Exam 2 Flashcards
1
Q
Of the billions of B cells circulating, what is special about the receptor specificity?
A
Each is different
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
3
Q
How is diversity in antigen binding site generated after B cell activation?
A
Somatic hypermutation
4
Q
How do variable segments differ?
A
In amino acid sequences that encode HVR1 and HVR2
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)
6
Q
Where are diversity segments found?
A
Only in heavy chain
7
Q
What do constant segments determine?
A
Isotype of heavy chains
8
Q
What is the antibody V region formed from?
A
Somatic recombination
9
Q
What does somatic recombination do?
A
Brings together a single V, J, and D gene segment
10
Q
Is rearrangement necessary in the antibody C region?
A
No, it is ready to be transcribed
11
Q
Does the C region contribute to the diversity in the antigen binding site?
A
No
12
Q
What is somatic recombination initiated by?
A
Recombination signal sequences
13
Q
What are the 2 types of recombination signal sequences (RSS)?
A
Sequences with a 12bp spacer
Sequences with a 23bp spacer
14
Q
What is the 12/23 rule?
A
12bp RSS can only associate with a 23bp RSS
15
Q
What does the 12/23 rule ensure?
A
That segments are joined in the correct order
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
17
Q
What is the sequence of events for the formation of a coding joint by V(D)J recombinase complex? (4)
A
- RAG complex aligns recombination signal sequences
- RAG complex cleaves DNA
- Broken end joined by non-homologous end joining
- Results in a coding joint and a single joint
18
Q
What is RAG?
A
Recombination activating gene
19
Q
What is junctional diversity?
A
Diversity at the coding joint
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
21
Q
What are P nucleotides?
A
Palindromic nucleotides
22
Q
What are N nucleotides?
A
Non-template nucleotides
23
Q
What happens after re-arrangement of the variable region?
A
The transcript is transcribed to mRNA
24
Q
For a heavy chain, where does transcription proceed through? What does it terminate before?
A
Cμ and Cδ
Cγ
25
What do naive B cells express? Where? By what?
IgM and IgD on the surface by alternative splicing
26
What is the first antibody secreted from naive B cells?
IgM
27
How often is IgD secreted?
Rarely
28
How many light chains and heavy chains are there?
295 light chains
| 5520 heavy chains
29
Because heavy and light chains associate randomly, how man possible combinations are there?
About 1.6 million
30
How are gene segments chosen?
Randomly during somatic recombination
31
Upon B-cell activation, what are immunoglobulin molecules produced as?
Soluble antibodies
32
What is produced by alternative splicing?
Membrane-bound and secreted immunoglobulin molecules
33
What produces high affinity antibodies?
Somatic hypermutation
34
What is required to produce antibodies of a different class?
Isotype/class switching
35
What does somatic hypermutation do?
Introduces random point mutations in the variable region after B-cell activation
36
What does somatic hypermutation result in?
Affinity maturation
37
What happens to antibody affinity for antigen over time?
It increases
38
What does somatic hypermutation require?
AID (activation induced cytidine deaminase)
39
What is AID made in?
Activated B cells
40
What does AID do?
Converts Cytosine to Uracil
41
What happens to U with AID in somatic hypermutation?
It is removed and replaced with another base
42
If there is a poor affinity what happens to B cells? (2)
Cannot compete for antigen
| Does not receive survival signal so apoptosis occurs
43
If there is a strong affinity what happens to B cells? (2)
Successfully competes for antigen and receives survival signals
Undergoes more rounds of somatic hypermutation and becomes a plasma cell
44
Which B cells continue to proliferate and differentiate?
B-cells with the highest affinity receptors
45
What is class switching regulate by?
Cytokines
46
What does class switching do?
Increases function diversity, but not antigen specificity
47
What is the sequence of events for isotype/class switching? (4)
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
48
What removes uracil?
Uracil DNA glycosylase
49
What excises an abasic nucleotide?
APE-1
50
What is AID responsible for?
Somatic hypermutation and class switching
51
What happens in variable regions with AID? What does that lead to?
Uracil is removed
| Somatic hypermutation
52
What happens in switch regions with AID? What does that lead to?
```
Nucleotides removed
DNA nick and class switching
```
53
Where do somatic hypermutation and isotope switching take place?
In the germinal center
54
Chapter 4 part 2 study guide
Chapter 4 part 2 study guide
55
What are the 2 broad groups of T cells?
CD4 T cells
| CD8 T cells
56
How do T cells carry out their functions?
Through direct cell-cell contact
57
What are CD8 T cells known as?
Cytotoxic T cells
58
What do cytotoxic T cells do?
Kill infected cells
59
What are the 2 broad groups of CD4 T cells?
Helper T cells
| Regulatory T cells
60
What do helper T cells do?
Help the function of the cells
61
What do regulatory T cells do?
Down regulate the immune response
| Anti-inflammatory
62
How is the type of T cell a CD4 cell turns into determined?
By the cytokines in the area which is determined by the pathogen
63
What is the structure of a T-cell receptor (TCR)?
One α chain
| One β chain
64
What does each chain of the TCR have?
A variable and constant region
65
What can the α chain compare to?
Light chain
66
What can the β chain compare to?
Heavy chain
67
How many antigen binding sites are on TCRs?
One
68
What is the antigen binding site on TCRs formed from?
V regions of α and β chains
69
How many hypervariable regions are the on TCRs?
6: 3 per chain
70
What does the TCRα chain contain?
V and J segments and a constant region
71
What is the variable region of the TCRα chain formed through?
Somatic recombination
72
What is the TCRβ chain composed of?
V, D, and J gene segments and constant regions
73
What is the variable region of the TCRβ chain formed through?
Somatic recombination
74
What is diversity in TCRs generated by? (3)
Somatic recombination
Junctional diversity
Random combination of chains
75
What are the two types of receptors on T cells?
α:β
| γ:δ
76
Are the functions of α:β receptors and γ:δ receptors the same or different?
Different
77
How much of the total T cell population do the α:β T cells account for?
95%
78
What are α:β T cells the T cells of?
The adaptive immune system
79
What do TCRs recognize?
Peptide antigens bound to MHC molecules
80
What are antigens degraded by?
Conventional dendritic cells
81
What is MHC?
Major histocompatibility complex
82
What does MHC do?
Present antigen on the surface of the cells
83
What does MHC class I present?
Antigens from intracellular pathogens
84
What does MHC class I activate?
Cytotoxic T cells
85
What does MHC class II present?
Antigens from extracellular pathogens
86
What does MHC class II activate?
Helper T cells
87
What is CD4 expressed on?
Helper T cells and regulatory T cells
88
What does CD4 bind?
MHC II
89
What is CD8 expressed on?
Cytotoxic T cells
90
What does CD8 bind?
MHC I
91
What is the structure of MHC class I molecules?
Variant α chain
| Invariant β2-microglobulin
92
What is the structure of MHC class II molecules?
Variant α chain
| Variant β chain
93
What are MHC molecules not composed of?
Gene segments
94
Where are intracellular pathogens present?
Cytoplasm
95
Where are intracellular pathogen peptides delivered?
To the ER
96
What are intracellular pathogen peptides in the ER bound by?
MHC class I
97
How many residues long are intracellular pathogen peptides?
8-10
98
What are extracellular pathogens brought into the cell in?
Endosomes
99
What are extracellular pathogens peptide breakdown products loaded onto? Where?
```
MHC class II
In the vesicular system
```
100
How many residues long are extracellular pathogen peptides?
13-25
101
What are extracellular antigens presented on?
MHC class I molecules
102
What does cross presentation allow?
Dendritic cells to activate cytotoxic T cells (CD8 T cells) even though the dendritic cell is not infected
103
In cross presentation, what are extracellular derived peptides presented on?
MHC class I molecules
104
What do most cell types express? Why?
```
MHC class I
Most can be infected with a virus
```
105
What types of cells express MHC class II?
Antigen presenting cells
| Dendritic cells, macrophages, B-cells
106
What are MHC molecules are also referred to as?
Human leukocyte antigens
107
What chromosome is the major histocompatibility complex located on/
6
108
What are the 3 MHC class I molecules on chromosome 6 that are involved in antigen presentation?
A, B, and C
109
What are the 3 MHC class II molecules on chromosome 6 that are involved in antigen presentation?
DP, DQ, and DR
110
How many molecules of MHC class I and MHC class II does each person have?
```
6 MHC class I
6 MHC class II
(3 of each type form the mother and 3 from father)
```
111
What are MHC molecules encoded by?
Conventional genes that do not rearrange
112
In terms of alleles, how can MHC genes be classified?
Polymorphic
113
Are most individuals homozygous or heterozygous for the highly polymorphic MHC genes?
Heterozygous
114
What are the different ways MHC molecules can appear in the human population? (3)
Polymorphism (multiple alleles)
Multiple genes
Polymorphism and multiple genes
115
Since most individuals are heterozygous for highly polymorphic isotypes of MHC molecules, what does it allow for?
A greater number of peptides to be presented during an infection
116
Since most individuals are heterozygous for highly polymorphic isotypes of MHC molecules, what does it reduce?
Probability that population will succumb to a particular pathogen
117
What does MHC polymorphism arise in?
Sequences that bind peptide and T-cell receptor
118
What do MHC molecules have?
Promiscuous binding specificity
119
What determines the antigens that bind to an MHC?
Anchor residues
120
At anchor residues, what do peptides that bind a particular MHC molecule have?
The same amino acids
121
What is the peptide binding motif?
Combination of anchor residues that bind an MHC isoform
122
What is the T cells receptor specific for?
Peptide and MHC allele
123
What MHC allele is the T cell receptor specific for?
HLA-A*0201
124
What peptide is the T cell receptor specific for?
Peptide X
125
What will most T cells be restricted to?
Recognizing antigen only when self bound to a "self" MHC molecule
126
Chapter 5 study guide
Chapter 5 study guide
127
What happens in the bone marrow?
Production of function B-cell receptor
128
What kind of tolerance is in the bone marrow?
Central tolerance
129
What is tolerance of B cells?
Removing self-reactive B cells
130
What happens in the periphery and secondary lymphoid tissues?
B-cell maturation
| B-cell activation
131
What are the stages of B cell development from common lymphoid progenitor to immature B cell? (8)
```
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
How many copies of the heavy gene are there in an individual?
2 copies–one maternal and one paternal
133
What takes place first in both heavy genes?
DhJh joining
134
What takes place on one chromosome at a time during B cell development?
Vh-DhJh rearrangement
135
What does each heavy chain V region have a 1/3 chance of?
Productive rearrangement
136
What can alter the reading frame in productive rearrangement?
Random addition of P and N nucleotides at junctions
137
What percentage of B-cells are signaled to die by apoptosis?
50%
138
What percentage of B-cells are signaled to survive and become pre B-cells?
50%
139
What does rearrangement one chromosome at a time ensure?
Only 1 type of heavy chain is expressed by the B-cell
140
What are rearranged heavy chains tested for?
Ability to form a pre B-cell receptor (checkpoint 1)
141
If the heavy chain on the first allele is non-functional, what happens to the V region on the second allele?
It completes rearrangemtn
142
If both heavy chains are non-functional, what happens to the cell?
It undergoes apoptosis
143
What is allelic exclusion?
A cell expresses only one allele of a gene pair
144
What does allelic exclusion ensure?
That each B cell make only one receptor
145
If the first heavy chain allele produces a function pre B-cell receptor, what happens to the second heavy chain?
It is not produced
146
Is heavy chain or light change rearrangement more efficient? Why?
Light chain
| Several attempts can be made instead of one attempt on each heavy chain gene
147
Which chain arrangements are tried first on each chromosome in light chain rearrangement?
κ chain
148
What is tried if there are no productive κ chain rearrangements?
λ chain rearrangements
149
What are rearranged light chains tested for?
Ability to form a functional B-cell receptor (second check point)
150
If the B-cell receptor is function in light chain rearrangement, what happens?
Light chain gene rearrangement ceases
151
What do many immature B cells have an affinity for?
Self-antigens
152
What can B cells not leave the bone marrow with?
Receptors that have a high affinity for self antigens
153
What are 2 things that self-reactive B cells can do?
Try somatic recombination again using different gene segments
Die by apoptosis
154
What is receptor editing?
Self-reactive B cells are allowed to continue rearranging the light chain
155
Why are B-cells eliminated?
If they cannot produce a receptor that does not self-react
156
What are the stages of B cell development from immature B cell to effector B cell? (9)
```
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
What are mature naive B cells contracted to secondary lymphoid tissues by?
Chemokines
158
What are chemises produced by?
Stromal cells and dendritic cells
159
What are mature naive B cells attracted to primary lymphoid follicles by?
Chemokines secreted by follicular dendritic cells
160
Where do B cells complete maturation?
Primary lymphoid follicle
161
What do B cells receive when the interact with follicular dendritic cells?
Pro-survival cytokines
162
What does continued B cell survival require?
Regular recirculation through primary lymphoid follicles
163
What happens to B cells if they don't gain access to primary follicles?
They die by apoptosis
164
What is peripheral tolerance?
Tolerance of self-antigens induced outside a primary lymphoid tissue
165
What do self-reactive immature B cells do in the periphery?
Die by apoptosis
| Become anergic
166
Is their receptor editing outside the bone marrow?
No
167
What are B cells activated by?
An encounter with an antigen
168
What do some B cells do? (2)
```
Differentiate immediately to plasma cells and secrete IgM
Move to the germinal center and undergo somatic hypermutation and class switching
```
169
What do some B cells in the germinal center do?
Become memory B cells
170
What percentage do B1 cells account for of all B cells?
Approximately 5%
171
What do B1 cells arise from?
A different precursor that B2 cells (what we have been discussing)
172
What can B1 cells do in the periphery?
Self-renew
173
What does self-renew mean?
Not continuously produced by bone marrow
174
What do B1 cells produce?
A quick supply of antibodies against common carbohydrate antigens in bacteria
175
What are B1 cells referred to as?
Thymus independent B cells
176
What could B1 cells be considered?
More of an innate-like immune cells
177
When are B1 cells first produced? B2?
Fetus
| After birth
178
How many N-regions in VDJ regions do B1 cells have? B2?
Few
| Extensive
179
What is the B1 V region repertoire? B2?
Restricted
| Diverse
180
What is the primary location of B1 cells? B2?
Peritoneal and pleural cavities
| Secondary lymphoid organs
181
What is the model of renewal for B1 cells? B2?
Self renewing
| Replaced from bone marrow
182
What is the level of spontaneous production of immunoglobulin for B1 cells? B2?
High
| Low
183
What are the isotypes secreted in B1 cells and which one is greater? B2?
IgM much greater than IgG
| IgG greater than IgM
184
Is there a requirement for T cell help for B1 cells? B2?
No
| Yes
185
What is the level of somatic hypermutation in B1 cells? B2?
Low-none
| High
186
Is there memory development in B1 cells? B2?
Little or none
| Yes
187
Chapter 6 study guide
Chapter 6 study guide
188
Where do T cell precursors originate?
Bone maroow
189
What do T cell precursors mature into T cells?
Thymus
190
What kind of selection is in the thymus?
Positive and negative selection
191
What happens to the production of T cells in the thymus with age?
It decreases
192
What are the stages of T cell development from common lymphoid progenitor to α:β or γ:δ T cells? (8)
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
How do the rearrangement of γ δ and β chains commence?
Simultaneously one chromosome at a a time for each gene
194
If γ and δ rearrange first, what happens to the cell?
It becomes a committed γ:δ T cell
195
If the β chain rearranges first, what happens to the cell?
It ceases rearrangements
196
How many times can each β chain attempt productive rearrangement?
2
197
What does each constant segment of a β chain have?
Its own associated D and J segments
198
How many attempts are there to produce a functional β chain since their is a D and J segment?
4
199
What are rearranged β chains tested for?
Ability to form a pre T cell receptor (checkpoint 1)
200
If the β chain on the first allele is non-functional, what happens to the β chain on the second allele?
It complete rearrangement
201
How many attempts can be made with α chain rearrangement?
Several
202
What does α chain rearrangement do?
Eliminates the δ chain gene segments
203
Is a functional α:β receptor or a γ:δ receptor more likely?
α:β receptor
204
What are rearranged α chains tested for?
Ability to form a T cell receptor
205
If a T cell receptor is formed, what happens?
Further rearrangements cease (checkpoint 2)
206
What are the stages of T cell development from committed α:β thymocyte to effector T cell? (9)
```
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
What are T cells positively selected for?
The ability to bind a self MHC molecule
208
What are self peptides presented on?
MHC class I and II by cortical epithelial cells
209
What do T cells that bind self MHC signaled to do?
Survive
210
What do T cells that do not bind self MHC signaled to do?
Continue with receptor editing
211
What do unsuccessful T cells undergo?
Apoptosis
212
What does positive selection determine?
Which co-receptor is expressed, CD8 or CD4
213
If the self peptide binds to MHC class I, what does it become?
CD8 T cell
214
If the self peptide binds to MHC class II, what does it become?
CD4 T cell
215
Since a T cell receptor is specific for MHC alleles, what does it mean for hematopoietic stem cell transplants?
There must be a match between donor and recipient MHC alleles
216
What are T cell that bind too strongly to self peptide:self MHC complex induced to undergo?
Apoptosis
217
What participates in the negative selection of T cells? (3)
Dendritic cells
Macrophages
Specialized medulla thyme epithelial cells
218
In regulatory T cells, what happens with peripheral tolerance?
Tolerance to self antigens continues to develop
219
What do T cells that recognize self antigen in the absence of inflammation become?
Anergic
220
What do regulatory T cells recognize? What does it do?
Self antigen bound to self MHC
| Suppress naive T cells that recognize an antigen presented by the same dendritic cell
221
Chapter 7 study guide
Chapter 7 study guide
222
Which cells undergo somatic recombination and junctional diversity to produce the receptor?
B cell and T cells
223
Which cells undergo hypermutation?
B cells
224
Which cells undergo class switching?
B cells
225
Which cell receptors recognize surface antigens? What about degraded peptides?
B cell receptors
| T cell receptors
226
Which cell receptors recognize antigen presented on MHC molecules?
T cell receptors
227
Which cell undergo positive selection?
T cells
228
Which cells undergo negative selection?
B cells and T cells
229
Which selection, positive or negative, are central tolerance and peripheral tolerance a part of?
Negative selection
