Antigen Recognition by T Cells Flashcards
1
Q
What is the reactive lymphocytes in the blood during mononucleosis caused by epstein barr virus?
A
T cells, not B cells
2
Q
EBV is a persistent and chronic infection of (blank) cells
A
B
3
Q
The CTLs recognize EBV proteins located (intracellular/extracellularly) of chronically infected B cells
A
intracellularly (in the nucleus)!!!
4
Q
There are (blank) major types of T cells and their roles
A
6
5
Q
T cell receptors are (blank-beta) or (gamma-(blank) chain dimers
A
delta
6
Q
CD (blank) is on all T cells
A
3
7
Q
T cells are (always resting/active) until antigen stimulated
A
resting until stimulated
8
Q
When do T cells proliferate?
A
upon antigen stimulation, then able to mediate functions
9
Q
How long do T cells last?
A
a lifetime
10
Q
Do memory T cells act quickly when re-stimulated by an antigen?
A
no, they must be restimulated, proliferate, then they can mediate functions
11
Q
What are the 6 T cell subsets?
A
4 types of CD4 T helper cells -TFH -TH1 -TH2 -TH17 AND CD4 T regulatory cells AND Cytotoxic T cells CD8
12
Q
What does TFH (follicular helper) do?
A
cells produce growth factors for B and T cells
13
Q
What does TH1 do?
A
increases cytotoxic T cell activity
14
Q
What does TH2 do?
A
increases antibody production; switch to IgE
15
Q
What does TH17 do?
A
brings neutrophils to site
16
Q
What does CD4 T regulatory cells do?
A
regulate proliferation of normal T and B responses
suppresses autoimmunity
17
Q
What do cytotoxic T cells CD8 do?
A
kill cells infected with viruses
18
Q
Where do you find follicular helper T cells?
A
you find these CD4 T cells in lymphoid follicles in spleen, lymph nodes peyers patches (small intestine)
19
Q
How do follicular helper T cells divide?
A
they must recognize and antigen then they can divide
20
Q
What is the function of follicular helper T cels?
A
provide cytokines required for T and B cell proliferation and are used for memory
21
Q
What do follicular helper T cells produce?
A
IL-2 (a growth factor for all T and B cells) IL-4, IL-5, and interferon g
22
Q
If you lack CD4 T helpers what can you leave your self susceptible to?
A
getting AIDS!!!!!
23
Q
(blank) cells support T cell division and direct B cell functions
A
TFH CD4 T cells
24
Q
Why is the loss of CD4 T helper cells critical in the development of AIDS?
A
This decline will result in a decline and loss of IL-2 secretion and thus T/B cell activation and proliferation.
25
Where do you find TFH in the spleen?
in the periarteriolar lymphoid sheath
26
What does CD4 Th1 secrete?
gIFN (mainly) and IL-2
27
What does CD4 TH2 secrete?
IL-4 and IL-5 and IL-2
28
Where do you find B cells in the spleen?
in the germinal center
29
What is the main function of CD4 Th1 cells?
activate infected macrophages, provide help to B cells for antibody production, support CD8 cytotoxic activity
30
What is the main function of CD4 TH2 cells?
provide help to B cells for antibody production, especially switiching to IgE
31
How can you differentiate between CD4 TH1 and TH2?
different cytokine production and TH1s support CD8 cytotoxic activity
32
TH1 and TH2 can (blank) the immune response.
polarize
33
TH1 and TH2 can polarize the immune response, what does this mean?
meaning that depending on which TH cell is activated the immune response can be driven more cellularly (via Th1 response) or more humoral (via the Th2 response).
34
(blank) is the signature cytokine that distinguishes a TH1 cell from TH2 and TH17 cells
Gamma interferon
35
(blank) is the signature cytokine that distinguishes a TH2 cell from TH1 and TH17 cells.
IL-4
36
(blank) is the signature cytokine of TH17 cells that distringuishes TH17 cells from TH1 and TH2 cells.
IL-17
37
TH1 responses drive (blank) immune responses
cellular (main goal is to make cytotoxic granules)
38
TH2 responses drive (blank) immune responses
humoral
| i.e main goal is to make antibodies
39
T or F
| many different cell types have receptors for gamma interferon
T
40
Gamma interferon is the (type I/type II) interferon.
type II (i.e cannot use alph and beta interferon receptors)
41
Do B cells have receptors for gamma interferon? What does this mean?
yes
| cause B cells to slow proliferation and to switch to IgG isotypes
42
What cell types have receptors for IL-4?
B cells and eosinophils
43
What does interferon gamma do?
IFNγ is an important activator of macrophages and inducer of Class II major histocompatibility complex (MHC) molecule expression
44
(blank) polarize T helper 1 or T helper 2 cell differentiation (and individual biases)
cytokines
45
(blank) from dendritic cells and macrophages direct conversion from TH0 (immature effector T cell) to TH1
IL-12
46
What releases IL-12 to allow from the conversion rom TH0 (immature effector T cell) to TH1
dendritic cells and macrophages
47
(blank) from ACTIVATED mast cells and TH2 cells directs THO conversion into TH2
IL-4
48
What releases IL-4 to direct THO conversion into TH2?
activated Mast cells and TH2 cells
49
(blank) control intracellular mycobacterium tuberculosis that cause TB, which is unaffected by Ab's
TH1 T cells
50
How does THI T cells control TB?
beating it up intracellularly
51
Mycobacterium tuberculosis prevents formation of (blank)
phagolysosomes
52
How do delayed type hypersensitivity T helper 1 cells kill bacteria?
it uses gamma interferon to instruct macrophages to kill bacteria inside the macrophages
53
What are delayed type hypersensitivity TH1 cells?
these are memory TH1 cells that were previously sensitized to the antigen, proliferated and became quiescent memory cells until they re-encountered their cognate antigen
54
Are delayed type hypersensitivity responses (DTH) quick?
no they take about 48 hours
55
What happens around 18 hours in the DTH response?
you get leakage of plasma into the skin site and fibrinogen is activated to fibrin.
56
In the DTH response when you get leakage of plasma into the skin and this is coupled with fibrin, what happens?
You get induration which is when a FIRM lesion forms
57
When does induration peak?
24-48 hrs after antigen introduction
58
What happens to macrophages when under the influence of TH1?
they become multinucleated
59
Memory TH1 cells take how long after activation to make gamma IFN? When does the macrophage response occur?
more than 4 hours
| hours after this response
60
When macrophages are induced to multinucleate by TH1 cells, what else do they do?
Make TNF alpha and other inflammatory cytokines and then make the skin response
NOTE::::: Macrophages make the skin response!!!!
61
What are the 2 essential cell types in DTH?
macrophages and TH1 T
62
What are memory CD8 T cells?
they are cells that when activated again will release granulysin which kills intracellular bacteria.
63
What does granulysin (the cytotoxin released from CD8) need to enter infected cells so they an kill stuff?
perforin
64
What are some examples of DTH immunopatholoy type IV responses?
poison ivy and nickel allergies (these are memory responses)
65
Control of TB bacteria; elimination of other bacteria is done by what?
CD4 TH1 and DTH
66
Long term control of TB and clearance of intracellular bacteria is done by what?
CD8 and CTL (w/ perforin and granulysin)
67
(blank) mediate delayed type hypersensitivity (DTH), our defense against bacteria that live inside macrophages.
TH1 cells
68
What are some intracellular bacteria that TH1 cells can kill with DTH?
mycobacterium TB, M. leprae, listeria, salmonella, erlichia
69
T or F
| infected macrophages themselves can kill their bacteria
T
70
How can infected macrophages themselves kill their bacteria?
they must be activated by antigen specific CD4+ memory TH1 cells
71
Why wont you see DTH on first exposure to a TB vaccine?
because you need a prior exposure to get your TH1 numbers up high enough to create DTH memory T cells
72
What is the antigen in the TB skin test?
PPD (purified protein derivative)
73
How do you get the DTH response in the TB skin test?
memory DTH TH1 CD4 cells recognize PPD and you get a macrophage inflammatory response which causes skin inflammation
74
What is the delay for DTH in skin tests? why?
about 48 hrs
| it takes time for 2 cell types to activate: resting memory Th1 cells and macrophages
75
In DTH, resting memory Th1 cells must induce what?
mRNA and make gamma IFN
76
In DTH, what do the macrophages make?
mRNA, iNOS and TNFalpha
77
What do T helper 2 T cells secrete and what does this allow for?
IL4, drives B cell to produce IgE
78
(blank) and (blank) are critical in control of helminths
IL-3 and IL-9
79
What does IgE do?
it arms mast cells and can mediate ADCC (antibody dependent cellular cytotoxicity)
80
TH2 cells drive mast cell recruitment against helminths via (blank) and (blank)
IL3 and IL9
81
IgE arms mast cells against (blank)
helminths
82
Mast cells produce mediators such as ....?
histamine, TNF alpha, MMCP (these recruit inflammatory cells and remodel the mucosa)
83
(blank) cell follicles are also found in tonsils and appendix
B
84
What do Thelper17 Ts secrete?
IL-17
85
What is the key activity of Th17?
to activate fibroblasts, epithelial cells and keratinocytes to produce inflammation and bring in neutrophils
86
The cells with receptors for IL-17 are inducible to secrete many (blank) cytokines
inflammatory
87
The nuclear transcription factor RORγt is the master regulator of (blank).
TH17 differentiation
88
How do you get Th17 to secrete IL 17 and then what happens once it gets secreted?
a dendritic cell must secrete TGF beta which will tell IL17 to make fibroblasts secrete CXCL8 which will make neutrophils kill bacteria?
89
CD 4 T regulatory cells are antigen-specifc in (blank) but often antigen-nonspeific in their (blank).
elicitation
| effects
90
T or F
In other words, it takes a specific antigen to induce a Treg (T regulatory cell) to secrete suppressive factors. It does not secrete suppressive factors constitutively.
T
91
What would happen without T regulation?
overactive immune system, large lymph nodes and enlarged spleen
92
Identify 7 types of lymphocytes that divide in response to specific antigens
TFH, THI, TH2, TH17, CD8, CTL, CD5 regulatory T cell, B cell
93
Excess T regs in fulminant TB will produce (blank)
clinical anergy
94
How do you turn off gamma IFN production?
IL-10 from Tregs
95
What does TGF beta do?
turns of all proliferative responses
96
```
What does this:
Patients are unable to respond to:
tuberculin skin test
Candida skin test
new antigens, e.g., the dye DNCB,
(dinitrochlorobenzene) as a reactive chemical that will elicit DTH responses
```
TGF beta and IL-10 when there is an excess of T regs
97
What leads to the inability to produce any new memory or memory response?
too much T regulatory cells
98
(blank) is a term in immunobiology that describes a lack of reaction by the body's defense mechanisms to foreign substances, and consists of a direct induction of peripheral lymphocyte tolerance.
anergy
99
What does this:
| ehances neutrophil response, promotes barrier integrity (skin, intestine)
CD4 Th17 cells
100
What suppress T cell responses?
CD4 regulatory T cells
101
What does CD4 regulatory T cells secrete?
IL-10 and TGF beta
102
Where do you find perforin?
in killer lymphocytes and NK cells
103
How do you get a CTL cell to kill?
needs to bind a MHC 1 peptide and an antigen and must proliferate to be effective
104
What besides being killing machines can CTLs do?
thye can generate (resting) memory cells
105
What cytokines do CTLs need to be effective?
IL-2l IL-15 an IL-21
106
CTL killing is dependent on what?
cytotoxic granules w/ perforin
OR
membrane molecules of the TNF receptor family (FasL, TRAIL)
107
When CTLs kill, do they die with the cell they destroy or can they keep killing?
They can keep killing
108
How can CTLs destroy viral mRNA within an infected cell without killing the cell?
by using gamma interferon
109
If a CTL decides to kill an infected cell how does it do it, by apoptosis or necrosis?
it can do it either way
110
If a CTL decides to kill an infected cell via necrosis, how does it do it?
it damages the outside of the cell and irreversibly damages the plasm membrane
111
If a CTL decides to kill an infected cell via apoptosis, how does it do it?
damages the cells insides and keeps the plasma membrane intact
112
(blank) is the disruption of the PM of a cell and can occur at the beginning or end of the death process. (blan) leaks out of the cell
lysis
| cytoplasm
113
(blank) is a form of cell death in which the cell is injured by external events. The cell itself is passive and just dies of injury.
necrosis
114
(blank) is a form of cell death in which a cell is induced to commit suicide and dies from the inside out. The plasma membranes are often left intact: the dead cell fragments into membrane-enclosed pieces which are cleared by phagocytic macrophages and neutrophils. This form of death has advantages since intracellular contents (for example, viruses) remain contained within membranes. Prior to the cell death, the nucleus appears condensed, the cell shrinks, and the plasma membrane blebs.
apotosis
115
Is it dangerous to be near a CTL when it is doing its killings?
no, innocent bystanders are fine and the killing is rapid.
116
How do CTLs make a cell undergo apoptosis?
they can polarize their cytotoxic granules toward the infected cell and the cell kills itself
OR
Can bind FasL to Fas on the infected cell which ill induce a cascade that starts apoptosis
117
(blank) and (blank) are released from the CTL granules. These are also released by (blank) cells in innate immunity and ADCC function
perforin
granyzme
NK
118
How do CTLs recognize only infected "targets"?
Dual recognition via a specific TCR to MHC 1 and viral peptides
119
To memory CTLs have FasL and cytotoxic granules?
no, they need IL-2 or other cytokines to induce these molecules
120
What is in the cytotoxic granules of CTLs?
perforin, granzyme A, granzym B, granulysin
| perforin creates the pore in the membrane to put the enzymes in
121
Perforin can fuck up a cells life 2 ways. what are they?
cause membrane disruption that causes immediate necrosis
OR
makes a pore so cytotoxic enzymes can enter
122
Granule-mediated death can cause apoptosis when (blank) or (blank) enter into the target cell via perforin permeability
granzymes A
| granzymes B
123
Once granzyme A or B enter a cell, how do they make the cell undergo apoptosis?
they cleave procaspases (by Grz B) or caspase-activated DNAse inhibitor (by Grz A)
124
Most CD8 T cells kill what?
viruses
125
Most CD8 T cells are anti-viral but (blank), faciliated by perforin, from CD8 CTLs can also kill TB bacteria
granulysin
126
The CD8 cytotoxic T cells respond with perforin an granulysin for long term defense to (blank)
TB
127
Can dead vaccines stimulate CTL? WHy is this important?
no only live vaccines
| because you need live vaccines to be able to create viral imunity so you can make CTL memory cells
128
What will dead vaccines give you?
antibodies but no CTLs. This is no good for viral infections because antibodies cannot control viral replication once the virus is inside the cell.
129
Patients w/ diGeorge syndrome can fight off (blank) infections but not (blank) infections, why?
bacterial
viral
because DiGeorge affects your T cell production
130
DiGeorge Syndrome is a congenital malformation caused by defective development of the (blank) and (blank) pharyngeal pouches.
3rd and 4th
131
What organs does diGeorge syndrome effect?
thymus, parathyroid (low calcium, tetany), and heart
| has low T cells and has antibodies present
132
How come DiGeorge patients are susceptible to not only viral infections, but to mycobacterial and fungal infections?
due to there 22q deletion they do not make enough T cells. Helper T cells activate macrophages to arrest TB and neutrophils to be more effective at killing yeast and fungi. WIthout the T cells you have weak protection
133
How can you cure DiGeorge?
graft with a younger than 14 week old fetus. (has to be young so you wont get Mature T cells that will cause graft host disease)
134
What is a conjugate?
making something that is not immunogenic into something that is and allows your body to produce an antibody to it (i.e attaching a bacteria to a sugar so that everytime you have that sugar you will elicit an immune response)
135
TCRs have (blank) recognition
dual
| recognition of peptide and recognition of MHC
136
(blank) and (blank) initiate recognition signals in TCRs when a peptide (Ag) has bound
CD3 and CD8
137
Why are recognition signals awesome for researchers to mess with?
because it allows you to compromise a T cell receptor by either blocking the signals or not allowing the receptor to get both signals so you can compromise the immune response
138
If a T cell makes an anti-self TCR what happens to it?
it is deleted or unresponsive
139
How can you displace a self peptide on an APC?
you can overwhelm it with a large amount of a substituted peptide
140
THe MHC class (blank) proteins hold peptides for CD4 T cells
II
141
how long are antigen peptides?
20-30 AAs long
142
The MHC class II alpha and beta cain dimer forms a binding site for (blank) peptides that "hang out" at the ends of the site.
larger
143
T or F
| Each MHC II allele can bind thousands of different peptides and interact with thousands of different T cells.
T
144
The MHC class (blank) proteins hold peptides for CD8 T Cells
I
145
What is the structure of an MHC I protein?
single alpha chain w. a beta2 microglobulin
146
THe MHC class I alpha chain forms a (blank) that binds peptides. What size peptides can fit into this?
cleft
| peptides smaller than 11 AAs
147
Each MHC I allele can bind thousands of different peptides and interact with thousands of different T cells
T or F
T
148
The peptides fit into the MHCI cleft by (covalent/non-covalent) “anchoring” of several amino acids of the peptides into the cleft. The N terminal AA of the peptide rarely anchors. Two internal amino acids of the peptide and the C terminal AA anchor. (think of anchors and seas) Since different MHCI alleles have different clefts formed by their different sequences, they anchor differ peptides.
non-covalent
149
Does MHC1 or MHC2 hold smaller peptides?
class 1
150
What are the 2 co-receptors for antigens that determine binding to MHCII and MHCI ?
CD4 and CD8
151
How do CD4 and CD8 intitate signaling?
via kinases when the TCR binds tightly to a MHC
152
CD4 cells bind only to MHC (blank) and CD8 cells bind only to (blank)
II
| I
153
How does a T cell recognize a nonpeptide antigen?
CD1s found on APCs can present lipid antigens
154
Which T cells can recognize CD1 molecules (non peptide antigens)
CD4 neg and CD8 neg
| can detect TB
155
Both CD4 and CD8 cells require co-stimulation (in addition to Ag) for responses. What are the 2 signals. (also they require danger signals IL-1/TNFalpha)
Signal 1: antigen
| Signal 2: B7 interacting with T CD28
156
What is B7?
it is CD80 and CD86 on APCs ad activated B cells
157
When T cells only get one signal what happens?
they die or become anergic
158
(blank) is on the APC and (blank) is on the T cell
B7
| CD28
159
When an APC secretes TNF alpha and IL-1, what does this mean? Why is this important?
they are sending out Danger signals
| you need these for T cell responses
160
What do T and B cell receptors have in common?
2 chains
variable binding sites at end of receptor
receptors have short intra cytoplasmic tails
other molecules perform transembrane signaling
161
Which type of receptor is this, B or T?
| Have Ig receptors that recognize native ag structures
B
162
Which type of receptor is this, B or T?
| Recognize "processed" proteins (peptides)
T
163
Which type of receptor is this, B or T?
| Receptor is unchanged in AA sequence for the life of that cell
T
164
Which type of receptor is this, B or T?
| May later secrete proteins similiar to their ag receptor proteins (Ab's without ig transmembrane domain)
B
165
Which type of receptor is this, B or T?
| Undergo gene mutation for affinity maturation of the receptor and Ig
B
166
T or F
| Co-stimulatory receptors and their counter-ligans differ for T and B cells
T
167
What are the 2 costimulatory signals for b cells?
CD40
| activated T cell
