Tolerance and Autoimmunity Flashcards

1
Q

What type of immune response is involved in autoimmunity?

A

Adaptive immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which cell type is always involved in autoimmunity?

A

Lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What proportion of people has lymphocytes with the capability of recognising self-antigens?

A

ALL of us – this is normal autoimmunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the three main factors that affect the transition from normal autoimmunity to autoimmune disease?

A

Genetic susceptibility
Infections
Environmental factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why are autoimmune conditions chronic?

A

Because self-tissue is always present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

The effector mechanisms in autoimmunity resemble those of which type of immune reaction?

A

Hypersensitivity reactions (types 2, 3 and 4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What proportion of people affected by autoimmune disease isfemale?

A

75% overall (this changes between diseases)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is a possible reason for the increase in incidence of autoimmune disease?

A

Hygiene hypothesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the pathophysiology of autoimmune haemolytic anaemia.

A

There are autoantibodies against red blood cells, which bind to red blood cells and activate complement
This results in clearance and complement-mediated lysis of the autologous erythrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is a type II hypersensitivity reaction?

A

Antibody response against cellular or ECM antigens (insoluble antigens)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is a type III hypersensitivity reaction?

A

Immune complex formation by antibody against soluble antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is a type IV hypersensitivity reaction?

A

T cell mediated disease – delayed type hypersensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is Goodpasture’s syndrome?

A

Type 2 hypersensitivity reaction in which there are IgG antibodies against a type IV collagen found on the basement membrane in the glomerulus
This results in deposition of autoantibodies in the renal corpuscle and activation of complement leading to infiltration of inflammatory cells and kidney damage
NOTE: the inflammatory cells (e.g. neutrophils) bind to the Fc portion of antibodies via their own Fc receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do type II and type III immune reactions recruit inflammatory cells?

A

Inflammatory cells are recruited via the binding of inflammatory cells to the Fc portion of antibodies via their Fc receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the main difference between type II and type III hypersensitivity reactions?

A

Type II – insoluble antigens

Type III – soluble antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the autoantigen in multiple sclerosis?

A

Myelin basic protein

17
Q

Other than antigen-TCR binding, what else is required for the activation of naïve T cells?

A

Costimulation

18
Q

What is the dominant genetic factor affecting susceptibility to autoimmune disease?

A

HLA (class II in particular)

19
Q

What did the freemartin cattle experiment show about tolerance?

A

It showed that early exposure to foreign antigens allows the development of tolerance to those antigens

20
Q

Define immunological tolerance.

A

The acquired inability to respond to an antigenic stimulus

21
Q

What are the main features of immunological tolerance?

A

It is acquired
It is antigen specific
It is an active process in neonates

22
Q

What are the two types of immunological tolerance?

A

Central Tolerance = happens during lymphocyte development

Peripheral Tolerance = once we’ve developed mature lymphocytes, there are mechanisms to develop tolerance

23
Q

What are the three main mechanisms of peripheral tolerance?

A

Anergy
Ignorance
Regulation

24
Q

What are the three outcomes for T cells based on how stronglythey bind to MHC in the thymus?

A

Useless –don’t recognise MHC at all – die by apoptosis
Useful – associate weakly with MHC
Dangerous – associate too strongly with MHC – die by apoptosis

25
Q

What percentage of thymocytes survives selection?

A

5%

26
Q

What class of immunoglobulin are the B cell surface receptors?

A

IgD and IgM

27
Q

What happens to B cells that recognise soluble autoantigens?

A

They will migrate to the periphery but they do not express normal levels of IgM and they are anergic (they are not very responsive)

28
Q

What is the role of the AIRE transcription factor?

A

It is important for the low-level expression of a large variety of self-peptides in the thymus, against which the T cells are selected

29
Q

What is APECED caused by?

A

Autoimmune polyendocrinolpathy candidiasis ectodermal dystrophy
Mutation in the AIRE transcription factor
This mutation means that the T cells can’t be selected against a wide range of self-peptides so lots of self-reactive T cells get released into the circulation and can cause autoimmune disease

30
Q

What is anergy caused by?

A

The presentation of an antigen in the absence of costimulation – this makes the lymphocytes enter a refractory state

31
Q

What is immunological ignorance caused by?

A

Occurs when the antigen concentration is too low
It can be due to the absence of antigen presenting molecules
It occurs at immunologically privileged sites where the immune cells don’t normally penetrate
This is ignorance – the T cells never see their antigen

32
Q

Give an example of a failure of ignorance.

A

Sympathetic ophthalmia
Damage to the eye can release eye antigens into the lymphatics and lymph nodes
These antigens are recognised by T cells, which become activated against the eye antigens
The T cells then go back to both eyes and cause damage

33
Q

What are the main receptors expressed by Tregs?

A

CD4
CD25 –IL-2 receptor, which is an important growth factor for T cells
CTLA-4 – binds to B7 and sends a negative signal
FOXP3 – essential transcription factor for Treg development

34
Q

What is IPEX caused by?

A

Mutation in FOXP3
FOXP3 encodes a transcription factor that is critical for the development of T regs
A mutation in FOXP3 leads to the accumulation of autoreactive T cells

35
Q

What are the two types of Treg?

A
Natural Tregs (nTregs) – these are generated in the thymus  
Inducible Tregs (iTregs) – these are produced as part of the normal T cell response as a mechanism of dampening down an immune response after it has happened
36
Q

How can infections affect tolerant states?

A

Molecular mimicry of self-molecules
Induction of costimulatory molecules or inappropriate MHC class II expression: pro-inflammatory environment
Failure of regulation: effects on Tregs
Immune deviation: shift in type of immune response
Activation of APCs by pathogens leads to upregulation of costimulatory molecules