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MICRO > Ch5: T Cells > Flashcards

Ch5: T Cells Flashcards

1
Q

T-cell precursoWrs are made where?

A

Bone marrow

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2
Q

T-cell precursors from bone marrow travel where?

A

Thymus to develop

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3
Q

Mature T cells leave what?

Where do they go?

A

Thymus

Secondary lymphoid tissues

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4
Q

Upon entering the thymus cortex what do T cells do?

A

Begin positive and negative gene selection

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5
Q

What cells are immature thymocytes next to? 2

A

Branched cortical epithelial cells

Macrophages

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6
Q

The thymus medulla contains what? 4

A
  1. Mature thymocytes
  2. medullary epithelial cells
  3. dendritic cells
    macrophages
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7
Q

What happens at Hassali’s corpuscles?

A

Cellular destruction

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8
Q

Function of macrophages in thymus?

A

Remove T cells that failed to mature

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9
Q

A birth, what happens to T-cell producing area of thymus?

A

Replaced with fatty tissue (Involution)

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10
Q

3 categories of mature peripheral T cells

A

Long-lived
Self-renewing
Both

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11
Q

What receptors do T cells display in the bone marrow? 2

A

CD34

CD44

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12
Q

What receptors do T cells display outside of bone marrow? 4

A

CD2, CD5, IL-7, CD1A

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13
Q

Can immature T cells outside of bone marrow recognize antigens?

A

No

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14
Q

T cell gene rearrangement occurs where?

A

Thymus

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15
Q

Why is T cell diversity greater?

A

T cells aren’t replenished throughout life

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16
Q

The Fab fragment of an antibody is similar to what?

How so? (2)

A

TCR

  1. 2 chains with variable and constant regions
  2. Antigen recognition occurs at tip of variable region
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17
Q

Major differences of Ab and TCR?

A
  1. Antibody monomers can bind 2 antigens simultaneously
  2. Antibodies recognize antigen in their native conformation
  3. Antibody recognition does not require processing and presentation of antigen
  4. MHC restriction is not required for antibodies
  5. Antibodies function as effector molecules while TCR is a receptor that activates an effector cell
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18
Q

What is the signaling that initiation maturation upon a T cell arriving in thymus?

A

Notch-1 Signaling

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19
Q

Describe Notch-1 signaling 4

A
  1. Notch-1 on thymocytes interact with Notch ligand on thymic epithelial cells
  2. Transcription repressors removed from thymocyte DNA
  3. Transcription co-activators attracted
  4. Transcription and maturation of T Cells occurs in thymus
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20
Q

Upon T cells arriving in Thymus, what rearrangement can occur?

A

Beta, Gamma and delta

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21
Q

Two possibilities of t cell rearrangement?

A
  1. Gamma and delta chains rearrange forming gamma:delta mature T cell that leaves the thymus
  2. Beta chain rearranges forming a pre-TCR. Induced expression of CD4 and CD8. Rearrangement resumes of alpha, gamma, and Beta genes
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22
Q

The pre-T cell Beta chain is tested where?

Using what?

A

Cell surface

Surrogate alpha chain known as pTalpha

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23
Q

The pre-T cell receptor is expressed when?

A

In context of signaling molecules that are required for T cell activation (CD3 complex)

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24
Q

Once an appropriate Beta chain has been identified in pre-T cell receptor, what occurs?

A

Removed from cell surface and rearrangement of alpha chian is induced

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25
Q

What are genes specific to T cells? 4

A

Zap-70, CD3, CD4, CD8

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26
Q

Positive selection of alpha:beta T cells is done by what cells? Where?

A

Cortical epithelial cells

Thymus

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27
Q

alpha:beta t cells are positively selected by recognition of what?

A

Self-MHC

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28
Q

Upon being positively selected, what is status of T cell?

A

Double positive: Has both CD4 and CD8 expressed

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29
Q

What aids in the formation of double-positive T cells?

A

Cells in thymus that express both MHC-I and MHC-II

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30
Q

What determines whether the T cells will commit to CD8 or CD4 type cell?

A

If the TCR expressed by the double-positive thymocyte interacts with MHC-I or MHC-II

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31
Q

Negative selection is what?

A

Removal of T cells that recognize self peptide

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32
Q

What TF turns on expression of non-thymic self antigens in thymus?
What does this allow for?

A 
Autoimmune Regulator (AIRE)
Negative selection based on reactivity toward self tissue-specific antigens from tissues they might not otherwise see
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33
Q

Central tolerance is derived from what?

A

Negative selection of T Cells

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34
Q

Do self-reactive T cells exist in circulation?

A

Small amounts in ALL individuals

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35
Q

Self-reactive T cells recognize what?

What does this allow them to become?

A

Self antigens expressed by self MHC

Regulatory T Cells (Tregs)

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36
Q

Do Tregs proliferate?

What do they produce?

A

No
Produce cytokines that suppress activity of other self-reactive T cells that have bound to the same MHC:peptide complex on the same APC

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37
Q

Steps in T cell maturation in thymus 5

A
  1. Double-negative CD3 thymocytes in subcapsular zone proliferate and differentiate into double positive CD3 thymocytes
  2. In the cortex, positive selection occurs
  3. In the cortex, negative selection occurs to form mature, self-restricted, self-tolerant, single-positive CD4 or CD8 T cells
  4. Leave the thymus through the blood
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38
Q

Naive mature T cells enter what?

A

Lymph nodes

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39
Q

If the T cell encounters its specific antigen, what happens?

A

T cell activates leading to proliferation and differentiation

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40
Q

T cells that do not recognize their specific peptide travel where?

A

Other lymph nodes and eventually re-enter circulation via efferent lymphatics

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41
Q

How are T cells attracted to lymph node?

A

Chemokines CCL21 and CCL19 are secreted by stromal and dendritic cells in lymph node cortex

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42
Q

What receptor must T-cells have to use the cytokines expressed by cortical lymph node cells?

A

CCR7

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43
Q

The initial interaction associated with the homing of T cells to the lymph node is between what?

A

Mucin-like vascular addressins (CD34 and GlyCAM-1) which bind L-selectin on T cells

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44
Q

L-selectin has what function?

A

Homes mature, unactivated T cells to lymph nodes

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45
Q

Steps of T cell entering lymph node? 5

A
  1. Circulating T cell enters high endothelial venule
  2. L-selectin on T cell binds to endothelial CD34 and GlyCAM-1 and starts rolling interaction
  3. LFA-1 on T Cell activated by chemokines bound to ECM.
  4. Activated LFA-1 binds to ICAM-1
  5. Diapedesis occurs and T cell enters lymph node
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46
Q

After T cell enters the lymph node, it interacts with what?

A

Professional APC’s

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47
Q

Initial interactions between T cells and DC’s are mediated by what? 4

A
  1. CD2 of T cell binds to LFA-3
  2. LFA-1 of T cell binds to ICAM-1
  3. LFA-1 of T cell binds to ICAM-2
  4. ICAM-3 of T cell binds to DC-SIGN
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48
Q

Are APC and T cell interactions transient?

A

Yes so the T cell can move through lymph node

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49
Q

T cells scan APC’s for what?

A

MHC expressing peptide that it recognizes

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50
Q

When the TCR and CD4 bind to the MHC, what happens?

A

Signal transduced to LFA-1 changing its conformation resulting in greater affinity for ICAM-1 that prolongs cell-cell contact

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51
Q

What is the immunological synapse?

A

Gathering of receptors on surface of an APC and a T Cell that work in coordinated effort to prolong their interaction and strengthen the signals associated with activation of T cell by APC

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52
Q

What induces expression of MHC-II peptide and B7 co-stimulatory molecule by the APC?

A

Phagocytosis of a pathogen

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53
Q

What is the first signal required for T cell activation?

A

TCR activation with peptide:MHC

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54
Q

Second signal required for T cell activation?

A

B7 co-stimulatory molecule interaction with CD28

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55
Q

B7 co-stimulatory molecules are known as what?

A

CD80 and CD86

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56
Q

What else can activated T cells express that will bind B7?

Result of this?

A

CTLA4

CTLA4 acts as antagonist that dampens activation and limits proliferation of activated T cells

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57
Q

When an antigen binds the antigen-specific B- cell receptor, the B cell expresses what?
Why?

A

B7 on the surface

To interact with CD28 on T cells

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58
Q

The T cell receptor recognizes what on the B cell?

And then expresses what?

A

Peptide:MHC complex

CD40 ligand

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59
Q

CD40 ligand on the T cell binds to what?

Which provides what?

A

CD40 on the APC

Second signal of activation of the APC

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60
Q

Activation of a B cell by foreign antigen can provide signals for T cell activation which leads to what?

A

further APC activation and induction of a cellular

response (antibody production).

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61
Q

How do co-stimulatory molecules differ between APC’s when interacting with T Cells?

A

They don’t

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62
Q

Do cytokines produced and cellular functions differ between APC’s when interacting with T cells?

A

No

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63
Q

The T cell receptor is similar to the B cell receptor in what respect?

A

too weak to signal by itself

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64
Q

The complete TCR has acessory proteins called what?

A

CD3 complex

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65
Q

The CD3 complex is made up of what chains? 4

A

2 ε chains
one δ chain
one γ chain
2 ζ (zeta) chains

66
Q

Each signal chain of CD3 complex has what?

Which have what action done to them?

A

ITAM’s (immunoreceptor tyrosine-based activation motifs)

phosphorylated by kinases

67
Q

Helper T cells express which Co-Receptor?

A

CD4

68
Q

Cytotoxic T cells express which co-receptor?

A

CD8

69
Q

Both CD4 and CD8 T cells express what? (2)

A

TCR and CD3 on their surface

70
Q

Uptake of antigen by a professional APC induces expression of what?

A

Co-stimulatory molecule B7

71
Q

What leads to T cell activation?

A

TCR and its co-receptor recognize specific peptide:MHC

72
Q

What keeps T cell and APC in close proximity?

A

LFA-1:ICAM-1

73
Q

What signals survival of T cell

A

CD28 of the T cell interacting with B7 of APC

74
Q

The IL-2 receptor on naive T cells is made up of what? (2)

A

Gamma and Beta chain

75
Q

The IL-2 receptor on naive T cells has a low affinity for what?

A

IL-2

76
Q

Upon activation, T cells express what? (2)

A

IL-2

IL-2 receptor alpha subunit

77
Q

What does the IL-2 receptor alpha subunit do upon synthesis?

A

binds with the b and g chains to increase the affinity of the IL-2 receptor for IL-2.

78
Q

What is signaled when IL-2 binds to IL-2 receptor?

A

signals the antigen-specific T cells to proliferate to produce multiple clones.

79
Q

Activated, effector T cell clones no longer require what?

A

costimulatory molecules to act on cells they recognize.

80
Q

What are 3 possibilites of results of interaction between APC and T cell?

A
  1. Activation of T cell
  2. Anergization of T cell
  3. No effect on T cell
81
Q

What must happen for T cell to activate?

A

Co-stimulatory signal and specific signal are both encountered by the T cell

82
Q

What causes a T cell to anergize?

A

Specific signal alone is encountered

83
Q

Why does a T cell anergize in response to specific signal only?

A

so that it does not respond to a potential self antigen

84
Q

What would APC-T cell interaction would have no effect on T cell

A

If only co-stimulatory signal is encountered. (no antigen = no attack)

85
Q

What do activated T cells turn off at their surface? 2

A

L-selectin

CD45RA

86
Q

What do activated T cell turn on at their surface or increase expression of? 5

A 
VLA-4
LFA-1
CD2
CD44
CD45RO
87
Q

After encountering an antigen in the lymph node, what must effector T cells do?

A

Move to site of infection

88
Q

What integrin does a T cell have to help it more out of node?

A

VLA-4

89
Q

VLA-4 of T cells interacts with what?

A

VCAM-1

90
Q

Where is VCAM-1 expressed?

A

activated endothelium around inflamed tissue

91
Q

Two types of effector T cells?

A

CD4 Helper

CD8 CTL

92
Q

Two types of memory T cells?

A

CD4

CD8

93
Q

CD4 cells do what

A

Activate other cells like macrophages and B cells

94
Q

CD8 cells do what? 2

A

Kill infected cells

Activate macrophages

95
Q

Two phases in the kinetics of T cell responses?

A
  1. Clonal expansion

2. Contraction

96
Q

7 Main steps of T cell activation starting with antigen recognition?

A
  1. Antigen recognition in lymphoid organs
  2. T cell expansion and differentiation
  3. Differentiated effector T cells enter circulation
  4. Migration of effector T cells and other leukocytes to site of infection
  5. Effector T cells encounter
97
Q

Cytokine receptors use what pathway of signaling?

A

JAK/STAT

98
Q

Explain the steps of cytokine receptor actions

A
  1. Cytokine receptors of at least two chain bind JAK’s
  2. Cytokine binding dimerizes the receptor bringing together the cytoplasmic JAK’s
  3. Cytoplasmic JAK’s activate each other and phosphorylate the receptor
  4. STAT’s bind to the phosphorylated receptors
  5. STAT’s are then phosphorylated by activated JAK’s
  6. Phosphoarylated STAT’s form dimers
  7. STAT dimers move to nucleus to initiate gene transcription
99
Q

What tells T cells what lineage they will commit to?

A

APC’s

100
Q

What allows T cells that are specific for a pathogen to be flexible in the type of effect that they will induce?

A

The ability to change phenotypes

101
Q

Signature cytokines of Th1 cells

A

IFN gamma

102
Q

Signature cytokines of Th2 cells? 3

A

IL-4
IL-5
IL-13

103
Q

Signature cytokines of Th17 cells? 3

A

IL-17A
IL-17F
IL-22

104
Q

Immune reactions of Th1 cells? (2)

A
  1. Macrophage activation

2. IgG production

105
Q

Host defense of Th1 cells?

A

Intracellular microbes

106
Q

What diseases do Th1 cells play a part? (2)

A
  1. Autoimmune disease

2. Chronic infections

107
Q

Immune reaction of Th2 cells? (3)

A
  1. Mast and eosinophil activation
  2. IgE production
  3. Alternative macrophage activation
108
Q

Host defense of Th2 cells?

A

Helminthic parasites

109
Q

Th2 have role in what diseases?

A

Allergic diseases

110
Q

Immune reactions of Th17 cells?

A
  1. Neutrophilic

2. Monocytic inflammation

111
Q

Host defense role of Th17 cells?

A

Extracelular bacteria

Fungi

112
Q

Th17 have a role in what types of diseases?

A

Autoimmune and inflammatory diseases

113
Q

Cytokiens produced during Th1 have what effect on Th2 response?

A

Inhibit it

114
Q

Cytokines produced during Th2 have what effect on Th1 response?

A

Inhibit it

115
Q

A macrophage infected with an intracellular bacteria expresses what on its surface?
And produces what cytokine?

A

Bacterial peptides bound to MHC-II

IL-12

116
Q

IL-12 induces what?

A

Th1 response

117
Q

The Th1 cell expresses what ligand on its surface?

A

CD40

118
Q

Th1 responds to IL-12 how?

Which then has what effect?

A

Produces IFN-gamma

Tells macrophage to kill bacteria in its vesicles

119
Q

Two things that tell an APC to kill whatever bacteria it has inside it?

A
  1. CD40 of T cell binding to CD40L of APC

2. IFN-gamma produced by CD40 binding

120
Q

Mycobacteria can survive in macrophages for what reason?

A

resisting the killing activity of Th1 cells

121
Q

Mycobacteria living in a macrophage cause formation of what?

A

multi-nucleated giant cell made up of

multiple fused macrophages that contain mycobacteria

122
Q

What defines a granuloma?

A

presence of these multi-nucleated giant cells surrounded by T cells, many of which are CD4

123
Q

Th1 cell releases what cytokines and ligands?

A
  1. IFN-gamma and CD40
  2. Fas ligand or LT
  3. IL-2
  4. IL-3 and GM-CSF
  5. TNF-alpha and LT
  6. CXCL2
124
Q

Effect of Th1 releasing IFN-gamma and CD40?

A

Activate macrophage to destroy engulfed bacteria

125
Q

Effect of Th1 releasing Fas ligand or LT?

A

Kills chronically infected macrophages

126
Q

Effect of Th1 releasing IL-2

A

Induces T-cell proliferation which increases the number of effector T cells

127
Q

Effect of Th1 releasing IL-3 and GM-CSF

A

Induces macrophage differentiation in bone marrow

128
Q

Effect of Th1 releasing TNF-alpha and LT?

A

Activates endothelium to induce macrophage adhesion and exit from blood vessel

129
Q

Effect of Th1 releasing CXCL2?

A

Causes macrophages to accumulate at site of infection

130
Q

Antigen recognition of a Th2 cell results in what being expressed? (4)

A
  1. CD40 ligand
  2. IL-4
  3. IL-5
  4. IL-6
131
Q

Can polysaccharides be presented to T cells?

A

No

132
Q

How do we get immunity to polysaccharides in steps?

A
  1. B cell binds bacterial polysaccharide component of vaccine conjugate
  2. Conjugate is internalized and degraded
  3. Peptides from the toxoid are presented to the T cell which activates the B cell
  4. Activated B cell differentiates into a plasma cell that produces anti-polysaccharide antibodies that bind to bacteria
133
Q

At the end of B and T cell interaction with a polysaccharide what is each cell specific for?

A

B cell: Polysaccharide

T-cell: the toxoid

134
Q

What is needed for activation of CD8 T cells? 2

A
  1. APC or tissue cell with microbe infection

2. Co-stimulation from cytokines

135
Q

3 general steps of CD8 T cell action?

A
  1. Antigen binding and recognition of CTL to target cell
  2. CTL activation and granule exocytosis
  3. Apoptosis of target cell
136
Q

3 main cytotoxins released by CD8 T cells?

A
  1. Perforin
  2. Granzymes
  3. Granulysin
137
Q

What does perforin do?

A

Forms pores in cell membranes of target cells

138
Q

What do granzymes do?

A

Serine esterases that enter the cytoplasm of target cells inducing apoptosis

139
Q

What does granulysin do?

A

Membrane-perturbing protein that works with perforin and serglycin to form pores in target cells.

140
Q

How do CD4 and CD8 cells work together?

A

CD4 cells activate killing of microbes in phagolysosomes

CD8 then kills the infected cell

141
Q

4 steps in T cell development from bone marrow to thymus to periphery

A
  1. T-cell precursor rearranges its T cell receptor genes in thymus
  2. Immature T cells that recognize self MHC receive signals for survival (too strong of recognition and cells are also removed)
  3. Mature T cells encounter foreign antigens in peripheral lymphoid organs and are activated
  4. Activated T cells proliferate and migrate to peripheral sites to eliminate infection
142
Q 
If a thymocyte has weak recognition of class II MHC + peptide it undergoes what?
To become what?
A

Positive selection

Mature CD4 T cell

143
Q 
If a thymocyte has weak recognition of class I MHC + peptide it undergoes what?
To become what?
A

Positive selection

CD8 T cell

144
Q 
If a thymocyte has no recognition of class I MHC or class II + peptide it undergoes what?
To become what?
A

Fails to go through positive selection

Apoptosis

145
Q 
If a thymocyte has strong recognition of class I MHC or class II + peptide it undergoes what?
To become what?
A

Negative selection

Apoptosis

146
Q

Naive T cells use L-selectin to bind to what on endothelial cell?
Function of this?

A

L-selectin ligand

Adhesion of naive T cells to HEV in lymph node

147
Q

Naive T cells use LFA-1 to bind to what on endothelial cell?

Function of this?

A

ICAM-1

Stable arrest on HEV

148
Q

Naive T cells use CCR7 to bind to what on endothelial cell?

Function of this?

A

CCL19 or CCL2

Activation of integrins and chemotaxis

149
Q

Activated T cells use E and P selectin ligands to bind to what on endothelial cell?
Function of this?

A

E or P selectin

Weak adhesion of effector and memory T cells to cytokine-activated endothelium at peripheral site of infection

150
Q

Activated T cells use LFA-1 or VLA-4 ligands to bind to what on endothelial cell?
Function of this?

A

ICAM-1 or VCAM-1

Stable arrest on cytokine activated endothelium

151
Q

Activated T cells use CXCR3 to bind to what on endothelial cell?
Function of this?

A

CXCL10

Activated of integrins and chemotaxis

152
Q

Cytokines that CD8 cells release at target cell? (2)

A

IFN-gamma

LT

153
Q

Cytokines that Th1 cells release at target cell? (5)

A 
IFN-gamma
GM-CSF
TNF-alpha
LT
IL-3
154
Q

Cytokines that Th2 cells release at target cell? (5)

A 
IL-4
IL-5
IL-10
IL-13
TGF-beta
155
Q

Action of IL-2?

A

Survival, proliferation, and differentiation of effector and regulatory T cells

156
Q

Effect of IL-4?

A

B cell switching to IgE

157
Q

Effect of IL-5

A

Activation of eosinophils

158
Q

Effect of IFN-gamma?

A

Activate macrophages

159
Q

Effect of TGF-Beta?

A

Inhibition of T cell activation

Differentiation of regulatory T cells

160
Q

Two main Th1 cell responses to antigen?

A
  1. Classical macrophage activation (IFN-gamma)

2. Complement binding and opsonizing IgG antibodies (IFN-gamma)

161
Q

5 main responses of Th2 cells to antigen?

A
  1. Antibody production (IL-4)
  2. Mast cell degranulation (IL-4)
  3. Intestinal mucus secretion and peristalsis (IL4 and IL13)
  4. Eosinophil activation (IL-5)
  5. Alternative macrophage activation (IL4, IL13)
162
Q

3 main responses of Th17 cells to antigen?

A
  1. Inflammation neutrophil response (IL-17)
  2. Antimicrobial peptides (IL-17 and IL-22)
  3. Increased barrier function (IL-22)

MICRO (22 decks)

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