1
Q
Complement
A
Group of plasma and cell surface proteins that fight invading organisms through inflammation, phagocytosis, and lysis
2
Q
Mannose Binding Protein (MBP)
A
Binds mannose on surface of bacteria, viruses, and parasites - tags organism for phagocytosis
Activates complement pathway
3
Q
C-reactive Protein
A
Binds to bacterial surface, acts like opsonin (binds to an Ag to promote phagocytosis)
Activates complement
4
Q
IL-10
A
Inhibits macrophage activity
5
Q
IL 12, 18, 23
A
Stimulate NK cells to produce IFN-γ
6
Q
IFN-α and β
A
Stimulate NK cells and promote class I MHC expression
7
Q
IFN-γ
A
Produced by NK cells, activates macrophages
8
Q
TGF-β
A
Stimulates macrophages
9
Q
MHC
A
Major histocompatibility complex - display antigens
10
Q
Class I MHC is associated with which responsive T cells?
A
CD8+ T Cells
11
Q
Class II MHC is associated with which responsive T cells?
A
CD4+ T cells
12
Q
Which cells express Class I MHC?
A
All nucleated cells
13
Q
Which cells express Class II MHC?
A
Dendritic cells, phagocytes, B lymphocytes, endothelial cells, thymic epithelium
14
Q
Src Tyrosine Kinases
A
c-Src, Lyn, Fyn, Lck
15
Q
Syk Tyrosine Kinases
A
Syk, ZAP-70
16
Q
Tec Family Kinases
A
Tec, Btk, Itk
17
Q
SH2 domains
A
bind phosphotyrosine-containing polypeptides
18
Q
SH3 domains
A
bind proline-rich stretches (hydrophobic areas)
19
Q
PH domains
A
recognize PIP3 (or other phosphatidylinositol-derived lipids)
20
Q
CD4 is associated with what type of T cells?
A
T helper
21
Q
CD8 is associated with what type of T cells?
A
Cytotoxic T cells
22
Q
Early Events in T Cell Activation
A
- Ag recognition - TCR complexes cluster with CD4 or CD8
- CD4-associated Lck becomes active, phosphorylates ITAMs of CD3 and zeta chains
- ZAP-70 binds phosphotyrosines of zeta chains that self-phosphorylate and are activated
- Active ZAP-70 activates (phosphorylates) adaptor proteins such as LAT
- Adaptors become docking sites for PLCγ11 and exchange factors that activate Ras and MAP kinases
23
Q
PI3k
A
converts PIP2 to PIP3
24
Q
Pro-B cells can eventually differentiate into:
A
follicular B cells, marginal zone B cells, and B-1 cells
25
Pro-T cells can commit to either:
αβ T cells or γδ T cells
26
Rag-1 and Rag-2
regulate BCR rearrangement - at the beginning of B cell life
27
Notch-1 and GATA-3
transcription factors that commit lymphocytes to T cell lineage
28
H-chain chromosome #
14
29
κ-chain chromosome #
2
30
λ-chain chromosome #
22
31
Order of BCR Diversity gene rearrangement
1. D segment chosen (DJ)
2. V segment chosen (VDJ)
3. J chosen (VDJC)
32
Which segments in BCR and TCR do NOT have D segment?
BCR - light chain
| TCR - α chain
33
What nucleotide sequence does RAG add?
p (palindromic)
34
What nucleotide sequence does TdT add?
n (nontemplated)
35
Which is the first polypeptide chain completed in B cells?
H
36
Which is the first polypeptide chain completed in T cells?
β
37
What are the three signals required for proliferation of T lymphocytes?
1. Ag recognition
2. Costimulation
3. Cytokines
38
What are the steps in T-Cell Receptor Signaling?
1. LCK is activated, phosphorlyation of CD3 and activation of ZAP70
2. Activated ZAP70 phosphorylates LAT and SLP76
3. LAT recruits GRB2, GADS, and PLC1
4. PLC1 results in production of IP3 and DAG
5. IP3 increases cytosolic free Ca2+
6. DAG activates PKC
7. LAT activates Ras and MAPK
39
CTLA-4
Mediates immune checkpoint induced in naive T cells at time of their initial response to Ag - inhibitor
40
PD1
Checkpoint that regulates inflammatory responses in tissues
41
IL-2
survival signal for T cells - increases expression of anti-apoptotic protein Bcl-2
42
CD69
Reduces surface expression of S1PR1 (keeps T cells in lymph node)
43
S1PR1
T cells will leave the lymph node
44
When is CD40 (CD154) increased in activated T cells?
24-48 hours after Ag recognition
45
When is CTLA-4 (CD152) increased in T cells?
24-48 hours after Ag recognition
46
T-bet
differentiation of effector cells in CD4+ T cells
47
Blimp-1
generation of memory cells
48
What are the two pathways from which memory T cells may develop?
1. linear - some effector T cells "stick around" and become memory cells
2. divergent - some cells will become memory cells "right away"
49
PLCγ - effect
catalyzes hydrolysis of PIP2 to IP3 and DAG
50
IP3
stimulates increase in cytosolic Ca2+ (from ER)
51
DAG
activates protein kinase C (PKC)
52
Ras*GTP pathway
activates ERK --> phosphorylates ELK --> transcribes fos --> combines with Jun and activates AP-1
53
Rac*GTP pathways
activate JNK --> phosphorylates Jun --> combines with fos and activates AP-1
54
Five NF-KB proteins
```
p65/RelA
Rel B
c-Rel
p50/NF-KB1 (no activation domain)
p52/NF-KB2 (no activation domain)
```
55
Canonical NF-KB pathway
1. p65/cRel + p50 is bound to IKB (NF-KB inhibitor)
2. activated IKK (IKB kinase) phosphorylates IKB protein and induces polyubiquiniation
3. protease recognizes IKB-UUUUUUU signal and degrades
4. NF-KB (the p65/cRel & p50) are released, translocated to nucleus, and activated
56
Alternative NF-KB pathway
1. IKKα activated
2. Phosphorylates RelB/p100 - partial proteolysis of P100 --> p52 (NF-KB2)
3. NF-KB2/p52 dimerizes with RelB and translocates to nucleus
57
T-Cell costimulators
CD28 and CD80/60
58
Coreceptors on T helper cells
CD4
59
Coreceptors on cytotoxic T cells
CD8
60
Coreceptors on B cells
CD21, CD32, CD 19
61
Difference between coreceptors and costimulators
Coreceptors: can bind to same Ag ligand complex recognized by Ag receptor
Costimulators: "second signals" do NOT recognize ligands
62
Inhibitory receptors in T cells
CTLA-4
63
Inhibitor receptors in B cells
CD22 and FCγRIIB
64
TCR complex structure
αβTCR noncovalently linked to CD3 and ζ proteins (signal transducing subunits)
65
Positive co-receptors on B cells
CR2 (CD21) complex w/ CD19, CD81 - lower threshold for B cell activation and increase signaling response
66
Negative co-receptors on B cells
CD32 - contains ITIM, negatively regulates BCR signaling
67
What is the role of complement in B cell activation?
Complex of the CR2 complement receptor - CD19 and CD81 (TAPA-1)
Ag bound to complement fragment C3d can engage both CR2 and membrane Ig, leading to signaling cascades form both BCR and CR2 complexes
68
How does CR2 complex enhance response of BCR?
Binding of C3d-CR2 brings CD19 closer to BCR-associated kinases
This phosphorylates CD19 cytoplasmic tail
1. Enhances phosphorylation of ITAM in Igα and Igβ
2. Activates PI3-kinase
PI3 kinase activates Btk and PLCγ
69
FcγRIIB
inhibits activated B cells, DCs, and macrophages
70
CD22
inhibits B cells only
71
SHP
SH2-domain containing phosphatase (associates with ITIM of inhibitor receptors)
72
SHIP
SH2-domain containing inositol phosphatase (associates with ITIM of inhibitor receptors)
73
What are the two mechanisms of inhibitory signaling?
1. Inhibitory receptors (recruit phosphatases)
| 2. E3 ubiquitin ligases
74
C3b and C4b activity and effect
Activity: opsonization of Ag
Effect: Increase phagocytosis by macrophages and neutrophils
75
C3a and C5a activity and effect
Activity: chemotaxis, degranulation
Effect: Attract neutrophils and monocytes to inflammatory sites, release of inflammatory mediators from mast cells and basophils
76
C3b activity and effect
Activity: clear immune complexes
Effect: reduce buildup of harmful Ab-Ag complexes
77
C3d activity and effect
Activity: B cell activation
Effect: Promote humoral immune response
78
Stages of lymphocyte maturation
stem cell --> pro lymphocyte --> pre lymphocyte --> immature lymphocyte --> mature lymphocyte
79
What cytokine stimulates development of T cell progenitors?
IL-7
80
What cytokine stimulates development of NK cells?
IL-15
81
Which transcription factors induce genes required for B cell development?
EBF, E2A, and PAX-5
82
What is the pre-BCR Ag receptor chain?
Ig μ heavy chain
83
What is the pre-TCR Ag receptor chain?
β chain
84
positive selection
process in which cells that have low avidity to self are stimulated to survive
* have low recognition of self-Ags, but can still recognize MHC
85
negative selection
T cells: if they have strong avidity to self-Ag, will be eliminated via apoptosis (clonal deletion)
B cells: get 2nd attempt in Ig rearrangement (receptor editing)
* κ to λ light chain
* if receptor editing fails, will have apoptosis
86
Pro B Cell options for proliferation and specialization
B1 cells
| B2 cells - follicular B2 cells or marginal zone B2 cells
87
B1 cells
* derived from fetal-liver HSCs
* express limited BCR diversity b/c TdT is not expressed in fetal liver
* secrete IgM
88
B2 cells
* develop from bone marrow HSCs
| * follicular B2 cells or marginal zone B2 cells
89
Follicular B2 cells
* require constant replenishment from bone marrow
* respond to Ag via T-cell dependent manner
* undergo Ig isotype switching
* after T-cell dependent activation, will develop to plasma cells and memory B cells
90
Marginal zone B2 cells
* localize to splenic marginal zone, respond to bloodborne Ag
* self-renewing
* respond independent of T cells
* limited BCR diversity
* respond to blood borne microbes and differentiate into short-lived IgM secreting plasma cells
91
αβ vs γδ T cells
10% T cells = γδ - have limited diversity
| 90% T cells = αβ
Immunology KCU
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