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Immunology > Effector T cells and cell mediated cytotoxicity > Flashcards

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
Q

What sort of interactions occur between the Th1/Th17 cells and the DCs?

A
  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
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26
Q

What is the sequential vs the simulatenous model?

A

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

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27
Q

What is the difference in activation between memory CTL-P and naive CTL-P ?

A

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
Q

Why do CTLs need IL-2?

A

expression of genes coding for cytotoxic effector molecules (perforin, granzymes) that are stored in cytoplasmic granules.

29
Q

What other cell type requires IL-2 for proliferation and differentiation?

30
Q

What happens if IL-2 levels drop?

A

Th1 and CTL cells undergo apoptosis

31
Q

What are the 2 types of CD8+ T cells that effector CTLs can differentiate into?

A

Tc1 and Tc2 cells

32
Q

What do Tc1 cells secrete? how do they kill?

A

Secrete IFN-y and kill by perforin and Fas ligand

33
Q

What do Tc2 cells secrete? How do they kill?

A

secrete IL-4 but only small amounts of IFN-γ and kill primarily by perforin

34
Q

What are the 4 steps in CTL mediated destruction?

A

Conjugate formation, membrane attack, CTL-target cell dissociation, and target cell destruction

35
Q

What stabilizes the conjugate interaction?

A

CD8 and LFA-1

36
Q

What causes increase avidity of LFA-1 for ICAMs on target cells?

A

TCR signaling

37
Q

What happens to perforin monomers in the presence of Ca++?

A

undergo a change in conformation that allows them to insert into the target cell membrane and polymerize into pores that trigger endocytosis

38
Q

How does Granzyme B enter the target cell?

A

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
Q

What do the perforin/granzyme and Fas ligand/Fas cytotoxic pathways depend on?

A

activation of caspases, which are cysteine proteases that cleave proteins after an aspartic acid residue

40
Q

Both cytotoxic pathways ultimately result in the activation of ? which in turn leads to the activation of?

A

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
Q

How does CTL killing prevent affect viruses?

A

Viral DNA is also fragmented during CTL killing of target cells, thereby preventing viral replication during the interval before target cell destruction

42
Q

How to CTLs protect against the cytotoxic molecules they release?

A

by expressing serpins (serine protease inhibitors) that inhibit granzyme B.

43
Q

NK cells are..

A

Nonspecific cytotoxic effector cells

44
Q

NK cells are important in defending against?

A

Viruses and cancer

45
Q

NK cells arise from the same progenitor cells as ____ but don’t mature exclusively in the __

A

T cells; thymus

46
Q

target cell recognition by NK cells is ___

A

not MHC- restricted

47
Q

What three receptors are expressed on NK cells ?

A

IL-2 receptor β chains, CD2, and CD16

48
Q

What do NK cells lack on their surface?

A

TCR, CD3 or CD8

49
Q

NK cells are an important source of __ which increases microbicidal activity of macrophages, promotes Th1 differentiation, and inhibits Th2 development

50
Q

Why are NK cells the first line of defense against viral infection

A

because of their rapid activation by IFN-α and -β, and by IL-12 produced by dendritic cells.

51
Q

NK cells are ___ active. Why?

A

Constitutively sincetheyhave cytoplasmic granules containing perforin and granzymes and also express Fas ligand

52
Q

What is the opposing signals model?

A

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
Q

What type of receptor recognizes altered carbohydrate structures on virus infected or cancerous cells?

A

C-type lectins

54
Q

What are the 2 types of inhibitory receptors on the NK cell?

A

lectin-like inhibitory receptors and killer cell inhibitory receptors

55
Q

which 5 cell types express receptors for the Fc region of IgG? What does this allow for?

A

NK cells,neutrophils, eosinophils, monocytes, and macrophages

allows ADCC reactions in which nonspecific killer cells are directed to IgG-coated target cells

56
Q

What receptor on the NK cell is specific for Fc region of IgG?

57
Q

What happens when NK cells are activated through CD16?

A

exocytose the contents of their cytoplasmic granules (granzymes and perforin) and kill by the Fas ligand/Fas pathway

58
Q

Activated NK cells, monocytes, and macrophages also secrete…

A

TNF which can kill certain target cells

59
Q

What is another important role of the CD16 for NK cells?

A

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
Q

What are NKT cells (what kind of pos. are they and what kind of receptor do they have etc.)

A

CD4+ and CD4- T cells that express NK cell markers and an invariant α/β TCR

61
Q

What does the NKT receptor interact with and on what cells? What kind of antigens are presented in this condition?

A

interacts with CD1d on APC and epithelial cells

Lipid and glycolipid antigens are presented

62
Q

NKT cells provide a bridge between…

A

the innate and adaptive immune responses

63
Q

NKT cells secrete large amounts of cytokines. What two processes do they support? what cytokines

A

can support antibody formation (IL-4) or inflammation and CTL expansion (IFN-γ)

64
Q

Do NKT cells have FASL?

65
Q

NKT cells provide early help against __ and __ why the Th development occurs

A

pathogens and malignant cells

Immunology (19 decks)

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