L2&3 Antigen Recognition by T Cells - Hudig Flashcards
1
Q
Macrophages and dendritic cells direct conversion from Th0 to (blank)
A
Th1
2
Q
ACTIVATED mast cells and Th2 cells direct conversion from Th0 to (blank)
A
Th2
3
Q
What IL is used in the conversion from Th0 to Th1?
A
IL-12
4
Q
What IL is used in the conversion from TH0 to Th2?
A
IL-4
5
Q
What are the five types of CD4 positive t cells?
A
- TFH
- TH1
- Th2
- Th17
- CD 25 regulatory
6
Q
What cytokines do TFH cells release?
A
IFNg, IL2, IL4, IL5
7
Q
Where do you find TFH cells?
A
spleen, lymph nodes, Peyer’s patches, and in the periarteriolar lymphoid sheath of white pulp
8
Q
What is the function of the cytokines released by TFH?
A
growth factors for B and T cells
9
Q
What role does TFH play in B cell development?
A
supports isotype switching and Ab production
10
Q
How many fold can an Ag-specific T cell increase after stimulation?
A
10,000x
11
Q
What is the function of TH1 cells?
A
increases the cytotoxic activity of CD8 t cells; causes pre-CTLs to mature into CTLs; activates infected macrophages to kill intracellular bacteria
12
Q
What cytokine does Th1 release?
A
IFNg ONLY
13
Q
Does TH1 drive cellular or humoral immunity?
A
cellular
14
Q
How does Th1 activate macrophages?
A
releases IFNg which tells the macrophage to kill the bacteria inside of it
15
Q
T/F: TB is not affected by Ab production
A
true
16
Q
What reaction are memory Th1 cells involved in?
A
Delayed type hypersensitivity reaction
17
Q
What is the function of TH2 cells?
A
Increases Ab production, helps B cells switch to IgE production
18
Q
what cytokines does Th2 release?
A
IL4 ONLY
19
Q
IgE from B cells arms (blank) cells and drives ADCC (which stands for blank)
A
mast cells
antigen dependent cell mediated cyototoxicity
20
Q
What cytokines does TH2 release to control helminths? What cells do they target?
A
IL3 and IL9, target mast cells
21
Q
What do mast cells release in response to IL3 and 9 from Th2 cells?
A
histamine, TNF-a, and MMCP
22
Q
What is the big picture goal of the activated mast cells from Th2 cells?
A
Recruit inflammatory cells and remodel the mucosa
23
Q
Do Th2 cells drive cell mediated or humoral immunity?
A
Humoral
24
Q
B cells and (blank) cells both have IL4 receptors
A
eosinophils
25
IL4 receptors on B cells allow them to (blank)
proliferate and begin Ab production
26
What is the function of TH17 cells?
brings neutrophils into the site, activates resident fibroblasts, epithelial cells, and keratinoctyes to produce inflammation`
27
The effectors of TH17 actions are a good example of a cytokine (blank)
network
28
What is the function of IL017?
promotes bacterial killing
29
TGF-beta and IL-6 from (blank) cells stimulates TH17 to divide
dendritic cells
30
When signaled by DC with TGF-b, TH17 releases IL-17 which targets (blank) cells
fibroblasts
31
The fibroblasts targeted by the IL17 of Th17 release (blank and blank) to activate neutrophils
CXCL8 and CXCL2
32
What cells is the end-effector of TH17 action?
Neutrophils killing the bacteria sensed originally by the Dc
33
What is the master regulator of TH17 differentiation?
RORyt
34
What other CD protein are Tregs positive for?
CD25
35
Tregs have a high affinity for the (blank) receptor?
IL2
36
T/F: Upon leaving the thymus, Tregs are the only cells that are CD25 postive
true
37
T/F: after Ag encounter, other T cells become CD25 positive
True
38
Why do other cells become CD25 positive after Ag encounter?
to increase affinity for the IL2 receptor to increase ability to proliferate
39
What is the function of Tregs?
Regulate proliferation of normal T and B cell responses
40
T/F: Tregs are capable of suppressing autoimmunity
true; important in SLE
41
What are the only cells that secrete suppressive factors?
Tregs
42
(blank) suppresses activated APCs from making cytokines
IL10
43
(blank) suppresses lymphocyte proliferation
TGF-b
44
Treg activation leads to less (blank and blank) rlease from Th cells, resulting in less lymphocyte proliferation and CTL granule release
IFNg and IL2
45
What is the critical transcription factor for Tregs?
Foxp3
46
Treg activation is antigen (specific/nonspecific), but its actions are antigen (specific/nonspecific)
specific, nonspecific
47
What cell type can produce clinical anergy, as seen in a negative skin TB test while having positive sputum?
Tregs
48
Explain how Tregs cause clinical anergy?
IL10 turns off IFNg production, TGF-b turns off all proliferation, Pts can't respond to skin test or new Ag stimulation to DTH
49
What cell type kills cells infected with viruses?
CTL CD8
50
What MHC class does CD8 use?
MHC I
51
What do all cells (except RBCs) use for MHC?
MHC II
52
What three cytokines do CD8 cells need to become cytotoxic?
IL2, IL5 (both from TFH?), and IL-21
53
what two cytokines stimulate CD8 proliferation and granule production?
IL2 and IFNg
54
What proteins are in the TNF receptor family on CD8 cells?
FasL and TRAIL
55
What MHC II chain components bind the peptide? What CD type uses this?
the a1/b1 chains; used by CD4
56
How long is the Ag peptide for MHCII?
20-30 aaa
57
Describe the alpha/beta dimer of the MHCII?
a1a2/b1b2
58
MHCII binds (intra/extra) cellular peptides?
extracellular
59
On MHC I, what chain components bind the peptide?
a2/a1
60
Describe the MHC I configuration?
a1a2a3/b2-microglobulin
61
What is the size of the protein bound in the MHC I cleft?
11 aa or smaller
62
T/F: peptides bind to MHC covalently
FALSE; noncovalently
63
Describe the way the peptide binds to the MHC?
binds at the peptide C terminus and anchors using a few amino acids
64
MHC I binds (intra/extra) cellular components
intracellular
65
The CD protein binds to the (blank) while the TCR binds to the (blank)
CD to MHC, TCR to Ag
66
Binding of both the peptide and the MHC is known as dual recognition and stimulates (blank) signaling
kinase
67
For T cells, what is signal 1?
Ag
68
For T cells, what is signal 2?
co-stimulatory signal
B7-1 aka CD80 (signal; APC)
B7-2 aka CD86 (signal; APC)
to CD28 (receptor; t cell)
69
What do you need besides signals 1 and 2 to get T cell activation?
IL-1/TNF-a innate danger signal
70
Do B cells use the same signal 2 as T cells?
no
71
What is the similarity between Ig molecules and TCR structurally?
both have 2 CHAINZ, both bind the Ag/Ab at the end of the receptor chain, both have short intracytoplasmic tails, both use 2nd messenger cascades
72
Do B cells recognize native or processed structures?
native
73
Do T cells recognize native or processed structures?
processed
74
The (TCR/Ig) undergoes affinity mutation
Ig
75
Compare an AB to the Ig molecule?
Ab is an Ig molecule missing the transmembrane domain
76
What is the signal 2 for B-cells?
CD40L (signal; t-cell) to CD40 (receptorl; B cell)
77
What macromolecule does CD1 present to T cells?
bacterial lipids; important for TB!
78
What is the only cell type that expresses CD1?
APCs
79
What is the CD profile of a T cell responding to CD1 activated APC?
CD4/CD8 negative!
80
What type of chain does the TCR of the CD1 responding T cell have?
alpha/beta
81
All people have the same (CD1/MHC proteins) and huge variation among (CD1/MHC proteins)
same CD1, lots of MHC variation
82
What immunologic concept does diGeorge syndrome illustrate?
as it affects T-cells, it shows that you need more than just Abs to control infection
83
What types of infections are diG pt's susceptible to?
Viral, mycobacterial, an fungal
84
What types of infections can diG pt's fight?
bacterial
85
T/F: diG pts will produce Abs
true!
86
What is a PREVENTABLE cause of diG?
FAS!
87
Compare T cell levels in diG and SCID?
diG: low
SCID: low
88
Compare B cell levels in DiG and SCID?
diG: normal
SCID: low
89
Compare serum Ig levels in diG and SCID?
diG: normal
SCID: low
90
What is the cause shitty T cells in diG?
missing branchial pouch 3 and 4, therefore no thymus!
91
What is the cause of shitty T-cells in SCID?
No IL-7 production and potentially bad RAG genes; mutation in the common gamma chain of the cytokine receptors
92
What cell is the end-effector of the activity of Tfh?
B cells
93
What cell is the end-effector of the activity of Th1?
macrophages and B cells
94
What cell is the end-effector of the activity of Th2?
eosinophils and B cells
95
What cell is the end-effector of the activity of TH17?
epithelial cells and neutrophils
96
What type of pathogen stimulates TFH?
any??
97
What type of pathogen stimulates TH1?
microbes
98
What type of pathogen stimulates TH2?
helminthic parasites
99
What type of pathogen stimulates TH17?
immunologic reactions
100
(blank) cell type is important in MS, IBS, RA, and other autoimmune disorders
Th17
101
What cell type mediates the DTH response?
Th1
102
DTH is specific to what four pathogens?
1. mycobacterium tuberculosis
2. M. leprae
3. Listeria
4. Salmonella
5. Erlichia
103
Is the DTH response active upon first-time Ag exposure?
No, the TH1 must have been previously sensitized to the Ag, proliferated, then went dormant
104
What is the function of the Th1 cell in DTH?
Immediate control of the TB and elimination of other bacteria
105
How does Th1 control TB in DTH?
production of IFNg which stimulates infected macrophages to kill the bacteria within themselves
106
How long does it take for Th1 to begin to produce IFNg during the DTH? Why?
4 hour minimum; they were dormant and need to up gene regulation
107
Upon IFNg stimulation in DTH, describe what the macrophage does to control its TB infection?
Secretes TNF-a
| Converts iNOS to NOx and creates ROS (microbicidal), but some TB persists and becomes latent
108
The cytokines from which cell actually causes the response in DTH?
The macrophages!! The Th1 just induces the macrophages to release their cytokines
109
What is the minimum time required for a DTH response? What is happening during this time?
18 hours; dormant Th1 wakes up, makes mRNA for IFNg, then more time for the macrophages to make mRNA for iNOS and express TNF-a
110
What are the clinical findings of the DTH?
leakage of plasma into skin, activation of fibrinogen to fibrin
111
What is the name of the firm lesion in DTH?
induration
112
At what time does DTH peak?
24-48 hours post Ag introduction
113
How doe the macrophages change morphologically during the DTH?
they become multinucleate
114
What are two common items that cause DTH?
poison ivy and nickel allergies
115
In alternate macrophage stimulation, what does TH1 do?
stimulates microbicidal activity
116
In alternate macrophage stimulation, what does TH2 do?
stimulates macrophages to begin tissue repair and ECM protein synthesis
117
What three cytokines inhibit microbicidal activity and suppress TH1 immunity?
IL4, IL10, and IL13
118
How do CTLs cure a cell without killing it?
they release IFNg which instructs the cell to destroy the viral mRNA
119
Is apoptosis or necrosis favorable for viral infections? Why?
Apoptosis; virions are always membrane-bound
120
Perforin and granzymes are also released from (blank) cells in innate immunity and in ADCC function
NK cells
121
Which cell has FasL and which has Fas?
Target cell has Fas, CTL has the FasL (I AM THE KEYMASTER, ARE YOU THE GATEKEEPER?)
122
Does the Fas system trigger apoptosis or necrosis?
Apoptosis
123
Do resting CD8 cells have the FasL or granules?
No
124
What stimulates CD8 cells to produce FasL and granules?
IL-2 (and maybe IFNg?) to produce them
125
What are the contents of the cytotoxic granules?
Perforin
Granzymes A/B
Granulysin
126
What does perforin do?
Creates a channel to let in the granzymes and causes an osmotic defect in the PM allowing Ca and H into the cell
127
Which granule content is able to kill TB bacteria?
granulysin
128
What two granule contents are necessary for long term TB control?
perforin and granulysin
129
Which granzyme cleaves procaspase?
Grz B
130
Which granzyme cleaves the inhibitor of caspase activated DNase?
Grz A
131
granule mediated cell death causes necrosis when (blank) lyse the cell membrane
polyperforins
132
What is the only type of vaccine that will boost memory CTLs?
LIVE vaccines
133
T/F: live vaccines are highly effective
true
