Tolerance and Autoimmunity

Question 1

define immunological tolerance

Answer 1

unresponsiveness of immune system to self antigens

Question 2

How is central and peripheral tolerance achieved?

Answer 2

Central tolerance
- negative selection of T and B cells during receptor formation and maturation

Peripheral tolerance
- induced through the function of Treg cells: cause anergy, suppression, and cell death of self-reactive T and B cells

Question 3

describe the structure and functions of Treg cells

Answer 3

structure: express Foxp3 and CD25 (also known as IL2 receptor)
functions: (1) prevent autoimmune disease, (2) down modulate immune response through release of TGF-beta and IL10, and (3) mediate transplant tolerance

Question 4

define autoimmunity

Answer 4

immune response against self (autologous) antigens

effector mechanisms: immune complexes, circulating autoantibodies, and autoreactive T lymphocytes

Question 5

what are the basic principles that lead to autoimmunity?

Answer 5

(1) susceptibility genes: HLA genes or non-HLA

(2) environmental factors - chronic disease, inflammation, molecular mimicry

Question 6

What HLA alleles are involved with the development of Type I diabetes and ankylosing spondylitis?

Answer 6

HLA-DR3/DR4

HLA-B27

Question 7

What other single gene defects have been found to cause autoimmune diseases?

Answer 7

AIRE - involved in presentation of peripheral (privileged) tissue to T cells during maturation
- autoimmune polyendocrine syndrome (APS-1)

Foxp3 - defective T reg cells
- X-linked polyendocrinopathy and enteropathy (IPEX)

Fas - defective apoptosis of self-reactive T and B cells
- autoimmune lymphoproliferative syndrom (ALPS)

Question 8

Describe 2 antibody mediated autoimmune disease.

Answer 8

Graves’ disease - formation of antibodies against thyroid stimulating hormone receptor leading to unregulated overproduction of thyroid hormones

Myasthenia gravis - formation of antibodies against AChR of the neuromuscular junction leading to blockage of receptor and muscle weakness

Question 9

what is multiple sclerosis

Answer 9

systemic autoimmune disease mediated by Th1 response against myelin protein which insulates neuron axons.

• more common in women and has been found to be associated with HLA-DR2
• symptoms: nervous system related including urinary incontinence, blindness, ataxia, muscle weakness, and paralysis of limbs