Unit 2 Flashcards
(182 cards)
1
Q
What are the two components of the B cell receptor complex?
A
- two molecules Igɑ and Igꞵ 2. associated with membrane Ig
2
Q
What are the first three steps that begin the signaling cascade?
A
- Cross-linking of BCR complex OR B cell receptor + CR2 receptor 2. Phosphorylation of tyrosine residues on the ITAMs of Igɑ and Igꞵ 3. Triggers downstream signaling events
3
Q
What are the co-receptors for B cells and T cells
A
Co-receptors for T cells are CD28 and CTLA4. Co-receptors for B cells are CR2 that bind to complement
4
Q
How does ubiquitin regulate B cell activation?
A
a protein gets recruited to TCR complex and can ubiquitinize CD3, ZAP70, Igɑ, and Igꞵ
5
Q
What T cell receptor is most like the B cell Ig ɑ and Ig ꞵ chains?
A
CD3 and zeta chains
6
Q
B cells can respond to multivalent antigens via BCR crosslinking, or to antigen+ coreceptor binding to complement proteins. But can B cells respond to small monovalent antigens?
A
By themselves, they cannot respond to small monovalent antigens
7
Q
What does ubiquitination mediate?
A
Signal inhibition and signal generation
8
Q
What are the first step and end outcome of cytokine receptors, TNF and JAK-STAT?
A
the first step is cytokine receptors contain inactive JAK enzymes and the end outcome is to activate gene transcription. All these receptors bind to different cytokines and have specific responses
9
Q
CD4 only binds to
A
MHC
10
Q
T cell receptor binds to
A
MHC + antigen
11
Q
2 antibodies cross-linking can activate
A
a B cell
12
Q
The purpose of inhibition of immune receptor signaling is?
A
control and prevent overstimulation of producing antibodies
13
Q
What helps form protein complexes?
A
adaptor proteins
14
Q
What drives differentiation of B cells and T cells?
A
Cytokines
15
Q
What are the five steps of signal transduction?
A
- Binding of receptor to ligand 2. Crosslinking/dimerization of receptors 3. Phosphorylation of ITAM motifs on cytoplasmic domains 4. Activation/recruitment of other proteins in a signaling cascade 5. Activate transcription factors which alter gene regulation to alter cell behavior
16
Q
What is one example of how binding of a cytokine receptor might change the “behavior” of a cell through cell signaling?
A
binding of a TNF receptor to TNF alpha would cause a cascade of activated protein complexes leading to apoptosis
17
Q
What are the steps of VDJ combination?
A
synapsis → cleavage → hairpin opening and end-processing → joining
18
Q
What is the difference between heavy and light chains?
A
light chains have a V and a J whereas heavy light chains have a V, D, and J
19
Q
What are all the things that contribute to binding site diversity?
A
Recombination between the V and J on a light chain and the recombination between the V, D, and J on a heavy chain
20
Q
What are the similarities and differences between B and T cell receptor development (where does it happen? What is the same/different?)?
A
Between B cells and T cells, they undergo VDJ recombination in the same way but happen in different places. For B cells, it happens in the bone marrow. For T cells, they rearrange in the thymus. B cells rearrange their heavy chain first and then their light chain after the second selection process. For T cells, it starts with the ꞵ chain (VDJ) and followed by the ɑ chain (VJ)
21
Q
What is the 12/23 rule of recombination?
A
A rule in which 12NT spacers can only join with 23NT spacers
22
Q
At what stage of T and B cell development is foreign antigen binding necessary?
A
foreign antigen is not required for B and T cell development
23
Q
What would be the result of a RAG1 knockout mouse?
A
no mature B or T cells
24
Q
What are two similarities between B and T cell receptor development?
A
B and T lymphocytes both have 2 main checkpoints and are both generated by the rearrangement in individual lymphocytes of different VDJ (variable diversity joining) gene segments
25
What is V(D)J recombination?
a specialized process of site-specific gene rearrangement
26
What role(s) do cytokines play in B and T cell development?
Cytokines are involved in the proliferation and differentiation of antigen-stimulated T and B cells and in the effector functions (autocrine + paracrine actions) of T cells
27
How is diversity generated in B and T cells?
rearrangement and expression of antigen receptor genes
28
Describe the process of V(D)J recombination
involves rearrangement of one V gene segment, one D segment, and one J segment in each lymphocyte to form a single V(D)J exon that will code for the variable region of an antigen receptor protein
29
What are the consequences of no V(D)J recombination?
If there is no V(D)J recombination, there would be no functional B and T cells as all of them die. The immune system would have no adaptive immunity.
30
Order of Lymphocyte Development
Commitment → proliferation → sequential and ordered rearrangement of antigen receptor genes → selection events → differentiation of B and T cells
31
What molecules are key to triggering committed progenitor cells to proliferate?
cytokines
32
What three signals are required for fully functional precursor proliferation?
a signal through the cytokine, a signal through the pre B/T cell receptor, and activation of cytokines
33
What is negative selection?
if cells are too specific for cell antigens, then the cells are eliminated
34
What are nonamers?
tells enzymes where to bind on the genes
35
How does a VDJ form?
has repeating v's, j's, and d's. Always end up with one V, one D, and one J that together form the variable region of the antigen. DJ (DJ starts the party) forms first followed by V
36
What is combinatorial diversity?
Random assortment of one V, one D, and one J
37
What is junctional diversity?
non homologous end joining joins the nucleotides mediated by terminal deoxynucleotidyl transferase (TdT) creating the same variable region that is different from any other cell because it is changed at DNA level
38
What are the components of a B cell and a T cell to form a single VDJ exon?
In B cells, the components are a light chain and heavy chain. In T cells, the components are an alpha chain and a beta chain
39
What recombination occurs to ensure one V, D, and J?
Recombination between VDJ and constant region
40
Compare and contrast TCR and BCR complexes (check w/ Dr. Mills Ko)
CD3 and ζ form the TCR complex whereas the Igɑ and Igꞵ form the BCR complex. Both complexes contain ITAMs in their cytoplasmic tails that mediate signaling functions
41
What are the early steps of complement pathway activation?
The alternative pathway is activated by C3b binding to various activating surfaces; the classical pathway is initiated by C1 binding to antigen-antibody complexes; the lectin pathway is activated by binding of a plasma lectin to microbes. C3b generated by action of C3 convertase binds to microbial cell surface and becomes a component of enzyme that cleaves C5 to initiate the late steps of complement activation
42
How can BCR complex activation demonstrate a link between innate and adaptive immune responses?
Activation of B cells is enhanced by signals that are provided by complement proteins and the CD21 coreceptor complex, which link innate immunity to the adaptive humoral immune response (p. 166 of txtbk)
43
What signaling pathways are downstream of B cell receptor activation?
Ras-MAP kinase, phosphatidylinositol-specific phospholipase C activation, PKC-ꞵ activation, and activation of P13-kinase (p. 168-169)
44
How do signaling pathways compare between naive and mature B cells? (check w/ Dr. Mills Ko)
The same signaling pathways are used by membrane IgM and IgD on both naive and mature B cells
45
Why does activation of lymphocytes need to be tightly controlled?
Activation of lymphocytes has to be tightly controlled to limit immune responses against foreign antigens in order to avoid collateral damage to host tissues (p. 169 of txtbk)
46
What mediates inhibitory signaling for lymphocytes?
inhibitory receptors and by enzymes known as E3 ubiquitin ligases that mark certain signaling molecules for degradation
47
Most cytokine receptors are activated by what property?
by ligand-induced receptor clustering, bringing together the cytoplasmic proteins of two or more receptor molecules, and thus inducing the activity of unique non-receptor tyrosine kinases (p. 170)
48
Discuss the downstream consequences of signaling mutations/dysfunction and their implications in immunological disorders
activation of the NF-ƙB pathway and the JNK MAP kinase pathway or the induction of apoptotic death
49
What are the consequences of no V(D)J recombination?
we would not have a huge diversity of antigen receptors for antigens to bind to, preventing many T and B lymphocytes from being matched and activated with a specific antigen
50
State the steps of VDJ Recombination
1. DJ starts the party (randomly select one J & select one D) 2. Enzyme connects 2 pieces & a 12 spacer RSS on both sides 3. 23 is looking for a 12 on the V side
51
Random nucleotides stick at the bottom (like glue) to combine two blunt ends for
creating junctional diversity
52
What is purpose of VDJ?
increases diversity of different antigens we can recognize
53
Name the steps of lymphocyte development of B cells in order
1. Rearrangement and expression of Ig genes in a precise order 2. Selection and proliferation of developing B cells at the preantigen receptor checkpoint 3. Selection of the mature B cell repertoire
54
Name the steps of lymphocyte development of T cells in order
Stem cell → Pro-T → Pre-T → Double positive → Single positive (immature T cell) → Mature T cell
55
What are some similarities and differences between B and T cell development?
In B cells, the heavy chain is rearranged while in T cells, the beta chain is rearranged. Also, in B cells, the light chain is rearranged while in T cells, the alpha chain is rearranged
56
How does V(D)J rearrangement connect to the checkpoints and steps of lymphocyte development?
First recombination is on heavy chain. VDJ joins. RNA processing connected to constant region and translates heavy chain protein. Checks against self-antigen and signal transductions tell us it worked triggering proliferation and recombination of light chain to make a fully functional receptor and see that it binds appropriately
57
What chains recombine first?
Heavy chains (B cells) & beta chains (T cells)
58
How does selection occur?
Through the expression of one chain. Double negative (no CD4 and CD8) becomes a double positive (has BOTH CD4 and CD8) by binding to either MHC I or MHC II
59
How does selection stimulate the next phase of recombination/proliferation?
In weak recognition (what we want), positive selection occurs stimulating cell survival. In strong recognition, negative selection occurs triggering apoptosis and delete any cell reactive B cells
60
How does the Pre-BCR regulate arrangement of the Ig genes?
- Rearranged heavy chain & a “placeholder” light chain
- Tells cell if 1st rearrangement is successful or not (if not, apoptosis; if yes, cell proliferates & light chain rearranges)
61
What is the difference between a Pre-B cell and an Immature B cell?
A Pre-B cell only has a rearranged heavy chain; an immature B cell has both a rearranged heavy chain and rearranged light chain
62
How does expression of co-receptors CD4 and CD8 influence T cell maturation?
CD4 & CD8 come as double negative and become double positive. T cell will pick either CD4 or CD8
63
What is the purpose of AIRE (autoimmune regulator) in lymphocyte maturation?
- Gene expressed in thymus cortical epithelial cells that present APCs to T cells
- Select out any T cells that bind to self-antigen
64
Compare and contrast the structure of the Pre-T Cell Receptor of immature T cells to the TCR of mature T cells
T cells get to decide what kinds of T cells they want to be. Environment created in thymus influences how T cells are developed
65
What does RAG expression do?
enzyme that does recombination (for B & T cells)
66
What is the purpose of checkpoints?
Checkpoints make sure recombinant events work and does not cause any autoimmunity
67
A weak binding
serves as a functional test to show that receptor works
68
What are the 2 checkpoints in the development of the B lymphocyte and what is their function?
After recombination, first checkpoint checks to see if the heavy chain binds to anything in large Pre-B cell. If heavy chain binds weakly, another checkpoint checks to see if light chain works and ensures weak binding worked in mature B
69
What are the 2 checkpoints in the development of the T lymphocyte and what is their function?
After recombination of beta chain, first checkpoint checks to see if recombination of beta chain works. If first checkpoint works, the T lymphocyte will proliferate and alpha chain recombines. Second checkpoint checks to see if alpha chain is still functioning and if it binds anything too strongly
70
If T cell receptor binds to MHC I and antigen (selection process),
signal transduction tells cells to become a CD8 T cells; don't make any more CD4 T cells
71
If T cell receptor binds to MHC II,
signal transduction tells cells to become a CD4 T cells; don't make any more CD8 T cells
72
If antigen does not bind to MHC I or II,
apoptosis is activated and cell dies
73
What happens when there is an active viral infection?
More CD8 cells are produced
74
Checkpoints during lymphocyte development are what?
Selection events that remove cells with non-functional or self-reactive receptors
75
What part of the B cell receptor is rearranged first during B cell development?
The heavy chain
76
When the pre-BCR or pre-TCR is expressed, and successfully passes the selection checkpoint, what is the outcome of the cell?
Proliferation
77
A double positive T cell (CD4+/CD8+/TCR+) binds loosely to a self antigen presented on MHC class I in the thymus. What is the outcome for that cell?
It becomes a CD8+ T cell and stops expressing CD4
78
A B cell successfully recombines both heavy and light chains and expresses a functional BCR. In the red pulp of the bone marrow, it encounters a cell presenting self antigen to which it binds, what is the outcome for this cell?
Apoptosis
79
If T cell receptor binds too tightly to MHC I or MHC II, what happens?
triggers apoptosis and cell dies
80
Goldilocks binding occurs when
the final checkpoint eliminating autoreactive cells and allows cell to mature and be released into circulation
81
How does the process of T cell maturation happen in the thymus?
double negative → double positive → single positive (CD4) or single positive (CD8)
82
Where does activation occur for naive T cells?
lymph nodes
83
Where does activation occur for effector T cells?
site of infection
84
What are the 3 signals necessary to activate T cells?
Signal to proliferate and differentiate (T cell receptor to MHC), costimulatory molecule (CD28 or B7), and production of cytokines (IL-2) for proliferation
85
What is the response when a T cell is activated?
CD69 are retained in the lymph node. IL-2 proliferates, CD4L affects effector function, and effector. CTLA-4 binds and triggers apoptosis
86
What is the naïve T cell activation in response to?
lymph node
87
S1P get into lymph nodes through what
High endothelial venules (HEVs)
88
Activation of effector T cells happens where?
At the site of infection
89
What is Costimulation in T cell Activation when there are no costimulatory molecules?
T cell binds to the MHC and antigen but without binding to costimulatory molecules, apoptosis is triggered and T cell dies to maintain tolerance
90
What are some potential designs for therapies that could block costimulatory signals in T cells?
Make a ligand that competes for the same site
91
What is CTLA-4-Ig?
An inhibitor molecule that if bound triggers apoptosis to deactivate costimulatory molecules
92
What is IL-2 and what is its role?
If MHC-antigen complex binds to T cell receptor and the costimulatory molecules later bind to other costimulatory molecules (CD28 and B7), then the T cell upregulates IL-2 receptor leading to T cell proliferation
93
What are two specific effector functions of T cells?
Help activate B cells to make antibodies and help CD4 T cells bind to MHC II
94
How are memory T cells formed?
They get activated and express CTLA-4 and die off. Some of the effector cells will become memory T cells and others get activated and skip straight to memory T cells
95
What causes the decline in T cell numbers?
CTLA-4
96
What would be the result if a T cell was unable to express costimulatory molecules?
the cell would be unable to activate without the costimulatory signal
97
What 3 properties are unique to central memory T cells?
Home to lymph nodes, limited effector functions, and rapid proliferation
98
What 3 properties are unique to effector memory T cells?
Home to peripheral sites, produce effector cytokines or become cytotoxic, and rarely proliferate
99
Clonal expansion of antigen-specific T cells requires 3 signals:
TCR, costimulatory molecules, and growth factors (IL-2)
100
What are the effector functions of activated CD4 helper T cells?
Produce cytokines and activate phagocytes and B cells
101
Where do effector memory cells reside?
in peripheral circulation and tissues
102
Where in the body are most effector CD4+ cells found?
the thymus
103
How are CD8 Cytotoxic cells activated?
by antigens presented by dendritic cells
104
What is the role of roll cross presentation by DCs in activating CD8 Cytotoxic cells?
Present antigens on MHC II and have those viral antigens enter the cytosol which are presented to MHC I activating CD8 Cytotoxic cells
105
What two roles do CD4 helper T cells play in CD8+ cell activation and differentiation?
They produce cytokines and enhance the ability of APCs to stimulate CTL differentiation
106
There are 2 antigen presentation events that occur to fully activate CD8 T cells. The first occurs in the Lymph Node where ________ cells present antigen to Nieve CD8 T cells.
dendritic cells
107
How is dendritic cell cross-presentation important in activating CD8 T cell responses?
allows DCs to present extracellular pathogens on MHC I to CD8 T cells
108
Why would a cell express a receptor that would lead to apoptosis? When would a cell express this?
cell knows it's infected and wants to die to not infect other cells
109
Why might T cell exhaustion be important/an advantage?
to prevent autoimmunity
110
What is T cell exhaustion? What causes it?
decreased proliferation, reduced production of IFN-γ, and poor cytotoxic activity. Caused by the antigen being persistent and does not go away
111
What are the two main components of CTL granules?
Granzymes and perforin
112
What is the function of granzymes?
cleaves/activates caspases that cause apoptosis
113
The second antigen presentation occurs in tissue at the site of infection
where _______ cells present antigen to Effector CD8 T cells (CTLs)
virally infected
114
What is the main function of CD8+ CTLs
to kill infected cells based on recognizing their antigen
115
What are the two ways CD8 T cells kill infected cells?
Fas/FasL and degranulation
116
What are the two characteristics of CD8 memory T cells?
1. Central memory cells proliferate quickly
| 2. Differentiate to become effector memory cells which have strong effector function
117
True or False: Each B cell has many receptors that bind many different antigens
False
118
What three signal(s) is the T cell giving the B cell?
Co-stimulatory receptor binding, cytokines, and binding to MHC II
119
How are B cells activated?
antigen reaches lymph node via lymph binding to the B cell. Antigen is taken inside and presented to a T cell to activate the helper T cell. T cell helps the B cell activate
120
What are the two ways B cells can be activated?
B cell activation can occur via T cell dependent and T-independent
121
What is the Hapten-Carrier effect?
T cells cannot respond to haptens without the carrier molecule. If a bunch of haptens are stuck on a carrier protein, antibodies are generated
122
Naive B cells express what Ig isotypes?
IgM and IgD (membrane version of antibodies)
123
What is T-independent B cell activation?
need an antigen with multiple epitopes and must bind to different receptor antibody molecules but without T cell, B cell can only produce IgM and low-affinity antibodies
124
What is T-dependent B cell activation?
B cell binds to antigen, antigen presented on surface, helper T cell binds, B cell differentiates and produces high-affinity antibodies
125
What are the two ways antigens can get to B cells?
through APC-independent activation and flows into the lymph node where B cells can bind directly or through APC-dependent activation in which antigen can be given from APC to B cell with T cell help
126
What occurs during BCR receptor complex signaling?
If B cell activates, TLR binding can lead to proliferation and differentiation
127
what is a hapten?
a small molecule that cannot activate an immune response
128
What is a germinal center
A cluster of reactions comprised of helper T cells designed to help activate and clonally expand B cells
129
Why is T cell help important?
B cells can only express IgM if they have no T cell help. T cells secrete cytokines to switch constant regions allowing the B cell to produce a different antibody to target the specific pathogen
130
Why is CD40 important?
Without CD40, B cells can't class switch, can't have affinity maturation, and cannot produce memory cells
131
What is affinity maturation?
change the antigen binding region which is mutated a bunch of times and checks to see if it's a better binding. Once higher affinity, B cell gets stronger survival signals and proliferates allowing the antibodies to have high affinity. If lower affinity, the B cell dies
132
How do CD4+ Th1, Th2, and Th17 cells develop?
antigen recognition and presentation → T cell activation by APCs and other cells at site of immune response → Conversion of antigen-stimulated T cell to effector cell is initiated → Developing effector cells become progressively committed to a particular cytokine profile → cytokines amplify differentiation pathway → progressive accumulation of T cell pop. that produce distinct sets of cytokines
133
What is inflammation?
Recruitment of other cells to site of infection
134
What are homing patterns?
receptors for certain kinds of chemokines
135
How do APCs know what cytokine to produce?
PRRs
136
What determines which cell type is differentiated?
cytokines
137
What do B cells NOT do once activated?
Undergo V(D)J rearrangement
138
Do B cells require T helper cells to activate?
No
139
What kind of antibody do B cells produce if they are activated via the T-independent pathway?
IgM
140
True or False: T helper cells are required for B cells to form memory
True
141
Can haptens induce an immune response by themselves? Why or why not?
No, because they are too small to bind to more than one antibody at a time
142
Can haptens induce an immune response by themselves? Why or why not?
No, because they are too small to bind to more than one antibody at a time
143
What is important for the specificity of the class switching recombination?
cytokine signaling
144
Hyper IgM syndrome is characterized by what?
defective CD40 signaling; via B cells affecting class switch recombination (CSR) and somatic hypermutation
145
What two enzymes are necessary for isotype switching to occur?
activation-induced deaminase (AID) and DNA uridine glycosylase
146
What 2 ways can B cells activate?
presenting an antigen to a T helper cell + CD40/CD40L and binding a polyvalent antigen
147
What kind of antibody is made by a B cell that activates WITHOUT T cell help?
IgM
148
What changes occur in B differentiation into plasma cells?
structural alterations in ER and secretory pathway, increased Ig production, and change in Ig heavy chains from the membrane to the secreted form
149
What is isotype class switching?
when the Ig heavy chain has to be switched
150
What co-receptors are involved in isotype class switching?
CD40/CD40 ligand
151
What is selection of high affinity receptors in the process of affinity maturation?
High-affinity B cells will bind tightly to the antigen presented on follicular dendritic cells → present antigen and bind tightly to Tfh cells → get all the necessary stimulation to become a high-affinity B cell → differentiate to a plasma cell or a memory B cell. Low-affinity B cells do not get any survival signals and undergo apoptosis
152
What is somatic hypermutation in the process of affinity maturation?
mutation event, which happens after B cell activation
153
What are the two characteristics of short-lived plasma cells?
generated during T-independent responses and extrafollicular B cell foci
154
What are the four characteristics of long-lived plasma cells?
generated during T-dependent responses, pump out lots of antibodies, germinal center, and home to bone marrow
155
What is the enzyme AID and what is its function?
Key enzyme required for isotype switching induced in activated B cells that converts C to U residues by taking off an amine group
156
What is the difference between the B cell zone and the germinal center?
B cell zone is where naive cells are located whereas the germinal center is where the B cells proliferate to have high-affinity antibodies
157
Where do different B cell effector changes occur?
in the lymph nodes
158
What role do follicular dendritic cells play in B cell activation and differentiation?
they give B cells survival signals to proliferate and differentiate to become plasma cells when they develop a high-affinity antibody
159
What triggers antibody isotype switching?
Enzyme AID
160
What is antibody feedback?
B cells express an Fc receptor which contains an ITIM leading to associated phosphatases that block receptor signaling preventing the B cell from continuing to be activated and produce more antibodies
161
How does affinity maturation differ from VDJ recombination?
VDJ recombination happens in the bone marrow whereas affinity maturation occurs in the germinal center
162
Enzyme AID is activated only with what?
T cell help through CD40/CD40 ligand interaction with T cells
163
How does enzyme AID allow isotype switching to occur?
uses DNA repair mechanisms that are not accurate introducing random mutations at sites of complementary determining regions and create double-stranded breaks
164
What is affinity maturation (from Lecture 18)?
combination of somatic hypermutation along with a selection event to increase the affinity over time
165
The variable region is also known as what?
Complementary determining region
166
Yes or No: Do T cells undergo mutations to change their T cell receptor bindng site?
No
167
What is part one of affinity maturation?
The shape of the antibody is changed to fit the antigen even better
168
What is part two of affinity maturation?
B cells are exposed to antigens again via T follicular helper (Tfh) cells and follicular dendritic cells in the germinal center
169
How does heavy chain isotype (class) switching occur?
switch from a B cell with IgM and IgD and it's going to specialize. IgG is the longest-lasting. IgE activates mast cell degranulation. IgA occurs in mucosal tissues to keep bad bacteria out
170
All specialized types of Ig isotypes (IgG, IgA, etc.) require what?
binding of CD40 on T cell and undergo affinity maturation to induce isotype switching
171
Antibodies have to be able to switch from a _______ form to a _______ form
membrane; secreted
172
What is switch recombination?
based on what cytokines are present on the B cell, the isotype switching will choose the correct type of Ig to create
173
How does switch recombination work?
grabs different segments of the gene and forming a loop. Loop is cut off and joins the segments together so that it's transcribed and translated to a secreted protein
174
How does switch recombination work?
grabs different segments of the gene and forming a loop. Loop is cut off and joins the segments together so that when it's transcribed and translated to a secreted protein
175
What four processes must occur for a VDJ region to be created?
VDJ recombination, recognition of antigen by the B cell receptor, presentation of the antigen to a Helper T cell, and somatic hypermutation and affinity maturation
176
What enzyme is responsible for both class switching and somatic hypermutation (affinity maturation) in activated B cells?
AID
177
What is the purpose of somatic hypermutation and affinity maturation?
to create a population of B cells which can produce high affinity antibody against an antigen
178
What signal determines what isotype of antibody a B cell should produce?
cytokines
179
What region of DNA undergoes somatic hypermutation?
the variable region
180
Is isotype switching and affinity maturation permanent or is it reversible?
permanent
181
What is the difference between primary and secondary response?
primary response takes longer and produces low-affinity antibodies. Secondary response undergoes affinity maturation again to be more specific
182
What is the difference between T cells and B cells in central tolerance?
T cells become Treg and B cells get one more chance to bind tightly to antigen
