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IMMUNO > Immune Tolerance > Flashcards

Immune Tolerance Flashcards

1
Q

Why is immune tolerance important?

A

To shut down an immune response after it is not needed to avoid inflammation and damage to our own tissues

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2
Q

What is autoimmunity?

A

System of immune responses in an organism against its own cells and tissues, mediated by self antigens

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3
Q

What is the fundamental problem in regulating immune responses?

A

The imbalance between immune activation and control

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4
Q

How are allergies considered an autoimmune disease?

A

An allergic response is a harmful immune response to an normally non-harmful antigen which causes tissue damage and disease

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5
Q

What is hypercytokinemia?

A

A cytokine storm

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6
Q

What is meant by self-limitation?

A

The immune systems first response is to eliminate the antigen which initiated the response, meaning the first signal for the lymphocytes has been eliminated

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7
Q

What are the three mechanisms which license a cell to respond?

A

Antigen recognition
Co-Stimulation
Cytokine release

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8
Q

What are the three possible outcomes of an immune response?

A

Resolution - no damage
Chronic Inflammation - active inflammation and attempts to repair damage
Repair - healing with scar tissue and regeneration

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9
Q

What is meant by self tolerance?

A

Self Antigens will not cause harm to us

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10
Q

Inducing tolerance may be exploited to prevent…

A

Graft rejection, treat autoimmune conditions and allergic diseases

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11
Q

What is central tolerance?

A

The destruction of self- reactive T and B cells in the sites of their production / maturation, before they enter circulation

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12
Q

Where does central tolerance occur?

A

In the bone marrow and the thymus for B and T cells

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13
Q

What is the central tolerance mechanism for B cells?

A

if immature B cells in the bone marrow encounter any antigen which can cross link their IgM, then death of that cell is triggered via apoptosis

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14
Q

What is the mechanism for central tolerance for T cells?

A

If the T cells binds MHC too strong = apoptosis (negative selection)
If the T cell doesn’t bind any MHC = apoptosis
If the T cell binds MHC too weakly, kept

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15
Q

How can a T cell developing in the thymus encounter MHC bearing peptides that might be expressed in other parts of the body?

A

AIRE is a specialised transcription factor which allows for the expression of genes that are normally expressed in peripheral tissues, so these proteins and therefore peptides can be made and presented to T cells

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16
Q

What does an AIRE deficiency lead to ?

A

Multi-organ autoimmunity

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17
Q

What is peripheral tolerance?

A

Ensures that self reactive T and B cells which escaped central tolerance do not cause autoimmunity

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18
Q

How does the high level of IL-2 receptors on Tregs affect peripheral tolerance?

A

The Tregs therefore soak up the IL-2, meaning other lymphocytes like B cells and T cells cannot get as much IL-2, and therefore are not stimulated to proliferate as much

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19
Q

What are some of the immunosuppresive cytokines that Tregs release?

A

TGF, IL-10

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20
Q

What are Tregs?

A

T Regulatory cells which regulate the activation of other T cells

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21
Q

What affect does IL-10 have?

A

Causes cells to express more death ligands

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22
Q

What affect do Tregs have on DC’s?

A

They inhibit dendritic cells

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23
Q

What are the two types of Tregs?

A

Natural Tregs (nTreg) and Inducible Treg (iTreg)

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24
Q

What is the Fas ligand?

A

a death ligand

25
Q

How does the Fas ligand result in antigen induced cell death?

A

As an immune response progresses, Fas protein expression is upregulated
When Fas is ligated by FasL on CD8 T killer cells, it triggers apoptosis of the cell

26
Q

What is ignorance in relation to peripheral tolerance?

A

When the antigen concentrations are too low to trigger a T cell response

27
Q

If you have an antigen, by no co-stimulation, what happens to the cell?

A

it becomes anergic

28
Q

How can cells become anergic due to the effect of Tregs?

A

Anergy occurs when there is no co-stimulation (CD28 on T cell to B7 on B cell). Treg cytokines cause B7 expression to decrease meaning less co-stimulation, leading to the cells becoming anergic

29
Q

What three things can happen to a B cell after it is exposed to an antigen?

A
  1. Antibody production
  2. Becomes a memory cell
  3. Affinity maturation
30
Q

What is affinity maturation?

A

A further round of differentation taken by the B cell so that it can bind to antigen better - this change occurs through somatic hypermutation

31
Q

What can affinity maturation sometimes lead to?

A

The production of self reactive B cells

32
Q

Where does somatic hypermutation occur?

A

In the germinal centers of lymph nodes and spleen

33
Q

What is Ig class switching?

A

When a b cell goes from producing one type of immunoglobulin to another

34
Q

During class switching, what is happening to the genome of the antibody?

A

Somatic hypermutation

35
Q

During class switching which part of the BCR changes?

A

The constant region of the heavy chain, not the variable region - this is so the antigen specificity is not affected

36
Q

Which enzyme is upregulated by cytokines to allow for class switching?

A

AID - allows cuts to be made in the DNA, thus producing VDJ rearrangement

37
Q

What three signals do immune cells need to be activated?

A
  1. Antigen
  2. Co-stimulation
  3. Cytokines
38
Q

What is FoxP3?

A

Protein which is important in the development and regulation of Treg, T cells which limit the immune response

39
Q

What do mutations in FoxP3 lead to?

A

Severe autoimmune diseases like IPEX and Tregs are not produced properly

40
Q

What does IL-10 do?

A

Blocks pro-inflammatory cytokine synthesis including TNF, IL-6, IL-8, IFN-gamma and down regulates macrophage functions

41
Q

What is an immune privileged area?

A

A site which can tolerance the introduction of new antigens without eliciting an immune response eg eyes and brain

42
Q

Where does immunological ignorance occur?

A

In the eyes or brain as they are immunologically privileged

43
Q

What type of animal are Tregs found in?

A

Mammals

44
Q

Why are Tregs only found in mammals?

A

They are critical in pregnancy, as you get half MHC from mum and half MHC from dad, which may be seen as foreign antigens so tolerance is critical

45
Q

Which Treg type develops in the thymus?

A

Natural Treg

46
Q

Where do inducible Treg’s come from?

A

Develop from mature CD4 T cells that are exposed to antigen in the periphery; no role for thymus

47
Q

How do T cells shape the immune response for different pathogens?

A

Through the use of cytokines

48
Q

Which T Helper cell is involved in controlling bacterial and fungal infections?

A

Th17

49
Q

What cytokines do TfH release?

A

IL-21

50
Q

where are T follicular helper cells located?

A

Tfh are located in secondary lymphoid organs (SLOs), including the tonsil, spleen and lymph nodes.

51
Q

What structures do TfH play a particular role in?

A

The development of germinal centers

52
Q

what co-stimulation and cytokines do TfH use to help B cells proliferate?

A

Co-stimulation = have CD40 which interacts with CD40L on B cell

Cytokine = produces IL-21

53
Q

Which T cell Cytokines drives Ig class switching?

A

IL-4, IL-5, TGF-Beta, IFN-gamma

54
Q

What is the definition of tolerance?

A

specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen (tolerogen vs immunogen)

55
Q

Why is it necessary to delete cells before they enter into circulation?

A

Approximately 1015 possible TCR and 1015 possible antibodies generated at random

Some of these will be self-reactive

Therefore need to be removed

56
Q

What is meant by anergy as a mechanism for peripheral toleance?

A

Naive T cells need antigen and CO-STIMULATION in order to be activated
When a T cell sees an antigen on MHC of APC, and bind, however does not have appropriate co-stimulation - becomes ANERGIC (unresponsive) and is therefore even less likely to stimulate a response in the future

57
Q

What is meant by ignorance as a mechanism of peripheral tolerance?

A

When the antigen is not in high enough concentration for the naive T cell to become activating - leading to the T cell to become unresponsive

58
Q

Where does ignorance as a peripheral tolerance mechanism occur?

A

in immunologically privileged sites

59
Q

What is AICD as a mechanism for peripheral tolerance

A

When the APC presents an antigen with Fas (death ligand) as its co-stimulatory molecules, drives the cell to apoptosis

IMMUNO (14 decks)

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