Immunology test 2 Flashcards
(188 cards)
1
Q
Antigen and MHC
Short linear peptides (a and B, not gamma)
A
What does a T cell have to have to be stimulated?
2
Q
Polymorphic residue of MHC
A
What goes in the pocket in the T cell receptor?
3
Q
The correct peptide and MHC
A
What does the T cell have to have to be activated by an antigen?
4
Q
- T cell MHC antigen complex
2. B7 binds to CD28
A
What are the 2 signals needed from a dendritic cell to a T cell?
5
Q
Dendritic cells
Macrophages
B cells
A
3 APCs
6
Q
Dendritic cells
A
Only APC that can present to naive T cells
7
Q
Cell mediated
A
What kind of immunity is a macrophage?
8
Q
Engulf microbe
Put antigen on MHC molecule
Presents antigen to mature T cells
Effector gives abck cytokines that help kill microbe
A
How does a macrophage effect T cell?
9
Q
Humoral immunity
A
What kind of immunity is a B cell?
10
Q
Antigen meets B cell receptor and goes in cell. Can recognize anything. Chews it up on MHC molecule to an effector T cell. This occurs in borders b/t T and B cell zones in lymph node/spleen. As B cell becomes activated by seeing its antigen, T cell has to be activated by dendritic cells in T cell zone. They come together and activate each other. T cell then helps B cell produce more Ab and can become plasma cell
A
How do B cells activate T cells?
11
Q
Border b/t T cell zone and B cell zone either in Lymph node/spleen
A
where does chewing up of antigen on MHC complex occur in B cell?
12
Q
T cell zone
A
Where is the T cell activated by dendritic cells?
13
Q
Costimulation
A
APCs display peptide MHC complexes in addition to other signals which provide a second signal.
Not including signal one
14
Q
Adjuvants
A
Enhance antigen presentation by exposing to microbial products
Activates innate immune response
Ex. aluminum hydroxide things given w/ vaccine, up regulates signal 2 and allows T cell response
15
Q
CD40-CD40L
A
Important for B cell activation and T cell help
16
Q
MHC
A
Genetic locus whose products were responsible for the rapid rejection b/t tissue grafts exchanged b/t inbred strains of mice
17
Q
Alleles
A
Variants in polymorphic genes
18
Q
Genetic polymorphisms
A
Genes whose products can be different b/t individuals
19
Q
Co dominant
A
Both alleles expressed
20
Q
MHC genes
A
Polymorphic and polygenic
Everything is expressed due to codominance
21
Q
Allogeneic
A
Express at least one different allele
22
Q
Syngeneic
A
Express the same alleles
23
Q
Class I: CD8 T cells, on all nucleated cells
Class II: CD4 helper cells, and only on restricted cells (APC)
A
Who do class I and II present to? Where are they?
24
Q
K,D,L = class one A,E = Class II
ALways uppercase
A
What are the letters in Class I vs class II of MOUSE MHC nomenclature?
25
H-2
How do you know it is a mouse MHC?
26
K of d. Class I gene, d allele on a mouse
What does H-2Kd mean?
27
HLA- Human leukocyte antigen
How do you know it is a human MHC?
28
Class I- A,B,C
| Class II- DP, DQ, DR
What are Class I vs Class II letters in human MHC nomenclature?
29
human MHC, Class I, allele 27
What does HLA-B27 mean?
30
human MHC, class II, allele 4
What does HLA-DR4 mean?
31
MHC haplotype
Set of alleles for a given individual
32
I: 2 alphas and b 2 microglobulin makes it shorter. Accommodates peptides of 8-11 residues
II: a and b (longer), peptides of 10-30 residues or more
Structural differences b/t Class I and II MHCs?
33
I: intracellular, cytosolic, CD8
II: Extracellular,vesicular, CD4
```
Are class I or class II extracellular/intracellular?
Cytosolic/vesicular?
```
34
a chain, B2 microglobulin, and a bound peptide (heterotrimer)
What must be present for expression of Class I on cells surface?
35
B/t a chains
Where does the peptide sit in a class I MHC?
36
b/t a and B chains
Where does the peptide sit in an MHC type II molecule?
37
Innate and adaptive
What types of immune responses can increase expression of MHC molecules?
38
Cell surface
Where are the ends of the peptide in the cleft cleaved off?
39
When CD4 contacts macrophage secretes IFN-y which helps activate the macrophage and increases expression of type II MHC
What does IFN-y do?
40
Only peptides bind to MHC molecules
Why do most T cells recognize peptides and no other molecules?
41
Cell-associated
What do T cells recognize? cell associated/ soluble antigens?
42
MHC restriction
T cells from a given individual only recognize antigens in the context of their own MHC
43
Adaptive immunity takes time, have to be activated in lymph nodes, undergo clonal expansion, differentiate, etc.
Why do you have to wait after a mouse is infected w/ a virus to get a good CD8 response?
44
Transports peptides into the ER in Class I MHC stuff
What does TAP do?
45
Golgi
Where does the MHC peptide complex bud from and put in vesicles?
46
Endocytosis of extracellular protein
What starts the process of antigen processing and presentation in type II MHC?
47
I: Proteasome
II: Lysosomal enzymes
What degrades the protein into peptides in type I vs type II?
48
MHCs are made
What happens in the ER in both classes of MHC?
49
Keeps Class II from picking up peptides by binding to peptide binding cleft .
What does invariant chain do?
50
CD8- cytolytic
| CD4- Helper
Is CD8/CD4 cytolytic/helper?
51
Chaperones in ER, invariant chain in ER, Golgi
Some things involved in transport of peptides and loading of MHC molecules Class II?
52
Ub
Tag that cells use to tell something to go to proteosome and be destroyed for normal turnover of cellular proteins.
Tags for degradation
Class I
53
TAP in ER
How do peptides cross the ER membrane?
54
Clip
What is left after the invariant chain has been cleaved?
55
HLADM
What holds Class II chains in an open configuration and removes Clip so other peptides can bind?
56
1. Specific recognition of antigen
2. Stable adhesion to the APC
3. Transduction of activating signals
T cell activation requires 3 things
57
ITAM
Immunoreceptor tyrosine based ACTIVATING motifs- Located on receptors for cell activation
58
ITIMS
Located on signalling chains remove phosphate group to counteract ITAMS via phosphotase, inhibits signal
59
Zeta and CD3
What phosphorylates the MHC T cell complex to transmit a signal?
60
CD3
Heterodimer, δ, E, and weird S, 1 ITAM/domain, signal transduction, Ab goes to this, often stimulates T cell responses that are identical to antigen induced responses
61
Zeta chain
Homodimer, 3 ITAMs/chain, in other cells (Fcy receptor of NK cells), signal transduction
62
CDR
3 of these located in variable region of a and B chain to recognize peptide-MHC complex
63
T cell receptor
Similar to Fab region on Ig molecule (in B cell)
64
```
Ig= heavy and light chains
TCR= a and b chains
```
Difference in components of T cell receptor and Ig
65
3
How many CDRs do Igs and TCRs have?
66
```
TCR= CD3 and z
Ig= Iga and Igb
```
What are the associated signaling molecules of a TCR and an Ig?
67
Ig
Production of secreted form, isotype switching, and somatic mutations
TCR or Ig?
68
Become phosphorylated and transmit a signal
What happens to 3 ITAMs when T cell is activated?
69
CD3
Required for T cell activation
70
MHC peptide ligand binds to TCR
Clustering of coreceptors (CD3 and Z)
Phosphorylation of ITAMs
Signal transduction
How is T cell activation initiated?
71
Fcy receptor on NK cells and T cells
What does z chain signal?
72
yS T cells
Only recognize antigens directly
Do not need MHC
Recognize target antigens directly
Innate like lymphocytes
73
aB
What are yS chains similar to in structure?
74
CD3 and z chains
What do yS T cells bind to?
75
No - generally
Do yS T cells express CD4/CD8?
76
yS T cells
May constitute a large percentage of IEL
77
CD4 and CD8
Co receptors that help signalling occur
78
CD28 T cell, B7-1, B7-2
Co stimulatory receptors
79
Accessory molecules of T cells
Non polymorphic and invariant
Many transduce signals that, in concert w/ TCR signals, regulate functional responses
Increase strength of adhesion b/t T cells and APCs
Binding of accessory molecules to endothelium mediates cellular homing
80
Cytokine receptors come together, jacks are activated and phosphorylated, stats attach to Jak and are phosphorylated, stat dimer migrates to nucleus, gene transcription
What happens in the Jak-Stat pathway?
81
NF-KB
Cytokine/TLR stimulus, inhibitory protein becomes phosphorylated and marked w/ obiquitin, IKBa is degraded releasing NF-KB, NF-KB enters nucleus to being transcription
82
BEcause they cooperate w/ the TCR in MHC recognition and T cell activation
Why are CD4 and CD8 called coreceptors?
83
CD2
On most naive T cells, NK cell, and thymocytes, binds to CD58 (CD48 in mice), adhesion molecule and signal transducer, compensates for CD28
84
SLAM
Co stimulatory receptor in T cells, NK cells, some B cells, signalling lymphocytic activation molecule reacts w/ itself in other cells.
85
2B4
NK cells, CD8 T cells, yS T cells, part of SLAM family
86
Non polymorphic regions of the MHC
What do CD4 and CD8 bind to?
87
Transduce signals to the T cell
F (CD4/8)
88
1. T cell receptor, CD3, Z, CD8, CD4
| 2. B7 w/ CD28
What are the 2 signals?
89
Cell becomes non functional and goes under apoptosis
What happens if signal one is activated but not signal two?
90
NOthing happens to T cell, no activation of TCR
What happens if you only have signal 2?
91
Signal 2: CD28 binding w/ B7 in combo w/ signal 1
How are naive T cells activated?
92
CD28, B7-1, B7-2,
Expressed on APCs
| Costimulatory molecules
93
Also binds to B7 but sends an inhibitory signal to the T cell
Competes w/ CD28 and has higher affinity for B7 after activation which is to stop activation, dont want continually activated
What does CTLA-4 do?
94
Nuclear receptors
Hormone that is lipid soluble that attaches to receptor in cytoplasm/nucleus
95
Tyrosine kinase
Cancer agents inhibit this, stop tumor production
96
Over productive, spread cancer production of vessels which help cancer grow
What happens when Tyrosine kinases are over activated?
97
TK is detached from receptor in nucleus and other is attached
What is the difference b/t non receptor and receptor as far as tyrosine kinase?
98
Vitamin D, glucocorticoid, thyroid hormone
Nuclear signalling receptors
99
G protein coupled receptors, leukotrienes, PG, histamine, chemokines,
Transmembrane receptors
100
Transmembrane receptors
Go in and out of membrane, receptors on cell by themselves not w/ T cell receptor
101
Hematopoeitic stem cell
What do all lymphocytes start as?
102
Outside the bone marrow
Where do signals for commitment to B/T cell lineage come from?
103
1. Commitment to T/B cell lineage
2. Proliferation of immature cells
3. Rearrangement of receptor genes
4. Selection
5. Differentiation of B and T cells into distinct subpopulations
Steps of lymphocyte development
104
Causes cell to proliferate cuz we want a big set of cells from bone marrow stroma/ thymus epithelial cells
What does IL-7 do?
105
```
B= bone marrow
T = thymus
```
Where does rearrangement occur for B/T cells?
106
When they are activated and have been selected ( they don't respond to self)
When do T cells become responsive to foreign antigen?
107
At the immature lymphocyte stage
When does a lymphocyte become self antigen dependent?
108
Mature lymphocyte to differentiated effector lymphocyte
When does a lymphocyte become foreign antigen dependent?
109
Liver used to produce WBCs and RBCs under sever circumstances revert back to fetal conditions
Why does a dog with an immunodisease that is killing RBCs have an enlarged liver?
110
B-1 B cells, T cells (before birth) YS T cells
What is made in the fetal liver?
111
yS T cells
Only derived from fetal liver and thymus
112
Majority of circulating B cells
T cells after birth
aB T cells
What comes from the bone marrow?
113
Thymus
Where do T cells fully mature?
114
NOTCH 1 which works w/ GATA3
Examples of transcription factors that cause a pluripotent stem cell to be a T cell?
115
EBF, E2A stimulate Pax5
What are the transcription factors that make something a B cell?
116
Causes proliferation of Pro B/T cell because we need lots of them to start w/. Then get gene rearrangement (heavy chain in B cell and B chain in T cell become rearranged and make a functional heavy or B chain)
What does the first IL 7 released do?
117
Heavy chain rearrangement w/ surrogate light chain or there is going to be a pre a chain.
What is a pre antigen receptor?
118
Cell death
What happens if pre antigen receptor fails to be expressed?
119
Because they have a K and lambda chain . Rearrange K then lambda. If this doesn't work still, get cell death
Why do B cells get a second chance if they responded to self antigen the first itme?
120
T cells because they don't get a 2nd chance
Which cells experience clonal deletion and why?
121
B cell, when lambda chain is given a chance to rearrange itself. If K doesn't work, undergoes receptor editing which is where lambda rearranges itself and then matures
What cells go thru receptor editing and why?
122
Positive selection
Facilitates survival of potentially usefull lymphocytes
123
Negative selection
Maintains tolerance to self,
| Central tolerance
124
CD4+
Differentiate into helper T cells upon activation by antigen
Secretes IL-2, which causes this to make itself proliferate and its neighboring cells. Then other cytokines push into Th1 vs Th2 vs Th17
125
CD8+
Cytotoxic lymphocytes that kill infected cells
| Can turn into memory cells
126
Follicular B cells
Recirculate and located in secondary lymphoid organs,
T cell DEPENDENT
Lymphnodes and spleen
127
Marginal zone B cells
Live in marginal sinus of spleen
Where blood pools which means can instantly respond so don't need T cells to present and activate.
In quick responding areas
T cell INDEPENDENT
128
H chain locus
In the B cell, which part of the DNA undergoes 2 rearrangements?
129
K and lambda
What chains only undergo one rearrangement? No diversity,
130
Lambda gets shut down, confirmationally changed, so can't get transcribed
What happens if the K is successful?
131
Alleic exclusion
Stops production/expressionof other heavy chain
| Only need one
132
Isotype exclusion
When lambda gets shut down and K stays. Lambda is confirmationally changed so can't get transcribed
133
Junction diversity
Produced when you add various end nucleotides going to be different when break apart
Only happens in heavy/B chain
134
Common notorial diversity
From recombining J,D, and V segments
135
Deletion
More common VDJ recombination because recombination sequences are facing opposite direction which is most common way it is setup
136
Inversion
Happens when heptamers are facing same direction.
137
Synapsis
2 coding segments brought together
| RSS
138
Cleavage
Rag-1 and Rag-2 complex; hold together chromosome
| Rag-1 makes nick in one strand b/t coding and heptamer forming a hairpin
139
1, but needs 2
Which Rag is responsible for the actual cutting part of cleavage?
140
Hairpin opening/end processing
Artemis opens up hair pins. Not even, P nucleotides match up missing sequences, so have cut and Ps fill in then there is a gap b/t which is where variability happens because N nucleotides aren't same everytime so adds junctional variability to recombination. Addition of bases to broken ends by TdT.
141
Artemis
Endonuclease responsible for opening up hairpins
142
Joining
Ligation of broken ends by DNA ligase
143
Where artemis cut and left hanging segments.
Where does P nucleotide fill in to match corresponding segments?
144
N nucleotide and cause juntional diversity
What fills the gap b/t the segments after P nucletides have been applied?
145
Addition of n nucleotides
Where does variability come from?
146
Receptor editing
When K is unsuccessful and rearrange y chain, 2nd chance
147
Stem cell> Pro B
| Pre B> Immature B
When does proliferation happen in B cell maturation?
148
Rag
Nicks DNA
149
Between Pro-B and Pre-B and b/t Pre-B and Immature B
When is Rag upregulated for recombination?
150
Adds N nucleotides
What does TdT do?
151
B/t Pro B and Pre B same time as first Rag
When is TdT upregulated?
152
B/t Pro B and Pre B
| recombines the heavy chain
When does the first B cell recombination happen?
153
B/t Pre B and immature B
When does light chain recombination happen
154
Immature> Mature B cell
| Forms Cu and Cs mRNA
When does splicing happen in B cell? What does it form?
155
On an immature B cell
When is IgM first expressed?
156
Mature B cell
When is membrane IgM and IgD expressed on B cell?
157
Immature B cell
When do B cells leave the bone marrow and go to the periphery?
158
Immature B
What stage does B cell negative selection and receptor editing occur?
159
Heavy chain has 2 recombinations. First, D and J, then V gets recombined w/ D and J
Light chain only rearranges V and J becaue it does not have D.
What is different b/t recombination and gene expresion in heavy vs light chain?
160
Excess J segments
What gets thrown out during RNA processing?
161
Pre-cell stage
When are surrogate light chains and a chains expressed?
162
1. Inititates survival and proliferation of that Pre-B cell,
2. signals inhibitiion of heavy chain recombination on opposite chromosome because it needs to be silenced.
3Also initiates rearrangement of K chain (recombination) and
4. eventually surrogate light chain will shut off
What does surrogate light chain do in pre B cell receptor?
163
Heavy chain and an invariant surrogate light chain
What is the pre-B cell receptor composed of?
164
Beta chain and a pre-T alpha chain
What is the pre-T cell receptor composed of?
165
1. Survival and proliferation of pre-T cells
2. Inhibition of B chain gene recombination
3. Stim of a chain recombination (causes expression of CD4 and CD8)
4. Shut off of pTa transcription
What does pre-T cell receptor do?
166
```
B-1 = fetal liver
B-2 = Bone marrow
```
Where does B-1 come from vs B-2
167
B-1
Come from fetal liver
Natural Ab
Limited receptor diversity
168
Spleen
Where do immature B cells from the B-2 lineage go next?
169
Transitional then either follicular or marginal zone B-2 cell
What happens to B-2 lineage in the spleen?
170
Marginal only has IgM
Does marginal or follicular only have IgM and not IgD?
171
```
Follicular = weird S
Marginal = µ
```
Follicular/ marginal have µ or weird S heavy chain?
172
Stem cell> Pro-T
| Pre T> Double positive
When does T cell maturation need IL-7 to cause proliferation?
173
Pro>Pre T
| Pre T- Double positive
When does Rag get upregulated in T cell maturation?
174
Pro-T to Pre-T
When is TdT upregulated?
175
Pre-T
At what point is there a recombine B chain only?
176
Recombination of B chain
What causes CD4 and CD8 to be expressed?
177
b/t pre-t and double positive
When does the a chain recombine?
178
Stem cell
What cell is in the bone marrow for T cell maturation?
179
Pro, Pre, Double positive, single positive
What T cells are in the thymus
180
Naive mature T cell
At what point do the T cells enter the periphery?
181
Double positive
When do +/- selection first occur in T cell maturation?
182
Naive, Pre T cell
In the bone marrow, what stage is the T cell at?
183
Death by neglect, Double positive, negative selection of DP T cells
WHat happens in the cortex of the thymus?
184
Goes thru positive selection and is either CD 4 or CD 8, or doesn't express either,
CD4 and CD8 go thru negative selection
What happens in the thymus medulla?
185
Either are CD4+ helper T lymphocyte, CD8+ cytotoxic T lymphocyte, yS T cell
What happens in the periphery to T cells?
186
2 recombinations
| D-J join, then V-D-J join.
What happens in recombination in the TCR gene B chain?
187
Only 1 recombination
| V-J joining, No D
What happens in a chain recombination?
188
B
Which a or B loses a constant in recombination?
