what type of cytokines? and name their role/function

IL-2 and IFN-y

lymphotoxin and other inflammatory cytokines

27

Th2 CD4 cells produce what cytokines?

IL-4, IL-5 and IL-10

28

CD4 cells activated in presence of IL-12 and IFN-γ will become 

Th1

29

CD4 cells activated in presence of IL-4 and IL-6 will become 

TH2 cells

30

What does a Th1 use its cytokines for? name them and overall function 

IL-2, IFN-y

  • macrophage activation
  • B cell activation
  • production of opsonizing Abs such as IgG1

31

What does a Th2 use its cytokines for? name them and overall function 

IL-4, IL-5

  • General activation of B cells to make Abs

32

Describe the differentiation from Th0 cells to Threg cells

A image thumb
33

Describe the differentiation to Th1 cells 

A image thumb
34

Describe the diffentiation to Th2 cells

A image thumb
35

antigen presented to TH0 cell influences differentiation pathway. What does low affinity or concentration go toward?

presentation of low affinity or low concentration of Ag >>>> TH2

36

antigen presented to TH0 cell influences differentiation pathway. What does high affinity or concentration go toward?

presentation of high affinity or high concentration of Ag >>>> TH1

37

What is the role of CTLs wrt infection?

 destroy infected cells, thereby limiting the infection

38

How do CTLs know how to target the correct cell?

proteins from these intracellular parasites (viruses and intracellular bacteria) are processed and presented on MHC class I molecules to CD8 T cells

39

When can an effector CD8 T cell initiate killing of the infected cell?

effector CD8 T cell (CTL) recognizes its cognate peptide antigen:MHC complex presented on any cell

40

the 1st step of specific antigen recognition by a CTL (or a CD4 T cell for that matter) is what?

  1.  interaction of the T cell with the target cell (or APC for CD4 T-helper cells) mediated by cell surface adhesion molecules
  2. once in close proximity, interaction between TCR and MHC:peptide complexes can occur

41

T/F TCR must recognize the specific peptide or will disengage

true

42

What does a CTL contain and express that help with the mechanism of cell killing by CTLs?

CTLs contain granules that contain perforin and granzymes;

CTLs also express Fas ligand

43

once a CTL recognizes its specific peptide antigen:MHC complex, what occurs?

 it degranulates

44

What are molecules polymerize to form a pore in the membrane of the target cell?

perforins

45

What a detergent like protein that associates with cellular membranes? 

granulysin

 

46

What  are serine proteases that activate programmed cell death (apoptosis) of the target cell?

granzymes

47

How do granzymes gain access to the interior of the cell?

repairative endocytosis  model via a cation-independent mannose-6-P receptor (CI-MPR)

48

What is the action on the target cells via perforin?

aids in delivering contents of granules into cytoplasm of target cell

49

What is the action on the target cells via granzymes?

Serine proteases, which activate apoptosis once in the cytoplasm of target cell

50

What is the action on the target cells via granulysin?

has antimicrobial actions and can induce apoptosis

51

What is the Fas ligand?

engages with Fas on the target cell, helping to induce apoptosis

52

What increases the chances that an infected cell will be recognized by an antigen-specific effector CTL?

CTLs also produce cytokines (IFN- , TNF- , and TNF- ) that stimulate cells to upregulate expression of proteins involved in antigen presentation to MHC I

53

What is a Th1 cytokine and CTL effector molecule?

IFN-y

54

Describe the process of apoptosis mediated by CD8 cells

  1. Fas ligand binds to Fas
  2. adaptor proteins recruit and activate caspase 8 which cleaves caspase 3
  3. Activated caspase 3 cleaves I-CAD which inhibits CAD (caspase-activatible DNase) that is released into nucleus and cleaves DNA

55

CTLs, as well as T helper cells, become polarized when their TCR is bound to MHC:peptide complexes- why is this important?

 this polarization focuses the effector molecules released by the T cell onto its specific target cell

56

How do the CTLs and T helper cells become polarized?

reorientation of the cytoskeleton of the T cell polarizes the T cell so that effector molecules are focused on the target cell 

57

What is the most important function of CTLs wrt its mechanism of killing cells?

ability of T cells to focus their effector molecules onto their specific target cells is vital to their function

effector function only on cells that bear the cognate peptide antigen:MHC complex that binds to the TCR of the effector T cell

58

What is the fate of cells targeted by CTLs? What other cell is this similar to?

programmed cell death is the ultimate fate of cells killed by antigen-specific effector CTLs

NK cells

59

What are the 2 stimuli that can cause apoptosis?

mediated by granzymes, which are serine proteases that initiate the programmed cell death pathway

initiated by interaction of Fas on a target cell with Fas ligand (FasL) expressed on effector cells

60

regardless of the initiation signal, all apoptosis initiators lead to what?

activation of a series of cysteine proteases known as caspases

61

the inactive form of CAD (I-CAD) is present in all cells of the body. What inhibits I-CAD to allow for DNA cleaving?

cascade of caspase activity

62

activate macrophages to kill bacteria and other pathogens is an effector function of what cells?

Th1 CD4 cells

63

both signals required to activate macrophages can be delivered by Th1 Cells. What are they?

  1. cytokine IFN- 
  2. CD40 ligand interacts with CD40 (on macrophage)

64

activation of a macrophage leads to a number of biochemical responses by the macrophage (5)

  1. •• upregulation of phagosome-to-lysosome fusion which leads to destruction of ingested pathogen
  2. •• production of NO and oxygen radicals, both of which have potent anti-bacterial activity
  3. •• production of antibacterial peptides and proteases that are released and can attack extracellular parasites
  4. •• upregulation of surface molecules; MHC class II molecules, B7 (costimulator for presenting antigen to T cells), CD40
  5. •• production of IL-12 which stimulates differentiation of TH0 cells into TH1 T cells

65

What cells coordinate the host response to intracellular pathogens?

TH1 cells

66

How do T cells regulate the activities of
macrophages during a cellular immune response?

T cells produce a variety of cytokines and cell surface markers 

67

in response to specific antigen recognition by an effector TH1 cell, the TH1 cell:

  1. •• produces IFN- and CD40 ligand which are the signals for activation of macrophages; makes macrophages more bacteriocidal
  2. •• produces TNF- apoptosis and Fas ligand; can induce a chronically-infected macrophage to undergo is the 1 required signal
  3. •• produces IL-2 which is a growth factor for T cells; can also assist the activation of naïve CD8+ T cells
  4. •• produces IL-3 and GM-CSF which induces macrophage differentiation in the bone marrow •• produces lymphotoxin and TNF- which facilitates macrophage binding to epithelium / exit from blood vessel at sites of infection
  5. •• produces macrophage chemotactic factor which causes macrophages to accumulate at sites of infection

68

once naive CD4 T cells are activated to differentiate into what, they can serve as what?

armed effector TH cells (either TH1 or TH2)

the effector cell that stimulates B cell activation by supplying the 2nd signal of B cell activation 

69

most TH2 effector cells reside where?

in the T cell zones of secondary lymphoid tissues

where they can perform their effector functions

70

as naïve B cells migrate thru the T cell zones, what occurs?

effector T cells sample the peptide:MHC class II complexes on their surface.

71

If a helper T cell recognizes its cognate peptide antigen:MHC complex displayed on the surface of a B cell, the effector T cell will do what?

will supply the second signal of activation (includes production of cytokines and CD40 ligand) to the B cell

72

 the remaining effector TH1 cells recirculate thru secondary lymphoid tissues where they can do what?

can activate antigen-presenting B cells

73

many effector TH1 cells remain in the circulation where they do what?

they patrol and enter tissues at sites of inflammation where they serve as activators of phagocyte activity,

74

effector TH1 cells produce cytokines that stimulate B cell activation and differentiation into cells that produce what? Why are these important?

  • antigen-specific antibodies of the IgG1 and IgG3 isotype;
  • these isotypes are very important opsonizing antibodies (cell-mediated immunity)

75

Why are the antigen-specific antibodies of the IgG1 and IgG3 isotype important?

these isotypes are very important opsonizing antibodies (cell-mediated immunity)

76

effector TH2 cells produce cytokines that stimulate B cell activation and differentiation into cells that produce what?

antigen-specific antibodies of the IgG2, IgG4, IgA, and IgE isotypes

77

Why are the antigen-specific antibodies of the IgG2, IgG4, IgA, and IgE isotypes important?

neutralization and complement fixation, which are important effector mechanisms for clearing extracellular pathogens

78

T/F CTLs Release Granular Contents in 
Polarized Fashion

True

79

TH1 Effector Cells Activate what? What is the ultimate result?

Infected Macrophages

killing of intravesicular bacteria

80

Activated Macrophages Become Better what?

APCs and More Bacteriocidal

81

What acts as the Maestro of Developing Immune Responses?

TH1 Effector Cells

82

If an activated Th1 cell secretes  IFN-y and CD40L, what is the result?

activates macrophages to destroy engulfed bacteria

83

Th1 secretes FasL or LT, what is the result?

kills chronically infected macrophages, releasing bacteria to be destroyed by healthy macrophages

84

Th1 secretes IL-2, what is the result?

Induces T cell proliferation thus increasing the number of effector T cells

85

Th1 secretes IL-3 + GM-CSF, what is the result?

induces macrophage differentiation in the bone marrow

86

Th1 secretes TNF-a + LT, what is the result?

activates endothelium to induce macrophage adhesion and exit from blood vessel at site of infection

87

Th1 secretes CXCL2, what is the result?

causes macrophages to accumulate at site of infection

88

What is the effect of IL-2 on T cells?

growth

89

What is the effect of IFN-y on macrophages?

  • activation
  • increase MHC class I and class II

90

What is the effect of lymphotoxin(LT) and TNF-B on macrophages?

  • activation
  • induces NO production

91

What is the effect of IL-4 on B cells? T cells?

B cells

  • activation
  • growth of IgG1 and IgE
  • increase MHC class II induction

T cells

  • growth
  • survival

92

hat is the effect of IL-3 on hematopoietic cells?

growth factor for progenitor hematopoietic cells (multi-CSF)

93

What is the effect of TNF-a on macrophages?

  • activation
  • induces NO production

94

What is the effect of GM-CSF on hematopoietic cells?

increase in production of granulocytes and macrophages and dendritic cells

95

How is Signaling Thru Cytokine Receptors done?

  1. cytokine receptors consist of at least 2 chains that the cytoplasmic domains bind JAKs
  2. cytokine binding dimerizes receptor to bring together JAKs which activate each other and phosphorylate receptor
  3. transcription factors (STATs) bind to phosphorylated receptors and phosphorylated by activated JAKs
  4. phosphorylated STATs form dimers that move into nucleus to initiate gene transcription

96

What occurs when a microbe resists destruciton by macrophages? What is the function of this?

granuloma

function is to prevent dissemination of microbe

97

Describe a granuloma

multinucleated giant cells that contain mycobacteria are walled of with T cells that cannot be removed