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POM 4 Immunology > 4.6 Immune Tolerance > Flashcards

4.6 Immune Tolerance Flashcards

(59 cards)

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1
Q

What are the reasons for having immune regulation (2)?

A

Avoid excessive inflammation and tissue damage during normal protective responses

Prevent inappropriate reactions against self-antigens

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2
Q

What is autoimmunity?

A

Systemic or organ specific immune response against self-antigens

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3
Q

What are allergies?

A

Harmful immune responses to non-infectious antigens that cause tissue damage and disease

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4
Q

What 2 things can mediate allergic responses?

A

IgE and mast cells – acute anaphylactic shock

T cells – delayed type hypersensitivity

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5
Q

What do hypercytokinemia and sepsis lead to?

A

Positive feedback loop

Too much immune response leads to cytokine production and damage

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6
Q

What are the 3 phases of cell mediated immunity, and explain each phase?

A

Induction phase – DCs load antigens onto MHC, migrate to lymph nodes and present antigens to lymphocytes

Effector phase – effector T cells migrate to sites of infection and elicit response

Memory phase – once all infected cells cleared, T cells move into contraction phase and immune response is shut down

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7
Q

What is meant by self-limitation?

A

The immune response declines once it has cleared the initial antigen

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8
Q

How do responses against pathogens decline as infection is cleared?

A

Apoptosis of lymphocytes as they lose their survival signals (the antigen)

Memory cells survive

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9
Q

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

A

Antigen recognition
Co-stimulation
Cytokine release

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10
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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11
Q

Inducing tolerance may be exploited to prevent…

A

Graft rejection, treat autoimmune conditions and allergic diseases

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12
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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13
Q

What is the central tolerance mechanism for B cells?

A

If immature B cells encounter antigens which cross link their IgM, apoptosis is triggered

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14
Q

What is the mechanism for central tolerance for T cells?

A

If the T cell binds self-MHC strongly, apoptosis
Doesn’t bind self-MHC, apoptosis
Binds self-MHC weakly, survives

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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 transcription factor allowing for the thymic expression of genes normally expressed in peripheral tissues

Thus these MHC bearing 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 reduce the availability of IL-2 for other B cells and T cells

Thus they are not stimulated to proliferate

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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 do Tregs do?

A

Inhibit other immune cells

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21
Q

What affect does IL-10 have?

A

Causes cells to express more death receptors and 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 happens when DCs present any antigen to naive T cells?

Study These Flashcards
A

Partial activation

25
What happens when DCs present specifically a **foreign** antigen to T cells?
Stimulates B7 expression on APC which binds CD28 on T cell, leading to **full activation**
26
What happens when a self-antigen binds a naive T cell?
Upregulation of **FOXP3** transcription factor Causes differentiation into T-reg
27
How do T-reg cells cause anergy?
Fully developed T-regs express **cytotoxic T lymphocyte associated antigen 4** (CTLA-4) CTLA-4 binds **B7** protein on APCs, preventing co-stimulation of other T cells, leading to **incomplete activation**
28
How do T-reg cells inhibit the proliferation of other T cells?
Express adenosine and IL-2 receptors to decrease availability for other T cells
29
What three things can happen to a B cell after it is exposed to an antigen?
1. Antibody production 2. Becomes a memory cell 3. Affinity maturation
30
What is affinity maturation?
A further round of differentiation for B cells so they can bind to antigens better Change occurs due to **somatic hypermutation**
31
What can affinity maturation sometimes lead to?
The production of self reactive B cells
32
Where does somatic hypermutation occur?
In the germinal centers of lymph nodes and spleen
33
What is Ig class switching?
When a B cell goes from producing one type of immunoglobulin to another
34
During class switching, what is happening to the genome of the antibody?
Somatic hypermutation
35
During class switching which part of the BCR changes?
The **constant** region of the **heavy** chain, not the variable region This is so the antigen specificity is not affected
36
Which enzyme is upregulated by cytokines to allow for class switching?
Activation induced cytidine deaminase Allows cuts to be made in the DNA, thus producing VDJ rearrangement
37
What three signals do immune cells need to be activated?
1. Antigen 2. Co-stimulation 3. Cytokines
38
What do mutations in FoxP3 lead to?
T-reg cells not produced properly Severe autoimmune diseases, like immune polyendocrinopathy enteropathy X-linked syndrome (IPEX)
39
What does IL-10 do?
**Blocks pro-inflammatory cytokine** synthesis including TNF, IL-6, IL-8, IFN-gamma and **downregulates macrophage** functions
40
What is an immune privileged area?
A site which can tolerance the introduction of new antigens without eliciting an immune response eg eyes and brain
41
Where does immunological ignorance occur?
In the eyes or brain as they are immunologically privileged
42
Why are T-regs only found in mammals?
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
43
Which Treg type develops in the thymus?
Natural Treg
44
Where do inducible Treg's come from?
Develop from mature CD4 T cells that are exposed to antigen in the periphery
45
How do T cells shape the immune response for different pathogens?
Through the use of cytokines
46
Which T helper cell is involved in controlling bacterial and fungal infections?
Th17
47
What cytokines do TfH release?
IL-21
48
Where are T follicular helper cells located?
Secondary lymphoid organs (tonsils, spleen, lymph nodes)
49
What structures do TfH play a particular role in?
The development of germinal centers
50
What co-stimulation and cytokines do TfH use to help B cells proliferate?
Co-stimulation – have **CD40** which interacts with **CD40L** on B cell Cytokine – produces **IL-21**
51
Which T cell cytokines drives Ig class switching?
IL-4, IL-5, TGF-Beta, IFN-gamma
52
What is the definition of tolerance?
**Specific unresponsiveness** to an antigen that is induced by exposure of lymphocytes to that antigen
53
Why is it necessary to delete cells before they enter into circulation?
Approximately 10^15 possible TCRs and antibodies generated at random Some of these will be self-reactive Therefore need to be removed
54
What is meant by anergy as a mechanism for peripheral toleance?
When an APC presents a **self-antigen** to a T cell, there is **no B7** expression on the APC and thus **no co-stimulation** Thus TCRs **cannot send activating signals** and T cells express **CTLA-4** which further reduces B7 availability, causing **inactivation**
55
What is meant by ignorance as a mechanism of peripheral tolerance?
When the antigen is not in high enough concentration for the naive T cell to become activated, thus the T cell becomes **anergic**
56
How does ignorance as a mechanism of peripheral tolerance occur?
Compartmentalisation and anti-inflammatory cytokines prevent migration of T cells out of **immunologically privileged sites**
57
What is AICD as a mechanism for peripheral tolerance
When the APC presents an antigen with Fas (death ligand) as its co-stimulatory molecules, drives the cell to apoptosis
58
What is antigen-induced cell death as a mechanism of peripheral tolerance?
When T cells repeatedly recognise self antigens and lack co-stimulation, this causes: **Decreased** IL2 and anti-apoptotic protein expression **Increased** pro-apoptotic protein expression, causing **apoptosis** **Increased** Fas and Fas ligands, causing **apoptosis**
59
How does the Fas ligand result in antigen induced cell death?
When Fas is ligated by FasL on CD8 T killer cells, it triggers **apoptosis** of the cell

POM 4 Immunology (14 decks)

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