Lecture 4- Autoimmunity

Question 1

Autoimmunity:

Answer 1

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

Question 3

Autoimmune disease:

Answer 3

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

Question 4

autoimmunity –> autoimmune disease

Answer 4

• organ specific or
• non-organ specific

Question 5

autoimmune disease is driven by the presence of

Answer 5

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

Question 6

risk factors of autoimmune disease

Answer 6

• 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.

Question 7

Autoimmune disease can also be triggered by

Answer 7

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

Question 8

common autoimmune diseases and their target autoantigens: hashimotos thyroiditis

Answer 8

thyroid peroxidase and thryoglobulin–> causes hypothyroidism

(Type IV hypersensitivity reaction- involves lymphocytes and macrophages)

Question 10

common autoimmune diseases and their target autoantigens: type 1 DM

Answer 10

pancreatic islet cells- hyperglycaemia (Type IV)

Question 11

common autoimmune diseases and their target autoantigens: Multiple sclerosis

Answer 11

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

Question 12

common autoimmune diseases and their target autoantigens: good pastures disease

Answer 12

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

Question 13

common autoimmune diseases and their target autoantigens: addisons disease

Answer 13

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

Question 14

common autoimmune diseases and their target autoantigens: myasthenia gravis

Answer 14

acetylcholine receptor (NMJ)- skeletal muscle weakness

Question 15

common autoimmune diseases and their target autoantigens: graves

Answer 15

thryoid stimulating hormone receptro- hyperthryoidism (Type II)

Question 16

common autoimmune diseases and their target autoantigens: pernicious anaemia

Answer 16

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

Question 17

common autoimmune diseases and their target autoantigens: autoimmune haemolytic anaemia

Answer 17

red blood cell antigens- anaemia- Type II

Question 18

common autoimmune diseases and their target autoantigens: RA

Answer 18

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

Question 19

common autoimmune diseases and their target autoantigens: SLE

Answer 19

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

Question 20

common autoimmune diseases and their target autoantigens: Sjorens syndrome

Answer 20

nuclear antigens (Ro and La)

dry eyes, drymouth and arthritis - Type IV

Question 21

Auto immune disease can be divided in to 2 groups:

Answer 21

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.

Question 22

Hypersensitivity reactions triggered by autoimmune disease

Answer 22

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

Question 23

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

Via…

Answer 23

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

Non-organ specific= systemic inflammation

Question 24

Set of criteria for the diagnosis of a disease as autoimmune

Answer 24

Question 25

types of autoantibodies

Answer 25

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

Question 26

Primary autoantibodies

Answer 26

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

Question 27

Secondary autoantibodies

Answer 27

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

Question 28

Primary antibodies can be cleared using

Answer 28

plasmapheresis ​

Question 29

detection fos erum autoantibodies and autoimmune disease

Answer 29

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.

Question 30

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

Answer 30

Question 31

can mother pass autoimmune disease to neonates

Answer 31

Autoimmune disease can be transferred to neonates as maternal autoantibodies can be transferred but this effect diminishes by 6 months when maternal IgE/IgG fades.

• in the third trimester

Question 32

example of women with autoimmune disease and neonate

Answer 32

Question 33

Induction of autoimmunity

Answer 33

Breakdown of central tolerance

• Failure to delete autoreactive T cells

Breakdown of peripheral tolerance

• Regulatory T cells (Treg) defects
• Impaired immunomodulation
• Altered self-antigens

Activation of autoreactive B cells

• T cell-independent activation of B cells
• Carrier effect (complex foreign-self antigens)

Question 35

What triggers autoimmunity?

Answer 35

Genetic factors

• Increased risk with an affected sibling (8X)
• Increased risk with an affected identical twin (30X)
• AIRE mutations (APECED syndrome) that affect central tolerance
• Autoimmune disease associated with MHC variants (HLADR3/DR4)

Environmental factors

• Hormones
• Infections
• Drugs

Question 36

hormonal factors and autoimmunity

Answer 36

Question 37

infectious factors and autoimmunity

Answer 37

Question 38

therapeutic drugs and autoimmunity

Answer 38

Question 39

x2 clinical examples of what triggers autoimmunity

Answer 39

Question 40

Current and future therapeutic strategies for autoimmune diseases

Answer 40

Treatments available include

❖ Plasma exchange to remove auto antibodies

❖ immunosuppressive drugs to suppress autoreactive T cells ( no specific targeted therapies exist and these will have adverse side effects within the patients)

❖ anti-inflammatory drugs (corticosteroids) to treat the tissue damage

❖ replacement therapy surgery to treat organ dysfunction.

Question 41

monoclonal antibodie and autoimmune diseases

Answer 41

huge advances in the treatment of autoimmune disease with the development of targeted monoclonal antibodies which although expensive have the potential to offer a dramatic improvement in patient quality of life.

Question 42

Which drug for which autoimmune disease

Answer 42

replacement e.g. injecting insulin to make up for faulty pancreas