Tolerance And Autoimmunity- Lecture 10/20/21

Question 1

Tolerance

Answer 1

Failure to respond to an antigen

Question 2

Central tolerance

Answer 2

Tolerance due to the elimination of self-reactive developing lymphocytes (i.e. negative selection in bone marrow and thymus)

Question 3

Peripheral tolerance

Answer 3

Tolerance due to the elimination, inactivation, or inhibition of self-reactive mature lymphocytes (T and B cells) in peripheral tissue

Question 4

Examples of peripheral tolerance development (2)

Answer 4

• Anergy

- T- regulatory cells

Question 5

Anergy

Answer 5

When a B cell or T cell recognizes pathogen, but is never activated by the second signal (B7 or CD40), it eventually dies by apoptosis

Question 6

Function of t regulatory cells (3)

Answer 6

• Turn off the response
• Prevent autoimmunity
• How they work is not fully understood

Question 7

Mechanisms of Treg action (2)

Answer 7

1) cytokines (IL-10 and TGFB)

2) contact- dependent mechanisms

Question 8

AIRE

Answer 8

Gene responsible for self antigen presentation in the thymus, defect results in defect in T cell negative selection (too many self reactive T cells in circulation)

Question 9

Genetic factors in autoimmunity (3)

Answer 9

• Autoimmune diseases are more common in family members
• Increased incidence in twins (But not 100%)
• Association of most autoimmune diseases with MHC (HLA) alleles

Question 10

Ankylosing spondylitis

Answer 10

Associated with the HLA-B27 allele

Question 11

Factors that can give rise to autoimmunity (not failure of neg selection)

Answer 11

1) Exposure of hidden antigens (through damage)
2) Polyclonal lymphocyte activation (nonspecific stimulation)
3) Molecular mimicry (Foreign ag resembles self)
4) Hormonal factors (More common in females)

Question 12

Antibody mediates autoimmunity examples (2)

Answer 12

• Autoimmune hemolytic anemia

- Myasthenia gravis

Question 13

T-cell mediated autoimmunity examples (5)

Answer 13

• Crohn’s disease
• Insulin dependent diabetes mellitus
• Psoriasis
• Multiple sclerosis
• Celiac disease

Question 14

Both T cell and B cell mediated autoimmunity example (1)

Answer 14

Rheumatoid arthritis

Question 15

Molecular mimicry example

Answer 15

Rheumatic fever- strep antigens similar to self

Question 16

Lupus (SLE)

Answer 16

Autoantibodies to DNA and other self antigens, results in clumps that cause tissue damage, especially nephritis

Question 17

Graves’ disease

Answer 17

Antibody stimulates TSH receptor, leading to an increase in thyroid hormone (hyperthyroidism)

Question 18

Myasthenia gravis

Answer 18

Auto-antibody blocks AchR on muscle cells, leading to weakness

Question 19

Type I diabetes mellitus

Answer 19

T-cells recognize insulin on MHC-class I, kill pancreatic B cells (glucagon and somatostatin still recognized)