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Immunology > Cytotoxic T cells and NK Cells > Flashcards

Cytotoxic T cells and NK Cells Flashcards

1
Q

What do CD8+ T cells recognise?

A

Peptides presenter by MHC class I

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2
Q

What do MHC class I sample?

A

Intracellular antigen

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3
Q

Why are CD8+ T cells important?

A

All viruses and some bacteria live in the cytoplasm of cells (CD4 will survey and protect extracellular pathogen) Once inside a cell they cannot be reached by antibodies To remove these pathogens, the infected cells have to be eliminated Need to be powerful but precise

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4
Q

What activates the dendritic cell?

A

The acquisition of virus

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5
Q

At the lymph node [priming CD8+ T cells]

A

Activation of naive CD8+ T cells [recognition phase] MHC class I recognises the T cell (signal 1) Brings signal 2 with cd28 costimulation Lead to signal 3/ cytokine response Leave the lymph node and go to tissue for an effector function Expansion of antigen specific clones (proliferation/differentiation)

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6
Q

At tissue cells (priming CD8+ T cells)

A

Killing of infected cells First antigen recognition event: priming (lymph node) Second, third, fourth of antigen recognition event: effector function (killing)

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7
Q

What does naive CD8+ cytotoxic T cell recognise?

A

Alpha-beta chain of TCR

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8
Q

What does TCR need to have?

A

CD3 domain to transmit signal inside the cell

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9
Q

Signal 1

A

MHC peptide + antigen recognise TCR + CD3

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10
Q

What is the stimulus transduced by?

A

CD8 recognising B3 chain of MHC I + peptide

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11
Q

What does tyrosine kinase do?

A

Phosphorylate CD3 to TCR which sets a response

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12
Q

What happens if CD28 is missing?

A

T cells become anergic

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13
Q

What does CD28 stabilise?

A

Transcription factors on IL-2 site

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14
Q

What does the production of IL-2 cause?

A

CD8 T cells to expand and proliferate

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15
Q

Where is CD40 present and why is it crucial?

A

Virally infected dendritic cell and is important for full activation

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16
Q

What are naive CD8+ cytotoxic T cell activated by?

A

Fully activated dendritic cell in the lymph nodes

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17
Q

What does the fully activated/mature dendritic cells express?

A

Fully complement of co-stimulators molecules e.g. B7 and CD40

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18
Q

How does CD4+ T cell help activate CD8 T cell?

A

Licence dendritic cell for stimulation of CD8+ T cells Recognise dendritic cell and make cytokines to activate CD8 T cell Interact with CD40 ligand Activation of CD80/86 will activate APC

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19
Q

High antigenic load

A

Sufficient for CD8 to recognise the DC

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20
Q

Low antigenic load

A

APC is not sufficiently activated to prime CD8 T cell

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21
Q

What happens once CD8+ cytotoxic T cells are activated by dendritic cells?

A

Armed CD8+ cytotoxic T cells recognise and kill virally/bacterially infected/tumour cells in the tissue

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22
Q

What cells have MHC class I molecules presenting virus peptides?

A

Only infected cells

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23
Q

Where does killing always happen?

A

In the tissue

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24
Q

How can cell death occur?

A

Apoptosis

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25
Q

Apoptosis

A

Quiet and controlled

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26
Q

Necrosis

A

Uncontrolled

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27
Q

What is Apoptosis

A

Programmed cell death

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28
Q

Apoptosis

A

Kills the host cell- this host cell cannot continue to make pathogens Cell membrane remains intact - no release of pathogens or toxic cellular components Apoptosis cells removed by phagocytes without induction of co-stimulators molecules Destroys any cytosolic pathogens due to enzymes involved

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29
Q

Necrosis

A

Caused by chemical or physical injury Uncontrolled Cell pops Pathogens would be released, propagating infection Toxic compound would be released

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30
Q

What are the characterises of apoptosis ?

A

Nuclear blebbing Alteration in cell morphology Cell membrane remain intact Shedding of small membrane vesicles DNA is fragmented by controlled digestion by nuclease enzymes Apoptotic bodies removed by phagocytic cells

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31
Q

What does armed cytotoxic T cells have?

A

Lytic granules (modified lysosomes)

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32
Q

What are the lytic granules?

A

Perforin Granzymes Granulysin SerglycinA

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33
Q

Perforin

A

Modifies the target cell to facilitate entry of granzymes [complement to C9]

34
Q

Granzymes

A

Proteases start chopping up proteins In the target cell

35
Q

What are two examples of Granzymes

A

Granzymes A: kill by chopping cell nuclear comments and cytoplasmic components Granzymes B: mitochondrial membrane become hyper-polarised and leaky - mitochondria pop

36
Q

Granulysin

A

Antimicrobial activity

37
Q

SerglycinA

A

scaffold protein that aids in delivery of perforin and granzymes

38
Q

How do cytotoxic T cell kill?

A

Granzymes and perforin

39
Q

What does granzymes and perforin release?

A

Granules from cytotoxic T cells

40
Q

What are 2 mechanisms in which perforin facilitate entry of granzymes into the cell

A

Perforin forms a ring structure on the outside of target cells and puncture it and granzymes go in through the perforin ring The perforin and granzymes are endocytosed completely - form endosomes and perforin form a ring structure on endosomes and granzymes goes in on endosomes

41
Q

What effect does granzymes have?

A

Upregulate caspase and activate them

42
Q

What do caspases remove?

A

Inhibitory domain of I-CAD and form functional caspases activated DNASEs ( enzymes that goes in and choose DNA)

43
Q

How are cytotoxic effector molecules released?

A

Precisely focused manner

44
Q

What do LFA-1 recognise?

A

I-CAM (intracellular adhesion molecule)

45
Q

What does the interaction of LFA- and I-CAM cause?

A

Pull cytotoxic T cell close to the target [directed-Hit]

46
Q

What are the characteristics of cytotoxic effector molecules?

A

Reorganisation of MTOC and Golgi Lytic granule release Cell death by Apoptosis

47
Q

What does the immunological synapse describe?

A

Contact of a T cell to its target

48
Q

What is the area of contact called of immunological synapse?

A

Supramolecular adhesion complex (SMAC)

49
Q

Peripheral SMAC

A

LFA-1: ICAM-1 [larger molecule]

50
Q

central SMAC

A

TCR:MHC:peptide, CD8

51
Q

1 CD8 can kill up to how many times?

A

26

52
Q

What is FAS ligand?

A

Death receptor - recruit death domain which activate caspases through removal of inhibitory domain - removed from caspases that then goes and cleaves DNA- shredding it and making to ready for Apoptosis

53
Q

Caspase

A

Enzyme that cleaves protein (stands for Cuts at Aspartic acid - ase)

54
Q

CAD

A

Caspase-Activatable DNAse

Enzyme that cleaves DNA

55
Q

I-CAD

A

A protein which inhibits CAD

56
Q

What do CD8+ T cells make?

A

Cytokines: IFN Gamma, TNF alpha and LTalpha

57
Q

What does IFN Gamma do?

A

Increase MHC class I expression Upregulate antigen processing machinery Increase macrophage recruitment and activation

58
Q

What are NK cells?

A

Natural killer cells

59
Q

Where is NK cell developed?

A

Bone marrow, part of lymphoid lineage

60
Q

What does NK cell express?

A

Low levels of CD8 but not the CD3 complex

61
Q

What is the role of NK cells?

A

Potent killers in the innate immune system

Kill target cell using similar machinery to CTL (performing, granzymes)

62
Q

What does NK cell not require?

A

Priming

63
Q

Where is NK cells important?

A

Early in infection (limit viral replication until CTL response develops)

64
Q

What are NK cells activated by?

A 
Cytokines 
Type I interferons and IL-12
IFN alpha 
IFN Beta 
TNF alpha
65
Q

What does NK cell respond rapidly to?

A

Viral infection

66
Q

What are NK cells important against and give examples

A 
Intercellular pathogens 
Herpes viruses
Leishmania (protozoan Parasite)
Listeria monocytogenes (bacterium) 
And against tumours
67
Q

What does NK cells not tend to eliminate?

A

Viruses

68
Q

What does NK cells possess?

A

Both activating and inhibitory receptors

69
Q

What does inhibitory receptors recognise?

A

Self component of healthy cells - MHC class I

70
Q

What does activating receptors recognise?

A

Molecules associated with cell stress

71
Q

What is NK cells?

A

Highly polymorphic

Undergo allelic conversions

72
Q

How does TCR and BCR get their variability?

A

Chromosomal rearrangement VDJ

73
Q

In the absence of infection

A 
Recognition of self and inhibition dominates 
Inhibitory receptors recognise MHC class I and cause production of phosphatases which remove the phosphorylated region of ITAM
74
Q

How do you keep the NK cells quiet?

A

Predominance of inhibitory receptors

75
Q

In the presence of infection

A

The balance shifts
The inhibitory signal is lost
Ligand associated with cell stress increase
Inhibitory signal lost because Virus will internalise MHC class I or loss of self-recognition
Lose the ability of phosphatases to cleave the activatory regions
Activatory signal predominates

76
Q

What are the 2 groups in humans the NK receptors are broken into?

A

LKC

NKC

77
Q

What are typical stress molecules?

A

MICA and MICB

78
Q

What is ADCC mediated by?

A

Cells expressing receptors for the Fc region of antibody molecules
FcgRIII/CD16 recognising IgG1/IgG3

79
Q

Where is low affinity for F.C. region of Antibodies found?

A

Constant region

80
Q

What is role in killing?

A

Virally infected cells
Helminths
Tumour cells
May be utilised for therapies e.g. Herceptin/trastuzumab

81
Q

What does CD16 recognise and bind to?

A

FC portion of the antibody such as IgG which has bound to the surface of pathogen infected target cell

Immunology (20 decks)

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