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Musculoskeletal > Immunology of Autoimmune disease > Flashcards

Immunology of Autoimmune disease Flashcards

1
Q

Everone has low levels of autoantibodies or autoreactive T cells.

True or false?

A

True

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2
Q

In order for autoimmunity to occur, there must be a _________ susceptibility followed by an ___________ ________ or ___________

A

Genetic

Initiating event or trigger

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3
Q

What is IPEX syndrome?

A

Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome

An inherited condition which involves a mutation in the FOXP3 gene

This gene is responsible for regulatory T cells which means autoimmunity is abundant in IPEX syndrome

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4
Q

How can IPEX syndrome treated?

A

Haematopoeitic stem cell transplant

Use of immunosuppressive drugs

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5
Q

How are hugely diverse B and T cell populations obtained?

A

T cell receptor alpha and beta chain gene segments are randomly re-arranged creating a huge variety of B and T cells

However, this also means the likelyhood of autoreactivity increases

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6
Q

What are the two tolerance mechanisms which try to counteract autoreactivity?

A
  1. Central tolerance - the removal of self-reactive lymphocytes in primary lymphoid tissues
  2. Peripheral tolerance - inactivation of self-reactive lymphocytes that escape central tolerance (mediated by regulatory T cells)
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7
Q

How do regulatory T cells cause suppression?

A

Secretion of IL-10 and TGF beta

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8
Q

Which HLA gene is associated with ankylosing spondylitis?

A

HLA B27

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9
Q

Which HLA gene is associated with rheumatoid arthritis?

A

HLA DR4

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10
Q

Which HLA gene is associated with SLE?

A

HLA-DR3

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11
Q

Which HLA gene is associated with multiple sclerosis?

A

HLA-DR2

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12
Q

Which HLA gene is associated with idiopathic diabetes mellitus?

A
  • HLA-DR3
  • HLA-DR4
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13
Q

Which HLA gene is associated with myasthenia gravis?

A

HLA-DR3

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14
Q

What are the three forms of HLA class I?

A
  1. HLA - A
  2. HLA - B
  3. HLA - C
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15
Q

What are the three forms of HLA class II?

A
  1. HLA - DR
  2. HLA - DQ
  3. HLA - DP
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16
Q

Genes for HLA are encoded on which chromosome?

A

6

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17
Q

What is the significance of having such variety in a population in terms of HLA alleles?

A

Different alleles can bind different peptides

Hence, some alleles will be more protective or susceptible to certain genetic conditions

18
Q

What is molecular mimicry?

A

This is when antibody produced to a foreign antigen can cross-react with self antigen.

This is due to the similar peptide structure of the foreign and self antigen

19
Q

What are superantigens?

A

Antigens which can activate lymphocytes outwith the binding sites

20
Q

What is antigen sequestration?

A

Release of antigen not normally available for recognition

21
Q

SLE involves which type of hypersensitivity reaction?

A

III

22
Q

Rheumatoid arthritis involves which type of hypersensitivity reaction?

A

IV

23
Q

When immune complexes form in the body, why is complement binding useful?

A

It aids removal

24
Q

In SLE, why is the clearance of apoptotic bodies and immune complexes delayed?

A

A C1Q mutation creating abnormal C2 and C4 which cannot aid in the removal process

A Mac1 mutation which hinders many processes including apoptosis

25
Q

Anti-dsDNA is associated with which condition?

A

SLE

26
Q

Anti-Sm is associated with which condition?

A

SLE

27
Q

Anti-Ro (SSA) and Anti-La (SSB) are associated with which conditions?

A

Sjogren’s syndrome

(also subacute cutaneous SLE and neonatal lupus syndrome)

28
Q

Anti-U3-RNP is associated with which condition?

A

Systemic sclerosis

29
Q

Anti-centromere antibody is associated with which condition?

A

Systemic sclerosis

30
Q

Anti Scl-70 antibody is associated with which condition?

A

Systemic sclerosis

31
Q

Anti-Jo-1 antibody is associated with which condition?

A

Polymyositis

32
Q

Why does rheumatoid arthritis occur?

A

Infiltration of the synovium by self reactive CD4+ T cells

Then

Secondary involvement of activated B cells and autoantibodies

33
Q

What is the role of TNF alpha and IL-1 in the disease process of rheumatoid arthritis?

A
  • Stimulates fibroblasts, osteoclasts and chrondrocytes
  • Stimulates release of matrix metalloproteinases
34
Q

What is a rheumatoid factor?

A

An autoantibody directed against the common (Fc) region of human IgG

35
Q

Which antibodies are highly apecific for rheumatoid arthritis?

A

Anti-citrullinated peptide antibodies (ANPA)

These are highly specific to RA, but only postive in around 70% of cases

36
Q

what is myasthenia gravis (MG)

A

autoimmune disorder characterised by severe muscle weakness and progressive fatigue

37
Q

what is the pathogenesis of myasthenia gravis

A

The autoimmune attack occurs when auto IgG autoantibodies form against the nicotinic acetylcholine postsynaptic receptors at neuromuscular junction of skeletal muscle - type II hypersensitivity

It is believed that the initial step triggering humoral immunity (CD4+ produces B cells) in MG takes place in thymic tissue and thymoma

38
Q

what causes myasthenia gravis

A

90% has no known cause, thymic tumour causes 10%

genetic predisposing factor = HLA association

medicatios linked = antibiotics, B blockers, lithium, magnesium

factors which worsen exacerbation: warm weather, surgery, emotional stress, menstruation, pregnancy

39
Q

what are symptoms of myasthenia gravis

A

facial droop, expressionless face, difficulty chewing and swallowing, drooling, episode of choking, nasal and low volume speech

less frequently = muscles of neck, shoulder girdle and hip flexors

in advanced stages = all muscles weak

40
Q

how is myasthenia gravis treated

A

increase neurotransmission = anticholinesterase agents (pyridostrigmine)

  • side effects = abdo cramps, diarrhoea, increased bronchial secretion, bradycardia, increased muscle cramps

reduce autoimmunity = immunosuppressants or corticosteroids, plasmapheresis (removes AChR antibodies), IVIg, eculizumab (inhibits cleavage of C5 preventing MAC)

surgery = thymectomy (eliminates source of continued antigenic stimulation)

Musculoskeletal (55 decks)

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