lecture 28 - autoimmune diseases

Question 1

What is the association of autoimmune diseases with alleles of the MHC locus?

Answer 1

Relative risk = the frequency of disease with HLA/without HLA
Ie. individuals who have HLA-B27 allele are 90 times more likely to develop inflammation of the vertebrae (ankylosing spondylitis) than B27 negative individuals

Question 2

What is tolerance and what are the different classes>

Answer 2

Immunological unresponsiveness to self antigens
T cell
Central tolerance
Occurs in the thymus
Strong recognition of self antigen in thymus → apoptosis
Development of regulatory T cells
Peripheral tolerance
Tregs → interact with self antigens → prevention of activation of lymphocytes
High expression of CD4/CD25
B cell
Central tolerance
High affinity → apoptosis
Receptor editing → expression of new antigen receptor

Question 3

What is the mechanism of peripheral tolerance?

Answer 3

Anergy: inability of immune cell to mount response
Deletion: cell death of reactive cells

Question 4

How does a break in tolerance occur?

Answer 4

Polyclonal B cell activation by viral infection

infection/molecular mimicry: overlapping sequences are enough to initiate response
Rheumatic fever development after strep
release of sequestered antigen
Some so unique they’re never shown to B and T cells, think they are foreign and attack

Question 5

What are the different types of autoimmune diseases?

Answer 5

II: cell membrane associated self antigen
III: circulating soluble self antigen
IV: involves T cells that recognize self peptides bound to MHC molecules on cell membrane
Insulin dependent diabetes mellitus: beta cell antigen → destruction
Rheumatoid arthritis: synovial joint antigen → inflammation and destruction
Multiple sclerosis: myelin basic protein/proteolipid protein → brain degradation and para;ysis

Question 6

What is grave’s disease

Answer 6

Antibody binds receptor → thyroid produces thyroid hormone –. Thyroid hormones shut down TS production but have no effect on autoantibody production → excessive thyroid hormone production

Question 7

What is myasthenia gravis?

Answer 7

Antibodies against Acetylcholine receptors→ cross linking of receptors → uptake by endocytosis → degradation and impaird muscle contraction

Question 8

What is rheumatoid arthritis

Answer 8

Immune complexes due to antibodi vis self antigen causing redness, pain, swelling in lining of joints
Rheumatoid factor is an antibody that binds antigens on IgG molecules

Question 9

What is lupus

Answer 9

Antibodies against self DNA that leaks out of dead cells