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Flashcards in T cell activation and differentiation Deck (135):
1

Activation of Naïve T cells occurs where?

• occurs exclusively in secondary lymphoid tissues

2

For Activation of Naïve T cells, what signals are required?

  TCR recognition of cognate peptide:MHC complex

co-stimulation signal (B7 binding to CD28)

3

For Activation of Naïve T cells, naïve T cells can only be activated by what? why is this important?

professional antigen-presenting cells (APCs)

 ••  APC are the only cells that express B7 molecules

4

Describe the steps of trafficking of naive T cells

  1. T cells enter a lymph node across high endothelial venules in cortex
  2. T cells monitor anitgen presented by macrophages and dendritic cells
  3. T cells that do not encounter specific antigen leave the node in the efferent lymph
  4. T cells that encounter specific antigen proliferate and differentiate to effector cells

5

What directs lymphocyte trafficking? 

adhesion molecules

6

• there are 4 classes of cell-surface adhesion molecules. Name them

  1. selectins
  2. mucin-like vascular addressins
  3. integrins
  4. Ig superfamily members

7

Describe the adhesion molecule: selectin. give examples

lectins that bind to carbohydrates

•  L-selectin, P-selectin

8

Describe the adhesion molecule: Mucin-like vascular addressins. give examples

have carbohydrate moities (targets for selectin binding)

• CD34, GlyCAM-1, MAdCAM-1

9

Describe the adhesion molecule: Integrins. give examples

bind to various cell adhesion molecules


•  lymphocyte function-associated antigen (LFA-1)

10

Describe the adhesion molecule: Immunoglobulin superfamily members. give examples

targets for integrin binding


•  intracellular adhesion molecules (ICAMs), CD2, LFA-3

11

Describe the process adhesion molecules direct lymphocyte trafficking

  1. Circulating T cell enters the high endothelial venule in lymph node
  2. Binding of L-selectin to GlyCAM-1 and CD34 allows rolling interaction
  3. LFA-1 is activated by chemokines bound to ECM
  4. activated LFA-1 binds tightly to ICAM-1
  5. diapedesis => lymphocyte leaves blood and enters lymph node

12

What are the professional APCs?

dendritic cells, macrophages, B cell

13

Name what it attacks, the location in the lymph node, how antigen is uptaken, MHC expression, co-stimulator delivery, how antigen is presented, and location within body of   dendritic cells

  • cell attacked => viral antigen
  • location in lymph node => T cell areas
  • antigen uptake => major macropinocytosis and phagocytosis by tissue dendritic cells, and viral infection
  • MHC expression => low on tissue DCs, High on DCs in lymphoid tissues
  • co-stimulator delivery => constitutive by mature, nonphagocytic lymphoid DCs 
  • antigen presented => peptides, viral antigens, allergens
  • location => ubiquitous throughout body

14

Name what it attacks, the location in the lymph node, how antigen is uptaken, MHC expression, co-stimulator delivery, how antigen is presented, and location within body of   macrophages

  • cell attacked => bacterium
  • location in lymph node => throughout lymph node
  • antigen uptake => phagocytosis
  • MHC expression => inducible by bacteria and cytokines from neg to very strong
  • co-stimulator delivery => inducible from neg to very strong
  • antigen presented => Particulate antigens, Intracellular and extracellular pathogens
  • location => lymphoid tissue, connective tissue, body cavities

15

Name what it attacks, the location in the lymph node, how antigen is uptaken, MHC expression, co-stimulator delivery, how antigen is presented, and location within body of                                                                                        B cells

  • cell attacked => microbial toxin
  • location in lymph node => follicle
  • antigen uptake => antigen-specific receptor (Ig)
  • MHC expression => constitutive and increases on activation 
  • co-stimulator delivery => inducible from negative to very strong
  • antigen presented => soluble antigens, toxins, viruses
  • location => lymphoid tissue, peripheral blood

16

Describe how DCs stimulate naive T cells

  1. antigen uptake by Langerhans cells in skin
  2. Langerhans cells leave skin and enter lymphatic system
  3. mature DCs enter lymph node from infected tissued and transfer some antigens to resident DCs
  4. B7-positive DCs stimulate naive T cells

17

What are the 5 mechanism of which antigen processing/presentation for DCs can be utilized?

  1. receptor mediated endocytosis
  2. macropinocytosis
  3. viral infection
  4. cross-presentation after phagocytic or macropinocytic uptake
  5. transfer from incoming DCs to resident DCs

18

Name the type of pathogen presented, MHC molecules loaded, type of naive T cell activated wrt DCs using the route of receptor-mediated endocytosis

type of pathogen presented: extracellular bacteria

MHC molecules: MHC II

Type of naive T cell activated: CD4 T cells

19

Name the type of pathogen presented, MHC molecules loaded, type of naive T cell activated wrt DCs using the route of macro-pinocytosis

type of pathogen presented: extracellular bacteria, soluble antigens, virus particles

MHC molecules: MHC II

Type of naive T cell activated: CD4 T cells

20

Name the type of pathogen presented, MHC molecules loaded, type of naive T cell activated wrt DCs using the route of viral infection

type of pathogen presented: viruses

MHC molecules: MHC I

Type of naive T cell activated: CD8 T cells

21

Name the type of pathogen presented, MHC molecules loaded, type of naive T cell activated wrt DCs using the route of cross-presentation after phagocytic or macropinocytic uptake

type of pathogen presented: viruses

MHC molecules: MHC I

Type of naive T cell activated: CD8 T cells

22

Name the type of pathogen presented, MHC molecules loaded, type of naive T cell activated wrt DCs using the route of transfer from incoming DCs to resident DCs

type of pathogen presented: viruses

MHC molecules: MHC I

Type of naive T cell activated: CD8 T cells

23

Describe the process of how Dendritic Cells (and Macrophages) Take Antigen to 2˚ Lymphoid Tissues

  1. DCs take up bacterial antigens in skin and move to enter a draining lymphatic vessel
  2. DCs bearing antigen enter draining lymph node where they settle in T cell areas

24

Describe antigen presentation by B cells

  1. antigen specific B cell binds antigen
  2. specific antigen efficiently internalized by receptor-mediated endocytosis
  3. high density of specific antigen fragments presented

25

T/F Adhesion Molecules Initiate Cell-Cell Interactions

true

26

Of the Ig superfamily, what is an intercellular adhesion molecule?

ICAMs

27

Describe the 3 steps of how adhesion molecules initiate contact for DCs

  1. T cell initially binds DCs through low-affinity LFA-1 : ICAM-1 interactions
  2. subsequent binding of TCRs sends signal to LFA-1
  3. conformational change in LFA-1 increases affinity and prolongs cell-cell contact

28

Describe the co-stimulatory molecule binding to naive T cell

co-stimulatory molecule B7 on the DC binds CD28 on naive T cell

29

What are the 1st and 2nd signals of activation for naive T cells?

  1. Recognition of cognate peptide:MHC complex on surface of APC thru the TCR
  2. Interaction between CD28 on T cell with B7 (co- stimulator) on APC

30

What is an autocrine T cell growth factor? What is the result? When does this occur?

Interleukin-2
 (IL-2)

Proliferation/Differentiation

occurs after stimulation of naive T cell

31

Describe how IL-2 is a growth signal for T cells (4 steps)

  1. naive T cells express low affinity IL-2 receptor
  2. Activated T cells express the high affinity IL-2 receptor and secrete IL-2
  3. binding of IL-2 to high-affinity receptor sends a signal to T cell
  4. signal sent from IL-2 receptor induces T cell proliferation

32

What is the difference of the structure of the IL-2 receptor between a naive T cell and activated T cell?

  • it gets higher affinity due to the addition of the IL-2 receptor of the alpha chain being added to the activated T cell

33

T/F some self-reactive T cells escape the negative selection process (thymus)

true

34

What is required for T cell activation? describe its expression. When is it upregulated?

B7 co-stimulation signaling is required for T cell activation

••  B7 expression is inducible
 

  upregulated when potential pathogen is recognized via    pattern-recognition receptors
    (signaling thru Toll-like receptors)

35

Activation signals for naive T cells can occur via co-stimulatory signal and specific signal. Give the signals for this to occur.

1st signal of activation:
TCR binding to cognate peptide:MHC complex


2nd signal of activation:
Interaction between CD28 on T cell with B7 (co- stimulator) on APC

36

For the activation of naive T cells, what must be present for this to occur wrt signaling (3 different possibilites)

  1. To activate a T cell, BOTH a co-stimulatory signal and specific signal must be present
  2. If there is only a specific signal alone, T cell becomes anergic
  3. if co-stimulatory signal alone then there is no effect on the T cell

37

Describe how the Co-Stimulator Molecule (B7) Expression is Inducible

  1. phagocytosis and breakdown of bacteria by macrophage induces expression of MHC II and B7
  2. Macrophage delivers a co-stimulatory signal to T cells recognizing bacterial peptide antigen
  3. proliferation and differentiation of T cells specific for bacterial protein

38

Describe non-bacterial protein antigen presentation by macrophages

unstimulated macrophages do NOT deliver a co-stimulatory signal to T cells recognizing a nonbacterial antigen

results => anergic T cells

39

Describe bacterial antigen presentation by macrophages

bacteria stimulate macrophages to deliver a co-stimulatory signal to T cells recognizing a bacterial antigen

results=> proliferation and differentiation of T cells specific for a bacterial protein

40

Describe antigen presentation of macrophages when they encounter both bacteria and nonbacterial proteins

bacteria stimulate macrophages to deliver a co-stimulatory signal to T cells recognizing a nonbacterial antigen

results => proliferation and differentiation of T cells specific for a non bacterial protein

41

Why is there more signaling required to activate naive CD8 T cells?

  • important because of the cytotoxic capacity of CTLs
  • built-in regulatory fail safe of the immune system

42

Describe the 3 ways for CD8 T cells to be activated

  1. DCs expess high levels of B7 and can activate naive CD8 T cells => activated CD8 T cell makes IL-2, driving its own proliferation and differentiation
  2. APC stimulates effector CD4 T cell, which in turn activates the APC => activated APC expresss B7, which co-stimulates naive CD8 T cell
  3. APC activates CD4 T cell to make IL-2 and naive CD8 T cell to express IL-2 receptors => IL-2 secreted by activated CD4 T cell is bound by CD8 T cell

43

What is an “Armed” Effector T cell? Name 2 important characteristics involved 

a fully differentiated T cell that is ready to perform its effector function

 •• does not require co-stimulation to perform function

••  express different array of adhesion molecules that direct them to appropriate tissues

44

What are the 3 main types of armed effector T cells?

  1. CD8 T cells
  2. CD4 Th1 cells
  3. CD4 Th2 cells

45

Describe the CD8 effector T cell wrt binding and secretions 

Binds to virus infected cell via Fas ligand on it and Fas on the virus

releases cytotoxins and cytokines

46

T cell secretes effector molecules onto surface of target cell. Name the cytotoxins and cytokines secreted from CD8

Cytotoxins 

  • perforin
  • granzymes
  • granulysin

Cytokines

  • IFN-y
  • LT

47

Describe the CD4 Th1 effector T cell wrt binding and secretions 

Th1 bind to macrophage containing bacteria via CD40 ligand on it and CD40 on the macrophage

secretes cytokines in response

48

What are the cytokines secreted by Th1 cells?

  • IFN-y
  • GM-CSF
  • TNF-a
  • LT
  • IL-3

49

Describe the CD4 Th2 effector T cell wrt binding and secretions 

Th2 uses CD40 ligand to bind to CD40 on the B cell presenting specific antigen
 
Secretes cytokines

50

What are the cytokines secreted by Th2 cells?

  • IL-4
  • IL-5
  • IL-10
  • IL-13
  • TGF-B

51

Describe the differentiation of helper T cells and function of Th1

  1. Naive CD4 T cell
  2. proliferating T cell
  3. immature effector T cell
  4. Th1 cell
  • IL-2, IFN-y
  • Macrophage activation, B cell activation, and production of opsonizing antibodies such as IgG1

52

Describe the differentiation of helper T cells and function of Th2

  1. Naive CD4 T cell
  2. proliferating T cell
  3. immature effector T cell
  4. Th2 cell
  • IL-4, IL-5
  • General activation of B cells to make Abs

 

53

What Drives Differentiation of TH0 to TH1/TH2? When does it occur?

“Decision” made during T cell activation; influenced by pathogen

  1. cytokine environment during activation
  2. antigen presented to TH0 cell influences differentiation pathway

 

54

Describe the cytokine environment during activation wrt Th1 and Th2 cells. What stimulates them to become each?

•  CD4 cells activated in presence of IL-12 and IFN-γ will become TH1 cells

•  CD4 cells activated in presence of IL-4 and IL-6 will become TH2 cells

55

Antigen presented to TH0 cell influences differentiation pathway. Describe how it influences Th1 and Th2 differentiation

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

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

56

Give an example with steps of how Differentiation of TH0 to TH1 

  1. Viruses and some bacteria induce IL-12 secretion by DCs that can activate NK cells to produce IFN-y
  2. Naive CD4 T cells, activated in the presence of IL-12 and IFN-y, are committed to differentiate into Th1 cells

57

Give an example with steps of how Differentiation of TH0 to Th2 

  1. Other pathogens may cause synthesis and secretion of IL-4 by NK T cells
  2. Naive CD4 T cells activated in the presence of IL-4 are committed to differentiate into Th2 cells

58

What is a dedicated population of T cells whose function is to suppress T cell  activation?

T regulatory Cells

59

T cells differentiate into T regs when?

during thymic development

60

Describe T regs wrt repertoire, expression and production of cytokines

• have large receptor repertoire that is biased towards self-peptides

• express the transcription factor Foxp3

• produce TGF-β and IL-10

61

What suppresses the activation and development of naive T cells?

T reg cells

62

What is a pro-inflammatory cell type that has important role in anti-microbial  immunity at epithelial/mucosal barriers?

Th17 cells

63

Describe the differentiation into Th17 and the cytokine production done by Th17

  • differentiation of TH0 into TH17 cells is driven by several cytokines  (TGF-β, IL-6, IL-21, and IL-23)
  • TH17 cells produce IL-17 (neutrophil recruitment/activation) and IL-22  (which stimulates epithelial cells to produce anti-microbial proteins)

64

What role does IL-17 have?

 

neutrophil recruitment/activation

65

What is the role of IL-22?

stimulates epithelial cells to produce anti-microbial proteins

66

T/F initiation of adaptive immune responses occurs at the sites of infection

false, initiation of adaptive immune responses does not occur at the sites of infection

pathogen- derived antigens are taken by the lymph to secondary lymphoid organs were the antigen is processed and presented (peptides bound to MHC) by professional APCs

67

What type of T cells leave the thymus by entering the bloodstream from which they migrate through the various secondary lymphoid tissues?

mature

68

Describe the process of how naive T cells enter the lymphoid organs?

by crossing the walls of high epithelial venules (HEV);

this process is mediated by adhesion molecules selectively expressed by naïve T cells

69

_____ is expressed by naïve T cells and binds to carbohydrate moieties of vascular addressins which are _____? Where are the vascular addressins expressed?

L-selectin

CD34 and GlyCAM-1 which are expressed on surface of HEVs

70

What allows naive T cells to interact via diapedesis?

L-selectin expressed by naïve T cells and binds to carbohydrate moieties of vascular addressins (CD34 and GlyCAM-1) that are expressed on the surface of HEVs allows for diapedesis

71

What is role of chemokines bound to the surface of HEVs?

activate lymphocyte-function-associated antigen-1 (LFA-1, on the T cell)

72

Describe the step by step process of diapedesis (3)

1) chemokines bound to the surface of HEVs activate lymphocyte-function-associated antigen-1 (LFA-1, on the T cell)
2) LFA-1 then binds tightly to intracellular adhesion molecule-1 (ICAM-1) on the HEV

3) the tight interaction allows the T cell to squeeze between two endothelial cells and enter the
2 ̊ lymphoid tissue (diapedesis)

73

Similar to positive selection of T cells in the thymus, what else is a survival signal for T cells?

contact between naïve T cells and dendritic cells (MHC:self peptides) also appears to act as a
survival signal for the T cell

74

initial interactions between T cells and APC are mediated by what? What is important about these interactions?

cell adhesion molecules 

these interactions facilitate interaction of the TCR of the T cell with the MHC complexes on APCs

75

adhesion molecules on the surface of the T cell are ___(3)___ bind to adhesion molecules on the surface of the antigen-presenting cell ___(3)___?

LFA-1, CD2, and ICAM-3

 ICAM-1 or 2, LFA-3, and LFA-1)

76

What happens if the T cell encounters its cognate peptide:MHC complex during this interaction (specific antigen recognition)?

LFA-1 on the surface of the T cell undergoes a conformational change that increases its affinity for ICAMs, which prolongs the cell-to-cell contact 

77

What happens to naïve T cells that do not encounter specific antigen?

  • enter the efferent lymphatic vessel,
  • return to the bloodstream,
  • recirculate back to other secondary lymphoid tissues

78

 each of the different antigen-presenting cells (APCs) are specialized to deal with a particular type of pathogen: name them
 

1) dendritic cells are most efficient at presentation of viral peptide antigens; also able to present antigens derived from the extracellular milieu

2) macrophages are best suited for capturing extracellular, independently replicating organisms such as bacteria and yeast; can also present antigens derived from intracellular pathogens

3) B cells most efficiently present peptide from soluble antigens; can present antigens derived
from intracellular and extracellular sources

79

What is one feature that distinguishes APCs from all other cells in the body? What is its role?

their ability to express a surface molecule known as co-stimulator molecule, or B7

B7 molecule binds to a T cell surface molecule known as CD28

80

What is the only way for activation of T cells to occur?

 only APCs can activate naïve T cells

81

 there are two signals that are required for T cell activation: Name them

1) binding of the TCR to its cognate peptide in the context of MHC

2) co-stimulation signaling that results from interaction between B7 (on the APC) and
CD28 (on the T cell)

82

What is the best APC? what is its main role as a cell?

mature dendritic cells are the most potent antigen-presenting cells

their sole function is to present antigen to T cells

83

Describe the path from beginning to end of a dendritic cell (DC) and where specifically they reside

1) common myeloid progenitor => immature DC,

2) leave the bone marrow and migrate to their peripheral sites 

generally found under most surface epithelia and in solid organs

84

What is the role of immature DC?

immature dendritic cells do not present antigen;

they are very active in taking up antigen

85

How do immature DCs generally take up antigen?

macropinocytosis

86

What signals immature DCs to mature? Where does this occur?

 immature dendritic cells are signaled by infection to migrate (via lymphatics) to the T cell
zones of secondary lymphoid tissues
where they become mature

87

mature DCs, or interdigitating reticular cells, cannot do what? what is their role?

can no longer take up antigen

now are able to productively present antigen to T cells 

88

What 3 things do mature DCs express? Name them specifically

  • express co stimulatory molecules (B7) and high levels of MHC I and II

 

  • adhesion molecules (ICAM-1, ICAM-2, LFA-1, and LFA-3)

89

mature DCs produce what and what is the purpose?

produce a chemotactic cytokine (or chemokine) that
attracts naïve T cells;

this chemokines is known as “DC-CK”

90

What is an immature DC of the skin? What is its main role?

Langerhans' cells

uptake of antigen

91

What are scavenger cells that can be induced by pathogens to present antigens to naïve T cells?

macrophages

92

Why are macrophages considered in the front line of defense against microorganisms?

they phagocytose and destroy many microbes without the aid of acquired immune responses

93

T/F resting macrophages do not express MHC class II and do not express B7 

false, resting macrophages express very low levels of MHC class II and do not express B7

94

What is peripheral tolerance wrt macrophages?

macrophages that encounter antigen in the absence of bacterial products will present antigen
(low level) but will not supply co-stimulation signals to T cells which induces anergy

95

When will a macrophage act as an APC?

macrophages in which microbes persist participate in the development of acquired immunity by
acting as professional antigen presenting cells

96

Once a macrophage uses its numerous receptors for microbes, it uptakes and phagocytosis them. What occurs next?

once phagocytosed, the microbe is processed and the resulting peptides are loaded onto and presented by MHC molecules

97

Once a macrophage phagocytosizes a microbe, what occurs wrt MHC  and other molecules??

upregulate their expression of MHC molecules 

upregulate expression of B7 molecules  

present peptides from the pathogen on MHC molecules

98

What is a unique characteristic that makes B cells a professional APC?

 bind to soluble antigenic molecules through their B cell receptors (surface Ig)

99

After binding to soluble antigenic molecules, B cell do what?

B cell internalizes antigen, processes antigen, and presents peptides on MHC class II molecules

100

What T cell does the B cell present to? Why?

since B cells constitutively express high levels of MHC class II molecules, and peptide:MHC complexes are displayed on the cell surface, B cells readily present antigen to antigen- specific CD4+ T cells

101

If the B cell presents to a T cell that is an effector cell, what will occur?

expression of B7 is upregulated by microbial products 

a B cell that has upregulated B7 expression can productively present peptide antigens to naïve CD4+ T cells (2nd signal of B cell activation)

102

What are the 2 signals required for the activation of T cells?

1) encounter with specific peptide antigen bound to an MHC molecule on an APC

2) interaction of CD28 (on the T cell) with B7 expressed on the surface of the APC to lead to upregulation of IL-2

103

What is important about the interaction of CD28 on the T cell with B7 expressed on the APC?

•• this signaling thru CD28 is thought to stabilize IL-2 mRNA (20-30 fold increase in IL-2 expression results);

CD28 signaling also appears to activate the transcriptional activators AP-1 and NF- B (increases IL-2 expression by 3 fold);

total upregulation of IL-2 is around 90-fold

104

a T cell that recognizes its specific antigen bound to MHC, but does not receive the co- stimulation signal, will become anergic. What term is this?

 peripheral tolerance

105

What affect will costimulation in the absence of specific antigen will have on the T cell? Why is this important?

costimulation in the absence of specific antigen will have no effect on the T cell 

helps to prevent autoimmune responsiveness

106

Why CD8+ T cells need more co-stimulation than do CD4+ T cells?

since the effector function of CD8+ T cells is so destructive, the mechanism for activation of these cells is somewhat more stringent 

107

What is a require to activate a CD8 T cell?

activated by dendritic cells (DCs they have intrinsically high costimulation activity)

108

If a DC does not present to a CD8, how can other APCs activate it? How specifically?

often requires that both the CD8+ T cell, and a CD4+ T cell must recognize antigen on the same APC simultaneously

CD4=> 1) induce macrophages to upregulate B7 expression (upregulate costimulation potential) on the macrophage

CD4=> 2)  produce IL-2 which could bind to IL-2 receptors on the CD8 cell

109

the proliferation and differentiation of activated T cells is driven by what molecule?

 autocrine growth factor, interleukin-2 (IL-2)

110

What is the role of IL-2 production and responsiveness in T cell activation? (3)

  1. IL-2 is produced by activated T cells upon activation
  2. T cells normally express a moderate affinity form of IL-2 receptor, allowing T cells to respond only to high [IL-2]; activation of T cell induces expression of a high affinity form of the IL-2 receptor which allows T cells to respond to lower [ IL-2]
  3. after proper activation signals and binding to IL-2 thru its high affinity IL-2 receptor, cell can divide 2-3x/day for several days
  4. IL-2 also stimulates differentiation of these new cells into armed effector cells

111

What is the structure of the IL-2 receptor?

  • the high affinity IL-2 receptor is a heterotrimer and consists of an alpha, beta, and gamma chain  => all 3 traverse membrane of T cell
  • the moderate affinity IL-2 receptor is composed of only the Beta and gamma chains

112

What is a T cell that can produce all of the proteins that are required for its specialized function?

an armed T cell effector cell

113

What are the 3 most important characteristics of armed effector T cells?

  1. armed effector T cells can become activated to perform their function by stimulation with specific antigen alone; no costimulation signal is needed (B7:CD28 signaling is not required)
  2. they express higher levels of the adhesion molecules LFA-1 and CD2, but lose cell-surface L- selectin (no longer recirculate through lymph nodes)
  3. they express VLA-4 (adhesion molecule) which allows them to bind to vascular epithelium at sites of inflammation (promotes movement into infection site)

114

When do activated T cells differentiate into effector T cells?

  1. once a naïve T cell receives the two signals required for activation, it secretes and responds to IL-2 which drives rapid proliferation of the particular T cell clonal line
  2. after 4-5 days of rapid proliferation, the newly generated cells then differentiate into effector cells that are able to respond to antigen without co-stimulation

115

What are the 3 primary classes of effector T cells?

  1. Effector CD8 T cells
  2. Th1 CD4 cells
  3. Th2 CD4 cells

116

Each class of effector T cells are specialized to deal with different types of pathogens. Describe effector CD8 T cells

cytotoxic T cells

  • recognize peptide antigens bound to MHC class I molecules presented on the surface of infected cells;
  • could be any nucleated cell in the body that is infected with a virus or intracellular bacteria or parasite;
  • CTLs kill these cells

117

Each class of effector T cells are specialized to deal with different types of pathogens. Describe Th1 CD4 

  • primarily involved in development of cell-mediated immune responses
  • recognize peptide antigens bound to MHC class II molecules presented on the surface of macs or B cells

118

Each class of effector T cells are specialized to deal with different types of pathogens. Describe Th2 CD4

  • primarily involved in development of humoral immune responses
  • recognize peptide antigens bound to MHC class II molecules presented on the surface of B cells (primarily)

119

in general, TH1 CD4 T cells produce cytokines that modulate the function of the APC that is
presenting the antigen to the CD4 T cell. Describe this in detail wrt to macs and B cells

  • TH1 cells supply helper signals (cytokines) that stimulate macrophages, making them more phagocytic and more bacteriocidal

 

  • supply help (in the form of cytokines) to B cells (2nd signal of activation)
  • influences class switching and initiates somatic hypermutation
  • TH1 CD4 cells induce B cells to produce Ab (class switching) that are efficient for opsonization (IgG1 and IgG3)

120

T/F Th2 CD4 cells supply help to B cells that can influence class switching and initiate somatic hypermutation

true

121

T/F TH2 CD4 cells induce B cells to produce all other isotypes of Ab

true

122

T/F Naïve CD8 cells emerging from the thymus are destined to become CTL

true

123

How is it decided whether a T helper Cell will be a TH1 or TH2 cell?

all CD4 cells that leave the thymus
are considered TH0 cells

the decision to become a TH1 or a TH2 cell is made upon 1st encounter with antigen

124

Why is the decision between Th1 and Th2 development vital?

 it determines whether the acquired immune response will be primarily cell-mediated or Ab-mediated

125

What are the factors that contribute to the decision bw Th1 and Th2 development?

  1. cytokine environment upon initial activation of a naïve T cell
  2. the “nature” and amount of antigen presented to a naïve TH0 cell also influences differentiation into either a TH1 or TH2 cell

126

WRT the “nature” and amount of antigen presented to a naïve TH0 cell also influences differentiation into either a TH1 or TH2 cell. Describe this in wrt concentration of the antigen

• TH0 cells that are presented with low concentrations of antigen that bind weakly to the TCR tend to differentiate into TH2 cells

• TH0 cells that are presented with high concentrations of antigen that bind tightly to the TCR tend to differentiate into TH1 cells

127

WRT cytokine environment upon initial activation of a naïve T cell. Describe the environment that will lead to Th1 cells. Give details of the cytokines as well

presence of IL-12 and IFN-y => Th1

IL-12 is produced by macrophages and dendritic cells in response to viral and some intracellular bacterial infections

NK cells and T cells produce IFN-y which inhibits development of Th2 cells

Th1 cells produce IFN-y which down-regulates proliferation of Th2

128

WRT cytokine environment upon initial activation of a naïve T cell. Describe the environment that will lead to Th2 cells. Give details of the cytokines as well

presence of IL-4 and IL-6 tend to differentiate into Th2 cells

•• IL-4 and IL-10(produced by Th2) inhibit the generation of TH1 cells

a possible source of IL-4 is a subset of CD4 T cells known as NK1.1+ CD4 T cells or NK T cells

129

What is a T reg cell?

CD4+ T cells that have these characteristics:

1) self antigen-specific T cell receptors,

2) express a surface protein known as CD25

3) express a transcriptional repressor known as FoxP3.

130

TH0 cells differentiate into Treg cells when they are activated in the presence of what?

TGF-B

131

How are T regs used in the active peripheral tolerance mechanism?

upon recognition of their cognate self antigen, Tregs produce mediators (cytokines) that suppress proliferation of naïve T cells that are responding to self-antigens presented on the same APC

132

Why does the deficiency of FoxP3 (an X-linked gene) produce a fatal autoimmune disease directed at a variety of host tissues? What is the only treatement for this disease known as IPEX?

Since FoxP3 is a transcriptional repressor, the Treg will not be able to cause apoptosis to the self-antigen specific TCR thus causing these cells to remain alive and attack the body

Tx=> bone marrow transplant from healthy HLA-identical sibling

133

What is a newly discovered subset of T helper cells that produce interleukin-17 (IL-17), IL- 21, and IL-22?

Th17 cells

134

deficiency of TH17 cells can leave the patient susceptible what?

susceptible to opportunistic pathogens

135

What is a newly discovered subset of helper T cells that produce TGF-B and IL-10?

Th3 cells