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Immunology Final Exam > Effector T cells and Cell-mediated Cytotoxicity > Flashcards

Effector T cells and Cell-mediated Cytotoxicity Flashcards

1
Q

Cell-Mediated Immunity

A
  • recognize and eliminate cells that have been infected by virus/transformed into cancerous cells
  • consists of antigen specific effector cells (CD4, CD8, natural killer T cells) an non specific effector cells (NK cells, macrophages, neutrophils, eosinophils)
  • cell mediated immunity requires cytokines made by T cells, NK cells, NKT cells, dendritic cells and macrophages
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2
Q

Effector T cells do not require ? for activation

A
  • do not require CD28 costimulation for activation following TCR triggering (unlike naive T cells)
  • costimulatory signal may be provided by LFA-1 binding to ICAMs on target cells
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3
Q

Effector T cells Express Higher Levels of ? adhesion molecules than naive T cells

A
  • CD2 and LFA-1

- allows efficient binding of effector T cells to target cells

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4
Q

Effector T cells express ?, low levels of ? and no ?

A
  • CD44, which is upregulated following TCR signalling
  • low levels of CD62L
  • no CCR7 to prevent recirculation to secondary lymphoid tissue
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5
Q

Effector T cells traffic to…

A
  • tertiary lymphoid tissues and sites of inflammation

- naive t cells traffic to high endothelial venules in secondary lymphoid tissues

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6
Q

Effector T cell lifespan

A

-live for days to weeks

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7
Q

Effector CD4+ T Cells-under the influence of…

A
  • polarizing cytokines

- naive T cells that encounter cognate antigen differentiate into Th1, Th2, Th17, Tfh and Treg cells

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8
Q

FoxP3

A

Master Tc Regulator of induced Treg cell

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9
Q

T-Bet

A

Master Tc Regulator of th1 cell

  • effector cytokines are IFN-gamma, TNF
  • effector fxns are cell-mediated immunity, macrophage activation, inflammation
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10
Q

Effector CD4+ T cells express…

A
  • membrane bound effector molecules (lymphotoxin, Cd40 ligand)
  • soluble effector molecules (IFN gamma, TNF, ILs)
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11
Q

Functions of IFN-gamma and lymphotoxin

A

-promote macrophage activation by Th1 cells

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12
Q

Functions of CD40 ligand and IL-4

A
  • promote B cell activation by Tfh and Th2 cells

- promote allergic inflammation by Th2 cells

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13
Q

Functions of IL-17 and IL-22 (Th17)

A
  • secreted by Th17 cells

- promote inflammation

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14
Q

Functions of IL-10 and TGF-beta (Treg)

A

-downregulate cell. immune responses and inflammation

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15
Q

Effector Cd8+ T cells

A
  • effector molecules are membrane bound Fas ligand, secreted IFN-gamma, TNF and cytotoxins (perforin and granzymes)
  • perforin, granzymes and Fas ligand mediate target cell destruction by CTL
  • secreted IFN-gamma and TNF enhance cell mediated immunity
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16
Q

CTL Effector molecules produced (4)

A
  • cytotoxins (perforin and granzyme)
  • IFN-gamma
  • TNF
  • FasL
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17
Q

CTL Mechanism of Killing

A
  • cytotoxic granule release

- FasL-Fas interactions

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18
Q

NK T cell Effector molecules produced (5)

A
  • IFN-gamma
  • IL-4
  • GMCSF
  • IL-2
  • TNF
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19
Q

NK T cell Mechanism of Killing

A
  • FASL interactions predominantly

- can activate NK cells indirectly

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20
Q

NK cell Effector molecules produced (4)

A
  • cytotoxins (performs and granzymes)
  • IFN-gamma
  • TNF
  • FASL
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21
Q

NK cell Mechanism of Killing

A
  • cytotoxic granule release

- FasL-Fas interactions

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22
Q

Generation of Antigen-specific CTL-class I MHC

A

-class I MHC restricted CD8+ T cells eliminate any altered cells (virus/cancer) in the body since all nucleated cells express MHC class I molecules

23
Q

Generation of Antigen-specific CTL-activation phase

A

-stimulation of naive precursor CTL (CTL-P)

24
Q

Generation of Antigen-specific CTL-Effector Phase

A

-differentiated CTL engage and kill targets

25
Q

Generation of Antigen-specific CTL-licensing

A
  • antigen presenting dendritic cells licensed by th1 or h17 cells via class II MHC-TCR and CD40-CD40L interactions
  • or by activation of TLRs on the dendritic cells by microbial products
26
Q

Generation of Antigen-specific CTL-Activation of Naive CTL-Ps

A
  • activated via TCR triggering by foreign antigen/class I MHC complexes
  • costimulation provided by CD28-CD80/CD86 interactions
  • IL-2 provided by CD4 t cells, CD8 T cells interacting with the high affinity IL-2 receptor
  • CTL-Ps express high affinity IL-2 receptors that enable them to respond to IL-2
  • also secrete IL2 but not in sufficient amounts for CTL autocrine growth and differentiation
27
Q

Memory CTL-Ps

A
  • may secrete sufficient IL-2 for proliferation and differentiation into effector CTL
  • CD4+ T cell helps development of memory CD8+ T cells
28
Q

Role of IL-2 in CTL Response

A
  • CTL and Th1 need IL2 for proliferation and differentiation
  • for expression of genes coding for cytotoxic effector molecules (perforin, granzymes) stored in cytoplasmic granules
  • in the absence of IL2, th1 and CTLs undergo apoptosis–> rapid termination of immune response once the pathogen has been eliminated
29
Q

Effector Phase of CTL Response- Tc1 or Tc2 cells

A

Activated CD8 T cells may develop into:

  • Tc1 that secrete IFN-gamma and kill by perforin and FasL
  • or Tc2 cells that secrete IL4 but only small amnts of IFN-gamma and kill by perforin
30
Q

Effector Phase of CTL Response-Conjuate Formation

A
  • involves TCR recognition of foreign peptide presented by class I MHC on the target cell
  • CD8 and LFA-1 stabilize this interaction
  • TCR signalling causes transient increase in avidity of LFA-1 for ICAMs on the target cell that persists for 5-10 mins
31
Q

Effector Phase of CTL Response-Release of Cytotoxins

A
  • golgi stacks and storage granules containing cytotoxins reorient in the cytoplasm and conc. near the interface b/w the CTL and target cell
  • CTL release storage granule contents into the space b/w the 2 cells
32
Q

Effector Phase of CTL Response-Perforin

A

-perforin monomers, in the presence of Ca change confirmation to allow them to insert into target cell membrane, polymerize into pores, trigger endocytosis in response to membrane damage

33
Q

Effector Phase of CTL Response-Granzyme B

A
  • Granzyme B binds to mannose-6P receptors on target cells, complexes are internalized within vesicles
  • perforin then allows granzyme B to be released from the vesicle into cytoplasm
  • cleaves substrates to initiate apoptosis
34
Q

Effector Phase of CTL Response-Fas/FasL Pathway

A
  • the interaction of FasL on CTL w/ Fas on target cells leads to apoptosis
  • independent of Ca
35
Q

Effector Phase of CTL Response-Caspases

A
  • cysteine proteases that cleave proteins after an aspartic acid residue
  • perforin/granzyme and Fas/FasL pathway result in activation of caspase-3
  • leads to activation of endonucleases that fragment nucleosomal DNA and additional proteases that disassemble the cytoskeleton of the cell
36
Q

Effector Phase of CTL Response-viral DNA

A
  • also fragmented during CTL killing of target cells

- prevents viral rep. during the interval before target cell destruction

37
Q

Effector Phase of CTL Response-Serpins

A

-CTL protect themselves from the cytotoxic effects on their own perforin and granzyme by expressing serine protease inhibitors (serpins) that inhibit granzyme B

38
Q

NK cells

A
  • non specific cytotoxic effector cells

- important in defending against viruses and cancer

39
Q

NK cell development

A
  • arise from the same progenitor cells as T cells but do not develop exclusively in the thymus
  • express IL2R beta chains, CD2, CD16
  • do not express TCR, CD3, CD8
40
Q

NK cell target cell recognition

A
  • not MHC restricted

- some NK cells appear to have immunological memory

41
Q

NK cells as a source of IFN-gamma (3)

A
  • increases the microbicidal activity of macrophages
  • promotes Th1 differentiation
  • inhibits th2 development
  • drives CTL generation
42
Q

NK cells as a first line of defence

A

-first line of defence against viral infection b/c rapidly activated by IFN alpha and beta (made by virus infected cells to inhibit vrep. and protect neighbouring cells), IL12 produced by dendritic cells

43
Q

NK Cell Effector Function-Constitutively active

A

-since they have cytoplasmic granules w/ perforin and granzyme and express FasL before encountering target cells

44
Q

NK Cell Effector Function-Opposing-signals model

A
  • to distinguish altered self cells from normal
  • one category delivers an activating signal, while the other delivers an inhibitory signal
  • the balance b/w opposing signals determines whether an NK cell will kill the target cell
  • inhibitory signals override activation signals–> prevents NK cell mediated cytotoxicity, cytokine synthesis and proliferation
45
Q

NK Cell Effector Function-Activating Receptor C-type lectins

A

-recognize altered carb structures on virus infected/cancer cells

46
Q

NK Cell Effector Function-Inhibitory Receptors

A
  • lectin like inhibitory receptors
  • killer cell inhibitory receptors
  • deliver an inhibitory signal following interaction w/ class I MHC
  • target cells w/ low levels of MHC class I are killed while target cells w/ normal expression are spared
47
Q

Antibody-dependent Cell mediated cytotoxicity (ADCC)

A
  • NK cells, neutrophils, eosinophils, monocytes and macrophages express receptors for the Fc region of IgG (e.g. CD16 on NK cells)
  • allows ADCC reactions-> non-specific killer cells are directed to IgG coated target cells
48
Q

Antibody-dependent Cell mediated cytotoxicity (ADCC)-Neutrophils, Eosinophils, macrophages

A
  • those activated through their Fc receptors become more metabolically active and release the lytic contents of their cytoplasmic lysosomes
  • monocytes and macrophages secrete TNF, which is able to kill certain target cells
49
Q

Antibody-dependent Cell mediated cytotoxicity (ADCC)-NK cells

A
  • those that are activated through CD16 exocytose the contents of their cytoplasmic granules and kill by Fas/FasL pathway
  • secretes TNF which is able to kill certain target cells
50
Q

Signalling through CD16

A
  • also an important activating receptor for NK cells
  • causes phosphorylation of itams
  • creates docking station for syk
  • phosphorylation of adaptor cells
  • activation of second messengers
  • results in activation (prod. of cytokines, enhancement of phagocytic activity)
51
Q

What are NKT cells?

A
  • CD+/CD4- T cells that express NK cells and an invariant alpha/beta TCR that interacts w/ CD1d on APC and epithelial cells, which presents lipid and glycolipid antigens
  • bridge innate and adaptive immunity
52
Q

NKT cells as helper cells

A
  • act as helper cells by secreting large amnts of cytokines that can support antibody formation (IL4) or inflammation and CTL expansion (IFN gamma) depending on the nature of the stimulus
  • have FasL mediated cytotoxic effector fxn
53
Q

NKT cell function

A
  • rapid response system to provide early help against pathogens and malignant cells while T helper cell development is taking place
  • guide development of the appropriate immune response (humeral or cellular)

Immunology Final Exam (5 decks)

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