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Autoimmune disease Flashcards

1
Q

Describe the double-edged sword concept around immunity

A

Immune system must be able to fight infection and tolerate self

Prevent autoimmunity without being immune deficient

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2
Q

What is autoimmunity?

A

Occurs when an immune response is mounted against a self antigen

Caused by loss of tolerance

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3
Q

TRUE or FALSE

All autoimmune conditions lead to disease

A

FALSE

Some have subclinical presentations

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4
Q

Which categories can autoimmune diseases be split into?

A

Organ specific - it is clear the specific organ which is targeted

Systemic - affects multiple parts of the body

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5
Q

Examples of organ-specific autoimmune diseases

A

Type I diabetes

Goodpasture’s

Multiple sclerosis

Grave’s diseases

Hashimotos thyroiditis

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6
Q

Examples of systemic autoimmune diseases

A

Rheumatoid arthritis

Scleroderma

Systemic lupus erythematosus

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7
Q

Why do mechanisms of peripheral tolerance exist?

A

Because central tolerance occurring in the thymus is incomplete

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8
Q

Where does peripheral tolerance take place?

A

Lymph nodes

Spleen

Secondary immune organs

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9
Q

What is a key component of peripheral tolerance?

A

T regulatory cells

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10
Q

Studies proving the importance of T regulatory cells in peripheral tolerance

A

Studies on Treg deficient mice showed they have dysregulated immune responses

They develop lymphadenopathy and splenomegaly

Due to lack of cell control

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11
Q

Marker for T regulatory cells

A

Foxp3

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12
Q

What is IPEX?

A

Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome

It is an aggressive autoimmune disorder leading to early death

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13
Q

What is the cause of IPEX?

A

Mutations in the Foxp3 gene

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14
Q

When is the onset of IPEX?

A

Within first months of life

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15
Q

Presentation of IPEX

A

> 80% IPEX patients have type I diabetes, IBD and allergy

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16
Q

Pathophysiology of IPEX

A

Individuals make T cells but are not able to make Treg cells

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17
Q

What causes autoimmunity?

A

Mixture of many factors including genes, environment and failed immune regulation

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18
Q

What gene plays the largest contribution to the genetic susceptibility of autoimmunity?

A

HLA genes

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19
Q

Proof that more that genetics is involved in the development of autoimmune disease

A

Individuals with the same mutation to the MHC have different phenotypes

Some develop autoimmunity, some do not

Low concordance rates between twins

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20
Q

MHC allele linked to increased risk of ankylosing spondylitis

A

HLA-27

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21
Q

MHC allele linked to increased risk of rheumatoid arthritis

A

HLA-DRB1

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22
Q

MHC allele linked to increased risk of type I diabetes

A

HLA-DRB1

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23
Q

Polymorphisms in genes other than HLA shown to contribute to autoimmune disease

A

PTPN22 - control of B and T cell receptor signalling

CTLA4 - regulatory T cells

24
Q

What diseases have been associated with PTPN22 mutations?

25
What diseases have been associated with NOD2 mutations?
Chron's disease
26
What diseases have been associated with IL23R mutations?
IBD PS AS
27
What diseases have been associated with CTLA4 mutations?
T1D RA
28
What diseases have been associated with C25 mutations?
MS T1D
29
What diseases have been associated with C2 and C4 mutations?
SLE
30
What diseases have been associated with FCGRIIB mutations?
SLE
31
Proof that genetics is involved in autoimmune disease predisposition
Autoimmune diseases frequently run in families
32
Examples of environmental influences increasing the predisposition for autoimmune diseases
Infection Sunlight Microbiome Obesity Stress Diet
33
What is molecular mimicry?
When a peptide from a microbe resembles a self-antigen Activation of the immune response by this microbial epitope causes the development of an immune response against the organ
34
Describe the impact of gender on autoimmune disease prevalence
Many autoimmune diseases have female bias
35
Explain the possible causes of female bias behind autoimmune diseases
Lots of different reasons - CD4 T cells - antibody - gene dosage effects due to genes on the X-chromosomes
36
What are the different mechanisms of autoimmunity?
Blocking a receptor Stimulating a receptor Facilitating phagocytosis of the cell coated by the autoantibody
37
Describe the pathogenesis behind Myasthenia gravis
Autoantibodies block the acetylcholine receptors Therefore the ACh effects on muscles is inhibited Autoantibodies = antagonists
38
Describe the pathogenesis behind Graves disease
Autoantibodies = agonists Acts on the thyroid through stimulating the hormone receptor This causes release of thyroid hormone
39
Describe how autoantibodies can lead to cell death
Autoantibodies coat the cell Same principle as opsonisation and phagocytosis of bacteria Fc portion bind to Fc receptors on innate cells
40
Example of autoimmune diseases caused by mechanisms of cell death
Autoimmune thrombocytopenia Autoimmune haemolytic anaemica Autoimmune neutropenia
41
What is thrombocytopenia?
Low platelet number
42
What is haemolytic anaemia?
Low erythrocytes
43
What is neutropenia?
Low neutrophils
44
Which autoantibody characteristically cause Grave's disease?
Antibody to TSH receptor
45
Which autoantibody characteristically cause Rheumatoid arthritis?
IgG
46
Which autoantibody characteristically cause Hashimoto's disease?
Thyroid peroxidase
47
Which autoantibody characteristically cause Sjorgen syndrome?
SS-A SS-B
48
Which autoantibody characteristically cause Penicious anaemia?
Intrinsic factor
49
Which autoantibody characteristically cause Multiple sclerosis?
Myelin basic protein
50
Which autoantibody characteristically cause ankylosing spondylitis?
Multiple connective and skeletal proteins
51
Which autoantibody characteristically cause type I diabetes?
Insulin
52
Which autoantibody characteristically cause SLE?
dsDNA SS-A SS-B Histones
53
Examples of T cell mediated autoimmune destruction
Multiple sclerosis Type I diabetes
54
Which cells are involved in the progression of MS?
CD4 T cells Macrophages B cells
55
What causes the presentation of multiple sclerosis?
Demyelination in brain and the spinal cord
56
Presentation of multiple sclerosis
Slower nerve conduction Axonal injury Neurological dysfunction
57
Pathogenesis of systemic lupus erythematosus
Autoantibodies against nuclear components Immune complex deposition Defective clearance of dead cells

IMM005 (17 decks)

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