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Immunology-Spring 2017 > Exam 2 > Flashcards

Exam 2 Flashcards

1
Q

Of the billions of B cells circulating, what is special about the receptor specificity?

A

Each is different

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2
Q

How is diversity in antigen binding site generated before activation/during B cell development? (3)

A

Somatic recombination
Random association of heavy and light chains
Junctional diversity

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3
Q

How is diversity in antigen binding site generated after B cell activation?

A

Somatic hypermutation

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4
Q

How do variable segments differ?

A

In amino acid sequences that encode HVR1 and HVR2

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5
Q

Where is HVR3 formed?

A

From diversity at the junction between V (variable region) and J (joining region) or V, J, and D (diversity region)

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6
Q

Where are diversity segments found?

A

Only in heavy chain

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7
Q

What do constant segments determine?

A

Isotype of heavy chains

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8
Q

What is the antibody V region formed from?

A

Somatic recombination

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9
Q

What does somatic recombination do?

A

Brings together a single V, J, and D gene segment

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10
Q

Is rearrangement necessary in the antibody C region?

A

No, it is ready to be transcribed

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11
Q

Does the C region contribute to the diversity in the antigen binding site?

A

No

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12
Q

What is somatic recombination initiated by?

A

Recombination signal sequences

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13
Q

What are the 2 types of recombination signal sequences (RSS)?

A

Sequences with a 12bp spacer

Sequences with a 23bp spacer

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14
Q

What is the 12/23 rule?

A

12bp RSS can only associate with a 23bp RSS

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15
Q

What does the 12/23 rule ensure?

A

That segments are joined in the correct order

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16
Q

What is the V(D)J recombinase complex composed of? (2)

A

RAG-1 and RAG-2 (lymphocyte specific components)

Ubiquitous DNA repair proteins

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17
Q

What is the sequence of events for the formation of a coding joint by V(D)J recombinase complex? (4)

A
  1. RAG complex aligns recombination signal sequences
  2. RAG complex cleaves DNA
  3. Broken end joined by non-homologous end joining
  4. Results in a coding joint and a single joint
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18
Q

What is RAG?

A

Recombination activating gene

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19
Q

What is junctional diversity?

A

Diversity at the coding joint

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20
Q

What is the sequence of events for junctional diversity? (5)

A

DNA cleavage by RAG complex leaves hairpin ends
Hairpins cleaved in a random location, generates P nucleotides
TdT randomly adds N nucleotides
Opposite strands pair
Gaps filled by DNA synthesis and ligation

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21
Q

What are P nucleotides?

A

Palindromic nucleotides

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22
Q

What are N nucleotides?

A

Non-template nucleotides

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23
Q

What happens after re-arrangement of the variable region?

A

The transcript is transcribed to mRNA

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24
Q

For a heavy chain, where does transcription proceed through? What does it terminate before?

A

Cμ and Cδ

Cγ

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25
Q

What do naive B cells express? Where? By what?

A

IgM and IgD on the surface by alternative splicing

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26
Q

What is the first antibody secreted from naive B cells?

A

IgM

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27
Q

How often is IgD secreted?

A

Rarely

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28
Q

How many light chains and heavy chains are there?

A

295 light chains

5520 heavy chains

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29
Q

Because heavy and light chains associate randomly, how man possible combinations are there?

A

About 1.6 million

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30
Q

How are gene segments chosen?

A

Randomly during somatic recombination

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31
Q

Upon B-cell activation, what are immunoglobulin molecules produced as?

A

Soluble antibodies

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32
Q

What is produced by alternative splicing?

A

Membrane-bound and secreted immunoglobulin molecules

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33
Q

What produces high affinity antibodies?

A

Somatic hypermutation

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34
Q

What is required to produce antibodies of a different class?

A

Isotype/class switching

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35
Q

What does somatic hypermutation do?

A

Introduces random point mutations in the variable region after B-cell activation

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36
Q

What does somatic hypermutation result in?

A

Affinity maturation

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37
Q

What happens to antibody affinity for antigen over time?

A

It increases

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38
Q

What does somatic hypermutation require?

A

AID (activation induced cytidine deaminase)

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39
Q

What is AID made in?

A

Activated B cells

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40
Q

What does AID do?

A

Converts Cytosine to Uracil

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41
Q

What happens to U with AID in somatic hypermutation?

A

It is removed and replaced with another base

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42
Q

If there is a poor affinity what happens to B cells? (2)

A

Cannot compete for antigen

Does not receive survival signal so apoptosis occurs

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43
Q

If there is a strong affinity what happens to B cells? (2)

A

Successfully competes for antigen and receives survival signals
Undergoes more rounds of somatic hypermutation and becomes a plasma cell

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44
Q

Which B cells continue to proliferate and differentiate?

A

B-cells with the highest affinity receptors

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45
Q

What is class switching regulate by?

A

Cytokines

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46
Q

What does class switching do?

A

Increases function diversity, but not antigen specificity

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47
Q

What is the sequence of events for isotype/class switching? (4)

A
  1. Transcription induced upstream of switch region
  2. AID converts Cs in desired switch regions to Us
  3. Us removed leaving a DNA nick in switch regions
  4. Recombination at switch regions brings desired V region next to new C region
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48
Q

What removes uracil?

A

Uracil DNA glycosylase

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49
Q

What excises an abasic nucleotide?

A

APE-1

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50
Q

What is AID responsible for?

A

Somatic hypermutation and class switching

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51
Q

What happens in variable regions with AID? What does that lead to?

A

Uracil is removed

Somatic hypermutation

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52
Q

What happens in switch regions with AID? What does that lead to?

A 
Nucleotides removed
DNA nick and class switching
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53
Q

Where do somatic hypermutation and isotope switching take place?

A

In the germinal center

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54
Q

Chapter 4 part 2 study guide

A

Chapter 4 part 2 study guide

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55
Q

What are the 2 broad groups of T cells?

A

CD4 T cells

CD8 T cells

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56
Q

How do T cells carry out their functions?

A

Through direct cell-cell contact

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57
Q

What are CD8 T cells known as?

A

Cytotoxic T cells

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58
Q

What do cytotoxic T cells do?

A

Kill infected cells

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59
Q

What are the 2 broad groups of CD4 T cells?

A

Helper T cells

Regulatory T cells

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60
Q

What do helper T cells do?

A

Help the function of the cells

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61
Q

What do regulatory T cells do?

A

Down regulate the immune response

Anti-inflammatory

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62
Q

How is the type of T cell a CD4 cell turns into determined?

A

By the cytokines in the area which is determined by the pathogen

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63
Q

What is the structure of a T-cell receptor (TCR)?

A

One α chain

One β chain

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64
Q

What does each chain of the TCR have?

A

A variable and constant region

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65
Q

What can the α chain compare to?

A

Light chain

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66
Q

What can the β chain compare to?

A

Heavy chain

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67
Q

How many antigen binding sites are on TCRs?

A

One

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68
Q

What is the antigen binding site on TCRs formed from?

A

V regions of α and β chains

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69
Q

How many hypervariable regions are the on TCRs?

A

6: 3 per chain

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70
Q

What does the TCRα chain contain?

A

V and J segments and a constant region

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71
Q

What is the variable region of the TCRα chain formed through?

A

Somatic recombination

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72
Q

What is the TCRβ chain composed of?

A

V, D, and J gene segments and constant regions

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73
Q

What is the variable region of the TCRβ chain formed through?

A

Somatic recombination

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74
Q

What is diversity in TCRs generated by? (3)

A

Somatic recombination
Junctional diversity
Random combination of chains

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75
Q

What are the two types of receptors on T cells?

A

α:β

γ:δ

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76
Q

Are the functions of α:β receptors and γ:δ receptors the same or different?

A

Different

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77
Q

How much of the total T cell population do the α:β T cells account for?

A

95%

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78
Q

What are α:β T cells the T cells of?

A

The adaptive immune system

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79
Q

What do TCRs recognize?

A

Peptide antigens bound to MHC molecules

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80
Q

What are antigens degraded by?

A

Conventional dendritic cells

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81
Q

What is MHC?

A

Major histocompatibility complex

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82
Q

What does MHC do?

A

Present antigen on the surface of the cells

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83
Q

What does MHC class I present?

A

Antigens from intracellular pathogens

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84
Q

What does MHC class I activate?

A

Cytotoxic T cells

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85
Q

What does MHC class II present?

A

Antigens from extracellular pathogens

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86
Q

What does MHC class II activate?

A

Helper T cells

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87
Q

What is CD4 expressed on?

A

Helper T cells and regulatory T cells

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88
Q

What does CD4 bind?

A

MHC II

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89
Q

What is CD8 expressed on?

A

Cytotoxic T cells

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90
Q

What does CD8 bind?

A

MHC I

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91
Q

What is the structure of MHC class I molecules?

A

Variant α chain

Invariant β2-microglobulin

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92
Q

What is the structure of MHC class II molecules?

A

Variant α chain

Variant β chain

93
Q

What are MHC molecules not composed of?

A

Gene segments

94
Q

Where are intracellular pathogens present?

A

Cytoplasm

95
Q

Where are intracellular pathogen peptides delivered?

A

To the ER

96
Q

What are intracellular pathogen peptides in the ER bound by?

A

MHC class I

97
Q

How many residues long are intracellular pathogen peptides?

A

8-10

98
Q

What are extracellular pathogens brought into the cell in?

A

Endosomes

99
Q

What are extracellular pathogens peptide breakdown products loaded onto? Where?

A 
MHC class II 
In the vesicular system
100
Q

How many residues long are extracellular pathogen peptides?

A

13-25

101
Q

What are extracellular antigens presented on?

A

MHC class I molecules

102
Q

What does cross presentation allow?

A

Dendritic cells to activate cytotoxic T cells (CD8 T cells) even though the dendritic cell is not infected

103
Q

In cross presentation, what are extracellular derived peptides presented on?

A

MHC class I molecules

104
Q

What do most cell types express? Why?

A 
MHC class I
Most can be infected with a virus
105
Q

What types of cells express MHC class II?

A

Antigen presenting cells

Dendritic cells, macrophages, B-cells

106
Q

What are MHC molecules are also referred to as?

A

Human leukocyte antigens

107
Q

What chromosome is the major histocompatibility complex located on/

A

6

108
Q

What are the 3 MHC class I molecules on chromosome 6 that are involved in antigen presentation?

A

A, B, and C

109
Q

What are the 3 MHC class II molecules on chromosome 6 that are involved in antigen presentation?

A

DP, DQ, and DR

110
Q

How many molecules of MHC class I and MHC class II does each person have?

A 
6 MHC class I
6 MHC class II
(3 of each type form the mother and 3 from father)
111
Q

What are MHC molecules encoded by?

A

Conventional genes that do not rearrange

112
Q

In terms of alleles, how can MHC genes be classified?

A

Polymorphic

113
Q

Are most individuals homozygous or heterozygous for the highly polymorphic MHC genes?

A

Heterozygous

114
Q

What are the different ways MHC molecules can appear in the human population? (3)

A

Polymorphism (multiple alleles)
Multiple genes
Polymorphism and multiple genes

115
Q

Since most individuals are heterozygous for highly polymorphic isotypes of MHC molecules, what does it allow for?

A

A greater number of peptides to be presented during an infection

116
Q

Since most individuals are heterozygous for highly polymorphic isotypes of MHC molecules, what does it reduce?

A

Probability that population will succumb to a particular pathogen

117
Q

What does MHC polymorphism arise in?

A

Sequences that bind peptide and T-cell receptor

118
Q

What do MHC molecules have?

A

Promiscuous binding specificity

119
Q

What determines the antigens that bind to an MHC?

A

Anchor residues

120
Q

At anchor residues, what do peptides that bind a particular MHC molecule have?

A

The same amino acids

121
Q

What is the peptide binding motif?

A

Combination of anchor residues that bind an MHC isoform

122
Q

What is the T cells receptor specific for?

A

Peptide and MHC allele

123
Q

What MHC allele is the T cell receptor specific for?

A

HLA-A*0201

124
Q

What peptide is the T cell receptor specific for?

A

Peptide X

125
Q

What will most T cells be restricted to?

A

Recognizing antigen only when self bound to a “self” MHC molecule

126
Q

Chapter 5 study guide

A

Chapter 5 study guide

127
Q

What happens in the bone marrow?

A

Production of function B-cell receptor

128
Q

What kind of tolerance is in the bone marrow?

A

Central tolerance

129
Q

What is tolerance of B cells?

A

Removing self-reactive B cells

130
Q

What happens in the periphery and secondary lymphoid tissues?

A

B-cell maturation

B-cell activation

131
Q

What are the stages of B cell development from common lymphoid progenitor to immature B cell? (8)

A 
Common lymphoid progenitor
Pro B-cell
Rearrangement of heavy chain
Large pre B-cell
Cell divisions
Small pre B-cell
Rearrangement of light chain
Immature B-cell
132
Q

How many copies of the heavy gene are there in an individual?

A

2 copies–one maternal and one paternal

133
Q

What takes place first in both heavy genes?

A

DhJh joining

134
Q

What takes place on one chromosome at a time during B cell development?

A

Vh-DhJh rearrangement

135
Q

What does each heavy chain V region have a 1/3 chance of?

A

Productive rearrangement

136
Q

What can alter the reading frame in productive rearrangement?

A

Random addition of P and N nucleotides at junctions

137
Q

What percentage of B-cells are signaled to die by apoptosis?

A

50%

138
Q

What percentage of B-cells are signaled to survive and become pre B-cells?

A

50%

139
Q

What does rearrangement one chromosome at a time ensure?

A

Only 1 type of heavy chain is expressed by the B-cell

140
Q

What are rearranged heavy chains tested for?

A

Ability to form a pre B-cell receptor (checkpoint 1)

141
Q

If the heavy chain on the first allele is non-functional, what happens to the V region on the second allele?

A

It completes rearrangemtn

142
Q

If both heavy chains are non-functional, what happens to the cell?

A

It undergoes apoptosis

143
Q

What is allelic exclusion?

A

A cell expresses only one allele of a gene pair

144
Q

What does allelic exclusion ensure?

A

That each B cell make only one receptor

145
Q

If the first heavy chain allele produces a function pre B-cell receptor, what happens to the second heavy chain?

A

It is not produced

146
Q

Is heavy chain or light change rearrangement more efficient? Why?

A

Light chain

Several attempts can be made instead of one attempt on each heavy chain gene

147
Q

Which chain arrangements are tried first on each chromosome in light chain rearrangement?

A

κ chain

148
Q

What is tried if there are no productive κ chain rearrangements?

A

λ chain rearrangements

149
Q

What are rearranged light chains tested for?

A

Ability to form a functional B-cell receptor (second check point)

150
Q

If the B-cell receptor is function in light chain rearrangement, what happens?

A

Light chain gene rearrangement ceases

151
Q

What do many immature B cells have an affinity for?

A

Self-antigens

152
Q

What can B cells not leave the bone marrow with?

A

Receptors that have a high affinity for self antigens

153
Q

What are 2 things that self-reactive B cells can do?

A

Try somatic recombination again using different gene segments
Die by apoptosis

154
Q

What is receptor editing?

A

Self-reactive B cells are allowed to continue rearranging the light chain

155
Q

Why are B-cells eliminated?

A

If they cannot produce a receptor that does not self-react

156
Q

What are the stages of B cell development from immature B cell to effector B cell? (9)

A 
Immature B cell
Negative selection
Self tolerant immature B cell (IgM receptor)
Alternative splicing of heavy chain mRNA
Self tolerant immature B cell (IgM and IgD receptors)
Maturation in secondary lymphoid tissue
Mature naive B cell
Activation by antigen 
Activated B cell
157
Q

What are mature naive B cells contracted to secondary lymphoid tissues by?

A

Chemokines

158
Q

What are chemises produced by?

A

Stromal cells and dendritic cells

159
Q

What are mature naive B cells attracted to primary lymphoid follicles by?

A

Chemokines secreted by follicular dendritic cells

160
Q

Where do B cells complete maturation?

A

Primary lymphoid follicle

161
Q

What do B cells receive when the interact with follicular dendritic cells?

A

Pro-survival cytokines

162
Q

What does continued B cell survival require?

A

Regular recirculation through primary lymphoid follicles

163
Q

What happens to B cells if they don’t gain access to primary follicles?

A

They die by apoptosis

164
Q

What is peripheral tolerance?

A

Tolerance of self-antigens induced outside a primary lymphoid tissue

165
Q

What do self-reactive immature B cells do in the periphery?

A

Die by apoptosis

Become anergic

166
Q

Is their receptor editing outside the bone marrow?

A

No

167
Q

What are B cells activated by?

A

An encounter with an antigen

168
Q

What do some B cells do? (2)

A 
Differentiate immediately to plasma cells and secrete IgM
Move to the germinal center and undergo somatic hypermutation and class switching
169
Q

What do some B cells in the germinal center do?

A

Become memory B cells

170
Q

What percentage do B1 cells account for of all B cells?

A

Approximately 5%

171
Q

What do B1 cells arise from?

A

A different precursor that B2 cells (what we have been discussing)

172
Q

What can B1 cells do in the periphery?

A

Self-renew

173
Q

What does self-renew mean?

A

Not continuously produced by bone marrow

174
Q

What do B1 cells produce?

A

A quick supply of antibodies against common carbohydrate antigens in bacteria

175
Q

What are B1 cells referred to as?

A

Thymus independent B cells

176
Q

What could B1 cells be considered?

A

More of an innate-like immune cells

177
Q

When are B1 cells first produced? B2?

A

Fetus

After birth

178
Q

How many N-regions in VDJ regions do B1 cells have? B2?

A

Few

Extensive

179
Q

What is the B1 V region repertoire? B2?

A

Restricted

Diverse

180
Q

What is the primary location of B1 cells? B2?

A

Peritoneal and pleural cavities

Secondary lymphoid organs

181
Q

What is the model of renewal for B1 cells? B2?

A

Self renewing

Replaced from bone marrow

182
Q

What is the level of spontaneous production of immunoglobulin for B1 cells? B2?

A

High

Low

183
Q

What are the isotypes secreted in B1 cells and which one is greater? B2?

A

IgM much greater than IgG

IgG greater than IgM

184
Q

Is there a requirement for T cell help for B1 cells? B2?

A

No

Yes

185
Q

What is the level of somatic hypermutation in B1 cells? B2?

A

Low-none

High

186
Q

Is there memory development in B1 cells? B2?

A

Little or none

Yes

187
Q

Chapter 6 study guide

A

Chapter 6 study guide

188
Q

Where do T cell precursors originate?

A

Bone maroow

189
Q

What do T cell precursors mature into T cells?

A

Thymus

190
Q

What kind of selection is in the thymus?

A

Positive and negative selection

191
Q

What happens to the production of T cells in the thymus with age?

A

It decreases

192
Q

What are the stages of T cell development from common lymphoid progenitor to α:β or γ:δ T cells? (8)

A

Common lymphoid progenitor
Uncommitted double negative thymocytes CD8- and CD4- (committed γ:δ T cells)
Rearrangement of γ δ β chains
Uncommitted double negative thymocytes pre T cell CD8- and CD4-
Cell divisions
Uncommitted double negative thymocytes CD8+ and CD4+(committed γ:δ T cells)
Rearrangement of γ δ α chains
Committed α:β thymocyte

193
Q

How do the rearrangement of γ δ and β chains commence?

A

Simultaneously one chromosome at a a time for each gene

194
Q

If γ and δ rearrange first, what happens to the cell?

A

It becomes a committed γ:δ T cell

195
Q

If the β chain rearranges first, what happens to the cell?

A

It ceases rearrangements

196
Q

How many times can each β chain attempt productive rearrangement?

A

2

197
Q

What does each constant segment of a β chain have?

A

Its own associated D and J segments

198
Q

How many attempts are there to produce a functional β chain since their is a D and J segment?

A

4

199
Q

What are rearranged β chains tested for?

A

Ability to form a pre T cell receptor (checkpoint 1)

200
Q

If the β chain on the first allele is non-functional, what happens to the β chain on the second allele?

A

It complete rearrangement

201
Q

How many attempts can be made with α chain rearrangement?

A

Several

202
Q

What does α chain rearrangement do?

A

Eliminates the δ chain gene segments

203
Q

Is a functional α:β receptor or a γ:δ receptor more likely?

A

α:β receptor

204
Q

What are rearranged α chains tested for?

A

Ability to form a T cell receptor

205
Q

If a T cell receptor is formed, what happens?

A

Further rearrangements cease (checkpoint 2)

206
Q

What are the stages of T cell development from committed α:β thymocyte to effector T cell? (9)

A 
Committed α:β thymocytes
Positive selection
Restricted single positive thymocytes
Negative selection
Restricted single positive, tolerant, naive T cells
Leave thymus
Restricted single positive, tolerant, naive T cells
Activation
Effector T cell
207
Q

What are T cells positively selected for?

A

The ability to bind a self MHC molecule

208
Q

What are self peptides presented on?

A

MHC class I and II by cortical epithelial cells

209
Q

What do T cells that bind self MHC signaled to do?

A

Survive

210
Q

What do T cells that do not bind self MHC signaled to do?

A

Continue with receptor editing

211
Q

What do unsuccessful T cells undergo?

A

Apoptosis

212
Q

What does positive selection determine?

A

Which co-receptor is expressed, CD8 or CD4

213
Q

If the self peptide binds to MHC class I, what does it become?

A

CD8 T cell

214
Q

If the self peptide binds to MHC class II, what does it become?

A

CD4 T cell

215
Q

Since a T cell receptor is specific for MHC alleles, what does it mean for hematopoietic stem cell transplants?

A

There must be a match between donor and recipient MHC alleles

216
Q

What are T cell that bind too strongly to self peptide:self MHC complex induced to undergo?

A

Apoptosis

217
Q

What participates in the negative selection of T cells? (3)

A

Dendritic cells
Macrophages
Specialized medulla thyme epithelial cells

218
Q

In regulatory T cells, what happens with peripheral tolerance?

A

Tolerance to self antigens continues to develop

219
Q

What do T cells that recognize self antigen in the absence of inflammation become?

A

Anergic

220
Q

What do regulatory T cells recognize? What does it do?

A

Self antigen bound to self MHC

Suppress naive T cells that recognize an antigen presented by the same dendritic cell

221
Q

Chapter 7 study guide

A

Chapter 7 study guide

222
Q

Which cells undergo somatic recombination and junctional diversity to produce the receptor?

A

B cell and T cells

223
Q

Which cells undergo hypermutation?

A

B cells

224
Q

Which cells undergo class switching?

A

B cells

225
Q

Which cell receptors recognize surface antigens? What about degraded peptides?

A

B cell receptors

T cell receptors

226
Q

Which cell receptors recognize antigen presented on MHC molecules?

A

T cell receptors

227
Q

Which cell undergo positive selection?

A

T cells

228
Q

Which cells undergo negative selection?

A

B cells and T cells

229
Q

Which selection, positive or negative, are central tolerance and peripheral tolerance a part of?

A

Negative selection

Immunology-Spring 2017 (4 decks)

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