T-cell Immunity Flashcards

(109 cards)

1
Q

What must occur for a T cell to be activated?

A

The adaptive immune system is initiated when naive T cells recognize peptide-MHC complex on the sruface of APCs;

Upon TCR signaling, T cells are “activated” leading to effector T cells

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2
Q

Do effector T cells act on target cells, pathogens, or both?

A

Effector T cells act on target cells, not the pathogens themselves

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3
Q

What is the surface marker for Naive T cells vs Memory T cells?

A

Naive: CD45RA
Memory: CD45RO

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4
Q

Differentiate effector memory T cells from central memory T cells

A

Effector: rapidly mature into effector cells upon reactivation and enter inflamed tissues

Central memory: take longer than effector T cells in producing cytokines; they remain in the lymphoid tissue and circulate as naive T cells

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5
Q

What is the relative life-span of memory T cells?

A

Long-lived

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6
Q

What are three signals required for productive activation of T cells upon meeting its antigen?

A

1) Activation: TCR binds to antigen:MHC complex
2) Survival: B7: CD28 co-stimulation
3) Differentiation: Cytokine production by APCs drive naive T cell to differentiate and proliferate

CD40/CD40L is also present

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7
Q

How do activated T cells respond to IL-2 signaling?

A

Activated T cells express high affinity IL2Ralpha (CD25) and proliferate in response to IL2 in an autocrine fashion.

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8
Q

What is the main function of CD8+ cytotoxic T cells?

A

Kill virus-infected cells.

CTLs target viruses and some intracellular bacteria

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9
Q

What is the primary function of CD4+ Th1 cells?

A

Activation of infected macrophages. Provides help to B cells for antibody production.

Th1 cells target microbes that persist in macrophages and extracellular bacteria

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10
Q

What is the main role of CD4+ Th2 cells?

A

Provide help to B cells for antibody production, especially switching to IgE

Effective against helminth parasites

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11
Q

What is the main role of CD4+ Th17 cells?

A

Enhance neutrophil response, and promotes barrier integrity (skin and intestines)

Targets fungus

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12
Q

What is the main role of Thf cells?

A

B-cell help: isotype switching + antibody production

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13
Q

What is the main role of Treg cells?

A

Suppression of T-cell responses

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14
Q

Which cytokines drive the differentiation of naive T cells into Th1 cells? What transcription factor is responsible for the differentiation?

A

IFN gamma
IL12

Transcription factor: Tbet

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15
Q

What cytokines are produced by Th1 cells?

A

IFN gamma, IL2, LTalpha

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16
Q

What cytokine drives the differentiation of naive T cells into Th2 cells? What transcription factor promotes this differentiation?

A

IL4

Transcription Factor: GATA3

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17
Q

Which cytokines are produced by Th2 cells?

A

IL4, IL5, IL13

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18
Q

Which cytokines drive the differentiation of naive T cells into Th17 cells? What transcription factor promotes this differentiation?

A

TGFbeta, IL6, IL21, IL23

Transcription Factor: RORgammaT

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19
Q

Which cytokines are produced by Th17 cells?

A

IL17, IL21, IL22

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20
Q

Which cytokines drive the differentiation of naive T cells to Thf cells? What transcription factor promotes this differentiation?

A

IL6

Transcription Factor: BCL6

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21
Q

Which cytokines are produced by Thf cells?

A

IL6, IL10, IL21

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22
Q

Which transcription factor promotes the differentiation of naive T cells to Treg cells?

A

FOXP3

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23
Q

Which cytokines are produced by Treg cells?

A

TGFbeta and IL10

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24
Q

Type I immune response (regulated by Th1 cells) are effective against what pathogens?

A

Intracellular pathogens

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25
Type II immune responses (regulated by Th2 cells) are effective against which type of pathogens?
Extracellular pathognes
26
iTreg cells are important for what process?
Immune tolerance/ regulation of immune response to self-antigens
27
Th17 cells are important for providing immunity to what?
The gut
28
Thf (T follicular helper cells) are important for what process related to B cells?
Thf cells aid in the formation of germinal centers and differentiation of B cells into memory B cells and plasma cells
29
What type of immune response is implicated in autoimmune diseases (e.g diabetes)
Th1 - type 1 response
30
What type of immune response is implicated in the immunopathology of allergies, asthma and dermatitis?
Th2 - type 2 response
31
what is the general definition of an interleukin?
IL's are heterodimers produced by leukocytes for the purposes of communication between leukocytes
32
Where in the cell are TLRs found?
TLRs are present on both the cell surface membrane and the membrane of intracellular vesicles
33
Which MHC is upregulated in mature DCs?
MHC II
34
Which co-stimulatory molecules are upregulated in mature DCs?
CD80, CD86, CD40
35
Discuss the translocation of DCs following activation.
Mature DCs migrate to lymphoid tissues following the CCR7 chemokine so that it can present antigen to T cells
36
Which cytokines are upregulated in mature DCs?
IL12 and IL18
37
T cells not activated by DCs in the lymph node exit via what?
The cortical sinus
38
What happens to T cells that do encounter their antigen in the lymph node?
They proliferate and differentiate into effector T cells and then exit the lymph node
39
Which T cells are involved in cell mediated inflammation?
Th1 cells
40
WHich T cells are involved in delayed-type hypersensitivity?
Th1 cells
41
Which factor, secreted by activated APCs maintains and stabilizes the Th1 response?
IL18
42
What is the main characteristic of IFN gamma?
IFN gamma is a potent pro-inflammatory cytokine
43
IFN gamma is the signature cytokine of what type of T cell response?
Th1
44
What two other cells produce IFN gamma and participate in the Th1 response to intracellular pathogens?
NK cells and CD8+ cells
45
How does IFN gamma affect macrophages?
IFN gamma activates macrophages to increase antigen processing, upregulate MHC I and MHC II expression, increase microbicidal activity and chemokine secretion
46
IFNgamma is a potent suppressor of what two T cell responses?
Th2 and Th17
47
What is the characteristic job of IL-2?
IL-2 is a T cell growth factor, particularly for regulatory T-cells (for most T cells)
48
Which T-cell receptor binds IL2?
HIgh affinity IL-2R (the alpha/beta/gamma)
49
Mutations in the gamma chain of IFNgamma leads to what immune deficiency?
Mutations in the gamma chain leads to SCID
50
Although LT alpha is a signature cytokine of Th1 cells, what other cells can produce LT alpha?
CD8, NK, B cells and macrophages
51
Lymphotoxin alpha, LT alpha, is implicated in the progression of what two diseases?
Rheumatoid arthritis and multiple sclerosis
52
What 4 cytokines make up the classic tetrad of macrophage produced pro-inflammatory cytokines?
IL1, IL6, IL8 and TNF alpha
53
What two cytokines are responsible for the production of a fever during a pro-inflammatory cytokine response?
IL1 and IL6
54
What is IL1Ra?
IL1 receptor antagonist
55
IL1 drives the differentiation of naive T cells to what?
IL1 promotes differentiation into Th17, along with TGF beta, IL6, IL21 and IL23
56
How does IL-6 affect B cells?
IL6 has strong growth and differentiation effects on B cells in the presence of other "B" cell cytokines
57
How does IL6 affect bone?
IL6 activates osteoclasts, and therefore has an effect on bone mineral metabolism
58
Which cytokine acts as the most potent stimulus for mobilizing and recruiting neutrophils to the site of infection?
IL8
59
By what cells/when is IL8 secreted?
IL8 is produced mainly by macrophages and neutrophils during intense inflammation by endothelial cells
60
What is another name for hypersensitivity reaction type IV?
Delayed-type hypersensitivity
61
Hypersensitivity type IV is mediated by what cells?
Th1 and CD8+ cytotoxic T cells
62
IL3/GM-CSF released during a type 1 immune response stimulate what?
IL-3/GM-CSF stimulate monocyte production by bone marrow stem cells
63
Which cytokine induces the expression of vascular adhesion molecules during a type 1 immune response?
IFN-gamma
64
TNFalpha is a pro-inflammatory cytokine with pleiotropic functons. Name some.
Potent macrophage activator Potent activator of endothelial homing and adhesion molecules Potent upregulator of MHC and other cytokines Potent inducer of apoptosis and angiogenesis Systemic effects range from flu-like symptoms to death
65
Soluble antigen, bacteria and multicellular parasites generate what type of immune response?
Th2 (type II)
66
Why would a macrophage produce IL4 instead of IL12 and generate a Th2 response (instead of a Th1 response)?
Depends on the TLR that binds the antigen. Certain TLRs lead to the production of IL4 rather than IL12
67
What role do Th2 cells play in the maintenance of B cell activation?
Th2 cells produce cytokines like IL4, IL5 and IL6 which act on b cells and maintain B cell activation
68
What MUST occur for the generation of a Th2 response?
Induction and maintenance of high GATA3 expression
69
How are high levels of GATA3 induced and maintained?
1) Initial interaction between TCR and peptide/MHC II , together with co-stimulatory molecules (CD20-CD80/86, CD40L-CD40) induces low initial levels of GATA3 2) IL2Ralpha (high affinity) and IL2 expression is induced --> high GATA3 levels There is a positive feedback of GATA3 inducing IL4 expression, which further induces expression of GATA3
70
What is the primary role of the Th2 cell response?
Enhance B cell function and ultimately antibody production
71
How does IL4 affect the development of Th1?
IL4 inhibits the development of Th1, EVEN WITH
72
How does IL4 affect class switching in B cells?
IL4 induces Ig class switching from IgG1 to IgE, thus plays a role in allergies.
73
Is Th2 pro-inflammatory or anti-inflammatory?
Th2 is anti-inflammatory.
74
What is the major role of IL5?
IgA and eosinophil recruitment
75
What cell types make IL-10?
Major source; Th2 | Other sources: Treg and Thf
76
What is IL10's major role?
IL10 is the major driver of B cell differentiation and isotype switching
77
How does IL10 affect the pro-inflammatory cytokines?
IL10 inhibits Th1 differentiation and DC function- therefore inhibits production of IL1, IL12 and TNF alpha (through the inhibition of NFkappaB)
78
Which T helper cell is implicated in organ specific autoimmune diseases?
Th17 Implicated in MS, type 1 diabetes, inflammatory bowel disease, airway inflammation disease
79
What are the two predominant forms of IL17?
IL17a and IL 17f IL17a is the most important form
80
IL17 induces the expression of which two pro-inflammatory cytokines?
IL6 and IL8
81
What is the role of IL22?
IL22 functions in protective immunity of the gut by restricting commensal bacteria to their niches- they induce expression of antimicrobial peptides
82
What is the role of Thf cells?
Thf cells facilitate a humoral immune response by assisting in B-lymphocytes with their production of pathogen-neutralizing antibodies
83
Where are Thf cells found?
B-cell zone of the secondary lymphoid organs (follicle, with or without a germinal center)
84
Recruitment of cells of the B cell zone of secondary lymphoid organs is mediated by what chemokine?
CXCR5
85
What is the main job of CD4+ regulatory T cells?
Control autoreactive T cells/ maintenance of self-tolerance
86
Differentiate iTregs from nTregs
Natural T regs, nTreg: develop in the thymus from the DP thymoctes iTregs: developed in the peripheral lymphoid tissues
87
Which cytokines induce the differentiation of naive T cells into Treg cells?
TGF beta and IL2
88
What is IPEX?
A common FOXP3 mutation. IPEX leads to failure of down
89
What is the mechanism by which Tregs suppress an immune response?
IL10 secretion,. IL10 is a key anti-inflammatory cytokine IL10 suppresses expression of MHC class II, co-stimulatory molecules CD80/86, reduces the release of proinflammatory cytokines by mast cells
90
CD8+ cytotoxic T cells are essential for controlling what type of infections?
Bacterial and most importantly, viral
91
In very general terms, how to activated CTL respond to an infection?
Acitvated CTL travel to the infected tissue and kill target infected cells
92
Describe the three phases of a CTL response
1) Effector phase: 1-2 days after the acute infection 2) Contracting phase: when the source of infection is eliminated, most CTL die by apoptosis and only 5-10% survive 3) Memory phase: the survived cells established the memory pool. Can last for up to 75 years in humans
93
Where in the lymph node does activation of CTLs occur?
Initial activation of naive CD8 occurs in the peripheral region near the marginal sinus where both naive CD8 and DC migrate into from the deeper T cell zone of the paracortical region. The marginal sinus is antigen-rich region in the early infection. This is opposed to CD4 T cell maturation which occurs in the paracortex.
94
Optimal activation of CD8 cells requires parallel activation of what other type of cell?
NK cells, CD4 helper cells and/or the presence of memory cells
95
NK cells secrete what major pro-inflammatory cytokine that helps to activate CD8 cells?
IFN gamma
96
What is needed to sustain a CD8 response?
IL21, IL2 and IFN gamma
97
CTLs bind to cells wth low affinity through LFA-1/iCAM interactions (non-specific adhesion molecules) in absence of antigen. What changes occur when the T-cell binds to its specific antigen?
Antigen-specific recognition stabilizes the pairing and focused release of effector molecules. The CTL is then able to induce apoptosis of the infected cell, and it can move on to kill subsequently infected cells.
98
What is the death-receptor pathway?
FAS-FASL mediated apoptosis: CD8 CTLs express FASL which engages with FAS on target cells This causes activation of caspase 8 --> caspase cascade and eventually DNA fragmetation
99
In addition to apoptosis, what is another way CTLs kill infected cells?
Release of cytotoxic granules or lysosomes
100
How does perforin destroy targets?
Oligomerization forms pores in target cells
101
How does granzyme B destroy targets?
apoptosis, both caspase-dependent and independent
102
How does granulysin destroy targets?
targets pathogen-infected cells and induces cytolysis of bacteria, fungi and parasites including M. tuberculosis, L. monocytogenes and Leshmania
103
Discuss the specificity of CTL killing through release of cytotoxic granules
Very specific- cytotoxic granules are released at the site of cell contact and will preferentially kill the target cell
104
Discuss the dependence of TCR gamma/delta cells on MHC
TCR gamma/delta cells are independent of Class I and Class II MHC
105
In contrast to alpha/beta TCRs what antigens do gamma/delta bind to?
Phospholipids, phosphoantigens, They do not bind to peptides.
106
Antigens are presented to TCR gamma/delta cells by what?
CD1a, b, and c
107
Differentiate TCR delta 1 from TCR delta 2
delta 1: protects mucosa tissue and is associated with epithelial cell functions delta 2: found in circulation- majority is generated in fetal liver and then expanded as an adult
108
How are TCRdelta 1 and 2 affected by HIV?
1 increases 2 decreases
109
How is TCRdelta 1 affected by parasitic infections?
increased