Autoimmunity (Lec 11)

Question 1

Specific vs Systemic autoimmune disorders

Answer 1

• Organ specific = target antigen is unique to an organ
• Systemic = target antigen is more widespread

Question 2

Positive feedback and chronic autoimmunity

Answer 2

• chronic inflammation occurs due to self-antigens
• results in tissue damage
• tissue damage results in the release of more self-antigens, which amplifies inflammation

Question 3

Autoimmune Disease Types

Answer 3

• resemble hypersensitivity reactions, except no type 1 because none are caused by IgE
  Type 2: Cell-bound Molecules (antibody mediated)
  Type 3: Immune complexes (antibody mated)
  Type 4: T cell mediated

Question 4

Type 2 autoimmune disease

Answer 4

• caused by antibodies binding directly to antigens
• Auto-antibodies can bind a receptor and act like a ligand to initiate signalling = receptor agonist
• Auto-antibodies can block ligand binding to a receptor = receptor antagonist

Question 5

Grave’s Disease

Answer 5

• agonist auto-antibodies, Type 2 autoimmune disease
• hyperactive thyroid gland due to agonist auto-antibodies
• Pituitary gland secretes thyroid
  stimulating hormone (TSH) , binds to TSH receptor and then releases T3 and T4 hormones, maintain basal metabolism
• anti-TSH receptor antibody binding to TSH receptor causes grave’s disease

Question 6

Transient autoimmune disorder

Answer 6

• condition where autoimmune symptoms appear temporarily but resolve on their own or with treatment, and do not persist long-term
• Pregnant mothers can pass on autoantibodies to fetus

Question 7

Plasmapheresis

Answer 7

• medical procedure used to remove harmful substances from the blood, especially autoantibodies
• removal and replacement of blood plasma

Question 8

Myasthenia Gravis

Answer 8

• Antagonist Auto-Antibodies, Type 2 autoimmune disorder
• Antagonistic antibodies
  make muscle less sensitive
  to neuronal stimulation
• acetylcholine receptors become internalized and degraded, which leads to impaired muscle contraction
• Can severely affect breathing

Question 9

Epitope spreading

Answer 9

• progressive involvement of more epitopes (and more auto-reactive immune cells) that can cause disease
  2 types:
• intramolecular
• intermolecular

Question 10

Intramolecular epitope spreading

Answer 10

New epitopes on the same protein become targets

Question 11

Intermolecular epitope spreading

Answer 11

Epitopes on different proteins (often part of the same tissue or complex) are targeted

Question 12

Systemic Lupus Erythematosus (SLE)

Answer 12

• type 3 autoimmune disorder
• Antibodies recognizing DNA in SLE result in the deposition of immune complexes (can lead to tissue damage and inflammation)
• Co-stimulation of BCR and TLR-9 by DNA activates B cells to produce autoantibodies towards DNA

Question 13

Rheumatic diseases

Answer 13

• Chronic and episodic inflammation of joints
• caused by immune complex deposition
• association with auto-reactive T cells

Question 14

Rheumatic fever

Answer 14

• inflammation in heart, joints and kidney after infection
• leads to transient autoimmunity due to viral molecular mimicry
• streptococcal cell wall stimulates antibody response
• some antibodies cross-react with heart tissue

Question 15

Rheumatoid Arthritis

Answer 15

• Type 4 autoimmune disorder
• can be initiated by conversion of arginine to citrulline = less stable protein
• can lead to autoreactive CD4 T cells
• trigger leads to inflammation in synovial (joint lining) membrane
• autoreactive CD4 T cells activate macrophages (production of cytokines), leading to sustained inflammation
• cytokines lead to production of MMP and RANK, that attack tissues and destroy the joints
• Autoreactive T cells can also result in activation of B cells that create autoantibodies and further contribute to disease progression

Question 16

Multiple Sclerosis

Answer 16

• Type 4 autoimmune disorder
• targets the central nervous system (CNS) leading to
  severe neurological symptoms
• trigger leads to initial inflammation focus in brain and blood-brain barrier becomes permeable
• T cells specific for CNS antigen reencounter antigen presented on microglia or dendritic cells in brain
• inflammatory reaction in brain occurs and demyelination of neurons occurs
• Immunological privilege in the brain means T cells never undergo negative selection on
  these antigens

Question 17

Type 1 Diabetes

Answer 17

• Type 4 autoimmune disorder
• Selective destruction of insulin producing cells (β cells) by CD8
  T cells
• effector T cell recognizes peptides from a β-cell specific protein and kills the β-cell
• no insulin can be made
• takes years to show symptoms, due to slow destruction of cells

Question 18

Immunological privilege

Answer 18

• phenomenon where certain sites in the body are protected from the normal immune surveillance and response
• protection allows tissues in these areas to avoid immune system attack
• can prevent damage to vital organs or tissues

Question 19

Insulitis

Answer 19

• Pancreatic islets get
  infiltrated by lymphocytes
• inflammation of the insulin-producing beta cells in the pancreas
• key feature in Type 1 diabetes