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OLD "MIC 660" > Exam 2 > Flashcards

Exam 2 Flashcards

1
Q

What do T cell receptors look like?

A

mirrored alpha and beta chain

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2
Q

What do B cell receptors (immunoglobulin) look like?

A

2 heavy chains
2 light chains

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3
Q

There are not enough genes to specify all B and T cell receptors, how is there still diversity though?

A

chromosomal rearrangment (VDJ recombination)

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4
Q

For B and T cell receptors, rearrangment occurs before or after transcription and translation?

A

before transcription and translation

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5
Q

What is the germline configuration?

A

gene segments before DNA rearrangment

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6
Q

What genes undergo VDJ recombination?

A

B and T cell receptor genes

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7
Q

Enzymes that mediate VDJ recombination are __________ which adds to the diversity

A

imprecise

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8
Q

What are the two domains of T cell receptors?

A

constant and variable

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9
Q

What holds the alpha and beta chain of TCR together?

A

disulfide bonds

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10
Q

What are the primary receptors (chains) for TCR in VDJ recombination? and what are the less likely options

A

alpha
beta

gamma
delta

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11
Q

________ begin as receptors on B cells but after activation they are secreted

A

antibodies

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12
Q

What segments are rearranged on light chain of BCR?

A

V
J

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13
Q

What segments are rearranged on heavy chain of BCR?

A

V
D
J

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14
Q

What does recombination signal sequences (RSSs) do in VDJ recombination?

A

where RAG binds to DNA ensuring recombination only occurs in gene segments encoding BCR and TCR

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15
Q

What does RAG1/2 do in VDJ recombination?

A

cleaves DNA

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16
Q

what does artemis do in VDJ recombination?

A

cleaves hairpins and forms overhangs

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17
Q

What does terminal deoxynucleotidyl transferase (TdT) do in VDJ recombination?

A

adds N nucleotides to gaps

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18
Q

Where is RSS located relative to the V segment?

A

downstream

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19
Q

Where is RSS located relative to the D segment?

A

flanking it

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20
Q

Where is RSS located relative to the J segment?

A

upstream

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21
Q

What does the RSS 12/23 rule prevent?

A

prevents joining of inappropriate segments

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22
Q

What are the steps of VJ recombination?

A
  1. RAG1/2 binds to RSS and cleaves DNA
  2. NHEJ repairs cleaved DNA creating a coding joint and signal joint
  3. DNA hairpin forms
  4. Artemis cleaves hairpins to create overhangs
  5. NHEJ fills overhangs with P nucleotides
  6. P nucleotides are removed and Tdt adds N nucleotides
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23
Q

What is the coding joint?

A

functional variable region

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24
Q

What is the signal joint?

A

removed circular piece of DNA

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25
Q

What does Artemis create?

A

overhangs

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26
Q

What nucleotides are filled into overhangs?

A

P nucleotides

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27
Q

___ and ___ chain use VDJ recombination not VJ

A

beta
gamma

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28
Q

_______ chain use VDJ recombination not VJ

A

heavy chain

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29
Q

In VDJ recombination, ___ and ___ segments link first then they link with ___

A

D J
V

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30
Q

What are the two additional diversity mechanisms for B cells besides VDJ recombination?

A
  1. class switching
  2. somatic hyper mutation
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31
Q

What is AID as a B cell diversity mechanism?

A

AID converts Cytosine into Uracil causing a mismatch which must be repaired via somatic hypermutation or class switching (double stranded breaks)

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32
Q

What 2 isotypes of B cells do not require class switching?

A

IgM
IgD

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33
Q

When a B cell encounters an _________ it induces class switching so the correct Ig is present

A

antigen

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34
Q

What 3 isotypes of B cells require class switching?

A

IgG
IgE
IgA

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35
Q

B cells cannot present Ig___ and Ig___ at the same time but Naive B cells can

A

IgM
IgG

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36
Q

Once you class switch can you go back?

A

no

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37
Q

B cell class switching requires _______ that generates DNA double stranded break in the switch region

A

AID

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38
Q

What region does AID act in class switching of B cells?

A

switch region

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39
Q

Does class switching affect antigen specificity?

A

no, affects effector function

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40
Q

What enhances the affinity of BCR to an antigen?

A

somatic hypermutation

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41
Q

somatic hypermutation involves _____ mediated introduction of mutations into the ______________

A

AID
complementary-determining regions (CDRs)

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42
Q

Where are mutations introduced by AID in somatic hypermutation?

A

complementary-determining regions (CDRs)

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43
Q

What are the three possible mechanisms of mutation in somatic hypermuation?

A
  1. DNA replication
  2. base excision repair
  3. mismatch repair
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44
Q

In somatic hypermutation what is the mutations that always cause point mutations?

A

DNA replication
mismatch repair

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45
Q

In somatic hypermutation what is the mutation that has a 75% chance of a point mutations?

A

base excision repair

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46
Q

What is the complementary-determining regions (CDRs) in somatic hypermutation?

A

point of mutation (change of antigen affinity) where antigen binds

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47
Q

There are high-affinity, lower affinity, and same-affinity BCR after somatic hypermutation, which is preferentially selected?

A

high-affinity

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48
Q

Does class switching or somatic hypermutation change antigen affinity?

A

somatic hypermutation

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49
Q

What are the 2 mechanisms T and B cell receptors use during VDJ recombination to increase diversity?

A
  1. random combination of segments
  2. junctional flexibility (N nucletides)
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50
Q

B or T cells recognize processed antigens

A

T cells

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51
Q

B or T cells recognize native (free floating) antigens

A

B cells

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52
Q

HLA class I is express on what cells?

A

all cells with a nucleus

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53
Q

HLA class I presents antigens from inside or outside the cell?

A

inside (endogenous)

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54
Q

HLA class I presents to what cell type?

A

cytotoxic T cells (CD8)

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55
Q

HLA class I deals with intracellular or extracellular pathogens?

A

intracellular

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56
Q

HLA class II is present on what cell types?

A

antigen presenting cells (APC)

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57
Q

HLA class II presents antigens from inside or outside the cell?

A

outside (exogenous)

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58
Q

HLA class II presents to what cell type?

A

helper T cells (CD4)

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59
Q

HLA class II deals with intracellular or extracellular pathogens?

A

extracellular

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60
Q

What is the antigen presenting region of HLA class I?

A

alpha 1
alpha 2

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61
Q

Does HLA class III deal with antigen presentation?

A

No

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62
Q

Which class of HLA requires a narrow range of peptides (more specific)?

A

HLA class II (has more binding motifs)

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63
Q

What are anchor residues in HLA class I?

A

allow peptides to bind tightly bringing regions together and allowing for more flexibility peptide type

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64
Q

What is the antigen presenting region (peptide binding cleft) on HLA class II?

A

alpha 1
beta 1

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65
Q

Which HLA class binds with longer/larger peptides?

A

class II

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66
Q

What is the most diverse gene cluster in human genome?

A

HLA

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67
Q

HLA genes vary at the ________ level

A

population

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68
Q

What causes organ transplant rejection?

A

HLA

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69
Q

Where in the cell does peptide loading occur for MHC class I?

A

ER

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70
Q

What does Calnexin do in HLA I loading?

A

facilitates proper folding of the HLA alpha chain and retains it in the ER

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71
Q

What does calreticulin, tapasin and ERp57 do together in HLA I loading?

A

they form the peptide loading complex

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72
Q

What does TAP do in HLA I loading?

A

translocate peptides from cytosol to ER lumen

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73
Q

What does proteasome do in HLA I loading?

A

cleaves intracellular proteins into peptides

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74
Q

What happens to the peptide once it enters the ER in HLA I loading?

A

peptide is associated with peptide-loading complex

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75
Q

What does tapasin do in HLA I loading?

A

ensures peptide bound tightly to HLA

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76
Q

What does endoplasmic reticulum aminopeptidase (ERAP) do in HLA I loading?

A

cleaves peptide if it is too long

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77
Q

When does peptide loading occur in HLA class II?

A

when HLA II is in a vesicle that fuses with a phagolysosome

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78
Q

Which class of HLA loads first?

A

class I

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79
Q

Where does HLA class II assemble itself?

A

ER

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80
Q

What does the invariant chain do for HLA II loading?

A

blocks peptide binding groove on HLA II preventing accidental binding to intracellular peptides (thats MHC I job)

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81
Q

What is the MHC compartment in HLA II loading?

A

specialized endosome for transport through the secretory pathway

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82
Q

What does the clip do in HLA II loading?

A

sits in the peptide groove until fusion with the phagolysosome

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83
Q

What does HLA-DM do in HLA II loading?

A

removes CLIP to allow peptide binding

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84
Q

What are the two chain lineages of T cells?

A
  1. alpha/beta
  2. delta/gamma
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85
Q

Which chain lineage of T cells do not require antigen processing?

A

delta/gamma

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86
Q

What does the alpha/beta T cell lineage recognize?

A

peptides presented on MHC

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87
Q

What does the delta/gamma T cell lineage recognize?

A

lipids on CD1d

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88
Q

What are the two subsets of the alpha/beta lineage of T cells?

A

CD8 Cytotoxic T cells
CD4 helper T cells

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89
Q

CD8 T cells use HLA class ____

A

class I

90
Q

CD4 T cells use HLA class ______

A

class II

91
Q

Where do T cells develop?

A

thymus

92
Q

What happens in the outer cortex of the thymus?

A

VDJ recombination of immature T cells

93
Q

What happens in the inner medulla of the thymus?

A

negative selection and become mature T cells

94
Q

What do thymic epithelial cells (TECs) do?

A

activates Notch which is required for commitment of T cell lineage

95
Q

What do thymic macrophages do?

A

clean up T cells that didn’t make it through recombination

96
Q

What do thymic denritic cells do?

A

present antigens to developing T cells to prevent self recognition

97
Q

What is the order of T cell development?

A
  1. double negative
  2. double positive
  3. positive selection
  4. single positive
  5. negative selection
98
Q

What happens during double negative stage of T cell development?

A

Notch I signaling and VDJ recombination of beta, gamma, and delta chain

99
Q

What is the commitment signal for T cells?

A

Notch I

100
Q

What happens during double positive stage of T cell development?

A

VDJ recombination of alpha, gamma, and delta chain

101
Q

What is positive selection in T cell development?

A

ensures TCR can recognize MHC (for activation)

102
Q

What is negative selection in T cell development?

A

removal of T cells with self reactive T cells (central tolerance)

103
Q

When does positive selection of T cells occur?

A

in between double positive and single positive

104
Q

When does negative selection of T cells occur?

A

single positive

105
Q

Which chain of T cells is rearranged first?

A

beta

106
Q

delta and gamma T cells do not express CD4 or CD8 so they remain ___________ T cells

A

double negative

107
Q

What is the pre-T alpha chain?

A

surrogate for alpha chain since beta chain is being rearranged first and needs alpha to test if it’s functional

108
Q

Once the TCR beta chain is successfully rearranged whats locks it so it cannot change?

A

allelic exclusion

109
Q

When the alpha chain of TCR successfully rearranges, the _______ chain is lost in VJ recombination

A

delta

110
Q

What are the 3 possible outcomes of TCR once they go through positive selection?

A
  1. death by neglect (no interaction to MHC = death)
  2. weak interaction to MHC = survive
  3. TIGHT interaction to MHC = death
111
Q

What are the two models of single positive for TCR?

A
  1. instructive model
  2. kinetic model
112
Q

What is the instructive model for single positive TCRs?

A

interactions between TCR and MHC on APC drive selection of CD8 or CD4

if TCR interacts with HLA I = CD8

113
Q

What is the kinetic model for single positive TCRs?

A

strong signaling = CD4
weak signaling = CD8

114
Q

What is AIRE (autoimmune regulator) responsible for in T cell development?

A

enables promiscuous expression of genes in thymus
(that are usually not present in thymus so T cells won’t become self reactive)

115
Q

What is an example of central tolerance?

A

AIRE

116
Q

Where does T cell activation occur?

A

secondary lymph tissue

117
Q

What are the 3 antigen presenting cells?

A
  1. B cells
  2. dendritic cells
  3. macrophages
118
Q

What is the most important APC for T cells?

A

dendritic cells

119
Q

What APC does not phagocytose but internalizes antigens?

A

B cells

120
Q

When do immature dendritic cells become mature?

A

once they phagocytose pathogen then reach secondary lymph tissue for presentation

121
Q

Expression of what brings DC to secondary lymph tissue?

A

CCR7

122
Q

What are the 2 ways antigens can be expressed to CD8 by dendritic cells?

A
  1. direct infection
  2. cross presentation
123
Q

What is cross presentation?

A

When extracellular antigens are presented on MHC I instead of II

(CD4 send signaling that redirect antigens to MHC I)

124
Q

Unlike dendritic cells, _________ remain in the tissue

A

macrophages

125
Q

macrophages are important for the ___________ response

A

inflammatory

126
Q

B cells do not phagocytose antigens, what do they do instead?

A

breaks antigen down in a lysosome and present peptide on HLA II

127
Q

What is T cell homing?

A

T cell migration to secondary lymphoid tissue

128
Q

In T cell homing, CCL21 and CCL19 are secreted by DCs and received by _____ on T cells attracting T cells to HEV

A

CCR7

129
Q

In T cell homing, CCR7 on T cells binds to ________ activating the gradient for T cells

A

high endothelial venules (HEV)

130
Q

In T cell homing (rolling adhesion), what is the adhesion molecule that binds to CD34 or GlyCAM on high endothelial venules (HEV)?

A

L-selectin

131
Q

In T cell homing (tight binding), ______ binds to the ICAM-1 receptor on high endothelial venules (HEV) allowing T cells to exit the and do diapedesis

A

LFA

132
Q

What does sphingosine-1-phosphate (S1P) do in T cell homing?

A

upregulated S1P tells T cells to leave secondary lymp tissue and go to site of infection

133
Q

What is the immunological synapse?

A

adhesion molecules bring T cells to DC for T cell activation

134
Q

What are the adhesion molecules required for thr TCR complex in the immunological synapse?

A
  1. TCR
  2. CD4/CD8
  3. CD3
  4. CD28
  5. CTLA4
135
Q

What is the job of CD3 for the immunological synapse?

A

signals in cytoplasm

136
Q

What is the job of CTLA4 for the immunological synapse?

A

prevents over activation of T cell activation

137
Q

What 2 signals are required to activate T cells through the immunological synapse?

A
  1. TCR binding with DC’s MHC (antigen present)
  2. CD28 on T cell binding to DC’s B7
138
Q

What is B7 expressed on?

A

APC

139
Q

What does the B7—CD28 prevent?

A

binding of self antigens (with the help of CTLA4)

140
Q

When is B7 present on APC?

A

only when an antigen is present

141
Q

What is the signaling cascade for T cells after the immunological synapse?

A
  1. CD3 signaling
  2. ITAMs
  3. ZAP 70
  4. Lck
  5. 3 pathways
142
Q

What are the 3 genes transcribed as a result of the 3 pathways of the signaling cascade for T cell acitvation?

A
  1. NFAT
  2. NFkB
  3. AP-1
143
Q

Increasing activated T cells increases their production in _______

A

IL-2

144
Q

depending on the type of infection, different ________ will be released by APC to mediate differentiation of T cells

A

cytokines

145
Q

What kinase regulates cytokine mediated T cell differentiation?

A

JAK

146
Q

Which T helper cells activate B cells for neutralization?

A

TH2
TFH

147
Q

Which T helper cells activate phagocytic cells?

A

TH1
TH17

148
Q

Which T helper cells help regulate immune response?

A

Treg

149
Q

What is the process of cytokine mediated T cell differentiation (kinases) ?

A
  1. JAK is phosphorylated
  2. STAT is phosphorylated and dimerized
  3. STAT enters nucleus and turns on genes to determine effector function and cytokine production
150
Q

_____ T cells require stronger activation between B7 and CD28 than ______ T cells

A

CD8
CD4

151
Q

CD4 T cells help induce more signaling of _______ on APC to help CD8 cell activation since they require more signaling

A

B7

152
Q

What 2 things do CD8 T cells contain?

A

perforin
granzymes

153
Q

T/F? CD8 T cells can jump from cell to cell in the same tissue to scan for infections

A

True

154
Q

While CD8 T cells have perforin/granzymes to induce apoptosis, what else do they have to induce apoptosis?

A

FasL pathway

155
Q

How does the FasL pathway cause apoptosis?

A

FasL binds to capase which enters cytosol and induces apoptosis

156
Q

T/F?? The perforin/granzyme and Fas pathway both cause apoptosis.

A

true

157
Q

What do TH1 do? (T helper)

A

recruit macrophages
CD8 differentiation
B cell class switching

158
Q

What do TH2 do? (T helper)

A

activate B cells and degranulation in response to parasites

159
Q

What does TFH do? (T helper)

A

activation and differentiation of B cells in germinal centers

160
Q

What does T17 do? (T helper)

A

recruits neutrophils

161
Q

What do Treg do? (T helper)

A

maintain peripheral tolerance

162
Q

TH1 cells activate macrophage activity by expressing _______ and _______

A

INF-gamma
CD40

163
Q

What happens to a macrophage if it cannot clear an infection?

A

TH1 induce apoptosis via FasL

164
Q

TH1 induce B cell class switching with activates the _________ complement pathway

A

classical

165
Q

TH1 cells induce the differentiation of naive CD8 into CTL with the secretion of ______ and ______

A

IL-2
INF-gamma

166
Q

What are helminths?

A

parasitic worms

167
Q

What T helper cell is specific for parasites?

A

TH2

168
Q

What two cytokines does TH2 release and what do they do?

A

IL-4 (IgE production)
IL-5 (degranulation)

169
Q

What 2 signals does TFH produce to help activate B cells?

A

CD40
IL-21

170
Q

What do TH17 specifically target?

A

extracelluar bacteria and fungi

171
Q

What cytokine does TH17 produce to recruit neutrophils?

A

IL-17

172
Q

What do thymic stromal lymphopietin (TSLP) trigger?

A

DCs to induce FOXP3 to help development of Treg

173
Q

What does FoxP3 expression induce?

A

activation of Treg cells

174
Q

What T helper cell prevents an overactive immune system?

A

Treg

175
Q

How do Treg cells help prevent an overactive immune system?

A

deactivate CD4 and CD8 cells once they do their job

176
Q

What do natural killer T cells (NKT) express?

A

express TCR
express surface receptors of NK cells

177
Q

On NKT cells, what does their alpha/beta receptors recognize?

A

glycolipids presented on CD1d

178
Q

How do NKT cells kill infected cells?

A

apoptosis via perforin/granzymes
apoptosis via FasL

179
Q

What is the T cell immunodeficiency, Omenn Syndrome? (inherited)

A

Rag1/2 are mutated causing VDJ recombination to not occur

180
Q

What is the T cell immunodeficiency, Mutations in Cytokine Receptor gamma(yc)-chain? (inherited)

A

prevent JAK3 activation preventing cytokines and important functions for T cells (like development, differentiation, activation and expansion)

181
Q

What is the T cell immunodeficiency, ADA deficiency? (inherited)

A

inhibiting DNA synthesis preventing cell proliferation

excess dATP which is toxic to cells causing apoptosis

182
Q

What is the T cell immunodeficiency,PNP deficiency? (inherited)

A

inhibiting DNA synthesis preventing cell proliferation

excess dGTP which is toxic to cells causing apoptosis

more common in T cells

183
Q

What is the T cell immunodeficiency, DiGeroge Syndrome? (inherited

A

absence of a portion on chromosome 22
impacts thymus development = decreased T cells

184
Q

What is the T cell immunodeficiency, Bare Lymphocyte Syndrome (BLS)? (inherited)

A

Class I: TAP (responsible for getting antigens from cytoplasm to ER for class I MHC) is mutated
Class II: MHC II isn’t expressed

185
Q

What is the T cell immunodeficiency, Mutations in Signaling Proteins? (inherited)

A

prevents activation of transcription factors (NFAT, NFkB, and AP-1) required for T cell activation

(signaling cascade)

186
Q

What is the T cell immunodeficiency, immunosuppressant drug cyclosporin? (aquired)

A

antiviral that prevents activation of NFAT and T cell activation

187
Q

What is the T cell immunodeficiency, immunosuppressant drug corticosteroid? (aquired)

A

blocks activation of NFkB, impairing T cell activation

188
Q

What is the T cell immunodeficiency, HIV and AIDS? (aquired)

A

reverse transcriptase of HIV infected CD4 cells and induces immunosuppression

189
Q

What 2 ways are self reactive T cells controlled?

A

negative selection
peripheral tolerance

190
Q

What is an example of failure of central tolerance of T cells?

A

lack of AIRE results in incomplete negative selection causing autoimmunity

191
Q

What is APECED? (autoimmunity)

A

absence of AIRE resulting in autoreactive cells that lead to malfunctions of endocrine glands that express tissue specific genes

192
Q

What are 2 examples of failure of peripheral tolerance of T cells

A

lack of CD28–B7 = no peripheral tolerance = anergic T cells and autoreactive T cells

lack of CTLA4 = prevents Treg = overactive T cells

193
Q

What is IPEX? (autoimmunity)

A

mutation in FOXP3 causing loss of Treg resulting in autoimmune response

194
Q

The variable region on TCR contains the ________ binding site

A

antigen

195
Q

How many antigen binding sites does BCR have?

A

2

196
Q

VJ recombination occurs with the ____ and _____ chain?

A

alpha
light

197
Q

VDJ recombination occurs with the _____ and ____ chain?

A

beta
heavy chain

198
Q

Where on BCR does class switching occur?

A

heavy chain

199
Q

In VDJ recombination, what removes the P nucleotides so Tdt can add N nucleotides?

A

exonucleases

200
Q

Explain the mutation “DNA replication” in somatic hypermutation?

A

GC turns into TA causing a point mutation

201
Q

Explain the mutation “Base excision” in somatic hypermutation?

A

U is removed and replaced with a random N nucleotide (75% chance of point mutation)

202
Q

Explain the mutation “mismatch repair” in somatic hypermutation?

A

removes multiple nucleotides in the sequence and replaces it with a bunch of random N nucleotides causing lots of point mutations

203
Q

How many proteins make up the MHC I antigen binding groove?

A

one protein (alpha 1 alpha 2)

204
Q

What does RAG recognize in VDJ recombination?

A

RSS

205
Q

The antigen binding surface of immunoglobulins is ________ chain and _______ chain

A

1 heavy chain
1 light chain

206
Q

What are 2 diversity mechanisms in VDJ recombination?

A

segment joining
junctional flexibility (P nucleotides)

207
Q

Where does the majority of TCR and BCR come from?

A

VDJ recombination

208
Q

What is the structure of HLA I?

A

alpha chain with beta microglobulin

209
Q

What is the structure of HLA II?

A

identical alpha and beta chain

210
Q

What does HLA class I, -E, -F, and -G do?

A

(don’t present peptides)
E and G: ligands for NK cells
F: removed HLA when not needed

211
Q

What does HLA class II -DM and -DO do?

A

aid in HLA loading on APCs (dont present)

212
Q

Does HLA genes get rearranged?

A

no, diversity come from population level (one from mom and one from dad)

213
Q

What does HLA-DM do in HLA II loading?

A

removes CLIP when peptide is ready to be loaded

214
Q

What is the source of peptides degradation in HLA I loading?

A

proteasome

215
Q

What is the source of peptides degradation in HLA II loading?

A

phagolysosome

216
Q

Where are peptides loaded in HLA II?

A

endosome

217
Q

What is the job of CD3 for T cell chain rearrangement?

A

once beta chain of T cell rearranges it tests to see if it works

218
Q

How many chances does beta chain get to rearrange in double negative T cells?

A

4

219
Q

Does the alpha or beta chain of TCR get more chances to. successfully rearrange?

A

alpha

220
Q

What 2 chemokines are required for T cell homing and are secreted by DC cells?

A

CCL19 and CCL21

221
Q

IPEX syndrome affect the production of what cell type?

A

Treg

OLD "MIC 660" (10 decks)

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