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?

22
Q

Rheumatoid arthritis involves which type of hypersensitivity reaction?

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
Anti-dsDNA is associated with which condition?
SLE
26
Anti-Sm is associated with which condition?
SLE
27
Anti-Ro (SSA) and Anti-La (SSB) are associated with which conditions?
Sjogren's syndrome (also subacute cutaneous SLE and neonatal lupus syndrome)
28
Anti-U3-RNP is associated with which condition?
Systemic sclerosis
29
Anti-centromere antibody is associated with which condition?
Systemic sclerosis
30
Anti Scl-70 antibody is associated with which condition?
Systemic sclerosis
31
Anti-Jo-1 antibody is associated with which condition?
Polymyositis
32
Why does rheumatoid arthritis occur?
Infiltration of the synovium by self reactive CD4+ T cells ***_Then_*** Secondary involvement of activated B cells and autoantibodies
33
What is the role of TNF alpha and IL-1 in the disease process of rheumatoid arthritis?
* Stimulates fibroblasts, osteoclasts and chrondrocytes * Stimulates release of matrix metalloproteinases
34
What is a rheumatoid factor?
An autoantibody directed against the common (Fc) region of human IgG
35
Which antibodies are highly apecific for rheumatoid arthritis?
Anti-citrullinated peptide antibodies (ANPA) These are highly specific to RA, but only postive in around 70% of cases
36
what is myasthenia gravis (MG)
autoimmune disorder characterised by severe muscle weakness and progressive fatigue
37
what is the pathogenesis of myasthenia gravis
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
what causes myasthenia gravis
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
what are symptoms of myasthenia gravis
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
how is myasthenia gravis treated
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)