Immunology week 7 Flashcards
1
Q
everything up to slide 13 is a repeat from Week 6
A
2
Q
YES CARTA =
A
CAR T cell therapy
3
Q
When do you use Car T to tx adults?
A
TX adults with large B cell lymphoma
who have not responded or have
relapsed after 2 round of tx
4
Q
Yescarta uses CAR T cells which are:
A
Yescarta uses CAR T cells which are
genetically engineered t cells with a
chimeric AG receptor
5
Q
YESCARTA= CAR T cell therapy
MOA
T cells are taken from ? and what happens?
A
T cells are taken from peripheral blood
and genes are inserted into the T cells
6
Q
YESCARTA= CAR T cell therapy
MOA
T cells are taken from peripheral blood
and genes are inserted into the T cells
what then happens with the Chimeric AG Receptor?
what result?
that then happens?
A
The Chimeric AG Receptor then binds to
the tumor AG with high affinity as a
result the T cells will increase in number
(expansion) and then will be injected
back into the infected patient.
see slide pg. 15 for diagram
7
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
ARE DC important in the presentation and activation of naive T cells?
A
Remember DC are very important in the
presentation and activation of naive T
cells
8
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
T cell responses are initiated where?
A
T cell responses are initiated in the
peripheral lymphoid organs (lymph nodes,
spleen ,etc)
9
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
Pathogens that enter via skin, are taken where?
A
Pathogens that enter via skin, etc are
taken to the draining lymph nodes
10
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
pathogens that are in the
bloodstream go where?
A
whereas pathogens that are in the
bloodstream will be taken to the spleen
11
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
DC cells
strategically located where?
A
Strategically located at common sites of
entry of microbes
12
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
DC cells
they have express receptors that allow them to do what
A
Express receptors that enable them to
capture microbes
13
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
DC cells
They migrate where?
A
Migrate to t cell rich zone of lymph
nodes
14
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
DC cells
They express high levels or what that is needed to do what?
A
Express high levels or co-stim molecules
which are needed to activate naive t
cells!
15
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
DC cells
they can ingest what? and present them to what?
A
Ingest infected cell and tumor cells and
can present these cells to cd8 t cells
16
Q
AG presentation to Naive T cells & Dendritic cell (DC) Importance
DC cells
Ingest infected cell and tumor cells and
can present these cells to cd8 t cells
ONLY DC cells are capable of doing what?
A
Remember only DC are able to do
cross priming/ cross
presentation!!!!
17
Q
T cell activation
Naive T cells circulate where?
only have functional capabilities after what?
A
Naive t cells circulate in secondary
lymphoid organs and only have
functional capabilities after they are
activated by Dendritic cells!
18
Q
T cell activation
AG recognition by t cells:
3 features:
hint-what do they secrete?
A
Cytokine secretion
proliferation
Differentiation
19
Q
T cell activation
AG recognition by t cells
proliferation
what happens why is it important?
A
proliferation
■ Increase in # of t cells of a specific
clone b/c remember t cells are
specific so it is important that only
t cells for that AG are being made!!
20
Q
T cell activation
AG recognition by t cells:
Differentiation
explain
hint-Naive T cells –> ?
A
Differentiation
■ Naive t cells-> effector and
memory cells
21
Q
T cell activation
Recognition of the AG= ?
A
Recognition of the AG= the 1st signal
for the activation of T cells!(TCR, MHC
w/AG interaction)
22
Q
T cell activation
Recognition of the AG= the 1st signal
for the activation of T cells!(TCR, MHC
w/AG interaction)
2 examples:
A
Recognition of the AG= the 1st signal
for the activation of T cells!(TCR, MHC
w/AG interaction)
○ CD4= MHC 2
○ CD8= MHC1
23
Q
T cell activation
The 2nd signal for T cell activation is
called
A
The 2nd signal for T cell activation is
called costimulation CD28:B7
24
Q
T cell activation
The 2nd signal for T cell activation is
called costimulation CD28:B7
what is it required for?
why?
A
The 2nd signal for T cell activation is
called costimulation CD28:B7
○ It is a requirement for T cell activation!!!
○ w/o co stimulation there will be no t cell
response (anergy) or tolerance will occur
25
T cell activation
Signal 2= what?
Signal 2= aids in the survival,
proliferation, and differentiation of the
specific T cells
26
T cell activation
CD40: what? which causes what? by doing what?
CD40:CD40L enhances the T cell
response (proliferation and
differentiation) by activating APC
27
T cell activation
is a balance between what?
of the what?
T cell activation:
○ Balance between activating and
inhibitory receptors of the CD28 fam
■ inhibitory= CTLA4 &PD1
28
T cell activation
CD28-B7=
what is it? what is it's importance?
CD28-B7= **most important signal
(costimulation) and activation of naive t
cells!!**
29
T cell activation
ICOS-ICOS ligand=
what is it important for?
ICOS-ICOS ligand= important for T cell
dependent AB response
30
CTLA-4:B7=
what does it do?
where does it do it?
CTLA-4:B7= inhibits the activation of T
cells in **secondary lymphoid organs**
31
T cell activation
PD1:PD1-ligand=
what does it do?where does it do it?
PD1:PD1-ligand= inhibits the activation
of the effector cells in **peripheral
tissues**
32
T cell activation
This slide is sooooo important!! :)so lets repeat:
CD28:B7
what does it do why is it important?
interaction is most imortant for initiating responses by **activating Naive T Cells.**
33
T cell activation
This slide is sooooo important!! :)so lets repeat:
ICOS:ICOS-ligand
interactions are critical for **helper T cell-dependent antibody responses**
34
T cell activation
This slide is sooooo important!! :)so lets repeat:
CTLA-4:B7
onteractions **inhibit** the intitial activation of **T cells in seconary lymphoid organs**
35
T cell activation
This slide is sooooo important!! :)so lets repeat:
PD1:PD-ligand
interactions i**nhibit** the activation of **effector cells in the peripheral tissues.**
36
Therapeutic costimulatory blockade
what is it?
what does it treat?
what is it undergoing clinical trials to treat?
CTLA-4-Ig= approved therapy for
rheumatoid arthritis and transplant
rejection and is on clinical trials for the
tx of psoriasis and crohn's dz
37
Therapeutic costimulatory blockade
Inhibitors of the CD40L:CD40 pathway=
Inhibitors of the CD40L:CD40 pathway=
clinical trials for transplant rejection and
chronic inflamm. Dz
38
Therapeutic costimulatory blockade
AB against CTLA-4 and PD-1=
AB against CTLA-4 and PD-1= approved
or are in clinical trials for
immunotherapy of tumors.
39
What was important about CTLA-4 and
PD-1???
?
40
Functional responses of T cell activation
What are the 3 responses?
1. Increase surface molecule expression
2. IL2 secretion and IL2Ra expression
3. Clonal expansion of t cells
41
Functional responses of T cell activation
1. Increase surface molecule expression
what are the 6 steps in this process?
1. Increase surface molecule expression
a. CD69- early activation marker that is NB
for retention in the lymph node
b. CD25- increase expression of IL 2 on t
cells
c. CD40L- provides feedback to t cells
d. CTLA-4-regulation of IR
e. Adhesion molecules- for t cells to
interact w. others= need adhesion to
connect
f. Chemokine receptors - signals to move
from location to location
42
Functional responses of T cell activation
Increase surface molecule expression
How long does IR take?
Remember adaptive IR takes time! (5-7 days
from the time of infection)
43
Functional responses of T cell activation
IL2 secretion and IL2Ra expression
What is the function of IL2?
What is the therapeutic use of IL2?
****Fun. of IL2
○ Increases production of IFN-y and IL-4
○ Required for survival and fun of t reg cells
**○ IL2= growth, survival, and
differentiation factor for t cells**
■ Produced by CD4 t cells early
after AG recognition and co-
stim
● Therapeutic use of IL2
○ Pleiotropic cytokine- what does this
mean???
○ Can use tp tx certain viruses in cats
Graph on slide 21
44
Functional responses of T cell activation
Clonal expansion of t cells
Explain
Clonal expansion of t cells
○ Prolif results in increase in number of
the AG-specific clones- clonal expansion
○ Daughter cells all arising from a single
cell- so they all share the same AG
specificity
● This is NB b/c only TCR w/ specific
receptors will respond= clonal selection
will make daughter cells to respond
against the AG
Graph slide 22
45
Differentiation of Activated T cells-> effector & memory cells
Explain Effector cells
hint: effector CD4=
are they helper or cytotoxic cells?
effector CD8=
are they helper or cytotoxic cells?
Effector CD4 cells= have surface
molecules and secrete cytokines to
activate other cells
○ Makes sense bc CD4= helper cells
● Effector CD8 cells= cytotoxic kill infected
cells
○ Makes sense bc they are cytotoxic cells
46
Differentiation of Activated T cells-> effector & memory cells
Memory cells
cell mediated IR=?
Cell mediated IR= results in memory t cells
for that AG which can be around for years/
for life
47
Differentiation of Activated T cells-> effector & memory cells
Memory cells
explain Linear pathway
Linear pathway
○ naive-> effector-> memory
48
Differentiation of Activated T cells-> effector & memory cells
Memory cells
explain divergent differentiation
Divergent differentiation
○ Naive-> memory
49
Differentiation of Activated T cells-> effector & memory cells
Memory cells
why is it relevent that they are long lived cells?
Long lived cells- increase anti-apoptotic
proteins
50
Differentiation of Activated T cells-> effector & memory cells
Memory cells
How do they respond to AG?
Respond rapidly to AG (faster than naive)
● # of memory cells for AG > naive cells for
that AG
51
Differentiation of Activated T cells-> effector & memory cells
Memory cells
can they migrate?
Can migrate to peripheral tissues
52
Differentiation of Activated T cells-> effector & memory cells
Memory cells
how do they proliferate? why is it important?
Slow proliferation (aids in life span)
53
Differentiation of Activated T cells-> effector & memory cells
Memory cells
what is required for maintenance of memory cells?
Maintenance of memory cells needs
cytokines IL7!!!!! But not AG
54
Decline of TCR
how does it relate to homeostasis
what are the 3 results of decline?
NB for homeostasis
● Decline:
○ Cessation of co-stim
○ Cessation of growth hormones IL2
○ Stress receptor expression->
apoptosis
55
Cellular Immune
Response II
Role of CD4 t cells in eradicating infections
how does CD4 work?
CD4 cells don’t like to get their hands
dirty. The cytokines are what stimulate
the macs and the macs will kill
pathogens
56
Role of CD4 t cells in eradicating infections
what is the CD4 response:
CD4 response
○ Initial activation in lymphoid organs
○ Gen of effector and memory cells
○ Migration of effector cells
○ Elimination of infectious pathogens at
these sites
57
Role of CD4 t cells in eradicating infections
what is the fuction of CD4 cells?
● **Functions of CD4 cells= mediated by
cytokines**
58
Role of CD4 t cells in eradicating infections
What are the subsets?
Subsets of CD4 effector t cells:
○ Th1
○ Th2
○ Th17
● induction/ stable comm/ amp
**looks like really important diagram on slide 26
59
Role of CD4 t cells in eradicating infections
What are the subsets TH1
how is it induced?
what are the steps?
What is the function?
what does it stimulate?
what does it activate?
TH1
○ Induced by microbes ingested by
phagocytes
**○ Central rxn of cell- mediated immunity
○ Th1 differentiation in the presence of IL
12 and IFN y produced by DC, macs, NK
○ IFNy, IL12-> stim th1 diff by activating
Tbet, STAT1 and 4**
○ Function: activate macs
○ Stimulate the production of IgG
○ **Plssss know effector fun of TH1 are
mediated by IFNy**
○ Activate macs by contact mediated sig
CD40L- CD40 interactions and by IFNy
■ So rare occasion that they are
stimulating DIRECTLY
little diagrams on slide 27
60
Role of CD4 t cells in eradicating infections
Subsets of CD4 effector t cells:
IFN-y is soooo freaking important
what does it activate?
what does it amplify?
what does in enhance?
what are the 4 therapeutic uses in vet med?
IFN-y is soooo freaking important
● Activates macs
● Amps th1 subset and inhibits
development of th2 and th17
● Enhances AG presentation
● Therapeutic use in vet med
○ Recombinant canine INFy= atopic derm
○ hIFNy= against canine astrocytoma
(clinical trials)
○ fIFN-y combo with fIL2 and fGM -CSF=
clinical trials for tx for fibrosarcoma
○ Gene therapy in canine brain tumors
61
Role of CD4 t cells in eradicating infections
Subsets of CD4 effector t cells:
TH2
what does it mediate?
what is NB?
why is it relevant?
what other cytokines should you associate with it?
how is it stimulated?
what are the 3 functions?
● Mediates phagocyte-independent
defense
● Eosinophils and mast cells= NB
**● NB for helminthic infections
● Central to the development of allergic
DZ**
● Cytokines you should associate with
TH2-> IL4, IL5, IL13
● TH2 differentiation stim by IL4
● Functions of TH2:
○ Produce IgE
○ Mast cell & eosinophil stimulation
○ M2 activation
lots of graphs slide 29
62
Role of CD4 t cells in eradicating infections
Subsets of CD4 effector t cells:
TH17
NB for what?
critical for destroying what?
stimulated by what?
how is it initiated?
what does IL23 maintain?
TH17 combats what? where?
what does it produce and why is that important?
stimulates the production of what?
● NB for recruiting leukocytes and
inducing inflammation
● Critical for destroying extracellular bacT
and fungi
● Stim by proinflamm cytokines
● IL1 and 6-> initiate Th17 diff
● IL23 maintains proliferation and
differentiation
● Th17 combat recruiting neutrophils to
sites of infection
● They produce IL17-> induces
neutrophil-rich inflamm.
○ Stims production of antimicrobial
substances
**more diagrams slikde 30
63
Cellular
Immune
Response III
Role of CD8 cells
what is the function?
what does it eradicate?
what does it produce?
what is it's critical role?
● Function of killing cells w/ viruses in the
cytosol
● Eradication of tumors
● Cytokine production
● Critical role in acute rejection of organ
allografts
64
Cellular
Immune
Response III
Role of CD8 cells
explain differentiation of CD8 t cells
Differentiation of CD8 t cells
○ Acquisition of modified lysosomes-
granules that contain perforin and
granzymes
○ Acquisition to secrete cytokines (IFNy)
○ differentiation-> **T-bet and oesmodermin**
65
Cellular
Immune
Response III
Role of CD8 cells
CD--> ?
Naive CD8 cells--> ?
**remember CD->cytosol AG
● & naive CD8 cells-> activated by MHC1
on DC**
66
CD8 immune response
can DC cross-presentation to present tumor AG?
Remember DC can do
cross-presentation to present tumor AG
67
CD8 immune response
what are the steps? how does it work?
Infected cell w/ virus-> DC take it up->
release AG to cytosol-> MHC 1 path->
CD8 cells activated -> virus CD8 T cell
response
68
CD8 immune response
What does it illiminate?
what does it secrete?
what happens during secretion?
**Eliminate intracellular microbes (kill
infected cells)**
**Secrete IFNy**
○ M1 activation
○ Hypersensitivity rxns
69
CD8 immune response
what might CD8 need?
when wouldn't it be needed?
why is it needed?
what is the result to the IR?
what is really important not to forget?
Naive CD8 cells may need CD 4 cells to
help differentiate into fun CTLs &
memory cells
○ If APC= directly infected= not needed
○ Needed in latent viral infections, organ,
transplants and tumors
○ Weak innate IR
● PLSSSS do not forget
○ CD8 produce IFNy- activates macs
70
Cytokines to know
which 4?
● IL2
● IL12 & Type 1 IFN
● IL15
● IL21
71
Cytokines to know
IL2
explain
IL2
○ promotes prolif and differentiation of CD8-> effector CTL and memory cells
72
Cytokines to know
IL12 & Type 1 IFN
explain
IL12 & Type 1 IFN
○ naive CD8-> effector CTL
73
Cytokines to know
IL15
explain
IL15
○ survival of memory CD8 (NB for maintenance of memory)
74
Cytokines to know
IL21
explain
IL21
○ produced by CD4 and induced CD8 memory ( divergent pathway)
75
MOA
what does it do?
Recognition of target cells-> induce cell
death
76
MOA
what is the process -- 4 steps
The process
○ AG recognition
○ Activation of CTLs
○ Delivery of lethal compounds to kill
target cell
○ Release of the CTLS
77
MOA
how does recognition work--4 steps
● Recognition
○ Express MHC 1
○ Bind to CD8 co-receptor
○ Bind to intercellular adhesion molecule 1
○ Form and immunological synapse
78
MOA
what are the 2 killing pathways?
2 killing pathways
○ Cytotoxic proteins
■ Granzyme B and perforin
○ FasL and Fas (death receptor)
79
MOA
T cell exhaustion
what is it and what is the result?
T cell exhaustion
○ Response decreases due to
■ Reduced production of IFNy
■ Increase expression of multiple
inhibitory receptors
80
MOA
what are 4 examples of chronic viral infections?
EX of chronic viral infections
○ Feline viral rhinotracheitis
○ Feline calicivirus
○ Canine distemper
○ Feline leukemia
81
You are at monkey bar trying to enjoy your halloween.
When your immuno TA and Prof show up!!! What do say
whenever they ask you about the 2 killing pathways of
CD8 cells?????
Short answer :)
Answer
● Cytotoxic proteins
○ Granzyme B and perfornin
● FasL and Fas death receptors
82
Your immuno TA and Dr. toka aren’t going to let you get
off that easy. They are asking you why chinese shar
peis= commonly have skin allergies. What do you tell
them?
A. IgE def
B. IgG def
C. Too much IgE
D. IgM
E. IgA def
E
83
Your immuno Ta decides to leave but now Dr. toka is still
asking you questions. He wants to know how B cells are
activated. Which of the following is something you
would say?
A. MHC 2 activates all B cells
B. MHC 1 and co-stimulation
C. B cells do not have co-stimulation
D. BCR and AG / CD40 CD40 L
D
84
Now Dr. toka tells you that he will let you enjoy the rest
of your night if you will answer 1 last question
correctly.Explain the difference between primary and
secondary IR. (Ig levels and types)
Short answer :)
Answer
primary - low Ig levels IgM- main
Secondary- high Ig levels IgG- main
85
You are a new baby DOGtor in Romania. While you’re in your clinic, the NUN (from the conjuring
movies) comes in your clinic. She is questioning you about your immunology background, little
does she know that you are a master in immuno. Which of the following is something you would
tell her when she asks which of the following is not a mechanism of CD8 killing?
A. Apoptosis
B. Perforin
C. Granzyme
D. Fas/FasL
E. All of the above are mechs.
F. Throw holy water and run
E
86
The nun is still trying to trip you up. She tells you naive
CD8 cells can secrete INF-Y and recognize AG from any
cell. Is this true or false??
a. True
b. false
B
87
You’re starting to get real annoyed with the Nun taking up all of your appointment time. You tell
her you are a bomb a** immuno master and that she can ask you one from question before she
leaves but you have other appointments to get to. She wants to know what PD1: PD ligand is
important for.
a. Initiating responses by activating naive t cells
b. Inhibiting the activation of t cells in secondary lymphoid organs
c. Inhibiting the activation of effector cells in peripheral tissues
d. It is important for helper t cell dependent AB responses
C
88
You finally are able to get out of the exam room with the nun but your next appointment has
already been waiting for approx. 7 mins and they are very annoyed. You walk in an
apologize then you realize that your next client is edward scissorhands. While you are
conducting a PE on his pet blowfish he asks you what is clonal expansion. Which is the
most correct answer?
A. It results in an increase in the number of AG non-specific clones
B. It results in an decreased in the number of AG specific clones
C. It results in no change in the number of AG specific clones
D. It results in an increase in the number of AG specific clones
D
89
You are still conducting a PE on Mr. scissorhands
blowfish. He now wants to know what is the divergent
pathway that memory cells go undergo?
A. The divergent pathway is a way for effector cells to mature into memory
cells
B. It is how memory cells can go from naive cells to memory cells
C. It is how effector cells can go from naive to effector
D. It is how memory cells can go from naive to effector to memory cells
B
90
Mr. scissorhands is now asking about the different T cell
subsets. Which of the following is true?
A. CD4 cell function is mediated by cytokines
B. The Th1 subset is the central rxn of a cell mediated immunity and its
effector function is mediated by IFNy
C. The TH2 subset is important for helminthic infections and is central to the
development of allergic dz
D. The Th17 subset is important for recruiting leukocytes.
E. All of the above
E
91
You are finished with the wellness exam but Edward has
one more question. What is the function of CD69?
A. Retention in the lymph node
B. Retention in the placenta
C. Aids in keeping the cellular IR in check
D. Prevents AG from entering the lymph node
A
92
Jack the skeleton brings zero into the vet clinic. While
you are conducting a PE on zero he asks what is t cell
exhaustion. What do you tell him?
A. Response increases due to reduced production of IFNy or increase expression
of multiple inhibitory receptors.
B. Response decreases due to increase production of IFNy or increase expression
of multiple inhibitory receptors.
C. Response decreases due to reduced production of IFNy or increase expression
of multiple inhibitory receptors.
D. Response increases due to reduced production of IFNy or decrease expression
of multiple inhibitory receptors.
C
93
Now Jack is asking about the process of how CD8 cells
operate. Put them in the correct order (first to last).
1. Activation of CTLs
2. Release of CTLs
3. Delivery of the letal compounds to kill target cells
4. AG recognition
4,1,3,2
