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Effector T cells and cell mediated cytotoxicity Flashcards

1
Q

cell mediated immune responses recognize two types of abnormal cells:

A

cancerous or virus infected

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2
Q

What 3 cell classes are involved in CMCT?

A
  1. antigen specific effector cells
  2. cytotoxic T lymphocytes
  3. nonspecific effector cells
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3
Q

What do effector T cells NOT require that naive T cells do?

A

CD28 co-stimulation for activation following TCR triggering

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4
Q

What kind of co-stimulatory signal CAN be provided to effector T cells?

A

LFA-1 binding to ICAMs on target cells

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5
Q

What 2 adhesion molecules do effector TCs express high levels of? Why?

A

CD2 and LFA-1

allowing efficient binding of effector T cells to target cells

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6
Q

Why do effector T cells have high levels of CD44, low CD26L (l-selectin) and no CCR7?

A

to prevent recirculation to secondary lymphoid tissues

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7
Q

Where do effector TCs traffick to?

A

tertiary lymphoid tissues and sites of inflammation

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8
Q

What are the 5 types of effector CD4+ T cells that a naive CD4+ T cell can become?

A

Th1, Th2, Th17, Treg, and Tfh

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9
Q

What polarizing cytokines are responsible for differentiation into Th1 cells? What master transcriptional regulator is activated?

A

IL-12, IL-18, IFN-y

Activated T-Bet

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10
Q

What polarizing cytokines are responsible for differentiation into Th2 cells? What master transcriptional regulator is activated?

A

IL-4

GATA 3

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11
Q

What polarizing cytokines are responsible for differentiation into Th17 cells? What master transcriptional regulator is activated?

A

IL-1, IL-6, IL-23, TGF-ß

RORyt

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12
Q

What polarizing cytokines are responsible for differentiation into Treg cells? What master transcriptional regulator is activated?

A

IL-2 , TGF-ß

FOXP3

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13
Q

What polarizing cytokines are responsible for differentiation into Tfh cells? What master transcriptional regulator is activated? What are Tfh cells?

A

T follicular helper cells

IL-6, IL-21

Bcl-6

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14
Q

What is the role of Th1 cells? what are the effector cytokines that they produce?

A

Cell mediated immunity, macrophage activation, inflammation

Secrete IFN-y and TNF

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15
Q

What is the role of Th2 cells? what are the effector cytokines that they produce?

A

Anti helminth and allergic responses

IL-4, IL-5, IL-10, IL-13

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16
Q

What is the role of Th17 cells?

A

Inflammation

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17
Q

What is the role of Tfh cells?

A

Help B cells develop in germinal centers

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18
Q

What is the role of Treg cells? what are the effector cytokines that they produce?

A

Regulation and suppression of immune and inflammatory responses

Produce IL-10 and TGF-ß

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19
Q

What are the 4 effector molecules of CTLs?

A
  1. Fas ligand
  2. IFN-y
  3. TNF
  4. Cytotoxins (perforin and granzyme)
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20
Q

What do secreted IFN-y and TNF do

A

Enhance cell mediated immunity

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21
Q

how do CTLs (CD8+) and NK cells kill their target cells?

A

FASL-FAS interaction and cytotoxic granule release

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22
Q

How do NKT cells kill their targets?

A

FASL interactions predominantly

- indirectly activate NK cells

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23
Q

What are the 2 phases of CTL mediated immune responses? What happens in each

A

activation phase involving stimulation of naïve precursor CTL (CTL-P) and an effector phase in which differentiated CTL engage and kill target cells.

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24
Q

What 2 cell types license antigen presenting DCs?

A

Th1 or Th17 cells

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25
What sort of interactions occur between the Th1/Th17 cells and the DCs?
1. interact via antigen- class II MHC -TCR 2. CD40-CD40L * 3. PRRs like TLRs can also be activated on the APC by microbial products
26
What is the sequential vs the simulatenous model?
Sequential says that licensing by Th1/Th17 cell happens first and then licensed APC cell activated a Naive CD8_ T cell Simultaneous says that these processes occur at the same time
27
What is the difference in activation between memory CTL-P and naive CTL-P ?
memory CTL-Ps don't require as much IL-2 to be provided, they can synthesize enough themselves to proliferate and differentiate into effector CTLs
28
Why do CTLs need IL-2?
expression of genes coding for cytotoxic effector molecules (perforin, granzymes) that are stored in cytoplasmic granules.
29
What other cell type requires IL-2 for proliferation and differentiation?
Th1 cells
30
What happens if IL-2 levels drop?
Th1 and CTL cells undergo apoptosis
31
What are the 2 types of CD8+ T cells that effector CTLs can differentiate into?
Tc1 and Tc2 cells
32
What do Tc1 cells secrete? how do they kill?
Secrete IFN-y and kill by perforin and Fas ligand
33
What do Tc2 cells secrete? How do they kill?
secrete IL-4 but only small amounts of IFN-γ and kill primarily by perforin
34
What are the 4 steps in CTL mediated destruction?
Conjugate formation, membrane attack, CTL-target cell dissociation, and target cell destruction
35
What stabilizes the conjugate interaction?
CD8 and LFA-1
36
What causes increase avidity of LFA-1 for ICAMs on target cells?
TCR signaling
37
What happens to perforin monomers in the presence of Ca++?
undergo a change in conformation that allows them to insert into the target cell membrane and polymerize into pores that trigger endocytosis
38
How does Granzyme B enter the target cell?
binds to mannose-6-phosphate receptors on the target cells The receptors + granzyme B are internalized by endocytosis in the membrane repair mechanism Perforin then allows granzyme B to be released from the vesicle into the cytoplasm
39
What do the perforin/granzyme and Fas ligand/Fas cytotoxic pathways depend on?
activation of caspases, which are cysteine proteases that cleave proteins after an aspartic acid residue
40
Both cytotoxic pathways ultimately result in the activation of ? which in turn leads to the activation of?
caspase-3, which in turn leads to the activation of endonucleases that fragment nucleosomal DNA and additional proteases that disassemble the cytoskeleton of the target cell
41
How does CTL killing prevent affect viruses?
Viral DNA is also fragmented during CTL killing of target cells, thereby preventing viral replication during the interval before target cell destruction
42
How to CTLs protect against the cytotoxic molecules they release?
by expressing serpins (serine protease inhibitors) that inhibit granzyme B.
43
NK cells are..
Nonspecific cytotoxic effector cells
44
NK cells are important in defending against?
Viruses and cancer
45
NK cells arise from the same progenitor cells as ____ but don't mature exclusively in the __
T cells; thymus
46
target cell recognition by NK cells is ___
not MHC- restricted
47
What three receptors are expressed on NK cells ?
IL-2 receptor β chains, CD2, and CD16
48
What do NK cells lack on their surface?
TCR, CD3 or CD8
49
NK cells are an important source of __ which increases microbicidal activity of macrophages, promotes Th1 differentiation, and inhibits Th2 development
IFN-y
50
Why are NK cells the first line of defense against viral infection
because of their rapid activation by IFN-α and -β, and by IL-12 produced by dendritic cells.
51
NK cells are ___ active. Why?
Constitutively sincetheyhave cytoplasmic granules containing perforin and granzymes and also express Fas ligand
52
What is the opposing signals model?
NK cells use 2 different types of receptors to distinguish altered self-cells from normal self cells ``` Cells expressing class I MHC (not necessarily functional) deliver an inhibitory signal that always overrides the activation signal - cell is not killed ``` ``` Cells that DO NOT express class I MHC in any form deliver an activating signal via a ligand on the cell to the activating receptor on the NK cell - results in cell being killed ```
53
What type of receptor recognizes altered carbohydrate structures on virus infected or cancerous cells?
C-type lectins
54
What are the 2 types of inhibitory receptors on the NK cell?
lectin-like inhibitory receptors and killer cell inhibitory receptors
55
which 5 cell types express receptors for the Fc region of IgG? What does this allow for?
NK cells,neutrophils, eosinophils, monocytes, and macrophages allows ADCC reactions in which nonspecific killer cells are directed to IgG-coated target cells
56
What receptor on the NK cell is specific for Fc region of IgG?
CD16
57
What happens when NK cells are activated through CD16?
exocytose the contents of their cytoplasmic granules (granzymes and perforin) and kill by the Fas ligand/Fas pathway
58
Activated NK cells, monocytes, and macrophages also secrete...
TNF which can kill certain target cells
59
What is another important role of the CD16 for NK cells?
in the context of antibody-dependent cell- mediated cytotoxicity or ADCC, is also an important activating receptor for NK cells - similar to BCR and TCR signalling with PLCy...
60
What are NKT cells (what kind of pos. are they and what kind of receptor do they have etc.)
CD4+ and CD4- T cells that express NK cell markers and an invariant α/β TCR
61
What does the NKT receptor interact with and on what cells? What kind of antigens are presented in this condition?
interacts with CD1d on APC and epithelial cells Lipid and glycolipid antigens are presented
62
NKT cells provide a bridge between...
the innate and adaptive immune responses
63
NKT cells secrete large amounts of cytokines. What two processes do they support? what cytokines
can support antibody formation (IL-4) or inflammation and CTL expansion (IFN-γ)
64
Do NKT cells have FASL?
Yes
65
NKT cells provide early help against __ and __ why the Th development occurs
pathogens and malignant cells

Immunology (19 decks)

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