Lecture 4- Autoimmunity Flashcards Preview

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Autoimmunity:

Immune response against the host due to the loss of immunological tolerance of self- antigen(s)

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Autoimmune disease:

Disease caused by tissue damage or disturbed physiological responses due to an auto-immune response

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autoimmunity --> autoimmune disease

  • organ specific or
  • non-organ specific

 

 

 

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autoimmune disease is driven by the presence of

auto antibodies or auto reactive T cells resulting in organ fibrosis. 

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risk factors of autoimmune disease

  • Disease development is driven by genetic and environmental factors making familial history very important.
  • 80% of patients are female, usually presenting after puberty suggesting a strong link to hormonal factors but the link remains unknown.

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Autoimmune disease can also be triggered by

infectious microbes that have a similar epitope to one present withing the body – mimicry.

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common autoimmune diseases and their target autoantigens: hashimotos thyroiditis

thyroid peroxidase and thryoglobulin--> causes hypothyroidism

 

(Type IV hypersensitivity reaction- involves lymphocytes and macrophages)

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common autoimmune diseases and their target autoantigens: type 1 DM

pancreatic islet cells- hyperglycaemia (Type IV)

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common autoimmune diseases and their target autoantigens: Multiple sclerosis

myelin sheath (nerve fibers)- demyelinating disease (IV)

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common autoimmune diseases and their target autoantigens: good pastures disease

glmerular/alveolar basement membrane (kidney)- glomerulonephritis (type II hypersensitity- insoluble IgM/IgG)

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common autoimmune diseases and their target autoantigens: addisons disease

steroid-21 hydroxylase (adrenal cortex)- adrenal insufficiencys (Type II-IV)

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common autoimmune diseases and their target autoantigens: myasthenia gravis

acetylcholine receptor (NMJ)- skeletal muscle weakness

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common autoimmune diseases and their target autoantigens: graves

thryoid stimulating hormone receptro- hyperthryoidism (Type II)

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common autoimmune diseases and their target autoantigens: pernicious anaemia

intrinsic factor (terminal ileum)- vitamin B12 deficiency- Type II

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common autoimmune diseases and their target autoantigens: autoimmune haemolytic anaemia

red blood cell antigens- anaemia- Type II

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common autoimmune diseases and their target autoantigens: RA

rheumatoid factor (FC portion of the IgG)- inflammatory arthritis and systemic features (type IV)

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common autoimmune diseases and their target autoantigens: SLE

double stranded DNAA (dsDNA) and other nuclear proteins (histones)- mutisystem disease (type III- soluble IgG and IgM)

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common autoimmune diseases and their target autoantigens: Sjorens syndrome 

nuclear antigens (Ro and La)

dry eyes, drymouth and arthritis - Type IV

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Auto immune disease can be divided in to 2 groups:

Organ specific

When the auto antigen is only present in one organ resulting in organ/tissue specific damage

 

Non Organ specific

When the autoantigen is found in multiple sites resulting in damage throughout the body. Usually type III hypersensitivity.

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Hypersensitivity reactions triggered by autoimmune disease

(organ specific or non-organ specific) cause tissue fibrosis (non-reversible (no drugs to treat))

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Hypersensitivity reactions which cause fibrosis= Type IV, II and III

Via…

  • Autoantibody driven
    • Complement activation
    • Antibody-mediated cell
    • Cytotoxicity
    • Neutrophil activation 
  • Autoreactive T cell driven
    • Cytotoxic T cells
    • Macrophage

Non-organ specific= systemic inflammation

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Set of criteria for the diagnosis of a disease as autoimmune

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types of autoantibodies

primary (rare) and secondary (come later in disease)

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Primary autoantibodies 

driving the disease.

• Anti-TSHR antibodies in Graves’ disease

• Anti-acetylcholine receptor antibodies in Myasthenia gravis

• Anti-voltage-gated Ca2+ channel antibodies in Lambert-Eaton myasthenia syndrome

• Anti-anti-Glomerular basement membrane antibodies in Goodpasture’s syndrome

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Secondary autoantibodies

occurring much later is the disease course, they do not drive the disease.

• Anti-nuclear antibodies in SLE

• Anti-gastric parietal cell antibodies in pernicious anaemia

• Anti-thyroid peroxydase antibodies in Hashimoto thyroiditis

• Anti-Rheumatoid Factor antibodies in Rheumatoid arthritis

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Primary antibodies can be cleared using

plasmapheresis

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detection fos erum autoantibodies and autoimmune disease

Auto immune disease presents with the presence of auto reactive T cells / auto antibodies, determined by serology and biopsy, at a level of which correlates with disease severity and activity. The severity of the disease and clinical outcome that arises, depends upon the organ effected and the type of hypersensitivity reaction.

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imaging of Detection of autoantibodies/ autoreactive T cells at the site of tissue damage