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IMM005 > Autoimmune disease > Flashcards

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
Q

What diseases have been associated with NOD2 mutations?

A

Chron’s disease

26
Q

What diseases have been associated with IL23R mutations?

27
Q

What diseases have been associated with CTLA4 mutations?

28
Q

What diseases have been associated with C25 mutations?

29
Q

What diseases have been associated with C2 and C4 mutations?

30
Q

What diseases have been associated with FCGRIIB mutations?

31
Q

Proof that genetics is involved in autoimmune disease predisposition

A

Autoimmune diseases frequently run in families

32
Q

Examples of environmental influences increasing the predisposition for autoimmune diseases

A

Infection

Sunlight

Microbiome

Obesity

Stress

Diet

33
Q

What is molecular mimicry?

A

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
Q

Describe the impact of gender on autoimmune disease prevalence

A

Many autoimmune diseases have female bias

35
Q

Explain the possible causes of female bias behind autoimmune diseases

A

Lots of different reasons

  • CD4 T cells
  • antibody
  • gene dosage effects due to genes on the X-chromosomes
36
Q

What are the different mechanisms of autoimmunity?

A

Blocking a receptor

Stimulating a receptor

Facilitating phagocytosis of the cell coated by the autoantibody

37
Q

Describe the pathogenesis behind Myasthenia gravis

A

Autoantibodies block the acetylcholine receptors

Therefore the ACh effects on muscles is inhibited

Autoantibodies = antagonists

38
Q

Describe the pathogenesis behind Graves disease

A

Autoantibodies = agonists

Acts on the thyroid through stimulating the hormone receptor

This causes release of thyroid hormone

39
Q

Describe how autoantibodies can lead to cell death

A

Autoantibodies coat the cell

Same principle as opsonisation and phagocytosis of bacteria

Fc portion bind to Fc receptors on innate cells

40
Q

Example of autoimmune diseases caused by mechanisms of cell death

A

Autoimmune thrombocytopenia

Autoimmune haemolytic anaemica

Autoimmune neutropenia

41
Q

What is thrombocytopenia?

A

Low platelet number

42
Q

What is haemolytic anaemia?

A

Low erythrocytes

43
Q

What is neutropenia?

A

Low neutrophils

44
Q

Which autoantibody characteristically cause Grave’s disease?

A

Antibody to TSH receptor

45
Q

Which autoantibody characteristically cause Rheumatoid arthritis?

46
Q

Which autoantibody characteristically cause Hashimoto’s disease?

A

Thyroid peroxidase

47
Q

Which autoantibody characteristically cause Sjorgen syndrome?

48
Q

Which autoantibody characteristically cause Penicious anaemia?

A

Intrinsic factor

49
Q

Which autoantibody characteristically cause Multiple sclerosis?

A

Myelin basic protein

50
Q

Which autoantibody characteristically cause ankylosing spondylitis?

A

Multiple connective and skeletal proteins

51
Q

Which autoantibody characteristically cause type I diabetes?

52
Q

Which autoantibody characteristically cause SLE?

A

dsDNA

SS-A

SS-B

Histones

53
Q

Examples of T cell mediated autoimmune destruction

A

Multiple sclerosis

Type I diabetes

54
Q

Which cells are involved in the progression of MS?

A

CD4 T cells

Macrophages

B cells

55
Q

What causes the presentation of multiple sclerosis?

A

Demyelination in brain and the spinal cord

56
Q

Presentation of multiple sclerosis

A

Slower nerve conduction

Axonal injury

Neurological dysfunction

57
Q

Pathogenesis of systemic lupus erythematosus

A

Autoantibodies against nuclear components

Immune complex deposition

Defective clearance of dead cells

IMM005 (17 decks)

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