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Cell And Molecular Biology Of The Immune System > Lecture 7 > Flashcards

Lecture 7 Flashcards

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1
Q

Why do we need immuological tolerance?

A

Many self reactive specificities would be produced, and autoimmune diseases would results from the immune system attacking urself

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2
Q

What happens if we don’t have tolerance?

A

Would lead to serious pathology

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3
Q

What are the two types of bad tolerance for TCR?

A
  1. T cells fail to recognise self MHC
  2. T cells recognise self MHC + peptide (autoreactive)
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4
Q

What is a useful type of T cell tolerance?

A

Recognise self MHC + any other peptide not present in thymus

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5
Q

What is negative selection of TCR tolerance?

A

When the T cells recognise their own self-MHC

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6
Q

What is T cell survival and tolerance based on?

A

TCR affinity

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7
Q

What is the best mechanism for T cell survival?

A

A population with TCRs that have a medium affinity - capable of binding peptides derived from antigens NOT present in the thymus

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8
Q

Not all self antigen are expressed in thymus, what else can be?

A

Insulin

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9
Q

What does AIRE stand for?

A

Autoimmune regulator protein

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10
Q

What is AIRE?

A

A transcription factor

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11
Q

What is the job of AIRE?

A

Allows lots of tissues specific genes to be expressed in the thymus at low levels

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12
Q

What is the reasons for insulin being expressed in the thymus?

A

Deletes autoreactive T cells

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13
Q

What does a global transcription factor allow?

A

Allows us to become tolerant as it controls expression

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14
Q

What is AIRE deficiency?

A

When People have major autoimmune syndromes

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15
Q

What leads to b cell tolerance?

A

Random Ig gene arrangements leads to self reactive BCRs

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16
Q

Where are autoreactive B cells negatively selected?

A

In the bone marrow

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17
Q

What is different about b cells than T cells in tolerance?

A

B cells get another change to re-arrange the self-reactive BCR

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18
Q

What is it called when self-reactive BCR can rearrange?

A

Receptor editing

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19
Q

What is receptor editing?

A

A new chain may remove self-reactivity changing the specific of the BCR

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20
Q

What does binding of self antigen by immature B cells lead to?

A

Death or anergy

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21
Q

What happens in anergy?

A

Sneak out the bone marrow by lowering the B cell receptor so they don’t get killed

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22
Q

What are the levels of BCR like in a anergic B cell?

A

Low levels of BCR become unresponsive

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23
Q

What happens when receptors encounter an AG that is not multivalent?

A

They done regulate BCR and leave the bone marrow unresponsive

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24
Q

Can T cells be made anergic?

A

Yes - if a T cell encounters an Ag in the absence of co-stimulation becomes anergic

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25
Q

What happens if a T cell only gets signal 1?

A

The T cell will override and not work

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26
Q

What are some other mechanisms of tolerance?

A

Immunological ignorance and privileged sites

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27
Q

What is immunological ignorance?

A

When the T cells don’t get enough expression to drive signal 1 or 2

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28
Q

What are privileged sites?

A

Stops immune cells going into the central nervous system with barriers

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29
Q

Where are the barriers in privileged sites?

A

Eyes, testis, CNS

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30
Q

What do B cells hope in tolerance?

A

They are dependent on T cell tolerance, they hope they will never get help from an autoreactive T cell

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31
Q

What are regulatory T cells?

A

Subsets of cells which are there to portrol other cells

32
Q

What happens if you dont have regulatory T cells?

A

You will have autoimmunity

33
Q

Where do Treg cells arise?

A

In the thymus from T cells with high affinity receptors or self antigens

34
Q

What are induced Tregs (iTregs)?

A

Cells that have come out of the thymus that have avoided negative selection

35
Q

What does IL-10 do?

A

Turns off antigen presentation function

36
Q

What happens if a cell produces IL-10?

A

It is turning off potentially self reactive cells

37
Q

What are Breg/10?

A

They are crucial for preventing autoimmunity

38
Q

What is regulation of immune responses?

A

To make that the response that is targeted towards the pathogen is pathogen specific and is controlled and regulated once it has done its job

39
Q

What are cytokines in TH2 (helper cells)

A

IL-4,5 and 13

40
Q

What are cytokines in TH1 (helper cells)?

A

Infrerferongamma

41
Q

What does interferongamma do?

A

Activates macrophages

42
Q

Why is interferongamma good for TH1?

A

If you have a bacteria infection then response will go to TH1 - macrophage will do its job better at engulfing the bacteria

43
Q

What are cytokines 4,5 and 13 good for TH2 if you have a parasitic worm?

A

The recruitment of innate cells release things to kill large cellular parasites

44
Q

What do naive CD4+ T cell differentiate into?

A

Effector T cells

45
Q

What do CD4+TH1 do?

A

Activate macrophages, NK cells and cytotoxic T cells

46
Q

What do CDR4+Th2 do?

A

Promote responses mediated by enosiophils and mast cells, antibody IgE

47
Q

What do CD4+Th17 do?

A

Promote responses against fungi

48
Q

What do CD4+ Treg/Breg do?

A

Suppress unwanted responses

49
Q

What do CD4+TFH do?

A

Specialised Th found in GC to help B cells (GC - germinal centre)

50
Q

What can CD4+TH1 cells express?

A

CD40L which binds to CD40 on macrophages

51
Q

What can CD4+TH1 kill?

A

Chronically infected macrophages, bacteria

52
Q

What cells are involved in CD4+Treg? (Biomarkers)

A

CD4+CD25+ and some CD8+ CELLS

53
Q

What is the function of Treg cells?

A

To make anti inflammatory cytokines to suppress other T cell responses

54
Q

What cels do CD4+Treg cells suppress?

A

TFG-beta and IL-10

55
Q

What does IL-10 inhibit?

A

Antigen presenting cells

56
Q

What is the Th response influenced by (helper cells)?

A

By signal 3 - influenced by cytokines that are present when T cells are activated

57
Q

Can cells go down TH1 and TH2?

A

No only one route at a time

58
Q

What do cytokines do to T cells?

A

They polarise them

59
Q

What is another cytokine in TH1?

A

IL-12

60
Q

What is a key process in TH helper cells?

A

Autocrine positive feed back loop

61
Q

What do PAMPS drive on dendritic cells?

A

Il-12

62
Q

WHAT IS PAMPS recognised by?

A

PRR

63
Q

What does pRR lead to?

A

CD80/86

64
Q

WHAT IS SIGNAL 2 in th1 responses?

A

CD86

65
Q

What is signal 3 in th1?

A

IL-12 moves to TH1 to its effector cell

66
Q

What is signal 2 in TH2?

A

Upregulates co-stimulator

67
Q

How does each route (TH1 and tH2) turn off the other route?

A

They inhibit the opposite pathway

68
Q

What do TH1 cytokines inhibit?

A

TH2 and TH17

69
Q

What do TH2 cytokines inhibit?

A

TH1 an dTH17

70
Q

What do TH17 inhibit?

A

Treg

71
Q

What do Treg inhibit?

A

TH1,TH2,TH17

72
Q

What does Treg allow?

A

A successful pregnancy

73
Q

How does Treg work in pregnancy?

A

Prevents the mother from rejecting her unborn foetus

74
Q

What causes allergy?

A

Excessive TH2

75
Q

What is a way viruses use to stop a mechanisms form happening?

A

To not infect APC but use cross presentation

Cell And Molecular Biology Of The Immune System (12 decks)

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