Autoimmunity=> molecular mimicry

Question 1

Infections can cause autoimmunity through molecular mimicry. What types of infections can cause autoimmunity?

Answer 1

• Group A streptococcus
• Chlamydia trachomatis
• Shigella, Salmonella, Yersinia, Campylobacter
• Borrelia
• Coxsackie, echoviruses, rubella

Question 2

What consequence could be a result from Group A streptococcus? Is there any HLA association?

Answer 2

rheumatic fever (carditis, polyarthritis)

No=> HLA association

Question 3

What is the HLA association and consequence of Chlamydia?

Answer 3

HLA-B27

Reiter’s syndrome (arthritis)

Question 4

What is the HLA association and consequence of Shigella, Salmonella, Yersinia, or Campylobacter?

Answer 4

HLA-B27

Reactive arthritis

Question 5

What is the HLA association and consequence for Borrelia?

Answer 5

HLA-DR2, DR4

Chronic arthritis in Lyme disease

Question 6

What is the HLA associated and consequence of Coxsackie, echoviruses, rubella?

Answer 6

• HLA-DQ1,
• HLA-DQ8
• DR4

Type I diabetes

Question 7

Describe the process of molecular mimicry wrt autoimmunity

Answer 7

1. same MHC molecule presents both a pathogen peptide and a self peptide that mimics it
2. Naive T cell activated by pathogen peptide presented by particular MHC molecule
3. Effector Th1 cell responds to self-peptide mimic and activates the macrophage, causing inflammation

Question 8

What are the 2 diseases of molecular mimicry?

Answer 8

Guillain Barre syndrome

Wegener’s granulomatosis

Question 9

How is Guillain Barre syndrome mediated? what is the results?

Answer 9

type II autoimmune disease mediated by IgG specific for gangliosides

demyelination results

Question 10

What is the typical onset of Guillain barre syndrome?

Answer 10

onset typically follows infection and immune response made against pathogen cross-reacts with gangliosides (Campylobacter jejuni)

Question 11

What are the symptoms of Guillain Barre syndrome?

Answer 11

symmetrical weakness of lower limbs

rapidly ascends to upper limbs and face

difficulty swallowing, breathing and drooling

Question 12

How is Wegener’s granulomatosis mediated by?

Answer 12

anti-neutrophil cytoplasmic Abs, or ANCAs (IgG)

most common determinant => proteinase-3

Question 13

Describe the Wegener’s granulomatosis mechanism of disease

Answer 13

ANCAs bind to neutrophils, causing them to become activated

cells upregulate adhesin molecule expression allowing them to bind to vascular endothelial cells

degranulate causing damaging to vasculature (vasculitis)