Cell Mediated Immunity Part 1&2 (Exam 1) Flashcards

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1
Q

What are the two major ways in which TCR differ from BCR

A

TCR is never secreted

TCR must recognize antigen via MHC and not free antigen

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2
Q

What chain in the T cell is synonymous to the heavy chain in B cells

A

Beta chain

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3
Q

What chain in the T cell is synonymous to the light chain in B cells

A

alpha chain

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4
Q

Describe the structure of TCR

A

two chains: one alpha, one beta

each chain composed of two domains

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5
Q

What does a TCR resemble

A

a Fab fragment (one arm of an Ab molecule)

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6
Q

when are TCR secreted

A

never

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7
Q

What is the signaling molecule for T cells

A

CD3

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8
Q

CD3 is analagous to what

A

Ig alpha and beta

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9
Q

What is CD3 composed of

A

5 proteins lodged in the membane

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10
Q

What are the 5 proteins of CD3

A

gamma-epsilon
epsilon delta
zeta zeta or zeta nu

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11
Q

How is CD3 attached to TCR

A

covalently

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12
Q

What is CD3 important in

A

t cell activation and differentiation

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13
Q

What marker can be used to measure total counts of T cells in a patient

A

CD3 as it is found on Th and Tc cells

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14
Q

What is the proportion of Th to Tc in a healthy individual

A

2 Th per 1 Tc

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15
Q

What would be the result of a CD3 mutation

A

lack of T cell activation and proliferation

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16
Q

How many isotypes do B and T cell receptors have

A

B cells: 2 (IgM and IgD)

T cells: 1 (Alpha/beta)

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17
Q

How many combining sites are on B and T cells

A

B cells 2

T cells 1

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18
Q

What components are involved in signal transduction in B cells and T cells

A

B cells: Ig alpha and beta, CD19, CD21

T cells: CD3

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19
Q

Compare B and T cell flexibility

A

B cells: flexible due to hinge

T cell: rigid

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20
Q

How does gene rearrangement occur in T cell receptors

A

similar to B cell gene arrangement

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21
Q

Which chain of TCR is rearranged first

A

Beta chain

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22
Q

What chain of TCR is rearranged second

A

Alpha chain

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23
Q

What segments comprise beta chain

A

VDJ

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24
Q

What segments comprise alpha chain

A

VJ

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25
Q

What are the main differences between B and T cell gene rearrangement

A

T cells can pick more than one D segment in beta chain

TDT is active during alpha and beta chain rearrangement in T cells, while it is turned off after heavy chain rearrangement in B cells

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26
Q

Where are T progenitor cells released from and what happens after release

A

Bone marrow. Migrate to thymus for maturation

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27
Q

What are the two steps of thymic education on developing T cells

A

positive selection

negative selection

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28
Q

What is positive selection

A

ensuring a cell can recognize MHC; if not it dies

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29
Q

What is negative selection

A

make sure cell does not attack self antigen; if it does it dies

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30
Q

What type of cells are found within the cortex of the thymus

A

immature lymphocytes and nurse cells

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31
Q

What occurs in the cortex to immature lymphocytes

A

selection occurs

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32
Q

What type of cells will be seen within the medulla of the thymus

A

cells that survive selection; many mature thymocytes

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33
Q

Where does the bulk of T cell development occur within the thymus

A

cortex

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34
Q

What is the function of macrophages and dendritic cells in the cortex of the thymus

A

provide MHC 2 for developing T cells

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35
Q

During T cell selection, what type of interaction will lead to formation of Th and Tc cells

A

If interact with MHC2 –> Th cell

If interact with MHC1–> Tc cell

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36
Q

How will an MHC1 and MHC2 deficiency affect T cell development

A

Patient with deficiency in TAP (associated with class 1 MHC) will prevent the production of CD8+ T cells due to lack of MHC, will still get CD4+ T cells

Class 2 deficiency: prevents production of CD4+ T cells, more severe

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37
Q

What association is required for differentiation of T cells

A

intimate association with thymic stromal cells (epithelial, macrophages, dendritic)

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38
Q

A cell is positive for CD4, CD8, CD3, and TCR. What type of cell is this

A

Pre-T cell

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39
Q

What are the cellular markers present on mature Tc cell

A

CD3
TCR
CD8

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40
Q

What are the cellular markers present on mature Th cell

A

CD3
TCR
CD4

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41
Q

Where are mature Tc and Th cells found in thymus

A

medulla

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42
Q

Where are Pro-T cells found

A

on the way to the thymus

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43
Q

Where are Pre-T cells found

A

cortex of thymus

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44
Q

What is the function of CD4

A

stabilizes MHC2/TCR interaction on TH cells

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45
Q

What is the function of CD8

A

stabilizes MHC1/TCR interaction on TC cells

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46
Q

How will De George’s syndrome affect T cells

A

lacking a thymus: no T cells will be made. Will have IgM

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47
Q

How will SCID affect T cells

A

no T cells entering the thymus, causing thymus atrophy

will not have igM

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48
Q

What is the purpose of positive selection in T cells

A

ensures that the alpha and beta TCRs expressed in an individual will recognize self MHC

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49
Q

How will Th vs Tc decision occur in thymus

A

whichever the pre-T cell binds to first determines which T cell it will become

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50
Q

What is the purpose of negative selection in T cells

A

ensures that thymocytes bearing a high affinity for self MHC or self Ag+ MHC are removed

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51
Q

What selection process can lead to immunodeficiencies if deficient

A

positive selection

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52
Q

What selection process can lead to autoimmune disease if deficient

A

negative selection

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53
Q

What determines whether a T cell will become Th or Tc

A

Interaction with MHC, MHC2 will become Th while MHC 1 will become Tc

54
Q

What type of cell is used for T cell positive selection

A

double positive T cell

55
Q

What is a double positive T cell

A

has both CD8 and CD4

56
Q

What type of cell will be selected against in T cell negative selection

A

cells that bind with high affinity to MHC will die via apoptosis

57
Q

What type of cell will be selected against in T cell positive selection

A

cells that cannot bind MHC will die via apoptosis

58
Q

What is bare lymphocyte syndrome

A

lack of class 1 expression due to a lack of CD8+ T cells caused by a Tap deficiency

59
Q

Where do T cells initially contact antigen

A

in secondary lymph tissue

60
Q

What interaction initiates activation of T cells

A

TCR with antigen on MHC

61
Q

List the signals that occur during T cell activation

A
  1. MHC class 2 and antigens
  2. CD28 adn B7 (co-stimulatory molecules)
  3. cytokines
62
Q

Which APC is the best. WHy

A

dendritic cells; always express B7 and only cell that can activate naive T cells

63
Q

What is required for macrophages to activate naive T cells

A

IFN gamma

64
Q

When can B cells activate naive T cells

A

after contact with an antigen

65
Q

What are the only cells that can present antigen to Th cells. Why

A

APCs; due to co-stimulatory molecules present

66
Q

What are the APCs

A

dendritic cells
macrophages
B cells

67
Q

Where are APCs found

A

DC: paracortex
B: cortex in germinal centers
M: everywhere

68
Q

What type of receptors are dendritic and macrophages

A

innate receptors

69
Q

What shares a similar structure to CD28

A

CTLA-4

70
Q

What do the 3 seignals required to activate T cells have in common

A

all are pro-inflamamtory cytokines

71
Q

List the steps in Th cell and macrophage interaction

A
  1. MHC and TCR complex with antigen
  2. Co-stimulatory molecules needed for activation of T cells
  3. cytokines: IL-1 drives T cell into activation
72
Q

Once activated, how does a Th cell upregulate

A

IL-2 receptor with higher affinity will then make IL-2

IL-2 made by T cells for Tcells will lead to production of IFN gamma

IFN gamma activates macrophages

73
Q

What is the function of IgCAM on T cells

A

tether t cells and macrophages long enough for interactions to occur

74
Q

How does a T cell shut itself off

A

downregulates CD28 and Upregulates CTLA

75
Q

What is a clinical use of CTLA-4 downregulator

A

may be manipulated in certain cancer: can be turned off to keep the immune system on

76
Q

What type of reaction does a Th1 mimic

A

type 4 hypersensitivity reaction

77
Q

How might a Th1 reaction be seen clinically

A

tuberculosis with granuloma

78
Q

Which cytokine from TH cells activates macrophages

A

IFN gamma

79
Q

Which cytokine from Th cells can be used to diagnose TB

A

IFN gamma through a quanteferon test

80
Q

Which cytokine from Th cells activates B cells

A

IL-4

81
Q

What cytokines do macropahges secrete

A

IL-1
IL-6
TNF alpha

82
Q

What are superantigens

A

viral or bacterial proteins that bind MHC outside of the peptide binding cleft

83
Q

What effects do superantigens have on T cells

A

causes less specificty and activation of numerous clones of T cells

84
Q

What is a disease caused by superantigens

A

toxic shock syndrome

85
Q

How is toxic shock syndrome caused

A

more T cells and macrophages are activate, leading to increased pro-inflammatory cytokines causing a cytokine storm

86
Q

What is ZAP 70

A

specific tyrosine kinase seen in T cell signaling

87
Q

What does activation mean in terms of T cells

A
changes in gene expression
functional changes
differentiation
cell division
cytokine production
88
Q

What effect would a gain of function mutation in ZAP70 have

A

excess T cell activation

89
Q

What could result from a loss of function mutation in ZAP70

A

T cells do not activate

90
Q

What are extracellular infections cleared by

A

antibody, complement, and phagocytes

91
Q

What type of pathogen always requires CMI for effective clearance

A

viral

92
Q

What is the goal of CMI

A

to destroy intracellular agent by destroying the host cell that harbors it

93
Q

What type of hypersensitivity reaction will be induced by intracellular bacteria or parasites

A

delayed type 4 through Th1 and macropahge activation

94
Q

How do Th1 affect class switching in B cells

A

release IFN gamma that promotes class switching to IgG

95
Q

What type of T cell will IL4 act on

A

Th2

96
Q

What is the affect of IL4 on T cell

A

Causes the release of IL4, IL10, IL13, and GF beta

97
Q

In which type of infection will IL 12 be made

A

intracellular infections

98
Q

In which type of infection will IL 4 be made

A

parasitic infections

99
Q

In which types of infections will IL6 and TGF beta be made

A

extracellular bacteria and fungal infections

100
Q

What type of T cell will IL12 act on

A

Th0

101
Q

What does IL 12 do to Th0

A

causes it to become Th1

102
Q

What cytokines drive isotype switching to IgE

A

IL4 and IL13

103
Q

What cytokine drives isotype switching to IgA

A

TGF beta

104
Q

What type of T cell will IL6 and TGF beta act on

A

Th0

105
Q

What do IL6 and TGF beta do to Th0

A

cause to become Th17

106
Q

What does Th17 secrete

A

IL17 and IL 22

107
Q

What is the function of IL 17

A

activates tissue cells and leukocytes to secrete inflammatory cytokines leading to recruitment of neutrophils

108
Q

How do Th0 cells differentiate into Th1 cells

A

when macrophages become activated they make IL12, which acts on Th0

109
Q

Which cytokine can inhibit TH1

A

IL10 and IL4 from Th2

110
Q

Which cytokine can inhibit Th2

A

IFN gamma from Th1

111
Q

What is the function of autocrine signaling of IL2 in TH1 cells

A

induces the t cell to stay activated

also activates Tc cells

112
Q

What is the function of regulatory T cell

A

prevents limits the activation of TH1 cells by releasing IL10

113
Q

What do T reg cells require for development

A

TGF beta

114
Q

What is the main cytokine produced by Tregs

A

IL10

115
Q

What would be the result in a lack of Tregs

A

IBS and other autoimmune diseases

116
Q

Which type of cells are often targeted by intracelllular infections

A

macrophages

117
Q

What is perforin

A

membrane punching, pore forming molecule

118
Q

What are granzymes

A

enzymes that damage the target cell

119
Q

What is a CTL

A

Tc that bind with class 1 MHC restricted endogenous peptides. Requires IL2 from activated Th1 cell

120
Q

What does CTL bind to

A

MHC class 1

121
Q

WHat receptors interacting on Tc cells will cause a cell to undergo apoptosis

A

FAs and FASL

122
Q

What are two ways in which a CTL can kill

A
  1. Binding MHC with antigen leads to holes in membrane of cell lackign MHC. Will release perforin leading to damage of membrane
  2. If Tc recognizes FAS will bind with it using FASL causing cells to die
123
Q

What cell markers are found on NK cells

A

CD16 and CD56

124
Q

What type of cell will recognize a lack of expression of class 1 MHC

A

NK cells

125
Q

What are the 2 types of receptors on NK cells

A

Inhibitory: killing inhibitory receptor (KIR)
Activating: killing activation receptor (KAR)

126
Q

What do inhibitory on NK cells recognize

A

MHC alpha chains

127
Q

What do activating receptors on NK cells recognize

A

possibly lectins conserved among many pathogens

128
Q

What receptor if present on any cell can bind to and kill a target cell

A

Fc gamma receptor

129
Q

What must be present on a cell that can undergo ADCC

A

anything with CD16 that can bind IgG can undergo ADCC

130
Q

What are the effector cells in cell-mediated immunity

A

CTL
NK cells
macrophages