3. Autoimmunity

Question 1

what is the difference between autoimmunity and autoimmune disease

Answer 1

autoimmunity = immune response against the host due to the loss of immunological tolerance to self-antigen(s) (e.g. in pregnancy, elderly)

autoimmune disease = disease caused by TISSUE DAMAGE or DISTURBED PHYSIOLOGICAL RESPONSES due to an auto-immune response

Question 2

what is the difference between organ specific and non-organ specific disease?

Answer 2

Organ specific = 1 or multiple self-antigen within a single organ or tissue

Non-organ specific = widely distributed self-antigen throughout the body

Question 3

name 3 examples of non-organ specific autoimmune diseases

Answer 3

1. autoimmune haemolytic anaemia (RBCs, rhesus Ag)
2. rheumatoid arthritis (IgG rheumatoid factor)
3. systemic lupus erythematosus (dsDNA + histones)

Question 4

name possible autoimmune diseases targeting the following organs and their self antigen

1. thyroid gland
2. adrenal gland
3. pancreas
4. skeletal muscle
5. nervous system
6. kidney

Answer 4

1. Hashimoto’s disease (thyroid peroxidase and thyroglobulin) or Graves’ disease (TSH R)
2. Addison’s disease (secretory cells adrenal cortex)
3. T1DM (pancreatic islet cells)
4. Myasthenia Gravis (ACh R)
5. Multiple sclerosis (intrinsic factor)
6. Goodpasture’s disease (glomerular/alveolar basement membrane)

Question 5

describe the 2 mechanisms by which autoimmunity can lead to disease

Answer 5

1. autoantibodies
   - complement activation
   - antibody-mediated cell cytotoxicity
   - neutrophil activation
2. autoreactive T cells
   - cytotoxic T cells
   - macrophages

Question 6

name the 6 criteria for the diagnosis of a disease as autoimmune

Answer 6

1. presence of autoantibodies/autoreactive T cells in serum
2. levels of autoantibodies correlate with disease severity
3. autoantibodies/autoreactive T cells found at the site of tissue damage
4. transfer of autoantibodies/autoreactive T cells to a healthy host induces the autoimmune disease
5. clinical benefit provided by immunomodulatory therapy
6. family history

Question 7

name the 3 mechanisms of autoimmunity induction

Answer 7

1. breakdown of central tolerance (e.g. gene mutation)
   - failure to delete autoreactive T cells
2. breakdown of peripheral tolerance
   - Treg defects
   - impaired immunomodulation
   - altered self-antigens
3. activation of autoreactive B cells
   - T cell-independent activation of B cells
   - carrier effect (complex foreign-self antigens)

Question 8

name 3 types of infection-induced autoimmune disorders

Answer 8

Infectious Ag has similarity with self-Ag

1. Rheumatic fever: Strep. pyogenes M protein similar to cardiac muscle Ag
2. Guillain-Barre syndrome: Campy. jejuni glycoproteins similar to myelin-associated gangliosides
3. T1DM: Coxsakievirus B4 nuclear protein similar to pancreatic islet cells